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Efficacy and Safety Study of Benralizumab in Adults and Adolescents Inadequately Controlled on Inhaled Corticosteroid Plus Long-acting β2 Agonist

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ClinicalTrials.gov Identifier: NCT01914757
Recruitment Status : Completed
First Posted : August 2, 2013
Results First Posted : January 25, 2017
Last Update Posted : January 25, 2017
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Asthma
Interventions Biological: Benralizumab
Biological: Placebo
Enrollment 2508
Recruitment Details  
Pre-assignment Details 2505 participants signed informed consent, 2181 entered screening/run-in period, 1306 participants were randomised to receive treatment with benralizumab 30 mg Q4W, Q8W, or placebo. Of the 1306 patients randomised, all (100.0%) received treatment with study drug.
Arm/Group Title Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Hide Arm/Group Description Benralizumab administered subcutaneously every 4 weeks Benralizumab administered subcutaneously every 8 weeks Placebo administered subcutaneously
Period Title: Overall Study
Started 425 441 440
Completed 389 390 402
Not Completed 36 51 38
Reason Not Completed
Severe non-compliance to protocol             3             1             2
Lost to Follow-up             5             8             6
Withdrawal by Subject             15             27             19
Death             2             2             1
Adverse Event             4             3             4
Study specific withdrawal criteria             0             1             0
Eligibility criteria not fulfilled             2             0             2
Other reasons             5             9             4
Arm/Group Title Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo Total
Hide Arm/Group Description Benralizumab administered subcutaneously every 4 weeks Benralizumab administered subcutaneously every 8 weeks Placebo administered subcutaneously Total of all reporting groups
Overall Number of Baseline Participants 425 441 440 1306
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 425 participants 441 participants 440 participants 1306 participants
50.0  (13.6) 49  (14.3) 48.8  (15.1) 49.2  (14.3)
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 425 participants 441 participants 440 participants 1306 participants
Female
270
  63.5%
273
  61.9%
264
  60.0%
807
  61.8%
Male
155
  36.5%
168
  38.1%
176
  40.0%
499
  38.2%
1.Primary Outcome
Title Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma for Patients With Baseline Eosinophils >=300/uL
Hide Description The annual exacerbation rate is based on unadjudicated annual exacerbation rate reported by the investigator in the eCRF.
Time Frame Immediately following the first administration of study drug through Study Week 56.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, Baseline eosinophils >=300/uL, High-dose ICS.
Arm/Group Title Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Hide Arm/Group Description:
Benralizumab administered subcutaneously every 4 weeks
Benralizumab administered subcutaneously every 8 weeks
Placebo administered subcutaneously
Overall Number of Participants Analyzed 241 239 248
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Events/year
0.6
(0.48 to 0.74)
0.66
(0.54 to 0.82)
0.93
(0.77 to 1.12)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.4 Weeks, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method Negative Binomial
Comments Model includes covariates treatment group, region, number of exacerbations in the previous year, and use of maintenance oral corticosteroids
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 0.64
Confidence Interval (2-Sided) 95%
0.49 to 0.85
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.8 Weeks, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.019
Comments [Not Specified]
Method Negative Binomial
Comments Model includes covariates treatment group, region, number of exacerbations in the previous year, and use of maintenance oral corticosteroids.
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 0.72
Confidence Interval (2-Sided) 95%
0.54 to 0.95
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma for Patients With Baseline Eosinophils <300/uL
Hide Description The annual exacerbation rate is based on unadjudicated annual exacerbation rate reported by the investigator in the eCRF.
Time Frame Immediately following the first administration of study drug through Study Week 56.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, Baseline eosinophils <300/uL, High-dose ICS.
Arm/Group Title Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Hide Arm/Group Description:
Benralizumab administered subcutaneously every 4 weeks
Benralizumab administered subcutaneously every 8 weeks
Placebo administered subcutaneously
Overall Number of Participants Analyzed 116 125 122
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Events/year
0.78
(0.59 to 1.02)
0.73
(0.55 to 0.95)
1.21
(0.96 to 1.52)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.4 Weeks, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.015
Comments [Not Specified]
Method Negative Binomial
Comments Model includes covariates treatment group, region, number of exacerbations in the previous year, and use of maintenance oral corticosteroids
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 0.64
Confidence Interval (2-Sided) 95%
0.45 to 0.92
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.8 Weeks, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments [Not Specified]
Method Negative Binomial
Comments Model includes covariates treatment group, region, number of exacerbations in the previous year, and use of maintenance oral corticosteroids.
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 0.6
Confidence Interval (2-Sided) 95%
0.42 to 0.86
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Mean Change From Baseline to Week 56 in Pre-bronchodilator FEV1 (L) Value for Patients With Baseline Eosinophils >=300/uL
Hide Description [Not Specified]
Time Frame Immediately following the first administration of study drug through Study Week 56.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, Baseline eosinophils >=300/uL, High-dose ICS
Arm/Group Title Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Hide Arm/Group Description:
Benralizumab administered subcutaneously every 4 weeks
Benralizumab administered subcutaneously every 8 weeks
Placebo administered subcutaneously
Overall Number of Participants Analyzed 216 211 221
Mean (Standard Deviation)
Unit of Measure: Liter
0.34  (0.469) 0.332  (0.518) 0.206  (0.471)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.4 Weeks, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes treatment, baseline pre-BD FEV1, region, use of OCS, visit, and treatment by visit
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.125
Confidence Interval (2-Sided) 95%
0.037 to 0.213
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.8 Weeks, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.01
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes treatment, baseline pre-BD FEV1, region, use of OCS, visit, and treatment by visit
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.116
Confidence Interval (2-Sided) 95%
0.028 to 0.204
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Mean Change From Baseline to Week 56 in Pre-bronchodilator FEV1 (L) Value for Patients With Baseline Eosinophils <300/uL
Hide Description [Not Specified]
Time Frame Immediately following the first administration of study drug through Study Week 56.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, Baseline eosinophils <300/uL, High-dose ICS
Arm/Group Title Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Hide Arm/Group Description:
Benralizumab administered subcutaneously every 4 weeks
Benralizumab administered subcutaneously every 8 weeks
Placebo administered subcutaneously
Overall Number of Participants Analyzed 101 98 99
Mean (Standard Deviation)
Unit of Measure: Liter
0.221  (0.441) 0.164  (0.358) 0.135  (0.437)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.4 Weeks, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.268
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes treatment, baseline pre-BD FEV1, region, use of OCS, visit, and treatment by visit
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.064
Confidence Interval (2-Sided) 95%
-0.049 to 0.176
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.8 Weeks, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.786
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes treatment, baseline pre-BD FEV1, region, use of OCS, visit, and treatment by visit
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.015
Confidence Interval (2-Sided) 95%
-0.127 to 0.096
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Mean Change From Baseline to Week 56 Asthma Symptoms Score for Patients With Baseline Eosinophils >=300/uL
Hide Description Asthma symptoms during night time and daytime are recorded by the patient each morning and evening in the asthma daily diary. Symptom score values are from 0 (No asthma symptom) to 3 (unable to sleep because of asthma). Baseline is defined as the average of data collected from the evening of study day -10 to the morning of study day 1. Each timepoint is calculated as bi-weekly means based on daily diary data. If more than 50% of scores are missing in a 14 day period then this is considered as missing. Symptom score lower is better.
Time Frame Immediately following the first administration of study drug through Study Week 56.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, Baseline eosinophils >=300/uL, High-dose ICS
Arm/Group Title Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Hide Arm/Group Description:
Benralizumab administered subcutaneously every 4 weeks
Benralizumab administered subcutaneously every 8 weeks
Placebo administered subcutaneously
Overall Number of Participants Analyzed 184 185 187
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
-1.33  (1.23) -1.4  (1.17) -1.2  (1.19)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.4 Weeks, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.224
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes treatment, baseline Asthma symptom score, region, use of OCS, visit, and visit by treatment.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.12
Confidence Interval (2-Sided) 95%
-0.32 to 0.07
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.8 Weeks, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.019
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes treatment, baseline Asthma symptom score, region, use of OCS, visit, and visit by treatment.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.23
Confidence Interval (2-Sided) 95%
-0.43 to -0.04
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Mean Change From Baseline to Week 56 Asthma Symptoms Score for Patients With Baseline Eosinophils <300/uL
Hide Description Asthma symptoms during night time and daytime are recorded by the patient each morning and evening in the asthma daily diary. Symptom score values are from 0 (No asthma symptom) to 3 (unable to sleep because of asthma). Baseline is defined as the average of data collected from the evening of study day -10 to the morning of study day 1. Each timepoint is calculated as bi-weekly means based on daily diary data. If more than 50% of scores are missing in a 14 day period then this is considered as missing. Symptom score lower is better.
Time Frame Immediately following the first administration of study drug through Study Week 56.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, Baseline eosinophils <300/uL, High-dose ICS
Arm/Group Title Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Hide Arm/Group Description:
Benralizumab administered subcutaneously every 4 weeks
Benralizumab administered subcutaneously every 8 weeks
Placebo administered subcutaneously
Overall Number of Participants Analyzed 88 85 89
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
-1.05  (1.14) -0.95  (1.13) -0.88  (1.12)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.4 Weeks, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.287
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes treatment, baseline Asthma symptom score, region, use of OCS, visit, and visit by treatment.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.16
Confidence Interval (2-Sided) 95%
-0.44 to 0.13
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.8 Weeks, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.966
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes treatment, baseline Asthma symptom score, region, use of OCS, visit, and visit by treatment.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.01
Confidence Interval (2-Sided) 95%
-0.28 to 0.29
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Change in Asthma Rescue Medication Use
Hide Description Change from Baseline to Week 56 in number of Rescue medication use (puffs/day)
Time Frame Immediately following the first administration of study drug through Study Week 56.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, Baseline eosinophils >=300/uL, High-dose ICS
Arm/Group Title Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Hide Arm/Group Description:
Benralizumab administered subcutaneously every 4 weeks
Benralizumab administered subcutaneously every 8 weeks
Placebo administered subcutaneously
Overall Number of Participants Analyzed 184 185 187
Mean (Standard Deviation)
Unit of Measure: Puffs per day
-2.0  (3.64) -2.92  (3.60) -2.65  (9.57)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.4 Weeks, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.603
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes treatment, baseline Asthma rescue medication use, region, use of OCS, visit, and visit by treatment.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.21
Confidence Interval (2-Sided) 95%
-0.58 to 0.99
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.8 Weeks, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.209
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes treatment, baseline Asthma medication use, region, use of OCS, visit, and visit by treatment.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.5
Confidence Interval (2-Sided) 95%
-1.29 to 0.28
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Home Lung Function Assessments Based on PEF
Hide Description Change from Baseline to Week 56 in Home lung function (morning and evening Peak expiratory flow [PEF])
Time Frame Immediately following the first administration of study drug through Study Week 56.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, Baseline eosinophils >=300/uL, High-dose ICS
Arm/Group Title Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Hide Arm/Group Description:
Benralizumab administered subcutaneously every 4 weeks
Benralizumab administered subcutaneously every 8 weeks
Placebo administered subcutaneously
Overall Number of Participants Analyzed 241 239 248
Mean (Standard Deviation)
Unit of Measure: L/min
Change at Week 56, Morning (n=194, 193, 197) 41.745  (78.534) 43.375  (91.865) 23.961  (71.509)
Change at Week 56, Evening (n=194, 192, 197) 35.142  (75.489) 39.270  (89.772) 15.448  (78.341)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.4 Weeks, Placebo
Comments Morning PEF Change from Baseline to Week 56
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.029
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes treatment, baseline morning PEF, region, use of OCS, visit, and visit by treatment.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 15.86
Confidence Interval (2-Sided) 95%
1.59 to 30.12
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.8 Weeks, Placebo
Comments Morning PEF Change from Baseline to Week 56
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.037
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes treatment, baseline morning PEF, region, use of OCS, visit, and visit by treatment.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 15.27
Confidence Interval (2-Sided) 95%
0.9 to 29.64
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.4 Weeks, Placebo
Comments Evening PEF Change from Baseline to Week 56
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.018
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes treatment, baseline evening PEF, region, use of OCS, visit, and visit by treatment.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 17.54
Confidence Interval (2-Sided) 95%
3.07 to 32
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.8 Weeks, Placebo
Comments Evening PEF Change from Baseline to Week 56
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes treatment, baseline evening PEF, region, use of OCS, visit, and visit by treatment.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 21.22
Confidence Interval (2-Sided) 95%
6.65 to 35.79
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Proportion of Nights With Awakening Due to Asthma
Hide Description Change from Baseline to Week 56 on Proportion of Nights with awakening due to asthma
Time Frame Immediately following the first administration of study drug through Study Week 56.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, Baseline eosinophils >=300/uL, High-dose ICS
Arm/Group Title Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Hide Arm/Group Description:
Benralizumab administered subcutaneously every 4 weeks
Benralizumab administered subcutaneously every 8 weeks
Placebo administered subcutaneously
Overall Number of Participants Analyzed 196 198 203
Mean (Standard Deviation)
Unit of Measure: Proportion of nights
-0.373  (0.388) -0.431  (0.4) -0.372  (0.405)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.4 Weeks, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes treatment, baseline prop of nights with nocturnal wakening, region, use of OCS, visit, and visit by treatment.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.02
Confidence Interval (2-Sided) 95%
-0.06 to 0.03
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.8 Weeks, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.146
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes treatment, baseline prop of nights with nocturnal wakening, region, use of OCS, visit, and visit by treatment.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.03
Confidence Interval (2-Sided) 95%
-0.08 to 0.01
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Mean Change From Baseline to Week 56 in ACQ-6 for Patients With Baseline Eosinophils >=300/uL
Hide Description ACQ-6 contains one bronchodilator question and 5 symptom questions. Questions are rated from 0 (totally controlled) to 6 (severely uncontrolled). Mean ACQ-6 score is the average of the responses. Mean scores of <=0.75 indicates well-controlled asthma, scores between 0.75 to <=1.5 indicate partly controlled asthma, and >1.5 indicates not well controlled asthma.
Time Frame Immediately following the first administration of study drug through Study Week 56.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, Baseline eosinophils >=300/uL, High-dose ICS
Arm/Group Title Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Hide Arm/Group Description:
Benralizumab administered subcutaneously every 4 weeks
Benralizumab administered subcutaneously every 8 weeks
Placebo administered subcutaneously
Overall Number of Participants Analyzed 192 185 197
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
-1.34  (1.13) -1.49  (1.13) -1.21  (1.12)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.4 Weeks, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.043
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes treatment, baseline ACQ-6 score, region, use of OCS, visit, and visit by treatment.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.19
Confidence Interval (2-Sided) 95%
-0.38 to -0.01
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.8 Weeks, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.008
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes treatment, baseline ACQ-6 score, region, use of OCS, visit, and visit by treatment.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.25
Confidence Interval (2-Sided) 95%
-0.44 to -0.07
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Mean Change From Baseline to Week 56 in ACQ-6 for Patients With Baseline Eosinophils <300/uL
Hide Description ACQ-6 contains one bronchodilator question and 5 symptom questions. Questions are rated from 0 (totally controlled) to 6 (severely uncontrolled). Mean ACQ-6 score is the average of the responses. Mean scores of <=0.75 indicates well-controlled asthma, scores between 0.75 to <=1.5 indicate partly controlled asthma, and >1.5 indicates not well controlled asthma.
Time Frame Immediately following the first administration of study drug through Study Week 56.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, Baseline eosinophils <300/uL, High-dose ICS
Arm/Group Title Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Hide Arm/Group Description:
Benralizumab administered subcutaneously every 4 weeks
Benralizumab administered subcutaneously every 8 weeks
Placebo administered subcutaneously
Overall Number of Participants Analyzed 88 83 92
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
-1.22  (1.16) -1.06  (1.02) -0.83  (1.07)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.4 Weeks, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.078
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes treatment, baseline ACQ-6 score, region, use of OCS, visit, and visit by treatment.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.24
Confidence Interval (2-Sided) 95%
-0.51 to 0.03
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.8 Weeks, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.449
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes treatment, baseline ACQ-6 score, region, use of OCS, visit, and visit by treatment.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.37 to 0.16
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Number of Patients With >=1 Asthma Exacerbation
Hide Description [Not Specified]
Time Frame Immediately following the first administration of study drug through Study Week 56
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, Baseline eosinophils >=300/uL, High-dose ICS
Arm/Group Title Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Hide Arm/Group Description:
Benralizumab administered subcutaneously every 4 weeks
Benralizumab administered subcutaneously every 8 weeks
Placebo administered subcutaneously
Overall Number of Participants Analyzed 241 239 248
Measure Type: Number
Unit of Measure: Participants
84 95 126
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.4 Weeks, Placebo
Comments Proportion of patients with >=1 asthma exacerbation
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Controlling for region, number of exacerbations in the previous year, use of OCS
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.46
Confidence Interval (2-Sided) 95%
0.31 to 0.69
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.8 Weeks, Placebo
Comments Proportion of patients with >=1 asthma exacerbation
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.023
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Controlling for region, number of exacerbations in the previous year, use of OCS
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.65
Confidence Interval (2-Sided) 95%
0.45 to 0.95
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Time to First Asthma Exacerbation
Hide Description [Not Specified]
Time Frame Immediately following the first administration of study drug through Study Week 56
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, Baseline eosinophils >=300/uL, High-dose ICS
Arm/Group Title Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Hide Arm/Group Description:
Benralizumab administered subcutaneously every 4 weeks
Benralizumab administered subcutaneously every 8 weeks
Placebo administered subcutaneously
Overall Number of Participants Analyzed 241 239 248
Measure Type: Number
Unit of Measure: Participants
84 95 126
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.4 Weeks, Placebo
Comments Time to first Exacerbation
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Regression, Cox
Comments Model includes treatment, region, number of exacerbations in the previous year, use of OCS
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.61
Confidence Interval (2-Sided) 95%
0.46 to 0.80
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.8 Weeks, Placebo
Comments Time to first asthma exacerbation
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.018
Comments [Not Specified]
Method Regression, Cox
Comments Model includes treatment, region, number of exacerbations in the previous year, use of OCS
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.73
Confidence Interval (2-Sided) 95%
0.55 to 0.95
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Annual Rate of Asthma Exacerbation Resulting Emergency Room Visits and Hospitalizations
Hide Description Annual rate of asthma exacerbations that are associated with an emergency room visit or a hospitalization (adjudicated)
Time Frame Immediately following the first administration of study drug through Study Week 56.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, Baseline eosinophils >=300/uL, High-dose ICS
Arm/Group Title Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Hide Arm/Group Description:
Benralizumab administered subcutaneously every 4 weeks
Benralizumab administered subcutaneously every 8 weeks
Placebo administered subcutaneously
Overall Number of Participants Analyzed 241 239 248
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Events/year
0.04
(0.02 to 0.06)
0.05
(0.03 to 0.08)
0.04
(0.02 to 0.07)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.4 Weeks, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.837
Comments [Not Specified]
Method negative binomial
Comments Model includes treatment, region, any prior exacerbation resulting ER/Hospitalization, use of OCS
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 0.93
Confidence Interval (2-Sided) 95%
0.48 to 1.82
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.8 Weeks, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.538
Comments [Not Specified]
Method negative binomial
Comments Model includes treatment, region, any prior exacerbation resulting ER/Hospitalization, use of OCS
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 1.23
Confidence Interval (2-Sided) 95%
0.64 to 2.35
Estimation Comments [Not Specified]
15.Secondary Outcome
Title Pharmacokinetics of Benralizumab
Hide Description Mean PK Concentration at each visit
Time Frame Baseline, Week 4, Week 8, Week 16, Week 24, Week 32, Week 40, Week 48, Week 56, Week 60
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set
Arm/Group Title Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Hide Arm/Group Description:
Benralizumab administered subcutaneously every 4 weeks
Benralizumab administered subcutaneously every 8 weeks
Placebo administered subcutaneously
Overall Number of Participants Analyzed 435 424 0
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Baseline (n=435, 419)
NA [1] 
(NA%)
NA [1] 
(NA%)
Week 4 (n=430, 416)
650.04
(154.61%)
703.16
(89.48%)
Week 8 (n=414, 395)
894.86
(148.91%)
939.45
(98.99%)
Week 16 (n=390, 378)
936.43
(247.46%)
252.54
(274.74%)
Week 24 (n=388, 361)
827.09
(370.64%)
188.99
(308.38%)
Week 32 (n=345, 323)
823.21
(362.43%)
166.53
(289.34%)
Week 40 (n=370, 338)
859.69
(364.28%)
172.28
(298.6%)
Week 48 (n=355, 337)
888.09
(333.98%)
186.5
(290.28%)
Week 56 (n=358, 344)
763.98
(309.18%)
173.41
(235.86%)
Week 60 (n=49, 45)
53.63
(1782.96%)
18.63
(756.47%)
[1]
Value is less than lower limit of quantification
16.Secondary Outcome
Title Immunogenicity of Benralizumab
Hide Description Anti-drug antibodies (ADA) responses at baseline and post baseline. Persistently positive is defined as positive at >=2 post-baseline assessments (with >=16 weeks between first and last positive) or positive at last post-baseline assessment. Transiently positive is defined as having at least one post-baseline ADA positive assessment and not fulfilling the conditions of persistently positive.
Time Frame Pre-treatment until end of follow-up
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Hide Arm/Group Description:
Benralizumab administered subcutaneously every 4 weeks
Benralizumab administered subcutaneously every 8 weeks
Placebo administered subcutaneously
Overall Number of Participants Analyzed 438 427 440
Measure Type: Number
Unit of Measure: Participants
Positive at any visit (n=438, 427, 440) 63 64 13
Base- and Post-baseline Postive (n=431, 414, 430) 5 5 5
Only post-baseline positive (n=431, 420, 436) 55 57 8
Persistently positive (n=431, 420, 436) 44 42 7
Transient positive (n=431, 420, 436) 16 20 6
Only baseline positive (n=438, 421, 434) 3 2 0
17.Secondary Outcome
Title Extent of Exposure
Hide Description Extent of exposure is defined as the duration of treatment in days
Time Frame Immediately following the first administration of study drug through Study Week 56
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Hide Arm/Group Description:
Benralizumab administered subcutaneously every 4 weeks
Benralizumab administered subcutaneously every 8 weeks
Placebo administered subcutaneously
Overall Number of Participants Analyzed 438 428 440
Mean (Standard Deviation)
Unit of Measure: Days
344.14  (73.129) 331.64  (88.839) 336.69  (82.148)
18.Secondary Outcome
Title Mean Change From Baseline to Week 56 in AQLQ(S)+12
Hide Description AQLQ(S)+12 overall score is defined as the average of all 32 questions in the AQLQ(S)+12 questionnaire. AQLQ(S)+12 is a 7-point scale questionnaire, ranging from 7 (no impairment) to 1 (severe impairment). Total or domain score change of >=0.5 are considered clinically meaningful.
Time Frame Immediately following the first administration of study drug through Study Week 56
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, Baseline eosinophils >=300/uL, High-dose ICS
Arm/Group Title Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Hide Arm/Group Description:
Benralizumab administered subcutaneously every 4 weeks
Benralizumab administered subcutaneously every 8 weeks
Placebo administered subcutaneously
Overall Number of Participants Analyzed 186 180 191
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
1.44  (1.15) 1.61  (1.24) 1.32  (1.19)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.4 Weeks, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.119
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes treatment, baseline AQLQ score, region, use of OCS, visit, visit by treatment.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.16
Confidence Interval (2-Sided) 95%
-0.04 to 0.37
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.8 Weeks, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.019
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes treatment, baseline AQLQ score, region, use of OCS, visit, visit by treatment.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.24
Confidence Interval (2-Sided) 95%
0.04 to 0.45
Estimation Comments [Not Specified]
19.Secondary Outcome
Title Change From Baseline to Week 56 in EQ-5D-5L VAS
Hide Description EQ-5D-5L VAS is to rate current health status on a scale of 0-100, with 0 being the worst imaginable health state.
Time Frame Immediately following the first administration of study drug through Study Week 56
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, Baseline eosinophils >=300/uL, High-dose ICS
Arm/Group Title Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Hide Arm/Group Description:
Benralizumab administered subcutaneously every 4 weeks
Benralizumab administered subcutaneously every 8 weeks
Placebo administered subcutaneously
Overall Number of Participants Analyzed 183 179 191
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
13.8  (21.52) 15.5  (20.36) 12.1  (20.13)
20.Secondary Outcome
Title Mean Work Productivity Loss Due to Asthma
Hide Description WPAI+CIQ (Work Productivity and Activity Impairment plus Classroom Impairment Questionnaire) contains 10 questions. Work productivity loss is derived by sum of percentage of missed work due to asthma and product of percentage of actual working hours times degree of asthma affecting work productivity while working. Percentage of missed work due to asthma is calculated by number of hours missed work due to asthma divided by total number of hours missed work plus number of hours actually worked. This is only applicable to patients who were employed.
Time Frame Immediately following the first administration of study drug through Study Week 56
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, Baseline eosinophils >=300/uL, High-dose ICS, who were employed
Arm/Group Title Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Hide Arm/Group Description:
Benralizumab administered subcutaneously every 4 weeks
Benralizumab administered subcutaneously every 8 weeks
Placebo administered subcutaneously
Overall Number of Participants Analyzed 92 74 85
Mean (Standard Deviation)
Unit of Measure: Percent of productivity loss
26.56  (25.589) 24.44  (24.689) 27.29  (25.802)
21.Secondary Outcome
Title Mean Productivity Loss Due to Asthma in Classroom
Hide Description WPAI+CIQ (Work Productivity and Activity Impairment plus Classroom Impairment Questionnaire) contains 10 questions. Classroom productivity loss is derived by sum of percentage of missed classes due to asthma and product of percentage of actual hours attending classes times degree of asthma affecting classroom productivity. Percentage of missed classes due to asthma is calculated by number of hours missed classes due to asthma divided by total number of hours missed classes plus number of hours actually attending classes. This is only applicable for patients who took classes.
Time Frame Immediately following the first administration of study drug through Study Week 56
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, Baseline eosinophils >=300/uL, High-dose ICS, who took classes
Arm/Group Title Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Hide Arm/Group Description:
Benralizumab administered subcutaneously every 4 weeks
Benralizumab administered subcutaneously every 8 weeks
Placebo administered subcutaneously
Overall Number of Participants Analyzed 14 5 5
Mean (Standard Deviation)
Unit of Measure: percent of productivity loss
19.92  (23.765) 14  (16.733) 33.5  (25.593)
22.Secondary Outcome
Title Number of Participants That Utilized Health Care Resources
Hide Description [Not Specified]
Time Frame Immediately following the first administration of study drug through Study Week 56
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, Baseline eosinophils >=300/uL, High-dose ICS
Arm/Group Title Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Hide Arm/Group Description:
Benralizumab administered subcutaneously every 4 weeks
Benralizumab administered subcutaneously every 8 weeks
Placebo administered subcutaneously
Overall Number of Participants Analyzed 241 239 248
Measure Type: Number
Unit of Measure: Participants
Hospitalizations 11 14 12
Emergency department visits 11 12 18
Unscheduled outpatient visits 72 75 83
Home visits 3 1 2
Telephone calls 50 63 58
Ambulance transports 2 3 5
23.Secondary Outcome
Title Patient and Clinician Assessment of Response to Treatment
Hide Description CGIC (clinician global impression of change), and PGIC (patient global impression of change) are overall evaluation of response to treatment, conducted separately by investigator and patient using a 7-point rating scale, ranging from 1 (Very much Improved), to 7 (Very much Worse). This endpoint was added after the second protocol amendment, thus not all patients had data to be analyzed.
Time Frame Immediately following the first administration of study drug through Study Week 56
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, Baseline eosinophils >=300/uL, High-dose ICS
Arm/Group Title Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Hide Arm/Group Description:
Benralizumab administered subcutaneously every 4 weeks
Benralizumab administered subcutaneously every 8 weeks
Placebo administered subcutaneously
Overall Number of Participants Analyzed 241 239 248
Measure Type: Number
Unit of Measure: Participants
CGIC, Improved 109 96 97
CGIC, Much Improved 82 71 65
CGIC, Very Much Improved 26 23 14
CGIC, Total 217 190 176
PGIC, Improved 109 95 99
PGIC, Much Improved 83 80 66
PGIC, Very Much Improved 34 30 17
PGIC, Total 226 205 182
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Hide Arm/Group Description Benralizumab administered subcutaneously every 4 weeks Benralizumab administered subcutaneously every 8 weeks Placebo administered subcutaneously
All-Cause Mortality
Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   46/438 (10.50%)      41/428 (9.58%)      61/440 (13.86%)    
Blood and lymphatic system disorders       
Anaemia  1  0/438 (0.00%)  0 0/428 (0.00%)  0 1/440 (0.23%)  1
Cardiac disorders       
Acute coronary syndrome  1  0/438 (0.00%)  0 1/428 (0.23%)  1 0/440 (0.00%)  0
Acute myocardial infarction  1  1/438 (0.23%)  1 0/428 (0.00%)  0 1/440 (0.23%)  2
Angina pectoris  1  0/438 (0.00%)  0 1/428 (0.23%)  1 0/440 (0.00%)  0
Aortic valve stenosis  1  0/438 (0.00%)  0 0/428 (0.00%)  0 1/440 (0.23%)  1
Atrial fibrillation  1  0/438 (0.00%)  0 1/428 (0.23%)  1 0/440 (0.00%)  0
Atrioventricular block complete  1  0/438 (0.00%)  0 0/428 (0.00%)  0 1/440 (0.23%)  1
Cardiac arrest  1  0/438 (0.00%)  0 0/428 (0.00%)  0 1/440 (0.23%)  1
Cardiac failure congestive  1  1/438 (0.23%)  1 0/428 (0.00%)  0 0/440 (0.00%)  0
Coronary artery disease  1  0/438 (0.00%)  0 0/428 (0.00%)  0 1/440 (0.23%)  1
Myocardial infarction  1  1/438 (0.23%)  1 0/428 (0.00%)  0 1/440 (0.23%)  1
Myocardial ischaemia  1  0/438 (0.00%)  0 0/428 (0.00%)  0 2/440 (0.45%)  2
Supraventricular tachycardia  1  0/438 (0.00%)  0 0/428 (0.00%)  0 1/440 (0.23%)  1
Eye disorders       
Cataract  1  0/438 (0.00%)  0 1/428 (0.23%)  1 0/440 (0.00%)  0
Gastrointestinal disorders       
Gastritis  1  0/438 (0.00%)  0 0/428 (0.00%)  0 1/440 (0.23%)  1
Gastroduodenitis  1  0/438 (0.00%)  0 1/428 (0.23%)  1 0/440 (0.00%)  0
Inguinal hernia  1  1/438 (0.23%)  1 0/428 (0.00%)  0 0/440 (0.00%)  0
Large intestine polyp  1  1/438 (0.23%)  1 0/428 (0.00%)  0 0/440 (0.00%)  0
Rectal polyp  1  0/438 (0.00%)  0 0/428 (0.00%)  0 1/440 (0.23%)  1
General disorders       
Chest pain  1  1/438 (0.23%)  1 1/428 (0.23%)  1 0/440 (0.00%)  0
Death  1  0/438 (0.00%)  0 1/428 (0.23%)  1 0/440 (0.00%)  0
Non-cardiac chest pain  1  0/438 (0.00%)  0 0/428 (0.00%)  0 1/440 (0.23%)  1
Hepatobiliary disorders       
Cholecystitis  1  0/438 (0.00%)  0 1/428 (0.23%)  1 0/440 (0.00%)  0
Cholecystitis acute  1  0/438 (0.00%)  0 0/428 (0.00%)  0 1/440 (0.23%)  1
Cholecystitis chronic  1  1/438 (0.23%)  1 0/428 (0.00%)  0 0/440 (0.00%)  0
Cholelithiasis  1  1/438 (0.23%)  1 0/428 (0.00%)  0 0/440 (0.00%)  0
Hepatitis alcoholic  1  1/438 (0.23%)  1 0/428 (0.00%)  0 0/440 (0.00%)  0
Immune system disorders       
Anaphylactic reaction  1  0/438 (0.00%)  0 1/428 (0.23%)  1 0/440 (0.00%)  0
Drug hypersensitivity  1  0/438 (0.00%)  0 1/428 (0.23%)  1 1/440 (0.23%)  1
Infections and infestations       
Appendicitis  1  0/438 (0.00%)  0 1/428 (0.23%)  1 0/440 (0.00%)  0
Bacterial infection  1  1/438 (0.23%)  1 0/428 (0.00%)  0 0/440 (0.00%)  0
Bronchitis  1  1/438 (0.23%)  1 1/428 (0.23%)  1 0/440 (0.00%)  0
Bronchitis haemophilus  1  0/438 (0.00%)  0 1/428 (0.23%)  1 0/440 (0.00%)  0
Chronic sinusitis  1  1/438 (0.23%)  1 0/428 (0.00%)  0 0/440 (0.00%)  0
Cytomegalovirus hepatitis  1  0/438 (0.00%)  0 0/428 (0.00%)  0 1/440 (0.23%)  1
Gastroenteritis  1  0/438 (0.00%)  0 1/428 (0.23%)  1 0/440 (0.00%)  0
Herpes zoster  1  0/438 (0.00%)  0 1/428 (0.23%)  1 0/440 (0.00%)  0
Influenza  1  0/438 (0.00%)  0 2/428 (0.47%)  2 0/440 (0.00%)  0
Liver abscess  1  0/438 (0.00%)  0 0/428 (0.00%)  0 1/440 (0.23%)  1
Pneumonia  1  2/438 (0.46%)  2 0/428 (0.00%)  0 4/440 (0.91%)  6
Pneumonia bacterial  1  2/438 (0.46%)  2 0/428 (0.00%)  0 3/440 (0.68%)  3
Pseudomonas bronchitis  1  0/438 (0.00%)  0 0/428 (0.00%)  0 1/440 (0.23%)  1
Pseudomonas infection  1  0/438 (0.00%)  0 0/428 (0.00%)  0 1/440 (0.23%)  1
Respiratory tract infection bacterial  1  1/438 (0.23%)  1 0/428 (0.00%)  0 0/440 (0.00%)  0
Sepsis  1  1/438 (0.23%)  1 0/428 (0.00%)  0 0/440 (0.00%)  0
Sinusitis  1  0/438 (0.00%)  0 0/428 (0.00%)  0 1/440 (0.23%)  1
Upper respiratory tract infection  1  0/438 (0.00%)  0 1/428 (0.23%)  1 0/440 (0.00%)  0
Urinary tract infection  1  0/438 (0.00%)  0 1/428 (0.23%)  1 0/440 (0.00%)  0
Injury, poisoning and procedural complications       
Anastomotic ulcer  1  0/438 (0.00%)  0 1/428 (0.23%)  1 0/440 (0.00%)  0
Humerus fracture  1  0/438 (0.00%)  0 0/428 (0.00%)  0 1/440 (0.23%)  1
Injury  1  0/438 (0.00%)  0 0/428 (0.00%)  0 1/440 (0.23%)  1
Joint injury  1  0/438 (0.00%)  0 0/428 (0.00%)  0 1/440 (0.23%)  1
Patella fracture  1  0/438 (0.00%)  0 1/428 (0.23%)  1 0/440 (0.00%)  0
Procedural complication  1  0/438 (0.00%)  0 1/428 (0.23%)  1 0/440 (0.00%)  0
Road traffic accident  1  1/438 (0.23%)  1 0/428 (0.00%)  0 0/440 (0.00%)  0
Thermal burn  1  0/438 (0.00%)  0 0/428 (0.00%)  0 1/440 (0.23%)  1
Toxicity to various agents  1  0/438 (0.00%)  0 1/428 (0.23%)  1 0/440 (0.00%)  0
Metabolism and nutrition disorders       
Obesity  1  0/438 (0.00%)  0 1/428 (0.23%)  1 0/440 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Back pain  1  0/438 (0.00%)  0 1/428 (0.23%)  1 0/440 (0.00%)  0
Dupuytren's contracture  1  0/438 (0.00%)  0 1/428 (0.23%)  1 0/440 (0.00%)  0
Epiphysiolysis  1  0/438 (0.00%)  0 0/428 (0.00%)  0 1/440 (0.23%)  1
Intervertebral disc disorder  1  1/438 (0.23%)  1 0/428 (0.00%)  0 1/440 (0.23%)  1
Jaw cyst  1  1/438 (0.23%)  1 0/428 (0.00%)  0 0/440 (0.00%)  0
Muscular weakness  1  1/438 (0.23%)  1 0/428 (0.00%)  0 0/440 (0.00%)  0
Osteoarthritis  1  1/438 (0.23%)  1 1/428 (0.23%)  1 1/440 (0.23%)  1
Rheumatoid arthritis  1  1/438 (0.23%)  1 0/428 (0.00%)  0 0/440 (0.00%)  0
Rotator cuff syndrome  1  0/438 (0.00%)  0 0/428 (0.00%)  0 1/440 (0.23%)  1
Spinal osteoarthritis  1  1/438 (0.23%)  1 0/428 (0.00%)  0 0/440 (0.00%)  0
Spondylolisthesis  1  0/438 (0.00%)  0 0/428 (0.00%)  0 1/440 (0.23%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Breast cancer female  1  0/438 (0.00%)  0 0/428 (0.00%)  0 1/440 (0.23%)  1
Colon neoplasm  1  0/438 (0.00%)  0 1/428 (0.23%)  1 0/440 (0.00%)  0
Gallbladder cancer  1  1/438 (0.23%)  1 0/428 (0.00%)  0 0/440 (0.00%)  0
Gastric cancer  1  1/438 (0.23%)  1 0/428 (0.00%)  0 0/440 (0.00%)  0
Thyroid adenoma  1  0/438 (0.00%)  0 0/428 (0.00%)  0 1/440 (0.23%)  1
Uterine leiomyoma  1  1/438 (0.23%)  1 0/428 (0.00%)  0 0/440 (0.00%)  0
Nervous system disorders       
Cerebrovascular accident  1  0/438 (0.00%)  0 0/428 (0.00%)  0 1/440 (0.23%)  1
Lumbar radiculopathy  1  0/438 (0.00%)  0 0/428 (0.00%)  0 1/440 (0.23%)  2
Sciatica  1  0/438 (0.00%)  0 0/428 (0.00%)  0 1/440 (0.23%)  1
Seizure  1  0/438 (0.00%)  0 1/428 (0.23%)  1 0/440 (0.00%)  0
Syncope  1  1/438 (0.23%)  1 1/428 (0.23%)  1 0/440 (0.00%)  0
Transient ischaemic attack  1  0/438 (0.00%)  0 0/428 (0.00%)  0 1/440 (0.23%)  1
Psychiatric disorders       
Completed suicide  1  1/438 (0.23%)  1 0/428 (0.00%)  0 0/440 (0.00%)  0
Depression  1  0/438 (0.00%)  0 1/428 (0.23%)  1 0/440 (0.00%)  0
Renal and urinary disorders       
Calculus ureteric  1  1/438 (0.23%)  1 0/428 (0.00%)  0 0/440 (0.00%)  0
Nephrolithiasis  1  2/438 (0.46%)  3 0/428 (0.00%)  0 0/440 (0.00%)  0
Reproductive system and breast disorders       
Benign prostatic hyperplasia  1  0/438 (0.00%)  0 0/428 (0.00%)  0 1/440 (0.23%)  1
Respiratory, thoracic and mediastinal disorders       
Asthma  1  21/438 (4.79%)  25 19/428 (4.44%)  27 23/440 (5.23%)  38
Hyperventilation  1  0/438 (0.00%)  0 0/428 (0.00%)  0 1/440 (0.23%)  1
Nasal polyps  1  0/438 (0.00%)  0 0/428 (0.00%)  0 1/440 (0.23%)  1
Nasal turbinate hypertrophy  1  1/438 (0.23%)  1 0/428 (0.00%)  0 0/440 (0.00%)  0
Pleural effusion  1  1/438 (0.23%)  1 0/428 (0.00%)  0 0/440 (0.00%)  0
Skin and subcutaneous tissue disorders       
Parakeratosis  1  0/438 (0.00%)  0 0/428 (0.00%)  0 1/440 (0.23%)  1
Urticaria  1  1/438 (0.23%)  1 0/428 (0.00%)  0 0/440 (0.00%)  0
Urticaria papular  1  0/438 (0.00%)  0 1/428 (0.23%)  1 0/440 (0.00%)  0
Vascular disorders       
Aortic stenosis  1  0/438 (0.00%)  0 0/428 (0.00%)  0 1/440 (0.23%)  1
Hypertension  1  0/438 (0.00%)  0 1/428 (0.23%)  1 1/440 (0.23%)  1
Hypertensive crisis  1  1/438 (0.23%)  1 0/428 (0.00%)  0 0/440 (0.00%)  0
Phlebitis  1  0/438 (0.00%)  0 0/428 (0.00%)  0 1/440 (0.23%)  1
Venous thrombosis  1  0/438 (0.00%)  0 0/428 (0.00%)  0 1/440 (0.23%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 3%
Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   244/438 (55.71%)      232/428 (54.21%)      264/440 (60.00%)    
General disorders       
Pyrexia  1  16/438 (3.65%)  20 13/428 (3.04%)  13 6/440 (1.36%)  6
Infections and infestations       
Acute sinusitis  1  6/438 (1.37%)  6 5/428 (1.17%)  6 14/440 (3.18%)  19
Bronchitis  1  40/438 (9.13%)  51 45/428 (10.51%)  54 54/440 (12.27%)  72
Influenza  1  24/438 (5.48%)  27 12/428 (2.80%)  17 25/440 (5.68%)  27
Nasopharyngitis  1  90/438 (20.55%)  132 82/428 (19.16%)  131 92/440 (20.91%)  147
Pharyngitis  1  17/438 (3.88%)  21 10/428 (2.34%)  10 8/440 (1.82%)  9
Rhinitis  1  12/438 (2.74%)  13 18/428 (4.21%)  24 17/440 (3.86%)  22
Sinusitis  1  23/438 (5.25%)  31 21/428 (4.91%)  30 39/440 (8.86%)  56
Upper respiratory tract infection  1  29/438 (6.62%)  35 37/428 (8.64%)  53 42/440 (9.55%)  53
Musculoskeletal and connective tissue disorders       
Arthralgia  1  8/438 (1.83%)  10 14/428 (3.27%)  16 10/440 (2.27%)  14
Back pain  1  17/438 (3.88%)  18 11/428 (2.57%)  11 16/440 (3.64%)  20
Nervous system disorders       
Headache  1  33/438 (7.53%)  63 34/428 (7.94%)  65 32/440 (7.27%)  57
Respiratory, thoracic and mediastinal disorders       
Asthma  1  50/438 (11.42%)  76 32/428 (7.48%)  50 52/440 (11.82%)  96
Cough  1  10/438 (2.28%)  11 14/428 (3.27%)  18 8/440 (1.82%)  12
Rhinitis allergic  1  21/438 (4.79%)  25 16/428 (3.74%)  19 24/440 (5.45%)  28
Vascular disorders       
Hypertension  1  12/438 (2.74%)  12 18/428 (4.21%)  23 22/440 (5.00%)  24
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
≥ 60 days prior to submission of material for publication/presentation, Institution and PI shall jointly provide AZ with material for review. No publication/presentation may include any of AZ’s Confidential Information without AZ’s written approval. AZ can request Inst. and PI to withhold material from submission for publication/presentation for an additional 90 days to allow AZ to establish and preserve its proprietary rights in the material being submitted for publication or presentation.
Results Point of Contact
Name/Title: Mitchell Goldman, Medical Science Director
Organization: AstraZeneca
Phone: +1 301 398 0323
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01914757     History of Changes
Other Study ID Numbers: D3250C00018
First Submitted: July 31, 2013
First Posted: August 2, 2013
Results First Submitted: September 8, 2016
Results First Posted: January 25, 2017
Last Update Posted: January 25, 2017