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Evaluation of Dupilumab in Patients With Persistent Asthma (Liberty Asthma Quest)

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ClinicalTrials.gov Identifier: NCT02414854
Recruitment Status : Completed
First Posted : April 13, 2015
Results First Posted : October 23, 2018
Last Update Posted : October 23, 2018
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Asthma
Interventions Drug: Dupilumab
Drug: Placebo
Drug: Inhaled corticosteroid (ICS) therapy
Drug: Albuterol/Salbutamol
Drug: Levalbuterol/Levosalbutamol
Enrollment 1902
Recruitment Details 4148 participants were screened from Apr 2015-Sep 2016. 1902 were randomized at 321 centers/22 countries. 2246 were screen failures. 1897 participants were treated; some received a different treatment than that assigned at randomization and for adverse event (AE) analysis were allocated to treatment actually received (see footnotes in below table)
Pre-assignment Details Randomization was stratified by age (<18 years, >=18 years), blood eosinophil count(<0.3 Giga/L, >=0.3 Giga/L), ICS dose level (medium, high), and country. Assignment to arms was done centrally using Interactive Voice/Web Response System in 2:2:1:1 ratio to Dupilumab 200 mg q2w, Dupilumab 300 mg q2w, Placebo (for 200 mg)q2w, Placebo (for 300 mg)q2w
Arm/Group Title Placebo (for Dupilumab 200 mg) q2w Dupilumab 200 mg q2w Placebo (for Dupilumab 300 mg) q2w Dupilumab 300 mg q2w
Hide Arm/Group Description 2 subcutaneous injections of matched Placebo (for Dupilumab 200 mg) as a loading dose on Day 1 (Week 0), followed by a single injection every 2 weeks (q2w) from Week 2 to Week 50 in combination with stable inhaled corticosteroid (ICS) and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication. 2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 0), followed by a single 200 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication. 2 subcutaneous injections of matched Placebo (for Dupilumab 300 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication. 2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 0), followed by a single 300 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
Period Title: Overall Study
Started [1] 317 631 321 633
Treated [1] 315 [2] 629 321 632 [3]
Completed 295 586 301 582
Not Completed 22 45 20 51
Reason Not Completed
Adverse Event             9             7             1             12
Poor compliance to protocol             1             1             2             2
Other than specified above             12             37             17             37
[1]
Randomized
[2]
2 got other treatment (1 each dupilumab 200+300) than assigned + were allocated to those in AE table
[3]
1 got other treatment (dupilumab 200) than assigned + was allocated to that in AE table
Arm/Group Title Placebo (for Dupilumab 200 mg) q2w Dupilumab 200 mg q2w Placebo (for Dupilumab 300 mg) q2w Dupilumab 300 mg q2w Total
Hide Arm/Group Description 2 subcutaneous injections of matched Placebo (for Dupilumab 200 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication. 2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 0), followed by a single 200 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication. 2 subcutaneous injections of matched Placebo (for Dupilumab 300 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication. 2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 0), followed by a single 300 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication. Total of all reporting groups
Overall Number of Baseline Participants 317 631 321 633 1902
Hide Baseline Analysis Population Description
Analysis was performed on all randomized participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 317 participants 631 participants 321 participants 633 participants 1902 participants
48.2  (15.6) 47.9  (15.3) 48.2  (14.7) 47.7  (15.6) 47.9  (15.3)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Adolescents (12-17 years) Number Analyzed 317 participants 631 participants 321 participants 633 participants 1902 participants
21
   6.6%
34
   5.4%
18
   5.6%
34
   5.4%
107
   5.6%
Adults (18-64 years) Number Analyzed 317 participants 631 participants 321 participants 633 participants 1902 participants
253
  79.8%
512
  81.1%
263
  81.9%
516
  81.5%
1544
  81.2%
From 65-84 years Number Analyzed 317 participants 631 participants 321 participants 633 participants 1902 participants
43
  13.6%
85
  13.5%
40
  12.5%
83
  13.1%
251
  13.2%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 317 participants 631 participants 321 participants 633 participants 1902 participants
Female
198
  62.5%
387
  61.3%
218
  67.9%
394
  62.2%
1197
  62.9%
Male
119
  37.5%
244
  38.7%
103
  32.1%
239
  37.8%
705
  37.1%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 317 participants 631 participants 321 participants 633 participants 1902 participants
Hispanic or Latino
81
  25.6%
171
  27.1%
79
  24.6%
159
  25.1%
490
  25.8%
Not Hispanic or Latino
236
  74.4%
460
  72.9%
242
  75.4%
474
  74.9%
1412
  74.2%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Caucasian/White Number Analyzed 317 participants 631 participants 321 participants 633 participants 1902 participants
265
  83.6%
510
  80.8%
273
  85.0%
529
  83.6%
1577
  82.9%
Black/of African descent Number Analyzed 317 participants 631 participants 321 participants 633 participants 1902 participants
14
   4.4%
33
   5.2%
12
   3.7%
21
   3.3%
80
   4.2%
Asian/Oriental Number Analyzed 317 participants 631 participants 321 participants 633 participants 1902 participants
33
  10.4%
78
  12.4%
33
  10.3%
79
  12.5%
223
  11.7%
American Indian or Alaska Native Number Analyzed 317 participants 631 participants 321 participants 633 participants 1902 participants
1
   0.3%
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.1%
Native Hawaiian or Other Pacific Islander Number Analyzed 317 participants 631 participants 321 participants 633 participants 1902 participants
0
   0.0%
1
   0.2%
0
   0.0%
0
   0.0%
1
   0.1%
Other Number Analyzed 317 participants 631 participants 321 participants 633 participants 1902 participants
4
   1.3%
9
   1.4%
3
   0.9%
4
   0.6%
20
   1.1%
Blood Eosinophil Group   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
<0.15 Giga/L Number Analyzed 317 participants 630 participants 320 participants 633 participants 1900 participants
85
  26.8%
193
  30.6%
83
  25.9%
181
  28.6%
542
  28.5%
>=0.15 - <0.3 Giga/L Number Analyzed 317 participants 630 participants 320 participants 633 participants 1900 participants
84
  26.5%
173
  27.5%
95
  29.7%
175
  27.6%
527
  27.7%
>=0.3 Giga/L Number Analyzed 317 participants 630 participants 320 participants 633 participants 1900 participants
148
  46.7%
264
  41.9%
142
  44.4%
277
  43.8%
831
  43.7%
[1]
Measure Analysis Population Description: Number analyzed = Number of participants with eosinophil data.
ICS Dose Level  
Measure Type: Count of Participants
Unit of measure:  Participants
High Number Analyzed 317 participants 631 participants 321 participants 633 participants 1902 participants
172
  54.3%
317
  50.2%
167
  52.0%
323
  51.0%
979
  51.5%
Medium Number Analyzed 317 participants 631 participants 321 participants 633 participants 1902 participants
144
  45.4%
310
  49.1%
151
  47.0%
303
  47.9%
908
  47.7%
Low Number Analyzed 317 participants 631 participants 321 participants 633 participants 1902 participants
1
   0.3%
4
   0.6%
3
   0.9%
7
   1.1%
15
   0.8%
1.Primary Outcome
Title Annualized Rate of Severe Exacerbation Events During The 52-Week Treatment Period: Intent-to-Treat (ITT) Population
Hide Description A severe exacerbation was defined as a deterioration of asthma requiring: use of systemic corticosteroids for >=3 days; or hospitalization or emergency room visit because of asthma, requiring systemic corticosteroids. Annualized event rate was the total number of exacerbations that occurred during the treatment period divided by the total number of participant-years treated.
Time Frame Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population that included all randomized population analyzed according to the treatment group allocated by randomization.
Arm/Group Title Placebo (for Dupilumab 200 mg) q2w Dupilumab 200 mg q2w Placebo (for Dupilumab 300 mg) q2w Dupilumab 300 mg q2w
Hide Arm/Group Description:
2 subcutaneous injections of matched Placebo (for Dupilumab 200 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 0), followed by a single 200 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of matched Placebo (for Dupilumab 300 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 0), followed by a single 300 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
Overall Number of Participants Analyzed 317 631 321 633
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Exacerbation per participant-year
0.871
(0.724 to 1.048)
0.456
(0.389 to 0.534)
0.970
(0.810 to 1.160)
0.524
(0.450 to 0.611)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (for Dupilumab 300 mg) q2w, Dupilumab 300 mg q2w
Comments Analysis was performed using negative binomial model with total number of events onset from randomization up to Week 52 or last contact date (whichever comes earlier) as response variable; with 4 treatment groups, age, region, baseline eosinophil strata, baseline ICS dose level, number of severe exacerbation events within 1 year prior to study as covariates; and log transformed standardized observation duration as an offset variable. Here, it is test no. 1 of testing order.
Type of Statistical Test Superiority
Comments Hierarchical testing procedure was used to control type I error rate at 0.05 level. The procedure included the 2 primary outcome measures and the first 13 secondary outcome measures reported and considered 2 pair-wise comparisons: Dupilumab 200 mg q2w vs Placebo (for Dupilumab 200 mg) q2w and Dupilumab 300 mg q2w vs Placebo (for Dupilumab 300 mg) q2w. Testing order is specified in analysis description.
Statistical Test of Hypothesis P-Value <0.0001
Comments Hierarchical testing sequence performed continued only when previous outcome measures was statistically significant at 0.05. Threshold for significance at 0.05 level.
Method Negative binomial regression model
Comments [Not Specified]
Method of Estimation Estimation Parameter Relative risk
Estimated Value 0.54
Confidence Interval (2-Sided) 95%
0.43 to 0.68
Estimation Comments Dupilumab 300 mg q2w vs Placebo (for Dupilumab 300 mg) q2w
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo (for Dupilumab 200 mg) q2w, Dupilumab 200 mg q2w
Comments Analysis was performed using negative binomial model with total number of events onset from randomization up to Week 52 or last contact date (whichever comes earlier) as response variable; with 4 treatment groups, age, region, baseline eosinophil strata, baseline ICS dose level, number of severe exacerbation events within 1 year prior to study as covariates; and log transformed standardized observation duration as an offset variable. Here, it is test no. 3 of testing order.
Type of Statistical Test Superiority
Comments Testing according to the hierarchical testing procedure (performed only if previous outcome measures were statistically significant).
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.05 level.
Method Negative binomial regression model
Comments [Not Specified]
Method of Estimation Estimation Parameter Relative risk
Estimated Value 0.523
Confidence Interval (2-Sided) 95%
0.413 to 0.662
Estimation Comments Dupilumab 200 mg q2w vs Placebo (for Dupilumab 200 mg) q2w
2.Primary Outcome
Title Absolute Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) at Week 12: ITT Population
Hide Description FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer.
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population. Here 'Number analyzed' signifies number of participants with available data for specified category.
Arm/Group Title Placebo (for Dupilumab 200 mg) q2w Dupilumab 200 mg q2w Placebo (for Dupilumab 300 mg) q2w Dupilumab 300 mg q2w
Hide Arm/Group Description:
2 subcutaneous injections of matched Placebo (for Dupilumab 200 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 0), followed by a single 200 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of matched Placebo (for Dupilumab 300 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 0), followed by a single 300 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
Overall Number of Participants Analyzed 317 631 321 633
Mean (Standard Deviation)
Unit of Measure: liter
Baseline Number Analyzed 317 participants 631 participants 321 participants 633 participants
1.76  (0.61) 1.78  (0.62) 1.75  (0.57) 1.78  (0.60)
Week 12 Number Analyzed 307 participants 611 participants 313 participants 610 participants
1.92  (0.70) 2.07  (0.76) 1.93  (0.68) 2.09  (0.70)
Change at Week 12 Number Analyzed 307 participants 611 participants 313 participants 610 participants
0.15  (0.36) 0.28  (0.45) 0.18  (0.39) 0.31  (0.43)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (for Dupilumab 300 mg) q2w, Dupilumab 300 mg q2w
Comments Analysis was performed using mixed-effect model with repeated measures (MMRM) model with change from baseline in FEV1 values up to Week 12 as response variable; and treatment, age, sex, baseline height, region, baseline eosinophil strata, baseline ICS dose level, visit, treatment by-visit interaction, baseline FEV1 value and baseline-by-visit interaction as covariates. Here, it is test no. 2 of testing order.
Type of Statistical Test Superiority
Comments Testing according to the hierarchical testing procedure (performed only if previous outcome measures were statistically significant).
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square (LS) Mean Difference
Estimated Value 0.13
Confidence Interval (2-Sided) 95%
0.08 to 0.18
Estimation Comments Dupilumab 300 mg q2w vs Placebo (for Dupilumab 300 mg) q2w
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo (for Dupilumab 200 mg) q2w, Dupilumab 200 mg q2w
Comments Analysis was performed using MMRM model with change from baseline in FEV1 values up to Week 12 as response variable; and treatment, age, sex, baseline height, region, baseline eosinophil strata, baseline ICS dose level, visit, treatment by-visit interaction, baseline FEV1 value and baseline-by-visit interaction as covariates. Here, it is test no. 4 of testing order.
Type of Statistical Test Superiority
Comments Testing according to the hierarchical testing procedure (performed only if previous outcome measures were statistically significant).
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.14
Confidence Interval (2-Sided) 95%
0.08 to 0.19
Estimation Comments Dupilumab 200 mg q2w vs Placebo (for Dupilumab 200 mg) q2w
3.Secondary Outcome
Title Percent Change From Baseline in Pre-Bronchodilator FEV1 at Week 12: ITT Population
Hide Description FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer.
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population. 'Overall number of participants analyzed'=participants evaluable for this outcome measure.
Arm/Group Title Placebo (for Dupilumab 200 mg) q2w Dupilumab 200 mg q2w Placebo (for Dupilumab 300 mg) q2w Dupilumab 300 mg q2w
Hide Arm/Group Description:
2 subcutaneous injections of matched Placebo (for Dupilumab 200 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 0), followed by a single 200 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of matched Placebo (for Dupilumab 300 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 0), followed by a single 300 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
Overall Number of Participants Analyzed 307 611 313 610
Mean (Standard Deviation)
Unit of Measure: percent change
10.16  (23.88) 18.74  (30.86) 11.87  (26.40) 20.89  (34.14)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (for Dupilumab 300 mg) q2w, Dupilumab 300 mg q2w
Comments Analysis performed using MMRM model(n=954 for 300 vs placebo)with percent change from baseline in FEV1 values up to Week 12 as response variable; & treatment, age, sex, baseline height, region, baseline eosinophil strata, baseline ICS dose level, visit, treatment by-visit interaction, baseline FEV1 value & baseline-by-visit interaction as covariates. Hierarchical testing procedure used to control type I error & handle multiple secondary endpoint analyses. Here, it is test no. 5 of testing order.
Type of Statistical Test Superiority
Comments Testing according to the hierarchical testing procedure (performed only if previous outcome measures were statistically significant).
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 9.41
Confidence Interval (2-Sided) 95%
5.74 to 13.07
Estimation Comments Dupilumab 300 mg q2w vs Placebo (for Dupilumab 300 mg) q2w
4.Secondary Outcome
Title Annualized Rate of Severe Exacerbation Events During The 52-Week Treatment Period: ITT Population With Baseline Eosinophil >=0.15 Giga/L
Hide Description A severe exacerbation was defined as a deterioration of asthma requiring: use of systemic corticosteroids for >=3 days; or hospitalization or emergency room visit because of asthma, requiring systemic corticosteroids. Annualized event rate was the total number of exacerbations that occurred during the treatment period divided by the total number of participant-years treated.
Time Frame Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed ITT population with baseline eosinophil >=0.15 Giga/L.
Arm/Group Title Placebo (for Dupilumab 200 mg) q2w Dupilumab 200 mg q2w Placebo (for Dupilumab 300 mg) q2w Dupilumab 300 mg q2w
Hide Arm/Group Description:
2 subcutaneous injections of matched Placebo (for Dupilumab 200 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 0), followed by a single 200 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of matched Placebo (for Dupilumab 300 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 0), followed by a single 300 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
Overall Number of Participants Analyzed 232 437 237 452
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Exacerbation per participant-year
1.007
(0.814 to 1.245)
0.445
(0.368 to 0.538)
1.081
(0.879 to 1.329)
0.434
(0.359 to 0.525)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (for Dupilumab 300 mg) q2w, Dupilumab 300 mg q2w
Comments Analysis was performed using negative binomial model with total number of events onset from randomization up to Week 52 or last contact date (whichever comes earlier) as response variable; with 4 treatment groups, age, region, baseline eosinophil strata, baseline ICS dose level, number of severe exacerbation events within 1 year prior to study as covariates; and log transformed standardized observation duration as an offset variable. Here, it is test no. 6 of testing order.
Type of Statistical Test Superiority
Comments Testing according to the hierarchical testing procedure (performed only if previous outcome measures were statistically significant).
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.05 level.
Method Negative binomial regression model
Comments [Not Specified]
Method of Estimation Estimation Parameter Relative risk
Estimated Value 0.402
Confidence Interval (2-Sided) 95%
0.307 to 0.526
Estimation Comments Dupilumab 300 mg q2w vs Placebo (for Dupilumab 300 mg) q2w
5.Secondary Outcome
Title Absolute Change From Baseline in Pre-Bronchodilator FEV1 at Week 12: ITT Population With Baseline Eosinophil >=0.15 Giga/L
Hide Description FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer.
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed ITT population with baseline eosinophil >=0.15 Giga/L. Here 'Number analyzed' signifies number of participants with available data for specified category.
Arm/Group Title Placebo (for Dupilumab 200 mg) q2w Dupilumab 200 mg q2w Placebo (for Dupilumab 300 mg) q2w Dupilumab 300 mg q2w
Hide Arm/Group Description:
2 subcutaneous injections of matched Placebo (for Dupilumab 200 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 0), followed by a single 200 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of matched Placebo (for Dupilumab 300 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 0), followed by a single 300 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
Overall Number of Participants Analyzed 232 437 237 452
Mean (Standard Deviation)
Unit of Measure: liter
Baseline Number Analyzed 232 participants 437 participants 237 participants 452 participants
1.77  (0.63) 1.81  (0.63) 1.75  (0.55) 1.79  (0.59)
Change at Week 12 Number Analyzed 224 participants 425 participants 229 participants 434 participants
0.17  (0.36) 0.34  (0.46) 0.21  (0.38) 0.35  (0.45)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (for Dupilumab 300 mg) q2w, Dupilumab 300 mg q2w
Comments Analysis was performed using MMRM model with change from baseline in FEV1 values up to Week 12 as response variable; and treatment, age, sex, baseline height, region, baseline eosinophil strata, baseline ICS dose level, visit, treatment by-visit interaction, baseline FEV1 value and baseline-by-visit interaction as covariates. Here, it is test no. 7 of testing order.
Type of Statistical Test Superiority
Comments Testing according to the hierarchical testing procedure (performed only if previous outcome measures were statistically significant).
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.15
Confidence Interval (2-Sided) 95%
0.09 to 0.21
Estimation Comments Dupilumab 300 mg q2w vs Placebo (for Dupilumab 300 mg) q2w
6.Secondary Outcome
Title Annualized Rate of Severe Exacerbation Events During The 52-Week Treatment Period: ITT Population With Baseline Eosinophil >=0.3 Giga/L
Hide Description A severe exacerbation was defined as a deterioration of asthma requiring: use of systemic corticosteroids for >=3 days; or hospitalization or emergency room visit because of asthma, requiring systemic corticosteroids. Annualized event rate was the total number of exacerbations that occurred during the treatment period divided by the total number of participant-years treated.
Time Frame Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population with baseline eosinophil >=0.3 Giga/L.
Arm/Group Title Placebo (for Dupilumab 200 mg) q2w Dupilumab 200 mg q2w Placebo (for Dupilumab 300 mg) q2w Dupilumab 300 mg q2w
Hide Arm/Group Description:
2 subcutaneous injections of matched Placebo (for Dupilumab 200 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 0), followed by a single 200 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of matched Placebo (for Dupilumab 300 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 0), followed by a single 300 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
Overall Number of Participants Analyzed 148 264 142 277
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Exacerbation per participant-year
1.081
(0.846 to 1.382)
0.370
(0.289 to 0.475)
1.236
(0.972 to 1.571)
0.403
(0.317 to 0.512)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (for Dupilumab 300 mg) q2w, Dupilumab 300 mg q2w
Comments Analysis was performed using negative binomial model with total number of events onset from randomization up to Week 52 or last contact date (whichever comes earlier) as response variable; with 4 treatment groups, age, region, baseline eosinophil strata, baseline ICS dose level, number of severe exacerbation events within 1 year prior to study as covariates; and log transformed standardized observation duration as an offset variable. Here, it is test no. 8 of testing order.
Type of Statistical Test Superiority
Comments Testing according to the hierarchical testing procedure (performed only if previous outcome measures were statistically significant).
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.05 level.
Method Negative binomial regression model
Comments [Not Specified]
Method of Estimation Estimation Parameter Relative risk
Estimated Value 0.326
Confidence Interval (2-Sided) 95%
0.234 to 0.454
Estimation Comments Dupilumab 300 mg q2w vs Placebo (for Dupilumab 300 mg) q2w
7.Secondary Outcome
Title Absolute Change From Baseline in Pre-Bronchodilator FEV1 at Week 12: ITT Population With Baseline Eosinophil >=0.3 Giga/L
Hide Description FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer.
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed ITT population with baseline eosinophil >=0.3 Giga/L. Here 'Number analyzed' signifies number of participants with available data for specified category.
Arm/Group Title Placebo (for Dupilumab 200 mg) q2w Dupilumab 200 mg q2w Placebo (for Dupilumab 300 mg) q2w Dupilumab 300 mg q2w
Hide Arm/Group Description:
2 subcutaneous injections of matched Placebo (for Dupilumab 200 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 0), followed by a single 200 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of matched Placebo (for Dupilumab 300 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 0), followed by a single 300 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
Overall Number of Participants Analyzed 148 264 142 277
Mean (Standard Deviation)
Unit of Measure: liter
Baseline Number Analyzed 148 participants 264 participants 142 participants 277 participants
1.78  (0.66) 1.81  (0.64) 1.73  (0.54) 1.75  (0.59)
Change at Week 12 Number Analyzed 144 participants 256 participants 139 participants 266 participants
0.19  (0.39) 0.39  (0.45) 0.20  (0.40) 0.43  (0.43)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (for Dupilumab 300 mg) q2w, Dupilumab 300 mg q2w
Comments Analysis was performed using MMRM model with change from baseline in FEV1 values up to Week 12 as response variable; and treatment, age, sex, baseline height, region, baseline eosinophil strata, baseline ICS dose level, visit, treatment by-visit interaction, baseline FEV1 value and baseline-by-visit interaction as covariates. Here, it is test no. 9 of testing order.
Type of Statistical Test Superiority
Comments Testing according to the hierarchical testing procedure (performed only if previous outcome measures were statistically significant).
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.24
Confidence Interval (2-Sided) 95%
0.16 to 0.32
Estimation Comments Dupilumab 300 mg q2w vs Placebo (for Dupilumab 300 mg) q2w
8.Secondary Outcome
Title Annualized Rate of Severe Exacerbation Events During The 52-Week Treatment Period: ITT Population With Baseline Eosinophil <0.3 Giga/L
Hide Description A severe exacerbation was defined as a deterioration of asthma requiring: use of systemic corticosteroids for >=3 days; or hospitalization or emergency room visit because of asthma, requiring systemic corticosteroids. Annualized event rate was the total number of exacerbations that occurred during the treatment period divided by the total number of participant-years treated.
Time Frame Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population with baseline eosinophil <0.3 Giga/L.
Arm/Group Title Placebo (for Dupilumab 200 mg) q2w Dupilumab 200 mg q2w Placebo (for Dupilumab 300 mg) q2w Dupilumab 300 mg q2w
Hide Arm/Group Description:
2 subcutaneous injections of matched Placebo (for Dupilumab 200 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 0), followed by a single 200 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of matched Placebo (for Dupilumab 300 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 0), followed by a single 300 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
Overall Number of Participants Analyzed 169 366 178 356
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Exacerbation per participant-year
0.675
(0.515 to 0.884)
0.512
(0.418 to 0.628)
0.732
(0.562 to 0.954)
0.610
(0.502 to 0.742)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (for Dupilumab 300 mg) q2w, Dupilumab 300 mg q2w
Comments Analysis was performed using negative binomial model with total number of events onset from randomization up to Week 52 or last contact date (whichever comes earlier) as response variable; with 4 treatment groups, age, region, baseline eosinophil strata, baseline ICS dose level, number of severe exacerbation events within 1 year prior to study as covariates; and log transformed standardized observation duration as an offset variable. Here, it is test no. 10 of testing order.
Type of Statistical Test Superiority
Comments Testing according to the hierarchical testing procedure (performed only if previous outcome measures were statistically significant).
Statistical Test of Hypothesis P-Value 0.2599
Comments Threshold for significance at 0.05 level.
Method Negative binomial regression model
Comments [Not Specified]
Method of Estimation Estimation Parameter Relative risk
Estimated Value 0.834
Confidence Interval (2-Sided) 95%
0.608 to 1.144
Estimation Comments Dupilumab 300 mg q2w vs Placebo (for Dupilumab 300 mg) q2w
9.Secondary Outcome
Title Annualized Rate of Severe Exacerbation Events During The 52-Week Treatment Period: ITT Population With High Dose ICS at Baseline
Hide Description A severe exacerbation was defined as a deterioration of asthma requiring: use of systemic corticosteroids for >=3 days; or hospitalization or emergency room visit because of asthma, requiring systemic corticosteroids. Annualized event rate was the total number of exacerbations that occurred during the treatment period divided by the total number of participant-years treated.
Time Frame Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population with high dose ICS at baseline.
Arm/Group Title Placebo (for Dupilumab 200 mg) q2w Dupilumab 200 mg q2w Placebo (for Dupilumab 300 mg) q2w Dupilumab 300 mg q2w
Hide Arm/Group Description:
2 subcutaneous injections of matched Placebo (for Dupilumab 200 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 0), followed by a single 200 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of matched Placebo (for Dupilumab 300 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 0), followed by a single 300 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
Overall Number of Participants Analyzed 172 317 167 323
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Exacerbation per participant-year
1.040
(0.824 to 1.314)
0.560
(0.455 to 0.690)
1.038
(0.818 to 1.317)
0.639
(0.523 to 0.780)
10.Secondary Outcome
Title Absolute Change From Baseline in Pre-Bronchodilator FEV1 at Week 12: ITT Population With High Dose ICS at Baseline
Hide Description FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer.
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population with high dose ICS at baseline. 'Overall number of participants analysed'=participants evaluable for this outcome measure at specified timepoint.
Arm/Group Title Placebo (for Dupilumab 200 mg) q2w Dupilumab 200 mg q2w Placebo (for Dupilumab 300 mg) q2w Dupilumab 300 mg q2w
Hide Arm/Group Description:
2 subcutaneous injections of matched Placebo (for Dupilumab 200 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 0), followed by a single 200 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of matched Placebo (for Dupilumab 300 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 0), followed by a single 300 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
Overall Number of Participants Analyzed 167 310 162 309
Mean (Standard Deviation)
Unit of Measure: liter
0.14  (0.34) 0.27  (0.42) 0.20  (0.40) 0.32  (0.43)
11.Secondary Outcome
Title Change From Baseline in Asthma Quality of Life Questionnaire With Standardized Activities (AQLQ [S]) Self-Administered Global Score at Week 24: ITT Population
Hide Description The AQLQ is a disease-specific, self-administered quality of life questionnaire designed to measure functional impairments that are most important to participants with asthma. The AQLQ comprises of 32 items in 4 domains: symptoms (12 items), activity limitation (11 items), emotional function (5 items), environmental stimuli (4 items). Each item is scored on a 7-point likert scale (1=maximal impairment, 7=no impairment). The 32 items of the questionnaire are averaged to produce one overall quality of life score ranging from 1 (severely impaired) to 7 (not impaired at all). Higher scores indicate better quality of life.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population. Here 'Number analyzed' signifies number of participants with available data for specified category.
Arm/Group Title Placebo (for Dupilumab 200 mg) q2w Dupilumab 200 mg q2w Placebo (for Dupilumab 300 mg) q2w Dupilumab 300 mg q2w
Hide Arm/Group Description:
2 subcutaneous injections of matched Placebo (for Dupilumab 200 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 0), followed by a single 200 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of matched Placebo (for Dupilumab 300 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 0), followed by a single 300 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
Overall Number of Participants Analyzed 317 631 321 633
Mean (Standard Deviation)
Unit of Measure: scores on a scale
Baseline Number Analyzed 299 participants 591 participants 314 participants 603 participants
4.26  (1.02) 4.31  (1.08) 4.30  (1.03) 4.28  (1.05)
Week 24 Number Analyzed 298 participants 592 participants 302 participants 596 participants
5.23  (1.07) 5.46  (1.12) 5.30  (1.15) 5.47  (1.09)
Change at Week 24 Number Analyzed 281 participants 560 participants 295 participants 569 participants
0.95  (1.03) 1.13  (1.14) 1.02  (1.10) 1.17  (1.11)
12.Secondary Outcome
Title Change From Baseline in AQLQ (S) Self- Administered Global Score at Week 24: ITT Population With Baseline Eosinophil >=0.3 Giga/L
Hide Description The AQLQ is a disease-specific, self-administered quality of life questionnaire designed to measure functional impairments that are most important to participants with asthma. The AQLQ comprises of 32 items in 4 domains: symptoms (12 items), activity limitation (11 items), emotional function (5 items), environmental stimuli (4 items). Each item is scored on a 7-point likert scale (1=maximal impairment, 7=no impairment). The 32 items of the questionnaire are averaged to produce one overall quality of life score ranging from 1 (severely impaired) to 7 (not impaired at all). Higher scores indicate better quality of life.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population with baseline eosinophil >=0.3 Giga/L. Here 'Number analyzed' signifies number of participants with available data for specified category.
Arm/Group Title Placebo (for Dupilumab 200 mg) q2w Dupilumab 200 mg q2w Placebo (for Dupilumab 300 mg) q2w Dupilumab 300 mg q2w
Hide Arm/Group Description:
2 subcutaneous injections of matched Placebo (for Dupilumab 200 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 0), followed by a single 200 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of matched Placebo (for Dupilumab 300 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 0), followed by a single 300 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
Overall Number of Participants Analyzed 148 264 142 277
Mean (Standard Deviation)
Unit of Measure: scores on a scale
Baseline Number Analyzed 136 participants 254 participants 138 participants 263 participants
4.24  (0.98) 4.24  (1.11) 4.21  (0.97) 4.36  (1.05)
Change at Week 24 Number Analyzed 129 participants 241 participants 130 participants 244 participants
0.97  (1.01) 1.39  (1.15) 1.02  (1.25) 1.30  (1.15)
13.Secondary Outcome
Title Change From Baseline in Asthma Control Questionnaire 5-item Version (ACQ-5) Score at Week 24: ITT Population
Hide Description The ACQ-5 has 5 questions, reflecting the top-scoring five asthma symptoms: woken at night by symptoms, wake in the mornings with symptoms, limitation of daily activities, shortness of breath and wheeze. Participants were asked to recall how their asthma had been during the previous week and to respond to each of the five symptom questions on a 7-point scale ranged from 0 (no impairment) to 6 (maximum impairment). ACQ-5 total score was mean of the scores of all 5 questions and, therefore, ranged from 0 (totally controlled) to 6 (severely uncontrolled). Higher score indicated lower asthma control.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population. Here 'Number analyzed' signifies number of participants with available data for specified category.
Arm/Group Title Placebo (for Dupilumab 200 mg) q2w Dupilumab 200 mg q2w Placebo (for Dupilumab 300 mg) q2w Dupilumab 300 mg q2w
Hide Arm/Group Description:
2 subcutaneous injections of matched Placebo (for Dupilumab 200 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 0), followed by a single 200 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of matched Placebo (for Dupilumab 300 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 0), followed by a single 300 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
Overall Number of Participants Analyzed 317 631 321 633
Mean (Standard Deviation)
Unit of Measure: scores on a scale
Baseline Number Analyzed 317 participants 631 participants 321 participants 633 participants
2.71  (0.73) 2.76  (0.80) 2.77  (0.77) 2.77  (0.76)
Week 24 Number Analyzed 296 participants 590 participants 297 participants 585 participants
1.67  (1.06) 1.33  (1.05) 1.58  (1.08) 1.37  (1.10)
Change at Week 24 Number Analyzed 296 participants 590 participants 297 participants 585 participants
-1.06  (1.01) -1.43  (1.05) -1.19  (1.10) -1.38  (1.10)
14.Secondary Outcome
Title Annualized Rate of Severe Exacerbation Events Resulting in Hospitalization or Emergency Room Visit During The 52-Week Treatment Period: ITT Population
Hide Description A severe exacerbation was defined as a deterioration of asthma requiring: use of systemic corticosteroids for >=3 days; or hospitalization or emergency room visit because of asthma, requiring systemic corticosteroids. Annualized event rate was the total number of exacerbations (resulted hospitalization or emergency room visit) that occurred during the treatment period divided by the total number of participant-years treated.
Time Frame Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population.
Arm/Group Title Placebo (for Dupilumab 200 mg) q2w Dupilumab 200 mg q2w Placebo (for Dupilumab 300 mg) q2w Dupilumab 300 mg q2w
Hide Arm/Group Description:
2 subcutaneous injections of matched Placebo (for Dupilumab 200 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 0), followed by a single 200 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of matched Placebo (for Dupilumab 300 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 0), followed by a single 300 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
Overall Number of Participants Analyzed 317 631 321 633
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Exacerbation per participant-year
0.081
(0.049 to 0.135)
0.043
(0.027 to 0.068)
0.034
(0.017 to 0.066)
0.025
(0.014 to 0.043)
15.Secondary Outcome
Title Absolute Change From Baseline in Pre-Bronchodilator FEV1 at Week 12: ITT Population With Baseline Eosinophil <0.3 Giga/L
Hide Description FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer.
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed ITT population with baseline eosinophil <0.3 Giga/L. 'Overall number of participants analysed'=participants evaluable for this outcome measure at specified timepoint.
Arm/Group Title Placebo (for Dupilumab 200 mg) q2w Dupilumab 200 mg q2w Placebo (for Dupilumab 300 mg) q2w Dupilumab 300 mg q2w
Hide Arm/Group Description:
2 subcutaneous injections of matched Placebo (for Dupilumab 200 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 0), followed by a single 200 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of matched Placebo (for Dupilumab 300 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 0), followed by a single 300 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
Overall Number of Participants Analyzed 163 354 173 344
Mean (Standard Deviation)
Unit of Measure: liter
0.12  (0.32) 0.21  (0.43) 0.17  (0.39) 0.21  (0.41)
16.Secondary Outcome
Title Percent Change From Baseline in Pre-Bronchodilator FEV1 at Week 12: ITT Population With Baseline Eosinophil >=0.3 Giga/L
Hide Description FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer.
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population with baseline eosinophil >=0.3 Giga/L. 'Overall number of participants analyzed'=participants evaluable for this outcome measure at specified timepoint.
Arm/Group Title Placebo (for Dupilumab 200 mg) q2w Dupilumab 200 mg q2w Placebo (for Dupilumab 300 mg) q2w Dupilumab 300 mg q2w
Hide Arm/Group Description:
2 subcutaneous injections of matched Placebo (for Dupilumab 200 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 0), followed by a single 200 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of matched Placebo (for Dupilumab 300 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 0), followed by a single 300 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
Overall Number of Participants Analyzed 144 256 139 266
Mean (Standard Deviation)
Unit of Measure: percent change
13.40  (27.01) 26.41  (33.69) 13.05  (25.27) 30.58  (38.22)
17.Secondary Outcome
Title Percent Change From Baseline in Pre-Bronchodilator FEV1 at Week 12: ITT Population With High Dose ICS at Baseline
Hide Description FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer.
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population with high dose ICS at baseline. 'Overall number of participants analysed'=participants evaluable for this outcome measure at specified timepoint.
Arm/Group Title Placebo (for Dupilumab 200 mg) q2w Dupilumab 200 mg q2w Placebo (for Dupilumab 300 mg) q2w Dupilumab 300 mg q2w
Hide Arm/Group Description:
2 subcutaneous injections of matched Placebo (for Dupilumab 200 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 0), followed by a single 200 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of matched Placebo (for Dupilumab 300 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 0), followed by a single 300 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
Overall Number of Participants Analyzed 167 310 162 309
Mean (Standard Deviation)
Unit of Measure: percent change
8.47  (20.94) 17.99  (28.43) 13.22  (26.52) 23.41  (37.26)
18.Secondary Outcome
Title Percent Change From Baseline in Pre-Bronchodilator FEV1 at Week 12: ITT Population With Baseline Eosinophil >=0.15 Giga/L
Hide Description FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer.
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population with baseline eosinophil >=0.15 Giga/L. 'Overall number of participants analyzed'=participants evaluable for this outcome measure at specified timepoint.
Arm/Group Title Placebo (for Dupilumab 200 mg) q2w Dupilumab 200 mg q2w Placebo (for Dupilumab 300 mg) q2w Dupilumab 300 mg q2w
Hide Arm/Group Description:
2 subcutaneous injections of matched Placebo (for Dupilumab 200 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 0), followed by a single 200 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of matched Placebo (for Dupilumab 300 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 0), followed by a single 300 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
Overall Number of Participants Analyzed 224 425 229 434
Mean (Standard Deviation)
Unit of Measure: percent change
11.43  (24.71) 22.04  (31.96) 13.49  (25.18) 24.04  (35.71)
19.Secondary Outcome
Title Absolute Change From Baseline in Pre-Bronchodilator FEV1 at Weeks 2, 4, 8, 24, 36, and 52: ITT Population
Hide Description FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer.
Time Frame Baseline, Weeks 2, 4, 8, 24, 36, and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population. Here 'Number analyzed' signifies number of participants with available data for specified category.
Arm/Group Title Placebo (for Dupilumab 200 mg) q2w Dupilumab 200 mg q2w Placebo (for Dupilumab 300 mg) q2w Dupilumab 300 mg q2w
Hide Arm/Group Description:
2 subcutaneous injections of matched Placebo (for Dupilumab 200 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 0), followed by a single 200 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of matched Placebo (for Dupilumab 300 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 0), followed by a single 300 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
Overall Number of Participants Analyzed 317 631 321 633
Mean (Standard Deviation)
Unit of Measure: liter
Change at Week 2 Number Analyzed 315 participants 610 participants 313 participants 625 participants
0.08  (0.35) 0.22  (0.38) 0.10  (0.34) 0.25  (0.40)
Change at Week 4 Number Analyzed 307 participants 613 participants 311 participants 614 participants
0.13  (0.35) 0.24  (0.40) 0.13  (0.34) 0.27  (0.41)
Change at Week 8 Number Analyzed 305 participants 604 participants 311 participants 609 participants
0.15  (0.38) 0.28  (0.42) 0.19  (0.40) 0.29  (0.43)
Change at Week 24 Number Analyzed 300 participants 599 participants 296 participants 596 participants
0.13  (0.40) 0.31  (0.45) 0.19  (0.44) 0.30  (0.44)
Change at Week 36 Number Analyzed 289 participants 590 participants 301 participants 584 participants
0.14  (0.41) 0.31  (0.48) 0.21  (0.42) 0.32  (0.45)
Change at Week 52 Number Analyzed 240 participants 477 participants 250 participants 488 participants
0.12  (0.38) 0.31  (0.50) 0.20  (0.42) 0.32  (0.44)
20.Secondary Outcome
Title Percent Change From Baseline in Pre-Bronchodilator FEV1 at Weeks 2, 4, 8, 24, 36, and 52: ITT Population
Hide Description FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer.
Time Frame Baseline, Weeks 2, 4, 8, 24, 36, and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population. Here 'Number analyzed' signifies number of participants with available data for specified category.
Arm/Group Title Placebo (for Dupilumab 200 mg) q2w Dupilumab 200 mg q2w Placebo (for Dupilumab 300 mg) q2w Dupilumab 300 mg q2w
Hide Arm/Group Description:
2 subcutaneous injections of matched Placebo (for Dupilumab 200 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 0), followed by a single 200 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of matched Placebo (for Dupilumab 300 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 0), followed by a single 300 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
Overall Number of Participants Analyzed 317 631 321 633
Mean (Standard Deviation)
Unit of Measure: percent change
Change at Week 2 Number Analyzed 315 participants 610 participants 313 participants 625 participants
5.78  (23.36) 14.32  (26.55) 6.60  (21.84) 17.38  (30.82)
Change at Week 4 Number Analyzed 307 participants 613 participants 311 participants 614 participants
9.61  (25.54) 16.11  (28.12) 8.67  (23.55) 18.77  (32.73)
Change at Week 8 Number Analyzed 305 participants 604 participants 311 participants 609 participants
10.27  (25.60) 18.81  (29.80) 12.24  (25.78) 19.85  (33.63)
Change at Week 24 Number Analyzed 300 participants 599 participants 296 participants 596 participants
9.42  (26.76) 19.76  (30.64) 12.86  (28.14) 20.75  (35.35)
Change at Week 36 Number Analyzed 289 participants 590 participants 301 participants 584 participants
10.57  (26.41) 19.92  (32.26) 13.45  (27.69) 22.08  (35.93)
Change at Week 52 Number Analyzed 240 participants 477 participants 250 participants 488 participants
8.37  (23.59) 19.96  (33.35) 12.89  (27.70) 21.57  (34.08)
21.Secondary Outcome
Title Change From Baseline in Percent Predicted FEV1 at Weeks 2, 4, 8, 12, 24, 36, and 52: ITT Population
Hide Description FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer.
Time Frame Baseline, Weeks 2, 4, 8, 12, 24, 36, and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population. Here 'Number analyzed' signifies number of participants with available data for specified category.
Arm/Group Title Placebo (for Dupilumab 200 mg) q2w Dupilumab 200 mg q2w Placebo (for Dupilumab 300 mg) q2w Dupilumab 300 mg q2w
Hide Arm/Group Description:
2 subcutaneous injections of matched Placebo (for Dupilumab 200 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 0), followed by a single 200 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of matched Placebo (for Dupilumab 300 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 0), followed by a single 300 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
Overall Number of Participants Analyzed 317 631 321 633
Mean (Standard Deviation)
Unit of Measure: percent predicted of FEV1
Change at Week 2 Number Analyzed 315 participants 610 participants 313 participants 625 participants
2.58  (11.36) 7.10  (12.28) 3.32  (10.98) 8.44  (13.20)
Change at Week 4 Number Analyzed 307 participants 613 participants 311 participants 614 participants
4.55  (11.69) 7.92  (12.81) 4.13  (11.41) 9.20  (14.10)
Change at Week 8 Number Analyzed 305 participants 604 participants 311 participants 609 participants
4.93  (12.30) 9.27  (13.13) 6.08  (12.55) 9.70  (14.15)
Change at Week 12 Number Analyzed 307 participants 611 participants 313 participants 610 participants
5.02  (12.10) 9.22  (13.87) 5.90  (13.02) 10.28  (14.44)
Change at Week 24 Number Analyzed 300 participants 599 participants 296 participants 596 participants
4.38  (12.85) 9.98  (13.94) 6.41  (14.02) 10.14  (14.75)
Change at Week 36 Number Analyzed 289 participants 590 participants 301 participants 584 participants
5.09  (12.99) 10.12  (14.61) 6.82  (13.54) 10.94  (15.06)
Change at Week 52 Number Analyzed 240 participants 477 participants 250 participants 488 participants
4.25  (12.06) 10.08  (14.79) 6.68  (13.56) 11.02  (14.59)
22.Secondary Outcome
Title Change From Baseline in Morning (AM)/Evening (PM) Peak Expiratory Flow (PEF) at Weeks 2, 4, 8, 12, 24, 36, and 52: ITT Population
Hide Description The PEF is a participant’s maximum speed of expiration, as measured with a peak flow meter. Peak flow testing for PEF was performed at home (morning and evening) while sitting or standing prior to using any medication (if needed) for asthma.
Time Frame Baseline, Weeks 2, 4, 8, 12, 24, 36, and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population. Here 'Number analyzed' signifies number of participants with available data for specified category.
Arm/Group Title Placebo (for Dupilumab 200 mg) q2w Dupilumab 200 mg q2w Placebo (for Dupilumab 300 mg) q2w Dupilumab 300 mg q2w
Hide Arm/Group Description:
2 subcutaneous injections of matched Placebo (for Dupilumab 200 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 0), followed by a single 200 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of matched Placebo (for Dupilumab 300 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 0), followed by a single 300 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
Overall Number of Participants Analyzed 317 631 321 633
Mean (Standard Deviation)
Unit of Measure: liters/min
AM: Change at Week 2 Number Analyzed 314 participants 620 participants 320 participants 630 participants
4.19  (31.30) 15.21  (39.45) 3.45  (28.95) 14.46  (36.29)
AM: Change at Week 4 Number Analyzed 313 participants 619 participants 319 participants 625 participants
6.23  (42.42) 21.81  (53.85) 5.55  (43.69) 19.67  (46.47)
AM: Change at Week 8 Number Analyzed 308 participants 614 participants 318 participants 613 participants
7.42  (49.30) 25.70  (58.52) 12.22  (50.50) 23.18  (52.65)
AM: Change at Week 12 Number Analyzed 305 participants 608 participants 314 participants 608 participants
9.85  (50.40) 27.81  (65.30) 14.23  (56.18) 25.88  (57.09)
AM: Change at Week 24 Number Analyzed 299 participants 590 participants 305 participants 588 participants
5.55  (53.27) 28.71  (69.64) 15.43  (60.83) 23.74  (63.71)
AM: Change at Week 36 Number Analyzed 289 participants 576 participants 297 participants 564 participants
3.24  (61.68) 31.19  (71.59) 12.57  (61.88) 23.93  (65.04)
AM: Change at Week 52 Number Analyzed 270 participants 544 participants 282 participants 529 participants
2.85  (64.60) 29.86  (75.44) 10.99  (64.68) 26.67  (71.63)
PM: Change at Week 2 Number Analyzed 313 participants 617 participants 319 participants 629 participants
3.33  (36.81) 13.80  (40.59) 3.87  (33.98) 11.35  (36.10)
PM: Change at Week 4 Number Analyzed 312 participants 617 participants 319 participants 623 participants
5.01  (45.09) 17.94  (55.30) 2.73  (46.83) 14.90  (47.42)
PM: Change at Week 8 Number Analyzed 308 participants 613 participants 315 participants 610 participants
2.82  (50.10) 21.06  (61.80) 7.68  (56.73) 17.26  (53.37)
PM: Change at Week 12 Number Analyzed 306 participants 606 participants 311 participants 605 participants
3.24  (53.42) 19.75  (68.14) 8.52  (56.74) 18.70  (55.60)
PM: Change at Week 24 Number Analyzed 299 participants 583 participants 300 participants 585 participants
-4.89  (55.07) 19.95  (71.50) 7.56  (63.25) 15.82  (61.91)
PM: Change at Week 36 Number Analyzed 286 participants 570 participants 291 participants 557 participants
-6.75  (62.44) 21.79  (75.00) 2.64  (65.21) 14.35  (64.66)
PM: Change at Week 52 Number Analyzed 269 participants 526 participants 268 participants 523 participants
-6.43  (62.82) 18.77  (77.37) 2.83  (67.01) 15.58  (72.51)
23.Secondary Outcome
Title Change From Baseline in Forced Vital Capacity (FVC) at Weeks 2, 4, 8, 12, 24, 36, and 52: ITT Population
Hide Description FVC is a standard pulmonary function test used to quantify respiratory muscle weakness. FVC is the volume of air that can forcibly be blown out after full inspiration in the upright position, measured in liters.
Time Frame Baseline, Weeks 2, 4, 8, 12, 24, 36, and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population. Here 'Number analyzed' signifies number of participants with available data for specified category.
Arm/Group Title Placebo (for Dupilumab 200 mg) q2w Dupilumab 200 mg q2w Placebo (for Dupilumab 300 mg) q2w Dupilumab 300 mg q2w
Hide Arm/Group Description:
2 subcutaneous injections of matched Placebo (for Dupilumab 200 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 0), followed by a single 200 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of matched Placebo (for Dupilumab 300 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 0), followed by a single 300 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
Overall Number of Participants Analyzed 317 631 321 633
Mean (Standard Deviation)
Unit of Measure: liter
Change at Week 2 Number Analyzed 315 participants 610 participants 313 participants 625 participants
0.08  (0.42) 0.23  (0.44) 0.10  (0.37) 0.25  (0.46)
Change at Week 4 Number Analyzed 307 participants 613 participants 311 participants 614 participants
0.12  (0.39) 0.26  (0.45) 0.12  (0.38) 0.27  (0.47)
Change at Week 8 Number Analyzed 305 participants 604 participants 311 participants 609 participants
0.13  (0.41) 0.28  (0.45) 0.18  (0.42) 0.29  (0.50)
Change at Week 12 Number Analyzed 307 participants 611 participants 313 participants 610 participants
0.13  (0.41) 0.29  (0.49) 0.18  (0.44) 0.29  (0.51)
Change at Week 24 Number Analyzed 300 participants 599 participants 296 participants 596 participants
0.11  (0.45) 0.29  (0.48) 0.18  (0.46) 0.29  (0.51)
Change at Week 36 Number Analyzed 289 participants 590 participants 301 participants 584 participants
0.11  (0.45) 0.30  (0.52) 0.19  (0.47) 0.31  (0.52)
Change at Week 52 Number Analyzed 240 participants 477 participants 250 participants 488 participants
0.08  (0.45) 0.29  (0.53) 0.18  (0.45) 0.31  (0.50)
24.Secondary Outcome
Title Change From Baseline in Forced Expiratory Flow (FEF) 25-75% at Weeks 2, 4, 8, 12, 24, 36, and 52: ITT Population
Hide Description FEF is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. FEF25-75% is defined as the mean forced expiratory flow between the 25% and 75% of the FVC.
Time Frame Baseline, Weeks 2, 4, 8, 12, 24, 36, and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population. Here 'Number analyzed' signifies number of participants with available data for specified category.
Arm/Group Title Placebo (for Dupilumab 200 mg) q2w Dupilumab 200 mg q2w Placebo (for Dupilumab 300 mg) q2w Dupilumab 300 mg q2w
Hide Arm/Group Description:
2 subcutaneous injections of matched Placebo (for Dupilumab 200 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 0), followed by a single 200 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of matched Placebo (for Dupilumab 300 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 0), followed by a single 300 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
Overall Number of Participants Analyzed 317 631 321 633
Mean (Standard Deviation)
Unit of Measure: liters/sec
Change at Week 2 Number Analyzed 315 participants 610 participants 313 participants 625 participants
0.09  (0.40) 0.22  (0.47) 0.11  (0.44) 0.27  (0.48)
Change at Week 4 Number Analyzed 307 participants 613 participants 311 participants 614 participants
0.16  (0.45) 0.24  (0.48) 0.15  (0.44) 0.29  (0.48)
Change at Week 8 Number Analyzed 305 participants 604 participants 311 participants 609 participants
0.18  (0.45) 0.29  (0.52) 0.20  (0.49) 0.32  (0.51)
Change at Week 12 Number Analyzed 307 participants 611 participants 313 participants 610 participants
0.18  (0.46) 0.30  (0.53) 0.19  (0.50) 0.35  (0.53)
Change at Week 24 Number Analyzed 300 participants 599 participants 296 participants 596 participants
0.17  (0.47) 0.34  (0.57) 0.22  (0.56) 0.35  (0.54)
Change at Week 36 Number Analyzed 289 participants 590 participants 301 participants 584 participants
0.18  (0.49) 0.35  (0.59) 0.22  (0.49) 0.36  (0.56)
Change at Week 52 Number Analyzed 240 participants 477 participants 250 participants 488 participants
0.16  (0.50) 0.36  (0.63) 0.24  (0.55) 0.36  (0.55)
25.Secondary Outcome
Title Change From Baseline in Post-Bronchodilator FEV1 at Weeks 2, 4, 8, 12, 24, 36, and 52: ITT Population
Hide Description FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer.
Time Frame Baseline, Weeks 2, 4, 8, 12, 24, 36, and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed ITT population. Here 'Number analyzed' signifies number of participants with available data for specified category.
Arm/Group Title Placebo (for Dupilumab 200 mg) q2w Dupilumab 200 mg q2w Placebo (for Dupilumab 300 mg) q2w Dupilumab 300 mg q2w
Hide Arm/Group Description:
2 subcutaneous injections of matched Placebo (for Dupilumab 200 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 0), followed by a single 200 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of matched Placebo (for Dupilumab 300 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 0), followed by a single 300 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
Overall Number of Participants Analyzed 317 631 321 633
Mean (Standard Deviation)
Unit of Measure: liter
Change at Week 2 Number Analyzed 310 participants 609 participants 311 participants 617 participants
-0.07  (0.31) 0.10  (0.37) -0.04  (0.33) 0.09  (0.34)
Change at Week 4 Number Analyzed 308 participants 614 participants 311 participants 615 participants
-0.02  (0.31) 0.10  (0.39) -0.04  (0.36) 0.10  (0.36)
Change at Week 8 Number Analyzed 305 participants 607 participants 305 participants 604 participants
-0.02  (0.31) 0.12  (0.40) 0.03  (0.35) 0.11  (0.37)
Change at Week 12 Number Analyzed 305 participants 610 participants 313 participants 612 participants
-0.02  (0.33) 0.12  (0.40) 0.01  (0.35) 0.11  (0.38)
Change at Week 24 Number Analyzed 302 participants 599 participants 302 participants 601 participants
-0.05  (0.36) 0.13  (0.43) -0.01  (0.40) 0.10  (0.39)
Change at Week 36 Number Analyzed 290 participants 586 participants 302 participants 589 participants
-0.03  (0.34) 0.12  (0.44) 0.01  (0.38) 0.11  (0.39)
Change at Week 52 Number Analyzed 239 participants 499 participants 255 participants 494 participants
-0.08  (0.38) 0.12  (0.44) -0.02  (0.39) 0.11  (0.40)
26.Secondary Outcome
Title Annualized Rate of Loss of Asthma Control (LOAC) Event During The 52-Week Treatment Period: ITT Population
Hide Description LOAC was defined as any of the following: >=6 additional reliever puffs of salbutamol/albuterol or levosalbutamol/levalbuterol in a 24-hour period (compared to baseline) on 2 consecutive days; increase in ICS >=4 times the dose at randomization; use of systemic corticosteroids for >=3 days; hospitalization or emergency room visit because of asthma, requiring systemic corticosteroids. Annualized event rate was the total number of LOAC that occurred during the treatment period divided by the total number of participant-years treated.
Time Frame Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population.
Arm/Group Title Placebo (for Dupilumab 200 mg) q2w Dupilumab 200 mg q2w Placebo (for Dupilumab 300 mg) q2w Dupilumab 300 mg q2w
Hide Arm/Group Description:
2 subcutaneous injections of matched Placebo (for Dupilumab 200 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 0), followed by a single 200 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of matched Placebo (for Dupilumab 300 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 0), followed by a single 300 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
Overall Number of Participants Analyzed 317 631 321 633
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: LOAC per participant-year
2.972
(2.573 to 3.432)
1.853
(1.654 to 2.076)
2.965
(2.572 to 3.420)
1.740
(1.554 to 1.947)
27.Secondary Outcome
Title Time to First Severe Exacerbation Event: Kaplan-Meier Estimates During The 52-Week Treatment Period: ITT Population
Hide Description The time to first severe exacerbation was defined as follows: date of the first event - randomization date +1. For participants who had no event on or before Visit 18 (Week 52) or last contact date, the time was censored at the date of Visit 18 or the last contact date, whichever was earlier. The median time to first severe exacerbation was not estimated; therefore, the probability of severe exacerbation at Weeks 12, 24, 36, and 52, are presented as the descriptive statistics.
Time Frame Baseline up to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population.
Arm/Group Title Placebo (for Dupilumab 200 mg) q2w Dupilumab 200 mg q2w Placebo (for Dupilumab 300 mg) q2w Dupilumab 300 mg q2w
Hide Arm/Group Description:
2 subcutaneous injections of matched Placebo (for Dupilumab 200 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 0), followed by a single 200 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of matched Placebo (for Dupilumab 300 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 0), followed by a single 300 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
Overall Number of Participants Analyzed 317 631 321 633
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: probability of severe exacerbation
Probability at Week 12
0.165
(0.127 to 0.209)
0.094
(0.073 to 0.119)
0.193
(0.152 to 0.238)
0.137
(0.112 to 0.166)
Probability at Week 24
0.275
(0.227 to 0.326)
0.177
(0.148 to 0.208)
0.297
(0.247 to 0.347)
0.211
(0.180 to 0.243)
Probability at Week 36
0.364
(0.311 to 0.418)
0.235
(0.203 to 0.270)
0.376
(0.322 to 0.428)
0.268
(0.234 to 0.303)
Probability at Week 52
0.434
(0.378 to 0.489)
0.295
(0.259 to 0.331)
0.437
(0.382 to 0.491)
0.325
(0.288 to 0.362)
28.Secondary Outcome
Title Time to First LOAC Event: Kaplan-Meier Estimates During The 52-Week Treatment Period: ITT Population
Hide Description The time to first LOAC event was defined as follows: date of the first event - first dose date +1. For participants who had no event on or before last dose date + 14 days or last contact date, the time was censored at the last dose date + 14 days or the last contact date, whichever was earlier.
Time Frame Baseline up to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population.
Arm/Group Title Placebo (for Dupilumab 200 mg) q2w Dupilumab 200 mg q2w Placebo (for Dupilumab 300 mg) q2w Dupilumab 300 mg q2w
Hide Arm/Group Description:
2 subcutaneous injections of matched Placebo (for Dupilumab 200 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 0), followed by a single 200 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of matched Placebo (for Dupilumab 300 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 0), followed by a single 300 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
Overall Number of Participants Analyzed 317 631 321 633
Median (95% Confidence Interval)
Unit of Measure: days
110.0
(84.00 to 144.00)
230.0
(187.00 to 276.00)
102.0
(74.00 to 130.00)
264.0
(207.00 to 319.00)
29.Secondary Outcome
Title Change From Baseline in ACQ-5 Score at Weeks 2, 4, 8, 12, 36, and 52: ITT Population
Hide Description The ACQ-5 has 5 questions, reflecting the top-scoring five asthma symptoms: woken at night by symptoms, wake in the mornings with symptoms, limitation of daily activities, shortness of breath and wheeze. Participants were asked to recall how their asthma had been during the previous week and to respond to each of the five symptom questions on a 7-point scale ranged from 0 (no impairment) to 6 (maximum impairment). ACQ-5 total score was mean of the scores of all 5 questions and, therefore, ranged from 0 (totally controlled) to 6 (severely uncontrolled). Higher score indicated lower asthma control.
Time Frame Baseline, Weeks 2, 4, 8, 12, 36, and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population. Here 'Number analyzed' signifies number of participants with available data for specified category.
Arm/Group Title Placebo (for Dupilumab 200 mg) q2w Dupilumab 200 mg q2w Placebo (for Dupilumab 300 mg) q2w Dupilumab 300 mg q2w
Hide Arm/Group Description:
2 subcutaneous injections of matched Placebo (for Dupilumab 200 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 0), followed by a single 200 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of matched Placebo (for Dupilumab 300 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 0), followed by a single 300 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
Overall Number of Participants Analyzed 317 631 321 633
Mean (Standard Deviation)
Unit of Measure: scores on a scale
Change at Week 2 Number Analyzed 304 participants 599 participants 305 participants 615 participants
-0.52  (0.85) -0.88  (0.91) -0.58  (0.97) -0.89  (0.94)
Change at Week 4 Number Analyzed 297 participants 599 participants 305 participants 605 participants
-0.76  (0.90) -1.07  (0.98) -0.77  (1.01) -1.06  (1.01)
Change at Week 8 Number Analyzed 301 participants 595 participants 310 participants 593 participants
-0.94  (0.96) -1.26  (1.03) -1.05  (1.04) -1.24  (1.06)
Change at Week 12 Number Analyzed 303 participants 605 participants 312 participants 603 participants
-0.98  (1.00) -1.33  (1.03) -1.09  (1.09) -1.35  (1.06)
Change at Week 36 Number Analyzed 285 participants 583 participants 299 participants 572 participants
-1.21  (1.01) -1.50  (1.14) -1.22  (1.09) -1.52  (1.09)
Change at Week 52 Number Analyzed 236 participants 470 participants 245 participants 477 participants
-1.07  (1.08) -1.50  (1.05) -1.25  (1.05) -1.50  (1.08)
30.Secondary Outcome
Title Change From Baseline in Asthma Control Questionnaire 7-item Version (ACQ-7) Score at Weeks 2, 4, 8, 12, 24, 36, and 52: ITT Population
Hide Description The ACQ-7 has 7 questions, the first 5 questions assess the most common asthma symptoms: woken at night by symptoms, wake in the mornings with symptoms, limitation of daily activities, shortness of breath and wheeze plus short-acting bronchodilator use, and FEV1 (pre-bronchodilator % predicted). Participants were asked to recall how their asthma had been during the previous week and to respond to each of the five symptom questions on a 7-point scale ranged from 0 (no impairment) to 6 (maximum impairment). Clinic staff scored the FEV1% predicted on a 7-point scale. The questions were equally weighted and the ACQ-7 total score was mean of the scores of all 7 questions and, therefore, ranged from 0 (totally controlled) to 6 (severely uncontrolled). Higher score indicated lower asthma control.
Time Frame Baseline, Weeks 2, 4, 8, 12, 24, 36, and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population. Here 'Number analyzed' signifies number of participants with available data for specified category.
Arm/Group Title Placebo (for Dupilumab 200 mg) q2w Dupilumab 200 mg q2w Placebo (for Dupilumab 300 mg) q2w Dupilumab 300 mg q2w
Hide Arm/Group Description:
2 subcutaneous injections of matched Placebo (for Dupilumab 200 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 0), followed by a single 200 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of matched Placebo (for Dupilumab 300 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 0), followed by a single 300 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
Overall Number of Participants Analyzed 317 631 321 633
Mean (Standard Deviation)
Unit of Measure: scores on a scale
Change at Week 2 Number Analyzed 304 participants 599 participants 305 participants 615 participants
-0.46  (0.70) -0.79  (0.77) -0.50  (0.80) -0.82  (0.81)
Change at Week 4 Number Analyzed 297 participants 599 participants 305 participants 605 participants
-0.65  (0.76) -0.94  (0.85) -0.65  (0.85) -0.97  (0.87)
Change at Week 8 Number Analyzed 301 participants 595 participants 310 participants 593 participants
-0.81  (0.80) -1.11  (0.90) -0.90  (0.89) -1.12  (0.92)
Change at Week 12 Number Analyzed 303 participants 605 participants 312 participants 603 participants
-0.85  (0.83) -1.17  (0.90) -0.92  (0.93) -1.20  (0.92)
Change at Week 24 Number Analyzed 296 participants 590 participants 297 participants 585 participants
-0.89  (0.91) -1.25  (0.92) -1.01  (0.96) -1.22  (0.96)
Change at Week 36 Number Analyzed 285 participants 583 participants 299 participants 572 participants
-1.04  (0.84) -1.32  (1.01) -1.05  (0.94) -1.35  (0.95)
Change at Week 52 Number Analyzed 236 participants 470 participants 245 participants 477 participants
-0.91  (0.92) -1.32  (0.91) -1.07  (0.91) -1.34  (0.93)
31.Secondary Outcome
Title Change From Baseline in Morning Asthma Symptom Score at Weeks 2, 4, 8, 12, 24, 36, and 52: ITT Population
Hide Description Morning asthma symptom score was determined using AM (ante meridiem) symptom scoring system which evaluated participant’s overall asthma symptoms experienced during the night. It ranged from 0 to 4 as: 0= No asthma symptoms, slept through the night, 1= Slept well, but some complaints in the morning, no night time awakenings, 2= Woke up once because of asthma (including early awakening), 3= Woke up several times because of asthma (including early awakening), 4= Bad night, awake most of the night because of asthma.
Time Frame Baseline, Weeks 2, 4, 8, 12, 24, 36, and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population. Here 'Number analyzed' signifies number of participants with available data for specified category.
Arm/Group Title Placebo (for Dupilumab 200 mg) q2w Dupilumab 200 mg q2w Placebo (for Dupilumab 300 mg) q2w Dupilumab 300 mg q2w
Hide Arm/Group Description:
2 subcutaneous injections of matched Placebo (for Dupilumab 200 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 0), followed by a single 200 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of matched Placebo (for Dupilumab 300 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 0), followed by a single 300 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
Overall Number of Participants Analyzed 317 631 321 633
Mean (Standard Deviation)
Unit of Measure: scores on a scale
Change at Week 2 Number Analyzed 314 participants 624 participants 321 participants 631 participants
-0.07  (0.43) -0.18  (0.49) -0.09  (0.49) -0.15  (0.50)
Change at Week 4 Number Analyzed 313 participants 623 participants 319 participants 627 participants
-0.16  (0.59) -0.26  (0.59) -0.16  (0.61) -0.27  (0.64)
Change at Week 8 Number Analyzed 308 participants 620 participants 318 participants 615 participants
-0.26  (0.64) -0.40  (0.68) -0.25  (0.62) -0.37  (0.70)
Change at Week 12 Number Analyzed 306 participants 614 participants 315 participants 609 participants
-0.30  (0.64) -0.45  (0.71) -0.30  (0.69) -0.44  (0.72)
Change at Week 24 Number Analyzed 302 participants 602 participants 306 participants 592 participants
-0.35  (0.69) -0.52  (0.76) -0.36  (0.73) -0.50  (0.73)
Change at Week 36 Number Analyzed 292 participants 583 participants 299 participants 572 participants
-0.38  (0.69) -0.54  (0.81) -0.38  (0.76) -0.56  (0.77)
Change at Week 52 Number Analyzed 275 participants 553 participants 286 participants 540 participants
-0.41  (0.71) -0.55  (0.84) -0.41  (0.78) -0.60  (0.79)
32.Secondary Outcome
Title Change From Baseline in Evening Asthma Symptom Score at Weeks 2, 4, 8, 12, 24, 36, and 52: ITT Population
Hide Description Evening asthma symptom score was determined using PM (post meridiem) symptom scoring system which evaluated participant’s overall asthma symptoms experienced during the day. It ranged from 0 to 4 as: 0=very well, no asthma symptoms, 1=one episode of wheezing, cough, or breathlessness, 2=more than one episode of wheezing, cough, or breathlessness without interference of normal activities, 3=wheezing, cough, or breathlessness most of the day, which interfered to some extent with normal activities, 4=asthma very bad, unable to carry out daily activities as usual.
Time Frame Baseline, Weeks 2, 4, 8, 12, 24, 36, and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population. Here 'Number analyzed' signifies number of participants with available data for specified category.
Arm/Group Title Placebo (for Dupilumab 200 mg) q2w Dupilumab 200 mg q2w Placebo (for Dupilumab 300 mg) q2w Dupilumab 300 mg q2w
Hide Arm/Group Description:
2 subcutaneous injections of matched Placebo (for Dupilumab 200 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 0), followed by a single 200 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of matched Placebo (for Dupilumab 300 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 0), followed by a single 300 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
Overall Number of Participants Analyzed 317 631 321 633
Mean (Standard Deviation)
Unit of Measure: scores on a scale
Change at Week 2 Number Analyzed 313 participants 624 participants 320 participants 631 participants
-0.05  (0.45) -0.17  (0.48) -0.06  (0.45) -0.16  (0.52)
Change at Week 4 Number Analyzed 313 participants 623 participants 319 participants 628 participants
-0.11  (0.59) -0.27  (0.61) -0.14  (0.58) -0.29  (0.64)
Change at Week 8 Number Analyzed 308 participants 619 participants 318 participants 612 participants
-0.24  (0.64) -0.41  (0.70) -0.22  (0.63) -0.40  (0.70)
Change at Week 12 Number Analyzed 307 participants 612 participants 314 participants 606 participants
-0.26  (0.66) -0.45  (0.72) -0.30  (0.68) -0.46  (0.73)
Change at Week 24 Number Analyzed 301 participants 596 participants 301 participants 590 participants
-0.33  (0.72) -0.52  (0.78) -0.36  (0.72) -0.52  (0.73)
Change at Week 36 Number Analyzed 289 participants 576 participants 292 participants 566 participants
-0.39  (0.73) -0.56  (0.81) -0.39  (0.75) -0.56  (0.80)
Change at Week 52 Number Analyzed 274 participants 536 participants 270 participants 535 participants
-0.41  (0.74) -0.57  (0.84) -0.42  (0.75) -0.61  (0.78)
33.Secondary Outcome
Title Change From Baseline in Number of Nocturnal Awakenings Per Night at Weeks 2, 4, 8, 12, 24, 36, and 52: ITT Population
Hide Description Participants recorded every morning on awakening the number of asthma-related nocturnal awakenings requiring use of rescue medication that occurred during the previous night.
Time Frame Baseline, Weeks 2, 4, 8, 12, 24, 36, and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population. Here 'Number analyzed' signifies number of participants with available data for specified category.
Arm/Group Title Placebo (for Dupilumab 200 mg) q2w Dupilumab 200 mg q2w Placebo (for Dupilumab 300 mg) q2w Dupilumab 300 mg q2w
Hide Arm/Group Description:
2 subcutaneous injections of matched Placebo (for Dupilumab 200 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 0), followed by a single 200 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of matched Placebo (for Dupilumab 300 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 0), followed by a single 300 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
Overall Number of Participants Analyzed 317 631 321 633
Mean (Standard Deviation)
Unit of Measure: number of nocturnal awakenings/night
Change at Week 2 Number Analyzed 314 participants 624 participants 321 participants 631 participants
-0.06  (0.49) -0.15  (0.55) -0.04  (0.62) -0.11  (0.67)
Change at Week 4 Number Analyzed 313 participants 623 participants 319 participants 627 participants
-0.10  (0.61) -0.19  (0.66) -0.11  (0.70) -0.20  (0.67)
Change at Week 8 Number Analyzed 308 participants 620 participants 318 participants 615 participants
-0.18  (0.65) -0.29  (0.72) -0.17  (0.62) -0.24  (0.72)
Change at Week 12 Number Analyzed 306 participants 614 participants 315 participants 609 participants
-0.21  (0.66) -0.33  (0.75) -0.18  (0.67) -0.28  (0.73)
Change at Week 24 Number Analyzed 302 participants 602 participants 306 participants 592 participants
-0.23  (0.78) -0.36  (0.81) -0.26  (0.65) -0.30  (0.73)
Change at Week 36 Number Analyzed 292 participants 583 participants 299 participants 572 participants
-0.25  (0.74) -0.34  (0.81) -0.26  (0.71) -0.36  (0.74)
Change at Week 52 Number Analyzed 275 participants 553 participants 286 participants 540 participants
-0.24  (0.69) -0.35  (0.88) -0.26  (0.74) -0.41  (0.78)
34.Secondary Outcome
Title Change From Baseline in Number of Puffs of Daily Reliever Medication Used Per 24 Hours at Weeks 2, 4, 8, 12, 24, 36, and 52: ITT Population
Hide Description Participants might administered salbutamol/albuterol or levosalbutamol/levalbuterol as reliever medication as needed during the study. The number of salbutamol/albuterol or levosalbutamol/levalbuterol inhalations were recorded daily by the participants in an electronic diary/peak expiratory flow (PEF) meter. In the case that Nebulizer solutions were used as an alternative delivery method, the nebulizer dose was converted to number of puffs as per following conversion factor: salbutamol/albuterol nebulizer solution (2.5 mg) corresponds to 4 puffs.
Time Frame Baseline, Weeks 2, 4, 8, 12, 24, 36, and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population. Here 'Number analyzed' signifies number of participants with available data for specified category.
Arm/Group Title Placebo (for Dupilumab 200 mg) q2w Dupilumab 200 mg q2w Placebo (for Dupilumab 300 mg) q2w Dupilumab 300 mg q2w
Hide Arm/Group Description:
2 subcutaneous injections of matched Placebo (for Dupilumab 200 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 0), followed by a single 200 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of matched Placebo (for Dupilumab 300 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 0), followed by a single 300 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
Overall Number of Participants Analyzed 317 631 321 633
Mean (Standard Deviation)
Unit of Measure: Number of puffs of reliever medication
Change at Week 2 Number Analyzed 313 participants 623 participants 318 participants 630 participants
-0.21  (1.55) -0.56  (1.96) -0.10  (1.71) -0.47  (1.91)
Change at Week 4 Number Analyzed 312 participants 622 participants 319 participants 626 participants
-0.26  (2.19) -0.68  (2.61) -0.34  (3.42) -0.73  (2.42)
Change at Week 8 Number Analyzed 308 participants 617 participants 314 participants 607 participants
-0.50  (2.23) -1.02  (2.86) -0.65  (2.96) -0.94  (2.86)
Change at Week 12 Number Analyzed 306 participants 610 participants 310 participants 603 participants
-0.52  (2.28) -1.23  (3.03) -0.89  (3.06) -1.08  (2.72)
Change at Week 24 Number Analyzed 294 participants 588 participants 300 participants 582 participants
-0.77  (2.60) -1.27  (3.05) -0.99  (3.21) -1.15  (2.83)
Change at Week 36 Number Analyzed 285 participants 564 participants 287 participants 558 participants
-0.99  (2.49) -1.30  (2.99) -1.06  (3.57) -1.23  (3.01)
Change at Week 52 Number Analyzed 270 participants 522 participants 265 participants 521 participants
-0.90  (2.58) -1.45  (3.33) -1.12  (3.64) -1.39  (2.97)
35.Secondary Outcome
Title Change From Baseline in AQLQ (S) Self-Administered Global Score at Weeks 12, 36, and 52: ITT Population
Hide Description The AQLQ is a disease-specific, self-administered quality of life questionnaire designed to measure functional impairments that are most important to participants with asthma. The AQLQ comprises of 32 items in 4 domains: symptoms (12 items), activity limitation (11 items), emotional function (5 items), environmental stimuli (4 items). Each item is scored on a 7-point likert scale (1=maximal impairment, 7=no impairment). The 32 items of the questionnaire are averaged to produce one overall quality of life score ranging from 1 (severely impaired) to 7 (not impaired at all). Higher scores indicate better quality of life.
Time Frame Baseline, Weeks 12, 36, and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population. Here 'Number analyzed' signifies number of participants with available data for specified category.
Arm/Group Title Placebo (for Dupilumab 200 mg) q2w Dupilumab 200 mg q2w Placebo (for Dupilumab 300 mg) q2w Dupilumab 300 mg q2w
Hide Arm/Group Description:
2 subcutaneous injections of matched Placebo (for Dupilumab 200 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 0), followed by a single 200 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of matched Placebo (for Dupilumab 300 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 0), followed by a single 300 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
Overall Number of Participants Analyzed 317 631 321 633
Mean (Standard Deviation)
Unit of Measure: scores on a scale
Change at Week 12 Number Analyzed 286 participants 573 participants 308 participants 586 participants
0.90  (0.97) 1.09  (1.03) 0.94  (1.01) 1.09  (1.09)
Change at Week 36 Number Analyzed 271 participants 554 participants 295 participants 548 participants
1.05  (1.08) 1.26  (1.17) 1.08  (1.16) 1.33  (1.15)
Change at Week 52 Number Analyzed 224 participants 465 participants 243 participants 459 participants
1.00  (1.12) 1.28  (1.16) 1.02  (1.10) 1.34  (1.16)
36.Secondary Outcome
Title Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions, 5 Levels (EQ-5D-5L) Scores at Weeks 12, 24, 36, and 52: ITT Population
Hide Description EQ-5D-5L is a standardized health-related quality of life questionnaire developed by EuroQol Group in order to provide a simple, generic measure of health for clinical and economic appraisal. EQ-5D consists of EQ-5D descriptive system and EQ visual analogue scale (VAS). EQ-5D descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The 5D-5L systems are converted into a single index utility score between 0 to 1, where higher score indicates a better health state. EQ-5D-5L-VAS records participant’s self-rated health on a vertical VAS that allows them to indicate their health state that can range from 0 (worst imaginable) to 100 (best imaginable).
Time Frame Baseline, Weeks 12, 24, 36, and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population. Here 'Number analyzed' signifies number of participants with available data for specified category.
Arm/Group Title Placebo (for Dupilumab 200 mg) q2w Dupilumab 200 mg q2w Placebo (for Dupilumab 300 mg) q2w Dupilumab 300 mg q2w
Hide Arm/Group Description:
2 subcutaneous injections of matched Placebo (for Dupilumab 200 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 0), followed by a single 200 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of matched Placebo (for Dupilumab 300 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 0), followed by a single 300 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
Overall Number of Participants Analyzed 317 631 321 633
Mean (Standard Deviation)
Unit of Measure: scores on a scale
Single Index: Change at Week 12 Number Analyzed 280 participants 567 participants 301 participants 576 participants
0.07  (0.17) 0.09  (0.18) 0.08  (0.18) 0.09  (0.18)
Single Index: Change at Week 24 Number Analyzed 275 participants 552 participants 292 participants 559 participants
0.07  (0.17) 0.09  (0.17) 0.08  (0.18) 0.08  (0.20)
Single Index: Change at Week 36 Number Analyzed 264 participants 548 participants 290 participants 537 participants
0.08  (0.19) 0.09  (0.20) 0.10  (0.18) 0.09  (0.20)
Single Index: Change at Week 52 Number Analyzed 220 participants 457 participants 238 participants 448 participants
0.07  (0.20) 0.10  (0.19) 0.08  (0.19) 0.10  (0.20)
VAS Score: Change at Week 12 Number Analyzed 280 participants 567 participants 301 participants 576 participants
7.69  (17.43) 11.10  (18.90) 6.39  (20.42) 9.80  (19.56)
VAS Score: Change at Week 24 Number Analyzed 275 participants 552 participants 292 participants 559 participants
8.33  (17.58) 11.44  (18.48) 8.59  (20.37) 9.21  (19.61)
VAS Score: Change at Week 36 Number Analyzed 264 participants 548 participants 290 participants 537 participants
9.70  (18.24) 11.61  (19.09) 9.31  (20.09) 11.41  (19.40)
VAS Score: Change at Week 52 Number Analyzed 220 participants 457 participants 238 participants 448 participants
8.35  (18.51) 12.98  (18.71) 9.52  (20.81) 11.90  (19.60)
37.Secondary Outcome
Title Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Total Score at Weeks 12, 24, 36, and 52: ITT Population
Hide Description The HADS is a general scale to detect states of anxiety and depression already used and validated in asthma, which includes HADS-A and HADS-D subscales. The instrument is comprised of 14 items: 7 related to anxiety (HADS-A) and 7 to depression (HADS-D). Each item on the questionnaire is scored from 0-3. The anxiety/depression score is the sum of the scores of the 7 related items; one can score between 0 and 21 for either anxiety or depression. And the total score is the sum of the scores of the 14 items ranging from 0 (no symptoms) to 42 (severe symptoms), with higher scores indicating higher anxiety/depression complains.
Time Frame Baseline, Weeks 12, 24, 36, and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population; 29 participants in Japan who received an incorrectly translated HADS questionnaire were excluded. Here 'Number analyzed' signifies number of participants with available data for specified category.
Arm/Group Title Placebo (for Dupilumab 200 mg) q2w Dupilumab 200 mg q2w Placebo (for Dupilumab 300 mg) q2w Dupilumab 300 mg q2w
Hide Arm/Group Description:
2 subcutaneous injections of matched Placebo (for Dupilumab 200 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 0), followed by a single 200 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of matched Placebo (for Dupilumab 300 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 0), followed by a single 300 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
Overall Number of Participants Analyzed 311 621 317 624
Mean (Standard Deviation)
Unit of Measure: scores on a scale
Change at Week 12 Number Analyzed 274 participants 551 participants 297 participants 569 participants
-2.11  (5.29) -1.91  (5.65) -1.55  (6.11) -1.98  (5.89)
Change at Week 24 Number Analyzed 270 participants 537 participants 286 participants 552 participants
-2.17  (5.71) -1.93  (5.97) -1.73  (6.36) -1.88  (6.39)
Change at Week 36 Number Analyzed 260 participants 535 participants 286 participants 532 participants
-2.52  (5.89) -2.02  (6.34) -2.67  (6.80) -2.13  (6.67)
Change at Week 52 Number Analyzed 213 participants 443 participants 234 participants 438 participants
-2.00  (6.29) -2.36  (6.28) -1.86  (6.79) -2.17  (7.04)
38.Secondary Outcome
Title Change From Baseline in 22-Item Sino Nasal Outcome Test (SNOT-22) Score at Weeks 12, 24, 36, and 52: ITT Population With Bilateral Nasal Polyposis/Chronic Rhinosinusitis
Hide Description The SNOT-22 is a validated measure of health related quality of life in sinonasal disease. It is a 22 item questionnaire with each item assigned a score ranging from 0-5. The total score may range from 0 (no disease) -110 (worst disease), lower scores represent better health related quality of life.
Time Frame Baseline, Weeks 12, 24, 36, and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population with bilateral nasal polyposis/chronic rhinosinusitis. Here 'Number analyzed' signifies number of participants with available data for specified category.
Arm/Group Title Placebo (for Dupilumab 200 mg) q2w Dupilumab 200 mg q2w Placebo (for Dupilumab 300 mg) q2w Dupilumab 300 mg q2w
Hide Arm/Group Description:
2 subcutaneous injections of matched Placebo (for Dupilumab 200 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 0), followed by a single 200 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of matched Placebo (for Dupilumab 300 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 0), followed by a single 300 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
Overall Number of Participants Analyzed 63 126 70 123
Mean (Standard Deviation)
Unit of Measure: scores on a scale
Change at Week 12 Number Analyzed 51 participants 113 participants 61 participants 102 participants
-6.82  (17.19) -13.55  (16.85) -11.30  (16.11) -16.07  (20.54)
Change at Week 24 Number Analyzed 52 participants 111 participants 58 participants 102 participants
-7.21  (17.10) -14.68  (18.77) -9.55  (16.04) -17.41  (20.81)
Change at Week 36 Number Analyzed 49 participants 111 participants 57 participants 100 participants
-6.10  (19.03) -15.23  (18.20) -8.51  (20.36) -18.86  (21.34)
Change at Week 52 Number Analyzed 42 participants 89 participants 49 participants 85 participants
-6.95  (17.10) -15.78  (17.72) -9.98  (18.01) -19.81  (22.39)
39.Secondary Outcome
Title Change From Baseline in Standardized Rhinoconjunctivitis Quality Of Life Questionnaire, Ages 12+ (RQLQ[S]+12) Score at Weeks 12, 24, 36, and 52: ITT Population With Comorbid Allergic Rhinitis
Hide Description RQLQ(S)+12 is a self-administered questionnaire with standardized activities developed to measure health-related quality of life signs and symptoms that are most problematic in those 12 to 75 years of age, as a result of perennial or seasonal allergic rhinitis. There are 28 items on RQLQ(S) in 7 domains: activities (3 items), sleep (3 items), non-nose/eye symptoms (7 items), practical problems (3 items), nasal symptoms (4 items), eye symptoms (4 items) and emotional (4 items). RQLQ(S)+12 responses are based on 7-point likert scale with responses ranging from 0 (not troubled) to 6 (extremely troubled). Individual items within RQLQ(S)+12 are equally weighted. The overall score is calculated as the mean score of all items. Higher scores indicated more health-related quality of life impairment (lower scores better).
Time Frame Baseline, Weeks 12, 24, 36, and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population with comorbid allergic rhinitis. Here 'Number analyzed' signifies number of participants with available data for specified category.
Arm/Group Title Placebo (for Dupilumab 200 mg) q2w Dupilumab 200 mg q2w Placebo (for Dupilumab 300 mg) q2w Dupilumab 300 mg q2w
Hide Arm/Group Description:
2 subcutaneous injections of matched Placebo (for Dupilumab 200 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 0), followed by a single 200 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of matched Placebo (for Dupilumab 300 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 0), followed by a single 300 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
Overall Number of Participants Analyzed 194 390 214 409
Mean (Standard Deviation)
Unit of Measure: scores on a scale
Change at Week 12 Number Analyzed 167 participants 332 participants 192 participants 348 participants
-0.50  (0.98) -0.70  (0.99) -0.44  (1.05) -0.64  (1.06)
Change at Week 24 Number Analyzed 164 participants 322 participants 182 participants 342 participants
-0.50  (0.92) -0.73  (1.09) -0.54  (1.10) -0.60  (1.10)
Change at Week 36 Number Analyzed 158 participants 323 participants 184 participants 332 participants
-0.56  (0.96) -0.78  (1.15) -0.58  (1.20) -0.75  (1.12)
Change at Week 52 Number Analyzed 129 participants 263 participants 149 participants 274 participants
-0.41  (0.97) -0.90  (1.17) -0.47  (1.33) -0.76  (1.13)
Time Frame All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 64) or entry in the LTS12551 open-label extension study regardless of seriousness or relationship to investigational product.
Adverse Event Reporting Description Reported AEs are treatment emergent AEs that developed/worsened during ‘treatment-emergent period’ (from first dose of IMP until 98 days after last dose of IMP or entry in the LTS12551 study). Safety population:all participants who received at least 1 dose or part of a dose of IMP, analyzed according to treatment that participants actually received.
 
Arm/Group Title Placebo (for Dupilumab 200 mg) q2w Dupilumab 200 mg q2w Placebo (for Dupilumab 300 mg) q2w Dupilumab 300 mg q2w
Hide Arm/Group Description 2 subcutaneous injections of matched Placebo (for Dupilumab 200 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication. 2 participants were excluded, who were randomized to this arm but received single injection of Dupilumab 200 mg q2w and 300 mg q2w, respectively. 2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 0), followed by a single 200 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication. 2 participants were included, who were randomized to Placebo (for Dupilumab 200 mg) arm and Dupilumab 300 mg arm, respectively but both received Dupilumab 200 mg. 2 subcutaneous injections of matched Placebo (for Dupilumab 300 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication. 2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 0), followed by a single 300 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines (second or third controller therapy). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication. 1 participant was excluded, who was randomized to this arm but received single injection of Dupilumab 200 mg q2w. 1 participant was included, who was randomized to Placebo (for Dupilumab 200 mg) arm but received Dupilumab 300 mg.
All-Cause Mortality
Placebo (for Dupilumab 200 mg) q2w Dupilumab 200 mg q2w Placebo (for Dupilumab 300 mg) q2w Dupilumab 300 mg q2w
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/313 (0.96%)   1/631 (0.16%)   0/321 (0.00%)   5/632 (0.79%) 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo (for Dupilumab 200 mg) q2w Dupilumab 200 mg q2w Placebo (for Dupilumab 300 mg) q2w Dupilumab 300 mg q2w
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   26/313 (8.31%)   51/631 (8.08%)   28/321 (8.72%)   56/632 (8.86%) 
Blood and lymphatic system disorders         
Eosinophilia  1  0/313 (0.00%)  0/631 (0.00%)  0/321 (0.00%)  1/632 (0.16%) 
Neutropenia  1  0/313 (0.00%)  0/631 (0.00%)  1/321 (0.31%)  0/632 (0.00%) 
Cardiac disorders         
Acute coronary syndrome  1  0/313 (0.00%)  1/631 (0.16%)  0/321 (0.00%)  0/632 (0.00%) 
Acute myocardial infarction  1  0/313 (0.00%)  0/631 (0.00%)  0/321 (0.00%)  2/632 (0.32%) 
Angina pectoris  1  0/313 (0.00%)  0/631 (0.00%)  0/321 (0.00%)  1/632 (0.16%) 
Atrial fibrillation  1  0/313 (0.00%)  0/631 (0.00%)  0/321 (0.00%)  1/632 (0.16%) 
Atrioventricular block second degree  1  0/313 (0.00%)  0/631 (0.00%)  0/321 (0.00%)  1/632 (0.16%) 
Cardiac failure congestive  1  0/313 (0.00%)  0/631 (0.00%)  0/321 (0.00%)  1/632 (0.16%) 
Cardio-respiratory arrest  1  0/313 (0.00%)  0/631 (0.00%)  0/321 (0.00%)  2/632 (0.32%) 
Coronary artery disease  1  0/313 (0.00%)  1/631 (0.16%)  0/321 (0.00%)  0/632 (0.00%) 
Ischaemic cardiomyopathy  1  0/313 (0.00%)  0/631 (0.00%)  0/321 (0.00%)  1/632 (0.16%) 
Myocardial ischaemia  1  0/313 (0.00%)  1/631 (0.16%)  0/321 (0.00%)  1/632 (0.16%) 
Tachyarrhythmia  1  0/313 (0.00%)  1/631 (0.16%)  0/321 (0.00%)  0/632 (0.00%) 
Congenital, familial and genetic disorders         
Sickle cell anaemia  1  0/313 (0.00%)  1/631 (0.16%)  0/321 (0.00%)  0/632 (0.00%) 
Endocrine disorders         
Primary hyperaldosteronism  1  1/313 (0.32%)  0/631 (0.00%)  0/321 (0.00%)  0/632 (0.00%) 
Eye disorders         
Retinal detachment  1  0/313 (0.00%)  0/631 (0.00%)  0/321 (0.00%)  1/632 (0.16%) 
Retinal tear  1  0/313 (0.00%)  0/631 (0.00%)  0/321 (0.00%)  1/632 (0.16%) 
Gastrointestinal disorders         
Abdominal hernia  1  0/313 (0.00%)  0/631 (0.00%)  0/321 (0.00%)  1/632 (0.16%) 
Abdominal pain  1  0/313 (0.00%)  1/631 (0.16%)  0/321 (0.00%)  0/632 (0.00%) 
Diverticular perforation  1  0/313 (0.00%)  1/631 (0.16%)  0/321 (0.00%)  0/632 (0.00%) 
Diverticulum  1  0/313 (0.00%)  0/631 (0.00%)  1/321 (0.31%)  0/632 (0.00%) 
Diverticulum intestinal  1  0/313 (0.00%)  1/631 (0.16%)  0/321 (0.00%)  0/632 (0.00%) 
Enteritis  1  0/313 (0.00%)  1/631 (0.16%)  0/321 (0.00%)  0/632 (0.00%) 
Gastric volvulus  1  0/313 (0.00%)  1/631 (0.16%)  0/321 (0.00%)  0/632 (0.00%) 
Haemorrhoids  1  0/313 (0.00%)  0/631 (0.00%)  1/321 (0.31%)  0/632 (0.00%) 
Hiatus hernia  1  0/313 (0.00%)  1/631 (0.16%)  0/321 (0.00%)  0/632 (0.00%) 
Impaired gastric emptying  1  0/313 (0.00%)  1/631 (0.16%)  0/321 (0.00%)  0/632 (0.00%) 
Inguinal hernia  1  0/313 (0.00%)  0/631 (0.00%)  1/321 (0.31%)  0/632 (0.00%) 
Large intestine polyp  1  0/313 (0.00%)  0/631 (0.00%)  1/321 (0.31%)  0/632 (0.00%) 
Oesophageal motility disorder  1  0/313 (0.00%)  0/631 (0.00%)  0/321 (0.00%)  1/632 (0.16%) 
Oesophageal ulcer  1  0/313 (0.00%)  0/631 (0.00%)  0/321 (0.00%)  1/632 (0.16%) 
Pancreatitis acute  1  0/313 (0.00%)  0/631 (0.00%)  0/321 (0.00%)  1/632 (0.16%) 
Strangulated umbilical hernia  1  0/313 (0.00%)  0/631 (0.00%)  0/321 (0.00%)  1/632 (0.16%) 
Umbilical hernia  1  0/313 (0.00%)  0/631 (0.00%)  0/321 (0.00%)  1/632 (0.16%) 
General disorders         
Chest pain  1  0/313 (0.00%)  1/631 (0.16%)  0/321 (0.00%)  1/632 (0.16%) 
Impaired healing  1  0/313 (0.00%)  0/631 (0.00%)  0/321 (0.00%)  1/632 (0.16%) 
Injection site erythema  1  0/313 (0.00%)  0/631 (0.00%)  0/321 (0.00%)  1/632 (0.16%) 
Injection site inflammation  1  0/313 (0.00%)  0/631 (0.00%)  0/321 (0.00%)  1/632 (0.16%) 
Injection site oedema  1  0/313 (0.00%)  0/631 (0.00%)  0/321 (0.00%)  1/632 (0.16%) 
Non-cardiac chest pain  1  0/313 (0.00%)  0/631 (0.00%)  1/321 (0.31%)  0/632 (0.00%) 
Hepatobiliary disorders         
Cholecystitis  1  0/313 (0.00%)  0/631 (0.00%)  0/321 (0.00%)  1/632 (0.16%) 
Cholecystitis acute  1  0/313 (0.00%)  0/631 (0.00%)  0/321 (0.00%)  2/632 (0.32%) 
Cholecystitis chronic  1  0/313 (0.00%)  1/631 (0.16%)  0/321 (0.00%)  1/632 (0.16%) 
Cholelithiasis  1  0/313 (0.00%)  1/631 (0.16%)  0/321 (0.00%)  0/632 (0.00%) 
Portal vein thrombosis  1  1/313 (0.32%)  0/631 (0.00%)  0/321 (0.00%)  0/632 (0.00%) 
Immune system disorders         
Anaphylactic reaction  1  0/313 (0.00%)  1/631 (0.16%)  0/321 (0.00%)  1/632 (0.16%) 
Anaphylactic shock  1  0/313 (0.00%)  1/631 (0.16%)  0/321 (0.00%)  0/632 (0.00%) 
Infections and infestations         
Abscess  1  0/313 (0.00%)  0/631 (0.00%)  0/321 (0.00%)  1/632 (0.16%) 
Appendicitis  1  0/313 (0.00%)  1/631 (0.16%)  0/321 (0.00%)  0/632 (0.00%) 
Atypical pneumonia  1  1/313 (0.32%)  0/631 (0.00%)  0/321 (0.00%)  0/632 (0.00%) 
Bronchitis  1  0/313 (0.00%)  0/631 (0.00%)  0/321 (0.00%)  2/632 (0.32%) 
Capnocytophaga infection  1  1/313 (0.32%)  0/631 (0.00%)  0/321 (0.00%)  0/632 (0.00%) 
Chronic sinusitis  1  0/313 (0.00%)  0/631 (0.00%)  0/321 (0.00%)  1/632 (0.16%) 
Clostridium difficile colitis  1  0/313 (0.00%)  0/631 (0.00%)  0/321 (0.00%)  1/632 (0.16%) 
Diverticulitis  1  0/313 (0.00%)  0/631 (0.00%)  1/321 (0.31%)  0/632 (0.00%) 
Gastroenteritis  1  0/313 (0.00%)  0/631 (0.00%)  1/321 (0.31%)  1/632 (0.16%) 
Hepatitis A  1  0/313 (0.00%)  0/631 (0.00%)  0/321 (0.00%)  1/632 (0.16%) 
Hepatitis C  1  1/313 (0.32%)  0/631 (0.00%)  0/321 (0.00%)  0/632 (0.00%) 
Mastoiditis  1  0/313 (0.00%)  1/631 (0.16%)  0/321 (0.00%)  0/632 (0.00%) 
Medical device site infection  1  0/313 (0.00%)  0/631 (0.00%)  0/321 (0.00%)  1/632 (0.16%) 
Otitis media  1  0/313 (0.00%)  1/631 (0.16%)  0/321 (0.00%)  0/632 (0.00%) 
Pneumonia  1  0/313 (0.00%)  0/631 (0.00%)  2/321 (0.62%)  4/632 (0.63%) 
Post procedural cellulitis  1  0/313 (0.00%)  1/631 (0.16%)  0/321 (0.00%)  0/632 (0.00%) 
Pyelonephritis  1  0/313 (0.00%)  0/631 (0.00%)  0/321 (0.00%)  1/632 (0.16%) 
Pyelonephritis chronic  1  1/313 (0.32%)  0/631 (0.00%)  0/321 (0.00%)  0/632 (0.00%) 
Tick-borne viral encephalitis  1  0/313 (0.00%)  0/631 (0.00%)  0/321 (0.00%)  1/632 (0.16%) 
Upper respiratory tract infection  1  0/313 (0.00%)  0/631 (0.00%)  1/321 (0.31%)  0/632 (0.00%) 
Urinary tract infection  1  0/313 (0.00%)  1/631 (0.16%)  0/321 (0.00%)  0/632 (0.00%) 
Injury, poisoning and procedural complications         
Concussion  1  0/313 (0.00%)  0/631 (0.00%)  1/321 (0.31%)  0/632 (0.00%) 
Contusion  1  0/313 (0.00%)  0/631 (0.00%)  0/321 (0.00%)  1/632 (0.16%) 
Facial bones fracture  1  0/313 (0.00%)  0/631 (0.00%)  0/321 (0.00%)  1/632 (0.16%) 
Fall  1  0/313 (0.00%)  0/631 (0.00%)  0/321 (0.00%)  2/632 (0.32%) 
Femur fracture  1  0/313 (0.00%)  0/631 (0.00%)  0/321 (0.00%)  1/632 (0.16%) 
Fibula fracture  1  0/313 (0.00%)  0/631 (0.00%)  1/321 (0.31%)  0/632 (0.00%) 
Foot fracture  1  0/313 (0.00%)  1/631 (0.16%)  0/321 (0.00%)  0/632 (0.00%) 
Ligament rupture  1  1/313 (0.32%)  0/631 (0.00%)  0/321 (0.00%)  0/632 (0.00%) 
Lower limb fracture  1  0/313 (0.00%)  0/631 (0.00%)  0/321 (0.00%)  1/632 (0.16%) 
Multiple injuries  1  0/313 (0.00%)  1/631 (0.16%)  0/321 (0.00%)  0/632 (0.00%) 
Pneumothorax traumatic  1  0/313 (0.00%)  0/631 (0.00%)  1/321 (0.31%)  0/632 (0.00%) 
Post-traumatic pain  1  1/313 (0.32%)  0/631 (0.00%)  0/321 (0.00%)  0/632 (0.00%) 
Postoperative thoracic procedure complication  1  0/313 (0.00%)  0/631 (0.00%)  1/321 (0.31%)  0/632 (0.00%) 
Procedural pneumothorax  1  0/313 (0.00%)  0/631 (0.00%)  1/321 (0.31%)  0/632 (0.00%) 
Radius fracture  1  0/313 (0.00%)  1/631 (0.16%)  0/321 (0.00%)  0/632 (0.00%) 
Rib fracture  1  0/313 (0.00%)  0/631 (0.00%)  1/321 (0.31%)  0/632 (0.00%) 
Road traffic accident  1  1/313 (0.32%)  0/631 (0.00%)  2/321 (0.62%)  0/632 (0.00%) 
Spinal compression fracture  1  0/313 (0.00%)  0/631 (0.00%)  0/321 (0.00%)  1/632 (0.16%) 
Spinal cord injury  1  1/313 (0.32%)  0/631 (0.00%)  0/321 (0.00%)  0/632 (0.00%) 
Ulna fracture  1  0/313 (0.00%)  0/631 (0.00%)  0/321 (0.00%)  1/632 (0.16%) 
Upper limb fracture  1  0/313 (0.00%)  0/631 (0.00%)  0/321 (0.00%)  1/632 (0.16%) 
Wrist fracture  1  0/313 (0.00%)  0/631 (0.00%)  0/321 (0.00%)  1/632 (0.16%) 
Investigations         
Alanine aminotransferase increased  1  0/313 (0.00%)  2/631 (0.32%)  0/321 (0.00%)  0/632 (0.00%) 
Musculoskeletal and connective tissue disorders         
Costochondritis  1  0/313 (0.00%)  1/631 (0.16%)  0/321 (0.00%)  0/632 (0.00%) 
Intervertebral disc protrusion  1  0/313 (0.00%)  0/631 (0.00%)  1/321 (0.31%)  0/632 (0.00%) 
Musculoskeletal chest pain  1  1/313 (0.32%)  0/631 (0.00%)  0/321 (0.00%)  1/632 (0.16%) 
Myalgia  1  0/313 (0.00%)  1/631 (0.16%)  0/321 (0.00%)  0/632 (0.00%) 
Osteoarthritis  1  1/313 (0.32%)  0/631 (0.00%)  2/321 (0.62%)  2/632 (0.32%) 
Pathological fracture  1  0/313 (0.00%)  0/631 (0.00%)  0/321 (0.00%)  1/632 (0.16%) 
Polychondritis  1  0/313 (0.00%)  1/631 (0.16%)  0/321 (0.00%)  0/632 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Adenocarcinoma of colon  1  0/313 (0.00%)  1/631 (0.16%)  0/321 (0.00%)  1/632 (0.16%) 
Anaplastic thyroid cancer  1  1/313 (0.32%)  0/631 (0.00%)  0/321 (0.00%)  0/632 (0.00%) 
Basal cell carcinoma  1  0/313 (0.00%)  2/631 (0.32%)  0/321 (0.00%)  1/632 (0.16%) 
Breast cancer  1  1/313 (0.32%)  0/631 (0.00%)  1/321 (0.31%)  0/632 (0.00%) 
Clear cell renal cell carcinoma  1  1/313 (0.32%)  0/631 (0.00%)  0/321 (0.00%)  0/632 (0.00%) 
Dysplastic naevus  1  0/313 (0.00%)  1/631 (0.16%)  0/321 (0.00%)  0/632 (0.00%) 
Haemangioblastoma  1  0/313 (0.00%)  1/631 (0.16%)  0/321 (0.00%)  0/632 (0.00%) 
Malignant melanoma  1  0/313 (0.00%)  0/631 (0.00%)  0/321 (0.00%)  2/632 (0.32%) 
Papillary thyroid cancer  1  1/313 (0.32%)  0/631 (0.00%)  0/321 (0.00%)  0/632 (0.00%) 
Rectal adenocarcinoma  1  0/313 (0.00%)  1/631 (0.16%)  0/321 (0.00%)  0/632 (0.00%) 
Small intestine carcinoma  1  0/313 (0.00%)  1/631 (0.16%)  0/321 (0.00%)  0/632 (0.00%) 
Uterine leiomyoma  1  0/313 (0.00%)  1/631 (0.16%)  1/321 (0.31%)  1/632 (0.16%) 
Nervous system disorders         
Headache  1  0/313 (0.00%)  1/631 (0.16%)  0/321 (0.00%)  0/632 (0.00%) 
Ischaemic stroke  1  1/313 (0.32%)  0/631 (0.00%)  0/321 (0.00%)  0/632 (0.00%) 
Loss of consciousness  1  0/313 (0.00%)  1/631 (0.16%)  0/321 (0.00%)  1/632 (0.16%) 
Migraine  1  0/313 (0.00%)  0/631 (0.00%)  1/321 (0.31%)  0/632 (0.00%) 
Sciatica  1  0/313 (0.00%)  1/631 (0.16%)  0/321 (0.00%)  0/632 (0.00%) 
Seizure  1  0/313 (0.00%)  1/631 (0.16%)  0/321 (0.00%)  0/632 (0.00%) 
Syncope  1  1/313 (0.32%)  0/631 (0.00%)  1/321 (0.31%)  1/632 (0.16%) 
Pregnancy, puerperium and perinatal conditions         
Abortion threatened  1  0/313 (0.00%)  0/631 (0.00%)  1/321 (0.31%)  0/632 (0.00%) 
Ectopic pregnancy  1  0/313 (0.00%)  0/631 (0.00%)  1/321 (0.31%)  0/632 (0.00%) 
Pregnancy  1  0/313 (0.00%)  0/631 (0.00%)  0/321 (0.00%)  1/632 (0.16%) 
Product Issues         
Device material issue  1  0/313 (0.00%)  1/631 (0.16%)  0/321 (0.00%)  0/632 (0.00%) 
Psychiatric disorders         
Adjustment disorder with depressed mood  1  0/313 (0.00%)  1/631 (0.16%)  0/321 (0.00%)  0/632 (0.00%) 
Anxiety  1  0/313 (0.00%)  0/631 (0.00%)  1/321 (0.31%)  1/