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A Phase 3 Study to Evaluate the Efficacy and Safety of Tralokinumab in Adults and Adolescents With Uncontrolled Asthma (STRATOS2)

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ClinicalTrials.gov Identifier: NCT02194699
Recruitment Status : Completed
First Posted : July 18, 2014
Results First Posted : March 21, 2018
Last Update Posted : May 15, 2018
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 Uncontrolled Asthma
Interventions Biological: Experimental: Tralokinumab
Other: Placebo
Enrollment 856
Recruitment Details

First patient enrolled: 30 Oct 2014; Last Patient Last Visit: 21 Sep 2017. Study performed at 242 sites in 13 countries.

Patients were maintained on their currently prescribed inhaled corticosteroid long-acting β2-agonist therapy and any additional maintenance asthma controller medications throughout the study period.

Pre-assignment Details

1696 patients signed informed consent, 1163 entered screening/run-in period, 856 patients were randomised to receive investigational product (IP) and 849 received treatment.

The primary population was the biomarker positive population, defined as all patients with baseline fractional exhaled nitric oxide (FeNO) ≥37 parts per billion (ppb).

Arm/Group Title Tralo 300 mg Q2W Placebo
Hide Arm/Group Description Tralokinumab 300 milligrams (mg) administered subcutaneously every 2 weeks (Q2W) over a 52-week treatment period (up to 26 doses). Placebo administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses).
Period Title: Randomised
Started 428 428
Completed 420 417
Not Completed 8 11
Reason Not Completed
Did not receive treatment             1             5
Without potential for 52 weeks of IP             5             5
Duplicate patient             2             1
Period Title: With Potential to Receive 52 Weeks of IP
Started 420 [1] 417 [1]
Completed 370 365
Not Completed 50 52
Reason Not Completed
Adverse Event             4             3
Death             1             3
Lost to Follow-up             5             8
Protocol Violation             2             2
Withdrawal by Subject             14             20
Other             24             16
[1]
Includes all patients randomised with the potential to receive 52 weeks of IP and receiving any IP.
Arm/Group Title Tralo 300 mg Q2W Placebo Total
Hide Arm/Group Description Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Placebo administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Total of all reporting groups
Overall Number of Baseline Participants 420 417 837
Hide Baseline Analysis Population Description
All patients in the full analysis set (FAS) with the potential to receive 52 weeks of IP and who received any IP (tralokinumab or placebo) were included in the baseline analysis.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 420 participants 417 participants 837 participants
47.3  (15.6) 48.0  (15.5) 47.6  (15.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 420 participants 417 participants 837 participants
Female
276
  65.7%
290
  69.5%
566
  67.6%
Male
144
  34.3%
127
  30.5%
271
  32.4%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 420 participants 417 participants 837 participants
American Indian or Alaska Native
3
   0.7%
3
   0.7%
6
   0.7%
Asian
83
  19.8%
88
  21.1%
171
  20.4%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
27
   6.4%
24
   5.8%
51
   6.1%
White
283
  67.4%
281
  67.4%
564
  67.4%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
24
   5.7%
21
   5.0%
45
   5.4%
1.Primary Outcome
Title Annualised Asthma Exacerbation Rate (AAER) up to Week 52
Hide Description

Asthma exacerbation was defined as a worsening of asthma that led to any of the following:

  • Use of systemic corticosteroids for at least 3 days; a single depo-injectable dose of corticosteroids was considered equivalent to a 3-day course of systemic corticosteroids.
  • An emergency room (ER) or urgent care (UC) visit (defined as evaluation and treatment for <24 hours in an ER or UC centre) due to asthma that required systemic corticosteroids (see above).
  • An inpatient hospitalisation (defined as admission to an inpatient facility and/or evaluation and treatment in a healthcare facility for ≥24 hours) due to asthma.

AAER = number of exacerbations*365.25 / (follow-up date – date of randomisation + 1) (where maximum follow-up time for a patient was approximately 52 weeks).

AAER in the tralokinumab group was compared to that seen in the placebo group up to Week 52 using a negative binomial model; rate ratios and rate reductions are both presented for comparative statistical analyses.

Time Frame Baseline (Week 0) up to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised patients with the potential to receive 52 weeks of IP and receiving any IP, irrespective of their protocol adherence and continued participation in the study.
Arm/Group Title Biomarker Positive - Tralo 300 mg Q2W Biomarker Positive - Placebo Biomarker Negative - Tralo 300 mg Q2W Biomarker Negative - Placebo Tralo 300 mg Q2W Placebo
Hide Arm/Group Description:
Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker positive population (primary population) had baseline FeNO ≥37 ppb.
Placebo administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker positive population (primary population) had baseline FeNO ≥37 ppb.
Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker negative population (complement population) had baseline FeNO <37 ppb.
Placebo administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker negative population (complement population) had baseline FeNO <37 ppb.
Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses).
Placebo administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses).
Overall Number of Participants Analyzed 108 121 308 290 420 417
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events/year
0.80
(0.57 to 1.11)
0.95
(0.68 to 1.31)
0.87
(0.71 to 1.06)
0.77
(0.63 to 0.95)
0.84
(0.71 to 1.00)
0.82
(0.69 to 0.97)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Biomarker Positive - Tralo 300 mg Q2W, Biomarker Positive - Placebo
Comments

Comparison of AAER (rate ratio): Biomarker positive population; Tralo 300 mg Q2W vs placebo.

A variable for the biomarker population (positive, negative) as well as a treatment-by-biomarker population interaction term was included in the analysis model.

Type of Statistical Test Superiority
Comments The null hypothesis was that the exacerbation rate during the 52-week double-blind treatment period on tralokinumab was equal to the corresponding exacerbation rate on placebo.
Statistical Test of Hypothesis P-Value 0.4656
Comments [Not Specified]
Method Negative binomial
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate ratio
Estimated Value 0.84
Confidence Interval (2-Sided) 95%
0.53 to 1.34
Estimation Comments Covariates in the model included treatment group, geographical region, age group, periostin group at baseline and number of exacerbations in the year before the study.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Biomarker Negative - Tralo 300 mg Q2W, Biomarker Negative - Placebo
Comments

Comparison of AAER (rate ratio): Biomarker negative population; Tralo 300 mg Q2W vs placebo.

A variable for the biomarker population (positive, negative) as well as a treatment-by-biomarker population interaction term was included in the analysis model.

Type of Statistical Test Superiority
Comments The null hypothesis was that the exacerbation rate during the 52-week double-blind treatment period on tralokinumab was equal to the corresponding exacerbation rate on placebo.
Statistical Test of Hypothesis P-Value 0.4126
Comments [Not Specified]
Method Negative binomial
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate ratio
Estimated Value 1.13
Confidence Interval (2-Sided) 95%
0.85 to 1.50
Estimation Comments Covariates in the model included treatment group, geographical region, age group, periostin group at baseline and number of exacerbations in the year before the study.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Biomarker Positive - Tralo 300 mg Q2W, Biomarker Positive - Placebo
Comments

Comparison of AAER (rate reduction): Biomarker positive population; Tralo 300 mg Q2W vs placebo.

A variable for the biomarker population (positive, negative) as well as a treatment-by-biomarker population interaction term was included in the analysis model.

Type of Statistical Test Superiority
Comments The null hypothesis was that the exacerbation rate during the 52-week double-blind treatment period on tralokinumab was equal to the corresponding exacerbation rate on placebo.
Statistical Test of Hypothesis P-Value 0.4656
Comments [Not Specified]
Method Negative binominal
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate reduction
Estimated Value 15.83
Confidence Interval (2-Sided) 95%
-33.71 to 47.01
Estimation Comments Covariates in the model included treatment group, geographical region, age group, periostin group at baseline and number of exacerbations in the year before the study.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Tralo 300 mg Q2W, Placebo
Comments Comparison of AAER (rate ratio): FAS population; Tralo 300 mg Q2W vs placebo.
Type of Statistical Test Superiority
Comments The null hypothesis was that the exacerbation rate during the 52-week double-blind treatment period on tralokinumab was equal to the corresponding exacerbation rate on placebo.
Statistical Test of Hypothesis P-Value 0.8027
Comments [Not Specified]
Method Negative binomial
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate ratio
Estimated Value 1.03
Confidence Interval (2-Sided) 95%
0.81 to 1.31
Estimation Comments Covariates in the model included treatment group, geographical region, age group, periostin group at baseline and number of exacerbations in the year before the study.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Tralo 300 mg Q2W, Placebo
Comments Comparison of AAER (rate reduction): FAS population; Tralo 300 mg Q2W vs placebo.
Type of Statistical Test Superiority
Comments The null hypothesis was that the exacerbation rate during the 52-week double-blind treatment period on tralokinumab was equal to the corresponding exacerbation rate on placebo.
Statistical Test of Hypothesis P-Value 0.8027
Comments [Not Specified]
Method Negative binominal
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate reduction
Estimated Value -3.14
Confidence Interval (2-Sided) 95%
-31.46 to 19.08
Estimation Comments Covariates in the model included treatment group, geographical region, age group, periostin group at baseline and number of exacerbations in the year before the study.
2.Secondary Outcome
Title Percent Change From Baseline to Week 52 in Pre-dose/Pre-bronchodilator (BD) Forced Expiratory Volume in 1 Second (FEV1)
Hide Description Lung function was assessed by FEV1 which was measured by spirometry. Spirometry was performed by the Investigator or authorised delegate according to American Thoracic Society/European Respiratory Society guidelines. The mean percent change from baseline in pre-BD FEV1 at Week 52 is presented.
Time Frame Baseline (Week 0) and Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised patients with the potential to receive 52 weeks of IP and receiving any IP, irrespective of their protocol adherence and continued participation in the study. Only patients with data available at the timepoints of testing were included in the analyses.
Arm/Group Title Biomarker Positive - Tralo 300 mg Q2W Biomarker Positive - Placebo Biomarker Negative - Tralo 300 mg Q2W Biomarker Negative - Placebo Tralo 300 mg Q2W Placebo
Hide Arm/Group Description:
Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker positive population (primary population) had baseline FeNO ≥37 ppb.
Placebo administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker positive population (primary population) had baseline FeNO ≥37 ppb.
Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker negative population (complement population) had baseline FeNO <37 ppb.
Placebo administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker negative population (complement population) had baseline FeNO <37 ppb.
Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses).
Placebo administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses).
Overall Number of Participants Analyzed 99 103 282 250 384 358
Mean (Standard Deviation)
Unit of Measure: Percent change from baseline
18.769  (29.628) 16.632  (31.906) 13.103  (24.641) 8.395  (21.962) 14.546  (26.065) 10.528  (25.475)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Biomarker Positive - Tralo 300 mg Q2W, Biomarker Positive - Placebo
Comments

Comparison of % change from baseline in pre-dose/pre-BD FEV1 at Week 52: Biomarker positive population; Tralo 300 mg Q2W vs placebo.

Restricted maximum likelihood (REML) based repeated measures analysis on patients with a baseline pre-dose/pre-BD FEV1 assessment.

A variable for the biomarker population (positive, negative) as well as a treatment-by-biomarker population interaction term and a 3-way biomarker population-by-treatment-by-visit interaction term was included in the analysis model.

Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6033
Comments [Not Specified]
Method Repeated measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Least square (LS) Mean difference
Estimated Value 1.86
Confidence Interval (2-Sided) 95%
-5.16 to 8.88
Estimation Comments Fixed categorical effects of treatment group, geographical region, age group, periostin group, visit and treatment-by-visit interaction and number of asthma exacerbations in year before study as a fixed covariate.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Biomarker Negative - Tralo 300 mg Q2W, Biomarker Negative - Placebo
Comments

Comparison of % change from baseline in pre-dose/pre-BD FEV1 at Week 52: Biomarker negative population; Tralo 300 mg Q2W vs placebo.

REML based repeated measures analysis on patients with a baseline pre-dose/pre-BD FEV1 assessment.

A variable for the biomarker population (positive, negative) as well as a treatment-by-biomarker population interaction term and a 3-way biomarker population-by-treatment-by-visit interaction term was included in the analysis model.

Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1276
Comments [Not Specified]
Method Repeated measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value 3.37
Confidence Interval (2-Sided) 95%
-0.97 to 7.70
Estimation Comments Fixed categorical effects of treatment group, geographical region, age group, periostin group, visit and treatment-by-visit interaction and number of asthma exacerbations in year before study as a fixed covariate.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Tralo 300 mg Q2W, Placebo
Comments Comparison of % change from baseline in pre-dose/pre-BD FEV1 at Week 52: FAS population; Tralo 300 mg Q2W vs placebo. REML based repeated measures analysis on patients with a baseline pre-dose/pre-BD FEV1 assessment
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1164
Comments [Not Specified]
Method Repeated measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value 2.95
Confidence Interval (2-Sided) 95%
-0.73 to 6.62
Estimation Comments Fixed categorical effects of treatment group, geographical region, age group, periostin group, visit and treatment-by-visit interaction and number of asthma exacerbations in year before study as a fixed covariate.
3.Secondary Outcome
Title Change From Baseline to Week 52 in Total Asthma Symptom Score (Bi-weekly Means)
Hide Description Asthma symptoms during night-time and daytime were recorded by the patient each morning and evening in the Asthma Daily Diary. Symptoms were recorded using a 4-point response scale, which ranged from 0 to 3, where 0 indicated no asthma symptoms. Asthma symptom daytime score (recorded in the evening), night-time score (recorded in the morning), and total score were calculated separately. The daily asthma symptom total score was calculated by taking the sum of the night-time and daytime asthma symptom scores recorded each day, ranging from 0 to 6. A lower symptom score indicated a better outcome. The change from baseline in bi-weekly mean daily asthma symptom total score is presented.
Time Frame Baseline (Week 0) and Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised patients with the potential to receive 52 weeks of IP and receiving any IP, irrespective of their protocol adherence and continued participation in the study. Only patients with data available at the timepoints of testing were included in the analyses.
Arm/Group Title Biomarker Positive - Tralo 300 mg Q2W Biomarker Positive - Placebo Biomarker Negative - Tralo 300 mg Q2W Biomarker Negative - Placebo Tralo 300 mg Q2W Placebo
Hide Arm/Group Description:
Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker positive population (primary population) had baseline FeNO ≥37 ppb.
Placebo administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker positive population (primary population) had baseline FeNO ≥37 ppb.
Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker negative population (complement population) had baseline FeNO <37 ppb.
Placebo administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker negative population (complement population) had baseline FeNO <37 ppb.
Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses).
Placebo administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses).
Overall Number of Participants Analyzed 79 81 215 223 297 309
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
-1.18  (0.98) -1.06  (1.25) -0.98  (1.04) -1.02  (1.24) -1.04  (1.04) -1.02  (1.24)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Biomarker Positive - Tralo 300 mg Q2W, Biomarker Positive - Placebo
Comments

Comparison of mean change from baseline in total asthma symptom score at Week 52: Biomarker positive population; Tralo 300 mg Q2W vs placebo.

REML based repeated measures analysis. A variable for the biomarker population (positive, negative) as well as a treatment-by-biomarker population interaction term and a 3-way biomarker population-by-treatment-by-visit interaction term was included in the analysis model.

Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1456
Comments [Not Specified]
Method Repeated measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -0.20
Confidence Interval (2-Sided) 95%
-0.47 to 0.07
Estimation Comments Fixed categorical effects of baseline asthma symptom score, treatment group, geographical region, age group, periostin group, visit and treatment-by-visit interaction and number of asthma exacerbations in year before study as a fixed covariate.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Biomarker Negative - Tralo 300 mg Q2W, Biomarker Negative - Placebo
Comments

Comparison of mean change from baseline in total asthma symptom score at Week 52: Biomarker negative population; Tralo 300 mg Q2W vs placebo.

REML based repeated measures analysis. A variable for the biomarker population (positive, negative) as well as a treatment-by-biomarker population interaction term and a 3-way biomarker population-by-treatment-by-visit interaction term was included in the analysis model.

Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6548
Comments [Not Specified]
Method Repeated measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value 0.04
Confidence Interval (2-Sided) 95%
-0.13 to 0.20
Estimation Comments Fixed categorical effects of baseline asthma symptom score, treatment group, geographical region, age group, periostin group, visit and treatment-by-visit interaction and number of asthma exacerbations in year before study as a fixed covariate.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Tralo 300 mg Q2W, Placebo
Comments Comparison of mean change from baseline in total asthma symptom score at Week 52: FAS population; Tralo 300 mg Q2W vs placebo. REML based repeated measures analysis.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5763
Comments [Not Specified]
Method Repeated measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -0.04
Confidence Interval (2-Sided) 95%
-0.18 to 0.10
Estimation Comments Fixed categorical effects of baseline asthma symptom score, treatment group, geographical region, age group, periostin group, visit and treatment-by-visit interaction and number of asthma exacerbations in year before study as a fixed covariate.
4.Secondary Outcome
Title Change From Baseline to Week 52 in Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ(S)+12) Total Score
Hide Description The AQLQ(S)+12 is a questionnaire that measures health-related quality of life for patients with asthma aged 12 and older. The questionnaire comprises 32 questions and has 4 separate domains (asthma symptoms, activity limitations, emotional function and environmental stimuli). Patients were asked to recall their experiences during the previous 2 weeks and to score each of the questions on a 7-point scale ranging from 7 (no impairment) to 1 (severe impairment). The total score was calculated as the mean response to all questions, ranging from 1 (severe impairment) to 7 (no impairment). Individual AQLQ(S)+12 total score changes of ≥0.5 were considered to be clinically meaningful. The mean change from baseline in AQLQ(S)+12 score at Week 52 is presented.
Time Frame Baseline (Week 0) and Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised patients with the potential to receive 52 weeks of IP and receiving any IP, irrespective of their protocol adherence and continued participation in the study. Only patients with data available at the timepoints of testing were included in the analyses.
Arm/Group Title Biomarker Positive - Tralo 300 mg Q2W Biomarker Positive - Placebo Biomarker Negative - Tralo 300 mg Q2W Biomarker Negative - Placebo Tralo 300 mg Q2W Placebo
Hide Arm/Group Description:
Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker positive population (primary population) had baseline FeNO ≥37 ppb.
Placebo administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker positive population (primary population) had baseline FeNO ≥37 ppb.
Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker negative population (complement population) had baseline FeNO <37 ppb.
Placebo administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker negative population (complement population) had baseline FeNO <37 ppb.
Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses).
Placebo administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses).
Overall Number of Participants Analyzed 77 84 242 230 321 318
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
1.35  (1.06) 1.20  (1.22) 1.13  (1.07) 1.23  (1.25) 1.18  (1.07) 1.21  (1.24)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Biomarker Positive - Tralo 300 mg Q2W, Biomarker Positive - Placebo
Comments

Comparison of change in mean score from baseline for AQLQ(S)+12 at Week 52: Biomarker positive population; Tralo 300 mg Q2W vs placebo.

REML based repeated measures analysis. A variable for the biomarker population (positive, negative) as well as a treatment-by-biomarker population interaction term and a 3-way biomarker population-by-treatment-by-visit interaction term was included in the analysis model.

Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0874
Comments [Not Specified]
Method Repeated measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value 0.27
Confidence Interval (2-Sided) 95%
-0.04 to 0.57
Estimation Comments Fixed categorical effects of baseline AQLQ(S)+12 score, treatment group, geographical region, age group, periostin group, visit and treatment-by-visit interaction and number of asthma exacerbations in year before study as a fixed covariate.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Biomarker Negative - Tralo 300 mg Q2W, Biomarker Negative - Placebo
Comments

Comparison of change in mean score from baseline for AQLQ(S)+12 at Week 52: Biomarker negative population; Tralo 300 mg Q2W vs placebo.

REML based repeated measures analysis. A variable for the biomarker population (positive, negative) as well as a treatment-by-biomarker population interaction term and a 3-way biomarker population-by-treatment-by-visit interaction term was included in the analysis model.

Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9083
Comments [Not Specified]
Method Repeated measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -0.01
Confidence Interval (2-Sided) 95%
-0.20 to 0.17
Estimation Comments Fixed categorical effects of baseline AQLQ(S)+12 score, treatment group, geographical region, age group, periostin group, visit and treatment-by-visit interaction and number of asthma exacerbations in year before study as a fixed covariate.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Tralo 300 mg Q2W, Placebo
Comments Comparison of change in mean score from baseline for AQLQ(S)+12 at Week 52: FAS population; Tralo 300 mg Q2W vs placebo. REML based repeated measures analysis.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4506
Comments [Not Specified]
Method Repeated measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value 0.06
Confidence Interval (2-Sided) 95%
-0.10 to 0.22
Estimation Comments Fixed categorical effects of baseline AQLQ(S)+12 score, treatment group, geographical region, age group, periostin group, visit and treatment-by-visit interaction and number of asthma exacerbations in year before study as a fixed covariate.
5.Secondary Outcome
Title Change From Baseline to Week 52 in Asthma Control Questionnaire-6 (ACQ-6) Score
Hide Description The ACQ-6 questionnaire is a shortened version of the ACQ (omitting FEV1 measurement) that assesses asthma symptoms (night-time awakenings, symptoms on waking, activity limitation, dyspnoea, wheezing) and rescue short-acting β2-agonists medication use during the past week. Questions were weighted equally and scored on a 7-point scale from 0 (totally controlled) to 6 (severely uncontrolled). The mean ACQ-6 score was the mean of the responses, ranging from 0 (totally controlled) to 6 (severely uncontrolled). Mean scores of ≤0.75 indicate well-controlled asthma, scores between 0.75 and ≤1.5 indicate partly controlled asthma and a score >1.5 indicates not well-controlled asthma. Individual changes of at least 0.5 were considered to be clinically meaningful. The mean change from baseline in ACQ-6 score at Week 52 is presented.
Time Frame Baseline (Week 0) and Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised patients with the potential to receive 52 weeks of IP and receiving any IP, irrespective of their protocol adherence and continued participation in the study. Only patients with data available at the timepoints of testing were included in the analyses.
Arm/Group Title Biomarker Positive - Tralo 300 mg Q2W Biomarker Positive - Placebo Biomarker Negative - Tralo 300 mg Q2W Biomarker Negative - Placebo Tralo 300 mg Q2W Placebo
Hide Arm/Group Description:
Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker positive population (primary population) had baseline FeNO ≥37 ppb.
Placebo administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker positive population (primary population) had baseline FeNO ≥37 ppb.
Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker negative population (complement population) had baseline FeNO <37 ppb.
Placebo administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker negative population (complement population) had baseline FeNO <37 ppb.
Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses).
Placebo administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses).
Overall Number of Participants Analyzed 85 86 254 243 341 334
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
-1.26  (1.01) -1.14  (1.12) -1.07  (1.02) -1.11  (1.13) -1.12  (1.02) -1.11  (1.13)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Biomarker Positive - Tralo 300 mg Q2W, Biomarker Positive - Placebo
Comments

Comparison of change in mean score from baseline for ACQ-6 at Week 52: Biomarker positive population; Tralo 300 mg Q2W vs placebo.

REML based repeated measures analysis. A variable for the biomarker population (positive, negative) as well as a treatment-by-biomarker population interaction term and a 3-way biomarker population-by-treatment-by-visit interaction term was included in the analysis model.

Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0400
Comments [Not Specified]
Method Repeated measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -0.27
Confidence Interval (2-Sided) 95%
-0.53 to -0.01
Estimation Comments Fixed categorical effects of baseline ACQ-6 score, treatment group, geographical region, age group, periostin group, visit and treatment-by-visit interaction and number of asthma exacerbations in year before study as a fixed covariate.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Biomarker Negative - Tralo 300 mg Q2W, Biomarker Negative - Placebo
Comments

Comparison of change in mean score from baseline for ACQ-6 at Week 52: Biomarker negative population; Tralo 300 mg Q2W vs placebo.

REML based repeated measures analysis. A variable for the biomarker population (positive, negative) as well as a treatment-by-biomarker population interaction term and a 3-way biomarker population-by-treatment-by-visit interaction term was included in the analysis model.

Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9735
Comments [Not Specified]
Method Repeated measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value 0.00
Confidence Interval (2-Sided) 95%
-0.16 to 0.16
Estimation Comments Fixed categorical effects of baseline ACQ-6 score, treatment group, geographical region, age group, periostin group, visit and treatment-by-visit interaction and number of asthma exacerbations in year before study as a fixed covariate.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Tralo 300 mg Q2W, Placebo
Comments Comparison of change in mean score from baseline for ACQ-6 at Week 52: FAS population; Tralo 300 mg Q2W vs placebo. REML based repeated measures analysis.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2432
Comments [Not Specified]
Method Repeated measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -0.08
Confidence Interval (2-Sided) 95%
-0.21 to 0.05
Estimation Comments Fixed categorical effects of baseline ACQ-6 score, treatment group, geographical region, age group, periostin group, visit and treatment-by-visit interaction and number of asthma exacerbations in year before study as a fixed covariate.
6.Secondary Outcome
Title AAER Associated With an ER/UC Visit, or a Hospitalisation up to Week 52
Hide Description

The annual rate of exacerbations associated with an ER/UC visit or hospitalisation up to Week 52 are presented for non-adjudicated data (i.e. events assessed by the Investigator and recorded in the electronic case report form).

AAER = number of exacerbations*365.25 / (follow-up date – date of randomisation + 1) (where maximum follow-up time for a patient was approximately 52 weeks).

Time Frame Baseline (Week 0) up to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised patients with the potential to receive 52 weeks of IP and receiving any IP, irrespective of their protocol adherence and continued participation in the study.
Arm/Group Title Biomarker Positive - Tralo 300 mg Q2W Biomarker Positive - Placebo Biomarker Negative - Tralo 300 mg Q2W Biomarker Negative - Placebo Tralo 300 mg Q2W Placebo
Hide Arm/Group Description:
Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker positive population (primary population) had baseline FeNO ≥37 ppb.
Placebo administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker positive population (primary population) had baseline FeNO ≥37 ppb.
Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker negative population (complement population) had baseline FeNO <37 ppb.
Placebo administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker negative population (complement population) had baseline FeNO <37 ppb.
Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses).
Placebo administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses).
Overall Number of Participants Analyzed 108 121 308 290 420 417
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events/year
0.06
(0.03 to 0.14)
0.16
(0.09 to 0.29)
0.09
(0.06 to 0.14)
0.11
(0.07 to 0.17)
0.08
(0.06 to 0.12)
0.12
(0.09 to 0.18)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Biomarker Positive - Tralo 300 mg Q2W, Biomarker Positive - Placebo
Comments

Comparison of AAER associated with an ER/UC visit or hospitalisation: Biomarker positive population; Tralo 300 mg Q2W vs placebo.

A variable for the biomarker population (positive, negative) as well as a treatment-by-biomarker population interaction term was included in the analysis model.

Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0576
Comments [Not Specified]
Method Negative binomial
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate ratio
Estimated Value 0.39
Confidence Interval (2-Sided) 95%
0.15 to 1.03
Estimation Comments Covariates in the model included treatment group, geographical region, age group, periostin group at baseline and number of exacerbations resulting in hospitalisation or ER treatment (yes/no) in the year before the study.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Biomarker Negative - Tralo 300 mg Q2W, Biomarker Negative - Placebo
Comments

Comparison of AAER associated with an ER/UC visit or hospitalisation: Biomarker negative population; Tralo 300 mg Q2W vs placebo.

A variable for the biomarker population (positive, negative) as well as a treatment-by-biomarker population interaction term was included in the analysis model.

Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5249
Comments [Not Specified]
Method Negative binomial
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate ratio
Estimated Value 0.83
Confidence Interval (2-Sided) 95%
0.46 to 1.48
Estimation Comments Covariates in the model included treatment group, geographical region, age group, periostin group at baseline and number of exacerbations resulting in hospitalisation or ER treatment (yes/no) in the year before the study.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Tralo 300 mg Q2W, Placebo
Comments Comparison of AAER associated with an ER/UC visit or hospitalisation: FAS population; Tralo 300 mg Q2W vs placebo.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1155
Comments [Not Specified]
Method Negative binomial
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate ratio
Estimated Value 0.67
Confidence Interval (2-Sided) 95%
0.41 to 1.10
Estimation Comments Covariates in the model included treatment group, geographical region, age group, periostin group at baseline and number of exacerbations resulting in hospitalisation or ER treatment (yes/no) in the year before the study.
7.Secondary Outcome
Title Change From Baseline in European Quality of Life - 5 Dimension 5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) Scores at Week 52
Hide Description The EQ-5D-5L questionnaire assesses 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response options (no problems, slight problems, moderate problems, severe problems and extreme problems) that reflect increasing levels of difficulty. The patient was asked to indicate his/her current health state by selecting the most appropriate level in each of the 5 dimensions. The questionnaire also included a VAS, where the patient was asked to rate current health status on a scale of 0 to 100, with 0 being the worst imaginable health state. The mean change from baseline in EQ-5D-5L VAS scores at Week 52 is presented.
Time Frame Baseline (Week 0) and Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised patients with the potential to receive 52 weeks of IP and receiving any IP, irrespective of their protocol adherence and continued participation in the study. Only patients with data available at the timepoints of testing were included in the analyses.
Arm/Group Title Biomarker Positive - Tralo 300 mg Q2W Biomarker Positive - Placebo Biomarker Negative - Tralo 300 mg Q2W Biomarker Negative - Placebo Tralo 300 mg Q2W Placebo
Hide Arm/Group Description:
Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker positive population (primary population) had baseline FeNO ≥37 ppb.
Placebo administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker positive population (primary population) had baseline FeNO ≥37 ppb.
Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker negative population (complement population) had baseline FeNO <37 ppb.
Placebo administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker negative population (complement population) had baseline FeNO <37 ppb.
Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses).
Placebo administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses).
Overall Number of Participants Analyzed 81 85 233 224 317 313
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
14.58  (15.21) 11.58  (17.26) 11.67  (17.18) 12.01  (17.43) 12.46  (16.67) 11.66  (17.41)
8.Secondary Outcome
Title Change From Baseline in Total Asthma Rescue Medication Use at Week 52 (Bi-weekly Means)
Hide Description Salbutamol, albuterol or levalbuterol were used as rescue medication during the study in the event of a worsening of asthma symptoms. Rescue medication use was measured by the bi-weekly mean number of inhalations (puffs) per day, calculated as: total morning puffs + total evening puffs + 2*(total morning nebuliser use + total evening nebuliser use)/ total number of days with data in bi-weekly period. The change from baseline in bi-weekly mean total asthma rescue medication use at Week 52 is presented.
Time Frame Baseline (Week 0) and Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised patients with the potential to receive 52 weeks of IP and receiving any IP, irrespective of their protocol adherence and continued participation in the study. Only patients with data available at the timepoints of testing were included in the analyses.
Arm/Group Title Biomarker Positive - Tralo 300 mg Q2W Biomarker Positive - Placebo Biomarker Negative - Tralo 300 mg Q2W Biomarker Negative - Placebo Tralo 300 mg Q2W Placebo
Hide Arm/Group Description:
Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker positive population (primary population) had baseline FeNO ≥37 ppb.
Placebo administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker positive population (primary population) had baseline FeNO ≥37 ppb.
Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker negative population (complement population) had baseline FeNO <37 ppb.
Placebo administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker negative population (complement population) had baseline FeNO <37 ppb.
Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses).
Placebo administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses).
Overall Number of Participants Analyzed 79 81 215 223 297 309
Mean (Standard Deviation)
Unit of Measure: Puffs/day
-2.86  (3.26) -1.73  (4.59) -2.01  (2.93) -2.08  (4.28) -2.25  (3.03) -1.97  (4.34)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Biomarker Positive - Tralo 300 mg Q2W, Biomarker Positive - Placebo
Comments

Comparison of mean change from baseline in rescue medication use at Week 52: Biomarker positive population; Tralo 300 mg Q2W vs placebo.

REML based repeated measures analysis. A variable for the biomarker population (positive, negative) as well as a treatment-by-biomarker population interaction term and a 3-way biomarker population-by-treatment-by-visit interaction term was included in the analysis model.

Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0360
Comments [Not Specified]
Method Repeated measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -0.95
Confidence Interval (2-Sided) 95%
-1.85 to -0.06
Estimation Comments Fixed categorical effects of baseline rescue medication use, treatment group, geographical region, age group, periostin group, visit and treatment-by-visit interaction and number of asthma exacerbations in year before study as a fixed covariate.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Biomarker Negative - Tralo 300 mg Q2W, Biomarker Negative - Placebo
Comments

Comparison of mean change from baseline in rescue medication use at Week 52: Biomarker negative population; Tralo 300 mg Q2W vs placebo.

REML based repeated measures analysis. A variable for the biomarker population (positive, negative) as well as a treatment-by-biomarker population interaction term and a 3-way biomarker population-by-treatment-by-visit interaction term was included in the analysis model.

Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5864
Comments [Not Specified]
Method Repeated measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value 0.15
Confidence Interval (2-Sided) 95%
-0.40 to 0.70
Estimation Comments Fixed categorical effects of baseline rescue medication use, treatment group, geographical region, age group, periostin group, visit and treatment-by-visit interaction and number of asthma exacerbations in year before study as a fixed covariate.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Tralo 300 mg Q2W, Placebo
Comments Comparison of mean change from baseline in rescue medication use at Week 52: FAS population; Tralo 300 mg Q2W vs placebo. REML based repeated measures analysis.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4689
Comments [Not Specified]
Method Repeated measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -0.17
Confidence Interval (2-Sided) 95%
-0.63 to 0.29
Estimation Comments Fixed categorical effects of baseline rescue medication use, treatment group, geographical region, age group, periostin group, visit and treatment-by-visit interaction and number of asthma exacerbations in year before study as a fixed covariate.
9.Secondary Outcome
Title Change From Baseline in Home Peak Expiratory Flow (PEF) (Morning and Evening) at Week 52
Hide Description Home PEF testing was performed by the patient using an electronic, hand-held spirometer (peak flow meter) and was performed in the morning upon awakening (prior to taking their morning asthma controller) and in the evening at bedtime (prior to taking their evening asthma controller). The mean change from baseline in home PEF values at Week 52 are presented separately for morning and evening.
Time Frame Baseline (Week 0) and Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised patients with the potential to receive 52 weeks of IP and receiving any IP, irrespective of their protocol adherence and continued participation in the study. Only patients with data available at the timepoints of testing were included in the analyses.
Arm/Group Title Biomarker Positive - Tralo 300 mg Q2W Biomarker Positive - Placebo Biomarker Negative - Tralo 300 mg Q2W Biomarker Negative - Placebo Tralo 300 mg Q2W Placebo
Hide Arm/Group Description:
Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker positive population (primary population) had baseline FeNO ≥37 ppb.
Placebo administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker positive population (primary population) had baseline FeNO ≥37 ppb.
Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker negative population (complement population) had baseline FeNO <37 ppb.
Placebo administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker negative population (complement population) had baseline FeNO <37 ppb.
Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses).
Placebo administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses).
Overall Number of Participants Analyzed 86 86 233 222 322 313
Mean (Standard Deviation)
Unit of Measure: L/min
Morning PEF Number Analyzed 84 participants 81 participants 231 participants 222 participants 318 participants 308 participants
22.35  (74.00) 18.80  (86.24) 6.72  (73.82) 6.10  (72.28) 10.66  (73.88) 9.43  (76.01)
Evening PEF Number Analyzed 86 participants 86 participants 233 participants 222 participants 322 participants 313 participants
18.15  (69.20) 8.88  (79.72) 1.72  (79.58) 0.17  (73.66) 5.72  (77.01) 2.91  (74.94)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Biomarker Positive - Tralo 300 mg Q2W, Biomarker Positive - Placebo
Comments

Comparison of mean change from baseline in morning PEF at Week 52: Biomarker positive population; Tralo 300 mg Q2W vs placebo.

REML based repeated measures analysis. A variable for the biomarker population (positive, negative) as well as a treatment-by-biomarker population interaction term and a 3-way biomarker population-by-treatment-by-visit interaction term was included in the analysis model.

Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5094
Comments [Not Specified]
Method Repeated measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value 6.15
Confidence Interval (2-Sided) 95%
-12.13 to 24.43
Estimation Comments Fixed categorical effects of baseline PEF (morning), treatment group, geographical region, age group, periostin group, visit and treatment-by-visit interaction and number of asthma exacerbations in year before study as a fixed covariate.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Biomarker Negative - Tralo 300 mg Q2W, Biomarker Negative - Placebo
Comments

Comparison of mean change from baseline in morning PEF at Week 52: Biomarker negative population; Tralo 300 mg Q2W vs placebo.

REML based repeated measures analysis. A variable for the biomarker population (positive, negative) as well as a treatment-by-biomarker population interaction term and a 3-way biomarker population-by-treatment-by-visit interaction term was included in the analysis model.

Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5984
Comments [Not Specified]
Method Repeated measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value 3.02
Confidence Interval (2-Sided) 95%
-8.22 to 14.26
Estimation Comments Fixed categorical effects of baseline PEF (morning), treatment group, geographical region, age group, periostin group, visit and treatment-by-visit interaction and number of asthma exacerbations in year before study as a fixed covariate.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Biomarker Positive - Tralo 300 mg Q2W, Biomarker Positive - Placebo
Comments

Comparison of mean change from baseline in evening PEF at Week 52: Biomarker positive population; Tralo 300 mg Q2W vs placebo.

REML based repeated measures analysis. A variable for the biomarker population (positive, negative) as well as a treatment-by-biomarker population interaction term and a 3-way biomarker population-by-treatment-by-visit interaction term was included in the analysis model.

Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3971
Comments [Not Specified]
Method Repeated measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value 7.84
Confidence Interval (2-Sided) 95%
-10.32 to 26.00
Estimation Comments Model included fixed categorical effects of baseline PEF (evening), treatment group, geographical region, age group, periostin group, visit and treatment-by-visit interaction and number of asthma exacerbations in year before study as fixed covariate.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Biomarker Negative - Tralo 300 mg Q2W, Biomarker Negative - Placebo
Comments

Comparison of mean change from baseline in evening PEF at Week 52: Biomarker negative population; Tralo 300 mg Q2W vs placebo.

REML based repeated measures analysis. A variable for the biomarker population (positive, negative) as well as a treatment-by-biomarker population interaction term and a 3-way biomarker population-by-treatment-by-visit interaction term was included in the analysis model.

Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5310
Comments [Not Specified]
Method Repeated measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value 3.59
Confidence Interval (2-Sided) 95%
-7.65 to 14.83
Estimation Comments Model included fixed categorical effects of baseline PEF (evening), treatment group, geographical region, age group, periostin group, visit and treatment-by-visit interaction and number of asthma exacerbations in year before study as fixed covariate.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Tralo 300 mg Q2W, Placebo
Comments Comparison of mean change from baseline in morning PEF at Week 52: FAS population; Tralo 300 mg Q2W vs placebo. REML based repeated measures analysis.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4764
Comments [Not Specified]
Method Repeated measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value 3.46
Confidence Interval (2-Sided) 95%
-6.06 to 12.97
Estimation Comments Model included fixed categorical effects of baseline PEF (morning), treatment group, geographical region, age group, periostin group, visit and treatment-by-visit interaction and number of asthma exacerbations in year before study as fixed covariate.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Tralo 300 mg Q2W, Placebo
Comments Comparison of mean change from baseline in evening PEF at Week 52: FAS population; Tralo 300 mg Q2W vs placebo. REML based repeated measures analysis.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4221
Comments [Not Specified]
Method Repeated measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value 3.88
Confidence Interval (2-Sided) 95%
-5.60 to 13.37
Estimation Comments Model included fixed categorical effects of baseline PEF (evening), treatment group, geographical region, age group, periostin group, visit and treatment-by-visit interaction and number of asthma exacerbations in year before study as fixed covariate.
10.Secondary Outcome
Title Change From Baseline in Night-time Awakenings Due to Asthma Requiring Rescue Medication Use at Week 52 (Bi-weekly Means [Percentage])
Hide Description The patient captured night-time awakenings (yes/no) and the use of rescue medication during these awakenings (yes/no) each morning in the Asthma Daily Diary. Night-time awakenings (percentage) was defined as the number of nights with awakenings due to asthma and requiring rescue medication divided by number of nights with data. The change from baseline in bi-weekly means (percentage) night-time awakenings due to asthma requiring rescue medication use at Week 52 is presented.
Time Frame Baseline (Week 0) and Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised patients with the potential to receive 52 weeks of IP and receiving any IP, irrespective of their protocol adherence and continued participation in the study. Only patients with data available at the timepoints of testing were included in the analyses.
Arm/Group Title Biomarker Positive - Tralo 300 mg Q2W Biomarker Positive - Placebo Biomarker Negative - Tralo 300 mg Q2W Biomarker Negative - Placebo Tralo 300 mg Q2W Placebo
Hide Arm/Group Description:
Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker positive population (primary population) had baseline FeNO ≥37 ppb.
Placebo administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker positive population (primary population) had baseline FeNO ≥37 ppb.
Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker negative population (complement population) had baseline FeNO <37 ppb.
Placebo administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker negative population (complement population) had baseline FeNO <37 ppb.
Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses).
Placebo administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses).
Overall Number of Participants Analyzed 94 96 270 247 368 348
Mean (Standard Deviation)
Unit of Measure: Percentage of nights with awakenings
-37.86  (38.36) -34.06  (34.96) -34.65  (34.34) -35.67  (37.37) -35.60  (35.40) -35.05  (36.63)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Biomarker Positive - Tralo 300 mg Q2W, Biomarker Positive - Placebo
Comments

Comparison of mean change from baseline in number (%) of awakenings at Week 52: Biomarker positive population; Tralo 300 mg Q2W vs placebo.

REML based repeated measures analysis. A variable for the biomarker population (positive, negative) as well as a treatment-by-biomarker population interaction term and a 3-way biomarker population-by-treatment-by-visit interaction term was included in the analysis model.

Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1099
Comments [Not Specified]
Method Repeated measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -5.04
Confidence Interval (2-Sided) 95%
-11.21 to 1.14
Estimation Comments Fixed categorical effects of baseline number (%) of awakenings, treatment group, geographical region, age group, periostin group, visit and treatment-by-visit interaction and number of asthma exacerbations in year before study as a fixed covariate.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Biomarker Negative - Tralo 300 mg Q2W, Biomarker Negative - Placebo
Comments

Comparison of mean change from baseline in number (%) of awakenings at Week 52: Biomarker positive population; Tralo 300 mg Q2W vs placebo.

REML based repeated measures analysis. A variable for the biomarker population (positive, negative) as well as a treatment-by-biomarker population interaction term and a 3-way biomarker population-by-treatment-by-visit interaction term was included in the analysis model.

Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8112
Comments [Not Specified]
Method Repeated measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value 0.46
Confidence Interval (2-Sided) 95%
-3.33 to 4.25
Estimation Comments Fixed categorical effects of baseline number (%) of awakenings, treatment group, geographical region, age group, periostin group, visit and treatment-by-visit interaction and number of asthma exacerbations in year before study as a fixed covariate.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Tralo 300 mg Q2W, Placebo
Comments Comparison of mean change from baseline in number (%) of awakenings at Week 52: FAS population; Tralo 300 mg Q2W vs placebo. REML based repeated measures analysis.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4645
Comments [Not Specified]
Method Repeated measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -1.19
Confidence Interval (2-Sided) 95%
-4.40 to 2.01
Estimation Comments Fixed categorical effects of baseline number (%) of awakenings, treatment group, geographical region, age group, periostin group, visit and treatment-by-visit interaction and number of asthma exacerbations in year before study as a fixed covariate.
11.Secondary Outcome
Title Number of Patients With ≥1 Asthma Exacerbation up to Week 52
Hide Description The number of patients with ≥1 asthma exacerbation up to Week 52 is presented.
Time Frame Baseline (Week 0) up to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised patients with the potential to receive 52 weeks of IP and receiving any IP, irrespective of their protocol adherence and continued participation in the study.
Arm/Group Title Biomarker Positive - Tralo 300 mg Q2W Biomarker Positive - Placebo Biomarker Negative - Tralo 300 mg Q2W Biomarker Negative - Placebo Tralo 300 mg Q2W Placebo
Hide Arm/Group Description:
Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker positive population (primary population) had baseline FeNO ≥37 ppb.
Placebo administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker positive population (primary population) had baseline FeNO ≥37 ppb.
Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker negative population (complement population) had baseline FeNO <37 ppb.
Placebo administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker negative population (complement population) had baseline FeNO <37 ppb.
Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses).
Placebo administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses).
Overall Number of Participants Analyzed 108 121 308 290 420 417
Measure Type: Count of Participants
Unit of Measure: Participants
38
  35.2%
50
  41.3%
125
  40.6%
117
  40.3%
163
  38.8%
171
  41.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Biomarker Positive - Tralo 300 mg Q2W, Biomarker Positive - Placebo
Comments Comparison of number of patients with ≥ 1 asthma exacerbations up to Week 52: Biomarker positive population; Tralo 300 mg Q2W vs placebo.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3440
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.77
Confidence Interval (2-Sided) 95%
0.44 to 1.33
Estimation Comments The estimate of each odds ratio was obtained from a Cochran-Mantel-Haenszel test controlling for geographical region, age group and periostin group at baseline.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Biomarker Negative - Tralo 300 mg Q2W, Biomarker Negative - Placebo
Comments Comparison of number of patients with ≥ 1 asthma exacerbations up to Week 52: Biomarker negative population; Tralo 300 mg Q2W vs placebo.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7768
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.05
Confidence Interval (2-Sided) 95%
0.75 to 1.46
Estimation Comments The estimate of each odds ratio was obtained from a Cochran-Mantel-Haenszel test controlling for geographical region, age group and periostin group at baseline.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Tralo 300 mg Q2W, Placebo
Comments Comparison of number of patients with ≥ 1 asthma exacerbations up to Week 52: FAS population; Tralo 300 mg Q2W vs placebo.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5276
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.91
Confidence Interval (2-Sided) 95%
0.69 to 1.21
Estimation Comments The estimate of each odds ratio was obtained from a Cochran-Mantel-Haenszel test controlling for geographical region, age group and periostin group at baseline.
12.Secondary Outcome
Title Work Productivity and Activity Impairment Questionnaire and Classroom Impairment Questions (WPAI+CIQ): Productivity Loss at Week 52
Hide Description

The WPAI+CIQ consists of questions about how asthma and asthma-related issues impact a patient’s ability to work, attend classes and perform regular daily activities. The questionnaire contains 10 questions relating to the patient’s experience over the previous 7 days.

The WPAI+CIQ outcomes for productivity loss are presented separately for those currently employed and for those currently in school and are expressed as mean productivity loss (percentage) at Week 52, with higher numbers indicating less productivity.

Work Productivity Loss = {Q2/(Q2+Q4)+[(1-Q2/(Q2+Q4))x(Q5/10)]}*100 (Absenteeism = Q2/(Q2+Q4)*100; Presenteeism = (Q5/10)*100).

Class Productivity Loss = {Q7/(Q7+Q8) + [(1-Q7/(Q7+Q8))x(Q9/10)]}*100 (Absenteeism = Q7/(Q7+Q8)*100; Presenteeism = (Q9/10)*100).

Note: QX refers to response to question number X on WPAI+CIQ questionnaire.

Time Frame At Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised patients with the potential to receive 52 weeks of IP and receiving any IP, irrespective of their protocol adherence and continued participation in the study. Only patients with data available at the timepoints of testing were included in the analyses.
Arm/Group Title Biomarker Positive - Tralo 300 mg Q2W Biomarker Positive - Placebo Biomarker Negative - Tralo 300 mg Q2W Biomarker Negative - Placebo Tralo 300 mg Q2W Placebo
Hide Arm/Group Description:
Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker positive population (primary population) had baseline FeNO ≥37 ppb.
Placebo administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker positive population (primary population) had baseline FeNO ≥37 ppb.
Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker negative population (complement population) had baseline FeNO <37 ppb.
Placebo administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker negative population (complement population) had baseline FeNO <37 ppb.
Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses).
Placebo administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses).
Overall Number of Participants Analyzed 46 46 105 104 154 151
Mean (Standard Deviation)
Unit of Measure: Percent productivity loss
Productivity loss - currently employed Number Analyzed 43 participants 34 participants 92 participants 90 participants 137 participants 125 participants
22.51  (24.47) 28.15  (27.39) 23.36  (23.39) 31.05  (27.20) 23.43  (23.66) 30.17  (27.08)
Productivity loss - currently in school Number Analyzed 3 participants 12 participants 13 participants 14 participants 17 participants 26 participants
28.89  (34.21) 37.92  (28.72) 25.99  (32.17) 19.67  (29.06) 28.03  (31.01) 28.09  (29.80)
13.Secondary Outcome
Title WPAI+CIQ: Activity Impairment at Week 52
Hide Description

The WPAI+CIQ consists of questions about how asthma and asthma-related issues impact a patient’s ability to work, attend classes and perform regular daily activities. The questionnaire contains 10 questions relating to the patient’s experience over the previous 7 days.

The WPAI+CIQ outcomes for activity impairment are presented separately for those currently employed and for those currently in school and are expressed as mean impairment percentages at Week 52, with higher numbers indicating greater impairment.

Activity impairment = (Q10/10)*100. Note: QX refers to response to question number X on WPAI+CIQ questionnaire.

Time Frame At Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised patients with the potential to receive 52 weeks of IP and receiving any IP, irrespective of their protocol adherence and continued participation in the study. Only patients with data available at the timepoints of testing were included in the analyses.
Arm/Group Title Biomarker Positive - Tralo 300 mg Q2W Biomarker Positive - Placebo Biomarker Negative - Tralo 300 mg Q2W Biomarker Negative - Placebo Tralo 300 mg Q2W Placebo
Hide Arm/Group Description:
Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker positive population (primary population) had baseline FeNO ≥37 ppb.
Placebo administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker positive population (primary population) had baseline FeNO ≥37 ppb.
Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker negative population (complement population) had baseline FeNO <37 ppb.
Placebo administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker negative population (complement population) had baseline FeNO <37 ppb.
Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses).
Placebo administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses).
Overall Number of Participants Analyzed 50 49 116 110 169 160
Mean (Standard Deviation)
Unit of Measure: Percent impairment
Activity Impairment - currently employed Number Analyzed 45 participants 36 participants 100 participants 94 participants 147 participants 131 participants
20.89  (18.81) 25.28  (28.63) 20.50  (20.42) 26.49  (23.59) 20.68  (19.82) 26.11  (24.89)
Activity Impairment - currently in school Number Analyzed 5 participants 13 participants 16 participants 16 participants 22 participants 29 participants
20.00  (18.71) 33.85  (26.63) 26.88  (30.49) 23.13  (30.27) 24.55  (27.38) 27.93  (28.71)
14.Secondary Outcome
Title Asthma-related Healthcare Encounters by Type up to Week 52
Hide Description

Broad-based healthcare utilisation asthma-related event information was collected by the Investigator/authorised delegate at each visit. At Visit 1, healthcare resource utilisation information was collected with a 1-year recall period; subsequent visits collected information with a recall period of ‘since the last scheduled visit’. Total number of times the healthcare encounter occurred was calculated across all patients for each of the following categories:

  • Ambulance transport,
  • Emergency room visits,
  • Unscheduled outpatient visits (visit to specialist and/or visit to primary healthcare physician and/or other healthcare visit),
  • Home visits (home visit, physician and/or other healthcare professional),
  • Telephone calls (telephone calls to physician and/or nurse), and
  • Advanced pulmonary function test.
Time Frame Baseline (Week 0) up to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised patients with the potential to receive 52 weeks of IP and receiving any IP, irrespective of their protocol adherence and continued participation in the study.
Arm/Group Title Biomarker Positive - Tralo 300 mg Q2W Biomarker Positive - Placebo Biomarker Negative - Tralo 300 mg Q2W Biomarker Negative - Placebo Tralo 300 mg Q2W Placebo
Hide Arm/Group Description:
Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker positive population (primary population) had baseline FeNO ≥37 ppb.
Placebo administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker positive population (primary population) had baseline FeNO ≥37 ppb.
Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker negative population (complement population) had baseline FeNO <37 ppb.
Placebo administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker negative population (complement population) had baseline FeNO <37 ppb.
Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses).
Placebo administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses).
Overall Number of Participants Analyzed 108 121 308 290 420 417
Measure Type: Number
Unit of Measure: Encounters
Ambulance transport 14 21 21 20 35 41
Emergency room visits 20 28 65 70 87 99
Unscheduled outpatient visits 513 579 1274 1216 1798 1834
Home visits 10 18 49 26 59 44
Telephone calls 51 76 112 117 163 196
Advanced pulmonary function test 16 20 35 26 51 46
15.Secondary Outcome
Title Asthma-related Healthcare Encounters by Type up to Week 52: Hospitalisations
Hide Description

Broad-based healthcare utilisation asthma-related event information was collected by the Investigator/authorised delegate at each visit. At Visit 1, healthcare resource utilisation information was collected with a 1-year recall period; subsequent visits collected information with a recall period of ‘since the last scheduled visit’. Total number of days spent in hospital was calculated across all patients for the following healthcare encounter category:

• Hospitalisations (hospitalisations, intensive care and/or general care).

Time Frame Baseline (Week 0) up to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised patients with the potential to receive 52 weeks of IP and receiving any IP, irrespective of their protocol adherence and continued participation in the study.
Arm/Group Title Biomarker Positive - Tralo 300 mg Q2W Biomarker Positive - Placebo Biomarker Negative - Tralo 300 mg Q2W Biomarker Negative - Placebo Tralo 300 mg Q2W Placebo
Hide Arm/Group Description:
Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker positive population (primary population) had baseline FeNO ≥37 ppb.
Placebo administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker positive population (primary population) had baseline FeNO ≥37 ppb.
Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker negative population (complement population) had baseline FeNO <37 ppb.
Placebo administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker negative population (complement population) had baseline FeNO <37 ppb.
Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses).
Placebo administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses).
Overall Number of Participants Analyzed 108 121 308 290 420 417
Measure Type: Number
Unit of Measure: Days
82 175 334 414 417 590
16.Secondary Outcome
Title Asthma-related Healthcare Encounters by Type up to Week 52: Spirometry
Hide Description

Broad-based healthcare utilisation asthma-related event information was collected by the Investigator/authorised delegate at each visit. At Visit 1, healthcare resource utilisation information was collected with a 1-year recall period; subsequent visits collected information with a recall period of ‘since the last scheduled visit’. Total number of assessments was calculated across all patients for the following healthcare encounter category:

• Spirometry.

Time Frame Baseline (Week 0) up to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised patients with the potential to receive 52 weeks of IP and receiving any IP, irrespective of their protocol adherence and continued participation in the study.
Arm/Group Title Biomarker Positive - Tralo 300 mg Q2W Biomarker Positive - Placebo Biomarker Negative - Tralo 300 mg Q2W Biomarker Negative - Placebo Tralo 300 mg Q2W Placebo
Hide Arm/Group Description:
Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker positive population (primary population) had baseline FeNO ≥37 ppb.
Placebo administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker positive population (primary population) had baseline FeNO ≥37 ppb.
Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker negative population (complement population) had baseline FeNO <37 ppb.
Placebo administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker negative population (complement population) had baseline FeNO <37 ppb.
Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses).
Placebo administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses).
Overall Number of Participants Analyzed 108 121 308 290 420 417
Measure Type: Number
Unit of Measure: Assessments
148 151 284 270 434 426
17.Secondary Outcome
Title Serum Trough Concentration (Ctrough) of Tralokinumab During the Treatment Period up to Week 72
Hide Description To evaluate the pharmacokinetics (PK), pre-dose blood samples were collected at each visit and tralokinumab concentrations in serum were determined. Mean Ctrough concentrations are presented at each indicated visit up to Week 72.
Time Frame Blood samples were collected pre-dose at Baseline (Week 0), and at Week 2, Week 8, Week 26, Week 56 (follow-up) and Week 72 (follow-up)
Hide Outcome Measure Data
Hide Analysis Population Description
All patients in the FAS who received tralokinumab and who had PK blood samples were included in the PK analysis set. Only patients in the biomarker positive and negative PK populations and with data available at the timepoints of testing were included in the analyses.
Arm/Group Title Biomarker Positive - Tralo 300 mg Q2W Biomarker Negative - Tralo 300 mg Q2W Total - Tralo 300 mg Q2W
Hide Arm/Group Description:
Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker positive population (primary population) had baseline FeNO ≥37 ppb.
Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Patients in the biomarker negative population (complement population) had baseline FeNO <37 ppb.
Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). 'Total' treatment arm represents all patients receiving tralokinumab in both the biomarker positive and biomarker negative patient populations.
Overall Number of Participants Analyzed 108 302 410
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: micrograms/millilitre
Baseline Number Analyzed 108 participants 302 participants 410 participants
NA [1] 
(NA%)
NA [1] 
(NA%)
NA [1] 
(NA%)
Week 2 Number Analyzed 103 participants 293 participants 396 participants
24.049
(172.475%)
20.916
(280.452%)
21.690
(248.876%)
Week 8 Number Analyzed 105 participants 280 participants 385 participants
55.887
(206.478%)
52.324
(226.298%)
53.272
(220.301%)
Week 26 Number Analyzed 99 participants 274 participants 373 participants
58.375
(145.256%)
47.707
(319.456%)
50.332
(264.686%)
Week 56 (follow-up) Number Analyzed 96 participants 275 participants 371 participants
12.363
(591.282%)
12.513
(707.267%)
12.474
(671.922%)
Week 72 (follow-up) Number Analyzed 92 participants 264 participants 356 participants
0.325
(251.436%)
0.384
(242.035%)
0.368
(244.398%)
[1]
Value was not calculable since below level of detection.
18.Secondary Outcome
Title Incidence Rate of Positive Anti-drug Antibodies (ADAs) Including the Characterization of Their Neutralizing Potential
Hide Description Assessments of ADA were performed using a tiered approach (screening, confirmatory and titering assays). Confirmed ADA positive samples were also tested for the presence of neutralising antibodies (nAb). ADA prevalence was defined as proportion of the study population having drug-reactive antibodies at any point in time. ADA incidence (treatment-emergent ADA) was defined as the sum of both treatment-induced (post-baseline ADA positive only) and treatment-boosted ADA. Persistently positive was 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 was defined as having at least 1 post-baseline ADA positive assessment and not fulfilling the conditions of persistently positive. Treatment-boosted ADA was defined as baseline positive ADA titer that was boosted to a 4-fold or higher level following drug administration. Note: 'positive' is denoted by 'pos' in some category titles.
Time Frame Baseline (Week 0), Week 26, Week 56 (follow-up) and Week 72 (follow-up)
Hide Outcome Measure Data
Hide Analysis Population Description
The ADA evaluable population included all patients in the safety analysis set (i.e. those who had received any IP) who had non-missing baseline ADA and at least 1 non-missing post-baseline ADA result.
Arm/Group Title Tralo 300 mg Q2W Placebo
Hide Arm/Group Description:
Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses).
Placebo administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses).
Overall Number of Participants Analyzed 405 394
Measure Type: Count of Participants
Unit of Measure: Participants
ADA prevalence
7
   1.7%
8
   2.0%
ADA incidence
5
   1.2%
3
   0.8%
ADA positive at baseline
2
   0.5%
5
   1.3%
ADA positive post-baseline
5
   1.2%
6
   1.5%
ADA pos post-baseline and pos at baseline
0
   0.0%
3
   0.8%
ADA pos post-baseline and not detected at baseline
5
   1.2%
3
   0.8%
ADA not detected post-baseline and pos at baseline
2
   0.5%
2
   0.5%
Persistent Positive
3
   0.7%
6
   1.5%
Transient Positive
2
   0.5%
0
   0.0%
Treatment-boosted ADA
0
   0.0%
0
   0.0%
nAB positive at any visit
5
   1.2%
2
   0.5%
Time Frame 72 weeks
Adverse Event Reporting Description

Serious and Other (non-serious) adverse event (AE) data is reported for the treatment period, from baseline (Week 0) to end of treatment (Week 52). Treatment-emergent AEs were defined with an onset date ≥ the first day of IP and ≤ (the last day of IP + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of IP.

All-Cause mortality is reported for the overall study period (including the extended follow-up period), up to Week 72.

 
Arm/Group Title Tralo 300 mg Q2W Placebo
Hide Arm/Group Description Tralokinumab 300 mg administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses). Placebo administered subcutaneously Q2W over a 52-week treatment period (up to 26 doses).
All-Cause Mortality
Tralo 300 mg Q2W Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   1/425 (0.24%)      4/422 (0.95%)    
Show Serious Adverse Events Hide Serious Adverse Events
Tralo 300 mg Q2W Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   35/425 (8.24%)      39/422 (9.24%)    
Cardiac disorders     
Angina pectoris  1  0/425 (0.00%)  0 1/422 (0.24%)  1
Angina unstable  1  0/425 (0.00%)  0 1/422 (0.24%)  1
Atrial fibrillation  1  1/425 (0.24%)  1 0/422 (0.00%)  0
Cardiac failure  1  0/425 (0.00%)  0 1/422 (0.24%)  1
Myocardial infarction  1  1/425 (0.24%)  1 0/422 (0.00%)  0
Gastrointestinal disorders     
Colitis ulcerative  1  0/425 (0.00%)  0 1/422 (0.24%)  1
Constipation  1  0/425 (0.00%)  0 1/422 (0.24%)  1
Dyspepsia  1  1/425 (0.24%)  1 0/422 (0.00%)  0
Haematochezia  1  0/425 (0.00%)  0 1/422 (0.24%)  1
Oesophageal ulcer  1  0/425 (0.00%)  0 1/422 (0.24%)  1
Oesophagitis  1  0/425 (0.00%)  0 1/422 (0.24%)  1
Umbilical hernia  1  0/425 (0.00%)  0 1/422 (0.24%)  1
General disorders     
Oedema peripheral  1  1/425 (0.24%)  1 0/422 (0.00%)  0
Hepatobiliary disorders     
Cholecystitis acute  1  1/425 (0.24%)  1 0/422 (0.00%)  0
Immune system disorders     
Eosinophilic granulomatosis with polyangiitis  1  0/425 (0.00%)  0 1/422 (0.24%)  1
Infections and infestations     
Appendicitis  1  0/425 (0.00%)  0 1/422 (0.24%)  1
Hepatitis A  1  0/425 (0.00%)  0 1/422 (0.24%)  1
Laryngitis viral  1  0/425 (0.00%)  0 1/422 (0.24%)  1
Osteomyelitis  1  1/425 (0.24%)  1 0/422 (0.00%)  0
Otitis media acute  1  1/425 (0.24%)  1 0/422 (0.00%)  0
Pneumonia  1  4/425 (0.94%)  4 3/422 (0.71%)  3
Pulmonary tuberculosis  1  1/425 (0.24%)  1 0/422 (0.00%)  0
Tracheobronchitis  1  1/425 (0.24%)  1 0/422 (0.00%)  0
Urinary tract infection  1  0/425 (0.00%)  0 1/422 (0.24%)  1
Urosepsis  1  1/425 (0.24%)  1 0/422 (0.00%)  0
Injury, poisoning and procedural complications     
Humerus fracture  1  1/425 (0.24%)  1 0/422 (0.00%)  0
Lumbar vertebral fracture  1  1/425 (0.24%)  1 0/422 (0.00%)  0
Tendon rupture  1  1/425 (0.24%)  1 0/422 (0.00%)  0
Investigations     
Alanine aminotransferase increased  1  1/425 (0.24%)  1 0/422 (0.00%)  0
Aspartate aminotransferase increased  1  1/425 (0.24%)  1 0/422 (0.00%)  0
Metabolism and nutrition disorders     
Obesity  1  0/425 (0.00%)  0 1/422 (0.24%)  1
Type 2 diabetes mellitus  1  1/425 (0.24%)  1 0/422 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Patellofemoral pain syndrome  1  1/425 (0.24%)  1 0/422 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Rectal cancer  1  0/425 (0.00%)  0 1/422 (0.24%)  1
Nervous system disorders     
Vascular headache  1  0/425 (0.00%)  0 1/422 (0.24%)  1
Psychiatric disorders     
Suicidal ideation  1  1/425 (0.24%)  1 0/422 (0.00%)  0
Renal and urinary disorders     
Urinary incontinence  1  0/425 (0.00%)  0 1/422 (0.24%)  1
Reproductive system and breast disorders     
Adnexa uteri pain  1  0/425 (0.00%)  0 1/422 (0.24%)  1
Ovarian cyst  1  1/425 (0.24%)  1 0/422 (0.00%)  0
Uterine haemorrhage  1  0/425 (0.00%)  0 1/422 (0.24%)  1
Respiratory, thoracic and mediastinal disorders     
Asthma  1  17/425 (4.00%)  17 23/422 (5.45%)  30
Bronchitis chronic  1  1/425 (0.24%)  1 0/422 (0.00%)  0
Nasal polyps  1  0/425 (0.00%)  0 1/422 (0.24%)  1
Skin and subcutaneous tissue disorders     
Vitiligo  1  1/425 (0.24%)  1 0/422 (0.00%)  0
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Tralo 300 mg Q2W Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   159/425 (37.41%)      152/422 (36.02%)    
General disorders     
Injection site reaction  1  23/425 (5.41%)  93 3/422 (0.71%)  5
Infections and infestations     
Bronchitis  1  34/425 (8.00%)  59 31/422 (7.35%)  50
Upper respiratory tract infection  1  29/425 (6.82%)  49 31/422 (7.35%)  39
Viral upper respiratory tract infection  1  50/425 (11.76%)  71 52/422 (12.32%)  80
Nervous system disorders     
Headache  1  40/425 (9.41%)  76 32/422 (7.58%)  49
Respiratory, thoracic and mediastinal disorders     
Asthma  1  35/425 (8.24%)  51 47/422 (11.14%)  79
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Global Clinical Lead
Organization: AstraZeneca
Phone: +1 301-398-0582
EMail: ClinicalTrialTransparency@astrazeneca.com
Layout table for additonal information
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02194699     History of Changes
Other Study ID Numbers: D2210C00008
First Submitted: July 17, 2014
First Posted: July 18, 2014
Results First Submitted: February 23, 2018
Results First Posted: March 21, 2018
Last Update Posted: May 15, 2018