Clinical Trial Results:
A Phase 2b, Randomized, Doubleblind Study to Evaluate the Efficacy of Tralokinumab in Adults with Uncontrolled, Severe Asthma
Summary


EudraCT number 
201100136021 
Trial protocol 
GB DE CZ ES PL 
Global end of trial date 
22 Feb 2014

Results information


Results version number 
v2(current) 
This version publication date 
22 Mar 2017

First version publication date 
15 Apr 2016

Other versions 
v1 
Version creation reason 
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information


Trial identification


Sponsor protocol code 
CDRICAT3541049


Additional study identifiers


ISRCTN number 
  
US NCT number 
NCT01402986  
WHO universal trial number (UTN) 
  
Sponsors


Sponsor organisation name 
MedImmune, LLC


Sponsor organisation address 
Milstein Building, Granta Park,, Cambridge, United Kingdom, CB21 6GH


Public contact 
Meena Jain, MB BChir, Director, Clinical Development,, MedImmune, LLC, JainM@medimmune.com


Scientific contact 
Meena Jain, MB BChir, Director, Clinical Development,, MedImmune, LLC, JainM@medimmune.com


Paediatric regulatory details


Is trial part of an agreed paediatric investigation plan (PIP) 
No


Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? 
No


Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? 
No


Results analysis stage


Analysis stage 
Final


Date of interim/final analysis 
22 Feb 2014


Is this the analysis of the primary completion data? 
No


Global end of trial reached? 
Yes


Global end of trial date 
22 Feb 2014


Was the trial ended prematurely? 
No


General information about the trial


Main objective of the trial 
The primary objective of this study was to evaluate two subcutaneous (SC) treatment regimens of 300 milligram (mg) tralokinumab compared with placebo by assessing the effect on asthma exacerbation rate over 52 weeks in adults with uncontrolled, severe asthma requiring highdose inhaled corticosteroids (ICS) and longacting beta2agonists (LABA), with or without additional asthma controller medications.


Protection of trial subjects 
The conduct of this clinical study met all local legal and regulatory requirements. The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and the International Conference on Harmonization guideline E6: Good Clinical Practice. Participating participant signed informed consent form and could withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.


Background therapy 
  
Evidence for comparator 
  
Actual start date of recruitment 
12 Aug 2011


Long term followup planned 
Yes


Long term followup rationale 
Safety  
Long term followup duration 
6 Months  
Independent data monitoring committee (IDMC) involvement? 
No


Population of trial subjects


Number of subjects enrolled per country 

Country: Number of subjects enrolled 
United States: 25


Country: Number of subjects enrolled 
Canada: 10


Country: Number of subjects enrolled 
France: 42


Country: Number of subjects enrolled 
Spain: 11


Country: Number of subjects enrolled 
United Kingdom: 3


Country: Number of subjects enrolled 
Germany: 37


Country: Number of subjects enrolled 
Poland: 23


Country: Number of subjects enrolled 
Philippines: 60


Country: Number of subjects enrolled 
Mexico: 30


Country: Number of subjects enrolled 
Argentina: 40


Country: Number of subjects enrolled 
Russian Federation: 33


Country: Number of subjects enrolled 
Chile: 22


Country: Number of subjects enrolled 
Czech Republic: 20


Country: Number of subjects enrolled 
Korea, Democratic People's Republic of: 32


Country: Number of subjects enrolled 
Japan: 64


Worldwide total number of subjects 
452


EEA total number of subjects 
136


Number of subjects enrolled per age group 

In utero 
0


Preterm newborn  gestational age < 37 wk 
0


Newborns (027 days) 
0


Infants and toddlers (28 days23 months) 
0


Children (211 years) 
0


Adolescents (1217 years) 
0


Adults (1864 years) 
397


From 65 to 84 years 
55


85 years and over 
0



Recruitment


Recruitment details 
  
Preassignment


Screening details 
A total of 689 participants were screened out of which 452 participants were randomized into this study.  
Period 1


Period 1 title 
Overall Study (overall period)


Is this the baseline period? 
Yes  
Allocation method 
Randomised  controlled


Blinding used 
Double blind  
Roles blinded 
Subject, Investigator, Carer, Assessor  
Arms


Are arms mutually exclusive 
Yes


Arm title

Placebo, Q2W  Cohort 1  
Arm description 
Participants received matching placebo subcutaneous injection every 2 weeks (Q2W) for a total of 26 doses up to 50 weeks.  
Arm type 
Placebo  
Investigational medicinal product name 
Placebo Q2W


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Injection


Routes of administration 
Subcutaneous use


Dosage and administration details 
Participants received matching placebo subcutaneous injection every 2 weeks (Q2W) for a total of 26 doses up to 50 weeks.


Arm title

Tralokinumab 300 mg, Q2W  Cohort 1  
Arm description 
Participants received tralokinumab 300 milligram (mg) subcutaneous injection every 2 weeks (Q2W) for a total of 26 doses up to 50 weeks.  
Arm type 
Experimental  
Investigational medicinal product name 
Tralokinumab


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Injection


Routes of administration 
Subcutaneous use


Dosage and administration details 
Participants received tralokinumab 300 milligram (mg) subcutaneous injection every 2 weeks (Q2W) for a total of 26 doses up to 50 weeks.


Arm title

Placebo, Q2/4W  Cohort 2  
Arm description 
Participants received matching placebo subcutaneous injection every 2 weeks (Q2W) for 12 weeks followed by every 4 weeks (Q4W) for 38 weeks (Q2/4W) for a total of 16 doses.  
Arm type 
Placebo  
Investigational medicinal product name 
Placebo, Q2/4W


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Injection


Routes of administration 
Subcutaneous use


Dosage and administration details 
Participants received matching placebo subcutaneous injection every 2 weeks (Q2W) for 12 weeks followed by every 4 weeks (Q4W) for 38 weeks (Q2/4W) for a total of 16 doses.


Arm title

Tralokinumab 300 mg, Q2/4W  Cohort 2  
Arm description 
Participants received tralokinumab 300 mg subcutaneous injection every 2 weeks (Q2W) for 12 weeks followed by every 4 weeks (Q4W) for 38 weeks (Q2/4W) for a total of 16 doses.  
Arm type 
Experimental  
Investigational medicinal product name 
Tralokinumab


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Injection


Routes of administration 
Subcutaneous use


Dosage and administration details 
Participants received tralokinumab 300 mg subcutaneous injection every 2 weeks (Q2W) for 12 weeks followed by every 4 weeks (Q4W) for 38 weeks (Q2/4W) for a total of 16 doses.





Baseline characteristics reporting groups


Reporting group title 
Placebo, Q2W  Cohort 1


Reporting group description 
Participants received matching placebo subcutaneous injection every 2 weeks (Q2W) for a total of 26 doses up to 50 weeks.  
Reporting group title 
Tralokinumab 300 mg, Q2W  Cohort 1


Reporting group description 
Participants received tralokinumab 300 milligram (mg) subcutaneous injection every 2 weeks (Q2W) for a total of 26 doses up to 50 weeks.  
Reporting group title 
Placebo, Q2/4W  Cohort 2


Reporting group description 
Participants received matching placebo subcutaneous injection every 2 weeks (Q2W) for 12 weeks followed by every 4 weeks (Q4W) for 38 weeks (Q2/4W) for a total of 16 doses.  
Reporting group title 
Tralokinumab 300 mg, Q2/4W  Cohort 2


Reporting group description 
Participants received tralokinumab 300 mg subcutaneous injection every 2 weeks (Q2W) for 12 weeks followed by every 4 weeks (Q4W) for 38 weeks (Q2/4W) for a total of 16 doses.  



End points reporting groups


Reporting group title 
Placebo, Q2W  Cohort 1


Reporting group description 
Participants received matching placebo subcutaneous injection every 2 weeks (Q2W) for a total of 26 doses up to 50 weeks.  
Reporting group title 
Tralokinumab 300 mg, Q2W  Cohort 1


Reporting group description 
Participants received tralokinumab 300 milligram (mg) subcutaneous injection every 2 weeks (Q2W) for a total of 26 doses up to 50 weeks.  
Reporting group title 
Placebo, Q2/4W  Cohort 2


Reporting group description 
Participants received matching placebo subcutaneous injection every 2 weeks (Q2W) for 12 weeks followed by every 4 weeks (Q4W) for 38 weeks (Q2/4W) for a total of 16 doses.  
Reporting group title 
Tralokinumab 300 mg, Q2/4W  Cohort 2


Reporting group description 
Participants received tralokinumab 300 mg subcutaneous injection every 2 weeks (Q2W) for 12 weeks followed by every 4 weeks (Q4W) for 38 weeks (Q2/4W) for a total of 16 doses.  
Subject analysis set title 
Placebo Total


Subject analysis set type 
Subgroup analysis  
Subject analysis set description 
Participants who received matching placebo subcutaneous injection every 2 weeks (Q2W) for a total of 26 doses up to 50 weeks, and participants who received matching placebo subcutaneous injection every 2 weeks (Q2W) for 12 weeks followed by every 4 weeks (Q4W) for a total of 16 doses up to 38 weeks.


Subject analysis set title 
Intenttotreat (ITT) population


Subject analysis set type 
Intentiontotreat  
Subject analysis set description 
The ITT population included all participants who were randomized into the study.



End point title 
Annual Asthma Exacerbation Rate (AER) ^{[1]}  
End point description 
The annual asthma exacerbation rate (AER) in participants, was calculated as the total number of observed exacerbations in each group up to week 53, divided by total duration of personyear followup in each group.
An asthma exacerbation defined as a progressive increase of asthma symptoms (cough, wheeze, chest tightness, and/or shortness of breath) that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids (tablets, suspension or injection) or increase of a stable systemic maintenance dose for a duration of at least 3 days as prescribed or administered by the investigator or healthcare provider; or 2) participant initiation of systemic corticosteroids for a duration of at least 3 days.
Data were summarized together for ‘Placebo, Q2W’ and ‘Placebo, Q2/4W’ arms. The intenttotreat (ITT) population included all participants who were randomized into the study.


End point type 
Primary


End point timeframe 
Week 1 up to Week 53


Notes [1]  The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint was reporting data for total number of participants of both the placebo reporting group, hence not reporting statistics for all the arms in the baseline period. 



Statistical analysis title 
Statistical analysis 1  
Statistical analysis description 
The 95 percent (%) confidence interval (CI) for rate ratio were estimated from the Poisson regression with treatment group, age, gender, number of exacerbations in past year (2 versus [vs] more than [>] 2 but less than or equal to [=<] 6), atopic asthma status (atopic/nonatopic), chronic oral corticosteroid (OCS) use (presence vs absence) and geographical region as the covariates.


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.709  
Method 
Poisson regression  
Parameter type 
Rate Ratio  
Point estimate 
0.94


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.67  
upper limit 
1.31  
Statistical analysis title 
Statistical analysis 2  
Statistical analysis description 
The 95% CI for rate ratio were estimated from the Poisson regression with treatment group, age, gender, number of exacerbations in past year (2 vs > 2 but =< 6), atopic asthma status (atopic/nonatopic), chronic OCS use (presence vs absence) and geographical region as the covariates.


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.904  
Method 
Poisson regression  
Parameter type 
Rate Ratio  
Point estimate 
1.02


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.71  
upper limit 
1.46 


End point title 
Mean Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 ^{[2]}  
End point description 
Pre and postbronchodilator FEV1 at clinic visits (morning) were measured. FEV1 was the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. Data were summarized together for ‘Placebo, Q2W’ and ‘Placebo, Q2/4W’ arms. The ITT population included all participants who were randomized into the study. Here "n" signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.


End point type 
Secondary


End point timeframe 
Baseline and Week 53


Notes [2]  The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint was reporting data for total number of participants of both the placebo reporting group, hence not reporting statistics for all the arms in the baseline period. 



No statistical analyses for this end point 


End point title 
Mean Change From Baseline in Forced Expiratory Volume in 6 Second (FEV6) at Week 53 ^{[3]}  
End point description 
Pre and postbronchodilator FEV6 at clinic visits (morning) were measured. FEV6 was the maximal volume of air exhaled in the six second of a forced expiration from a position of full inspiration. Data were summarized together for ‘Placebo, Q2W’ and ‘Placebo, Q2/4W’ arms. The ITT population included all participants who were randomized into the study. Here "n" signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.


End point type 
Secondary


End point timeframe 
Baseline and Week 53


Notes [3]  The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint was reporting data for total number of participants of both the placebo reporting group, hence not reporting statistics for all the arms in the baseline period. 



No statistical analyses for this end point 


End point title 
Mean Change From Baseline in Forced Vital Capacity (FVC) at Week 53 ^{[4]}  
End point description 
Pre and postbronchodilator FVC at clinic visits (morning) were measured. FVC was the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. Data were summarized together for ‘Placebo, Q2W’ and ‘Placebo, Q2/4W’ arms. The ITT population included all participants who were randomized into the study. Here "n" signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.


End point type 
Secondary


End point timeframe 
Baseline and Week 53


Notes [4]  The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint was reporting data for total number of participants of both the placebo reporting group, hence not reporting statistics for all the arms in the baseline period. 



No statistical analyses for this end point 


End point title 
Mean Change From Baseline in Ratio of Forced Expiratory Volume in 1 Second (FEV1)/Forced Vital Capacity (FVC) at Week 53 ^{[5]}  
End point description 
Pre and postbronchodilator FEV1 and FVC at clinic visits (morning) were measured. FEV1 was the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. FVC was the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. Ratio of FEV1/FVC was analysed. Data were summarized together for ‘Placebo, Q2W’ and ‘Placebo, Q2/4W’ arms. The ITT population included all participants who were randomized into the study. Here "n" signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.


End point type 
Secondary


End point timeframe 
Baseline and Week 53


Notes [5]  The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint was reporting data for total number of participants of both the placebo reporting group, hence not reporting statistics for all the arms in the baseline period. 



No statistical analyses for this end point 


End point title 
Mean Change From Baseline in Inspiratory Capacity (IC) at Week 53 ^{[6]}  
End point description 
Pre and postbronchodilator IC at clinic visits (morning) were measured. IC was measured by spirometry. Data were summarized together for ‘Placebo, Q2W’ and ‘Placebo, Q2/4W’ arms. The ITT population included all participants who were randomized into the study. Here "n" signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.


End point type 
Secondary


End point timeframe 
Baseline and Week 53


Notes [6]  The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint was reporting data for total number of participants of both the placebo reporting group, hence not reporting statistics for all the arms in the baseline period. 



No statistical analyses for this end point 


End point title 
Mean Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 at Home ^{[7]}  
End point description 
Pre and postbronchodilator FEV1 at home (morning and evening) were measured. FEV1 was the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. Data were summarized together for ‘Placebo, Q2W’ and ‘Placebo, Q2/4W’ arms. The ITT population included all participants who were randomized into the study. Here "n" signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.


End point type 
Secondary


End point timeframe 
Day 1  Day 7 (Baseline) and Day 365  Day 371 (Week 53)


Notes [7]  The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint was reporting data for total number of participants of both the placebo reporting group, hence not reporting statistics for all the arms in the baseline period. 



No statistical analyses for this end point 


End point title 
Mean Change From Baseline in Peak Expiratory Flow (PEF) at Week 53 at Home ^{[8]}  
End point description 
The PEF is a participant’s maximum speed of expiration, as measured with a peak flow meter. Peak flow testing for PEF was performed at home (morning and evening) while sitting or standing prior to using any medication (if needed) for asthma. Data were summarized together for ‘Placebo, Q2W’ and ‘Placebo, Q2/4W’ arms. The ITT population included all participants who were randomized into the study. Here "n" signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.


End point type 
Secondary


End point timeframe 
Day 1  Day 7 (Baseline) and Day 365  Day 371 (Week 53)


Notes [8]  The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint was reporting data for total number of participants of both the placebo reporting group, hence not reporting statistics for all the arms in the baseline period. 



No statistical analyses for this end point 


End point title 
Change from Baseline in Mean Asthma Control Questionnaire (6items) (ACQ6) Score at Week 53 ^{[9]}  
End point description 
Asthma Control Questionnaire (ACQ) is a participantreported questionnaire to assess the asthma control with 6 items assessing nighttime waking, symptoms on waking, activity limitation, shortness of breath, wheeze, and rescue shortacting beta agonist use. Each item was rated on a 7point Likert scale ranging from 0 (no impairment) to 6 (maximum impairment). Overall ACQ score was the mean of the 6 item scores with a score range of 0 (well controlled) to 6 (extremely poor controlled). Data were summarized together for ‘Placebo, Q2W’ and ‘Placebo, Q2/4W’ arms. Results were reported for overall ACQ score. Data was summarized together for placebo arm groups. The ITT population included all participants who were randomized into the study. Here "n" signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.


End point type 
Secondary


End point timeframe 
Baseline and Week 53


Notes [9]  The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint was reporting data for total number of participants of both the placebo reporting group, hence not reporting statistics for all the arms in the baseline period. 



No statistical analyses for this end point 


End point title 
Change from Baseline in Asthma Quality of Life Questionnaire Standardized Version (AQLQ[S]) Score at Week 53 ^{[10]}  
End point description 
AQLQ: a 32item questionnaire evaluating quality of life of participants with asthma including 4 domains (symptoms, activity limitations, emotional function, and environmental stimuli). Participants were asked to recall their experiences during the previous 2 weeks and to score each of the 32 questions on a 7point scale ranging from 7 (no impairment) to 1 (severe impairment). The overall score was calculated as the mean response to all questions. The 4 domain scores were the means of the responses to the questions in each of the domains. Overall AQLQ score and 4 domain scores ranged from 7 (no impairment) to 1 (severe impairment). Data were summarized together for ‘Placebo, Q2W’ and ‘Placebo, Q2/4W’ arms. The ITT population included all participants who were randomized into the study. Here "n" signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.


End point type 
Secondary


End point timeframe 
Baseline and Week 53


Notes [10]  The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint was reporting data for total number of participants of both the placebo reporting group, hence not reporting statistics for all the arms in the baseline period. 



No statistical analyses for this end point 


End point title 
Number of Participants With European Quality of Life 5 Dimensions (EQ5D) Scores at Week 53 ^{[11]}  
End point description 
The utilitybased EQ5D questionnaire comprises of two parts and provides a generic measure of health for clinical and economic appraisal. The health state valuation was the summary score of mobility, selfcare, usual activities, pain/discomfort and anxiety/depression on a 3 category scale (no problem, moderate problem, severe problems). The minimum possible value is 5 (one point for each dimension) and the maximum possible values is 15 (3 points for each dimension). Data were summarized together for ‘Placebo, Q2W’ and ‘Placebo, Q2/4W’ arms. The ITT population included all participants who were randomized into the study.


End point type 
Secondary


End point timeframe 
Week 53


Notes [11]  The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint was reporting data for total number of participants of both the placebo reporting group, hence not reporting statistics for all the arms in the baseline period. 



No statistical analyses for this end point 


End point title 
Change From Baseline in European Quality of Life 5 Dimensions (EQ5D) Visual Analog Scale (VAS) at Week 53 ^{[12]}  
End point description 
The utilitybased EQ5D questionnaire comprises of two parts and provides a generic measure of health for clinical and economic appraisal. The EQ5D VAS was measured from 0 (worst imaginable health state) to 100 (best imaginable health state). Data were summarized together for ‘Placebo, Q2W’ and ‘Placebo, Q2/4W’ arms. The ITT population included all participants who were randomized into the study.


End point type 
Secondary


End point timeframe 
Baseline and Week 53


Notes [12]  The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint was reporting data for total number of participants of both the placebo reporting group, hence not reporting statistics for all the arms in the baseline period. 



Notes [13]  ITT population with evaluable participants for this endpoint for the specified timepoint. [14]  ITT population with evaluable participants for this endpoint for the specified timepoint. [15]  ITT population with evaluable participants for this endpoint for the specified timepoint. 

No statistical analyses for this end point 


End point title 
Change From Baseline in Assessing Symptoms of Moderatetosevere Asthma (ASMA) at Week 53 ^{[16]}  
End point description 
There were 3 symptom questions in the ASMA diary: daytime frequency (question 1), daytime severity (question 2) and nighttime severity (question 6). All symptom questions were scored from 0 to 4 averaged, where a higher score indicated greater frequency or severity. Asthma symptom scores were averaged weekly for participants with at least 4 nonmissing records each week. The baseline score was calculated from Day 7 to Day 1. Data were summarized together for ‘Placebo, Q2W’ and ‘Placebo, Q2/4W’ arms. The ITT population included all participants who were randomized into the study. Here "n" signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.


End point type 
Secondary


End point timeframe 
Baseline (Day 7 – Day 1) and Week 53 (Day 365 – Day 371)


Notes [16]  The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint was reporting data for total number of participants of both the placebo reporting group, hence not reporting statistics for all the arms in the baseline period. 



No statistical analyses for this end point 


End point title 
Change From Baseline in Rescue Medication use at Week 53 ^{[17]}  
End point description 
Rescue medication use was collected from 3 questions: daytime use in response to symptoms (question 3), daytime prophylactic use (question 4) and nighttime use (question 7). Rescue medication use questions were first assessed using a dichotomous response option (YES/NO). If the participants reported YES, there was a subsequent question about the number of times rescue medication was used (questions 3a, 4a, and 7a). Daily average scores were summarized each week for all participants with at least 4 nonmissing records each week. Days with no reported rescue medication use were represented as 0 and included in the calculation with participants who reported yes and completed questions 3a, 4a and 7a. The baseline scores were calculated from Day 7 to Day 1. Data were summarized together for ‘Placebo, Q2W’ and ‘Placebo, Q2/4W’ arms. Here "n" signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.


End point type 
Secondary


End point timeframe 
Baseline (Day 7 – Day 1) and Week 53 (Day 365 – Day 371)


Notes [17]  The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint was reporting data for total number of participants of both the placebo reporting group, hence not reporting statistics for all the arms in the baseline period. 



Notes [18]  ITT population [19]  ITT population [20]  ITT population 

No statistical analyses for this end point 


End point title 
Number of Participants With TreatmentEmergent Adverse Events (TEAEs) and Serious Adverse Events (TESAEs) ^{[21]}  
End point description 
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; lifethreatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatmentemergent are events between administration of study drug and up to Week 75 that were absent before treatment or that worsened relative to pretreatment state. Data were summarized together for ‘Placebo, Q2W’ and ‘Placebo, Q2/4W’ arms. The safety population included all participants who received any investigational product and had safety data available for analysis.


End point type 
Secondary


End point timeframe 
Baseline and Week 75


Notes [21]  The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint was reporting data for total number of participants of both the placebo reporting group, hence not reporting statistics for all the arms in the baseline period. 



No statistical analyses for this end point 


End point title 
Observed Serum Tralokinumab Concentration at Week 53 ^{[22]}  
End point description 
Tralokinumab concentrations that were below limit of quantification (LOQ) of the pharmacokinetic (PK) assay (LOQ = 0.500 microgram per milliliter [mcg/mL]) were replaced by LOQ/2 = 0.250 mcg/mL; results were reported to 3 significant figures level of precision. Observed serum tralokinumab concentration at Week 53 was reported. The PK population included all participants who received at least one dose of tralokinumab and had at least one quantifiable PK observation. Here "N" signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.


End point type 
Secondary


End point timeframe 
Week 53


Notes [22]  The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint was reporting data for total number of participants of both the placebo reporting group, hence not reporting statistics for all the arms in the baseline period. 



No statistical analyses for this end point 


End point title 
Percentage of Participants with AntiDrug Antibodies (ADA) to Tralokinumab ^{[23]}  
End point description 
Immunogenicity assessment included determination of antidrug (tralokinumab) antibodies in serum samples. ADA positive was defined as a titer greater than or equal to (>=13) at any point in the study. Data were summarized together for ‘Placebo, Q2W’ and ‘Placebo, Q2/4W’ arms. The PK population included all participants who received at least one dose of tralokinumab and had at least one quantifiable PK observation. Here "N" signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.


End point type 
Secondary


End point timeframe 
Baseline and Week 75


Notes [23]  The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint was reporting data for total number of participants of both the placebo reporting group, hence not reporting statistics for all the arms in the baseline period. 



No statistical analyses for this end point 


End point title 
Severe Annual Asthma Exacerbation Rate (AER) ^{[24]}  
End point description 
Severe annualized AER was assessed based on AER data up to Week 53. Annualized AER was assessed based on AER data up to Week 53. An asthma exacerbation defined as a progressive increase of asthma symptoms that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 consecutive days as prescribed or administered by the investigator; or 2) participant initiation of systemic corticosteroids for a duration of at least 3 consecutive days. An asthma exacerbation event was considered resolved 7 days after the last dose of oral corticosteroids is administered (10 days after an injectable corticosteroid). Courses of corticosteroids initiated after this time period were considered a separate new asthma exacerbation. Data were summarized together for ‘Placebo, Q2W’ and ‘Placebo, Q2/4W’ arms.


End point type 
Secondary


End point timeframe 
Week 1 up to Week 53


Notes [24]  The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint was reporting data for total number of participants of both the placebo reporting group, hence not reporting statistics for all the arms in the baseline period. 



Notes [25]  ITT population [26]  ITT population [27]  ITT population 

Statistical analysis title 
Statistical analysis 1  
Statistical analysis description 
The 95% CI for rate ratio were estimated from the Poisson regression with treatment group, age, gender, number of exacerbations in past year (2 vs >2 but =<6), atopic asthma status (atopic/nonatopic), chronic OCS use (presence vs absence) and geographical region as the covariates.


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.293  
Method 
Poisson regression  
Parameter type 
Rate Ratio  
Point estimate 
0.62


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.26  
upper limit 
1.51  
Statistical analysis title 
Statistical analysis 2  
Statistical analysis description 
The 95% CI for rate ratio were estimated from the Poisson regression with treatment group, age, gender, number of exacerbations in past year (2 vs >2 but =<6), atopic asthma status (atopic/nonatopic), chronic OCS use (presence vs absence) and geographical region as the covariates.


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.27  
Method 
Poisson regression  
Parameter type 
Rate Ratio  
Point estimate 
0.62


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.27  
upper limit 
1.44 


End point title 
Time to First Exacerbation Through Week 53 ^{[28]}  
End point description 
Data were summarized together for ‘Placebo, Q2W’ and ‘Placebo, Q2/4W’ arms. In the below table, '99999' indicates the median and lower and upper limits of the 95% Confidence Interval were incalculable due to an insufficient number of events. The ITT population included all participants who were randomized into the study.


End point type 
Secondary


End point timeframe 
Week 1 up to Week 53


Notes [28]  The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint was reporting data for total number of participants of both the placebo reporting group, hence not reporting statistics for all the arms in the baseline period. 



Statistical analysis title 
Statistical analysis 1  
Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.257  
Method 
Regression, Cox  
Parameter type 
Hazard ratio (HR)  
Point estimate 
0.81


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.57  
upper limit 
1.16  
Statistical analysis title 
Statistical analysis 2  
Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.225  
Method 
Regression, Cox  
Parameter type 
Hazard ratio (HR)  
Point estimate 
0.8


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.56  
upper limit 
1.15 


End point title 
Time to First Severe Exacerbation Through Week 53 ^{[29]}  
End point description 
Data were summarized together for ‘Placebo, Q2W’ and ‘Placebo, Q2/4W’ arms. In the below table, '99999' indicates the median and lower and upper limits of the 95% Confidence Interval were incalculable due to an insufficient number of events. The ITT population included all participants who were randomized into the study.


End point type 
Secondary


End point timeframe 
Week 1 up to Week 53


Notes [29]  The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint was reporting data for total number of participants of both the placebo reporting group, hence not reporting statistics for all the arms in the baseline period. 



Statistical analysis title 
Statistical analysis 1  
Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.538  
Method 
Regression, Cox  
Parameter type 
Hazard ratio (HR)  
Point estimate 
0.79


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.37  
upper limit 
1.68  
Statistical analysis title 
Statistical analysis 2  
Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.561  
Method 
Regression, Cox  
Parameter type 
Hazard ratio (HR)  
Point estimate 
0.8


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.37  
upper limit 
1.71 


End point title 
Annual Asthma Exacerbation Rate (AER) by Baseline Serum Periostin ^{[30]}  
End point description 
Annualized AER was assessed based on AER data up to Week 53. An asthma exacerbation defined as a progressive increase of asthma symptoms that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable maintenance dose for a duration of at least 3 consecutive days as prescribed; or 2) initiation of systemic corticosteroids for a duration of at least 3 consecutive days. It was considered resolved 7 days after the last dose of OCS administered (10 days after an injectable corticosteroid). Courses of corticosteroids initiated after this time period were considered a separate new asthma exacerbation. AER was evaluated by subgroup baseline serum periostin >= or <median, >= or < 25th percentile and >= or < 75th percentile. Data were summarized together for ‘Placebo, Q2W’ and ‘Placebo, Q2/4W’ arms. Here "n" signifies evaluable participants for this measure.


End point type 
Secondary


End point timeframe 
Week 1 up to Week 53


Notes [30]  The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint was reporting data for total number of participants of both the placebo reporting group, hence not reporting statistics for all the arms in the baseline period. 



Notes [31]  ITT population [32]  ITT population [33]  ITT population 

Statistical analysis title 
Statistical analysis 1  
Statistical analysis description 
Baseline serum periostin >= median


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.19  
Method 
Poisson regression  
Parameter type 
Rate Ratio  
Point estimate 
0.73


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.46  
upper limit 
1.17  
Statistical analysis title 
Statistical analysis 2  
Statistical analysis description 
Baseline serum periostin >= median


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.856  
Method 
Poisson regression  
Parameter type 
Rate Ratio  
Point estimate 
0.95


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.56  
upper limit 
1.61  
Statistical analysis title 
Statistical analysis 3  
Statistical analysis description 
Baseline serum periostin < median


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.602  
Method 
Poisson regression  
Parameter type 
Rate Ratio  
Point estimate 
1.13


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.71  
upper limit 
1.81  
Statistical analysis title 
Statistical analysis 4  
Statistical analysis description 
Baseline serum periostin < median


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.703  
Method 
Poisson regression  
Parameter type 
Rate Ratio  
Point estimate 
0.91


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.55  
upper limit 
1.5  
Statistical analysis title 
Statistical analysis 5  
Statistical analysis description 
Baseline serum periostin >= 25th Percentile


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.455  
Method 
Poisson regression  
Parameter type 
Rate Ratio  
Point estimate 
0.86


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.58  
upper limit 
1.28  
Statistical analysis title 
Statistical analysis 6  
Statistical analysis description 
Baseline serum periostin >= 25th Percentile


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.929  
Method 
Poisson regression  
Parameter type 
Rate Ratio  
Point estimate 
1.02


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.66  
upper limit 
1.57  
Statistical analysis title 
Statistical analysis 7  
Statistical analysis description 
Baseline serum periostin < 25th Percentile


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.507  
Method 
Poisson regression  
Parameter type 
Rate Ratio  
Point estimate 
1.26


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.63  
upper limit 
2.51  
Statistical analysis title 
Statistical analysis 8  
Statistical analysis description 
Baseline serum periostin < 25th Percentile


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.805  
Method 
Poisson regression  
Parameter type 
Rate Ratio  
Point estimate 
0.91


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.44  
upper limit 
1.89  
Statistical analysis title 
Statistical analysis 9  
Statistical analysis description 
Baseline serum periostin >= 75th Percentile


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.716  
Method 
Poisson regression  
Parameter type 
Rate Ratio  
Point estimate 
0.88


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.44  
upper limit 
1.75  
Statistical analysis title 
Statistical analysis 10  
Statistical analysis description 
Baseline serum periostin >= 75th Percentile


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.328  
Method 
Poisson regression  
Parameter type 
Rate Ratio  
Point estimate 
1.51


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.66  
upper limit 
3.43  
Statistical analysis title 
Statistical analysis 11  
Statistical analysis description 
Baseline serum periostin < 75th Percentile


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.804  
Method 
Poission regression  
Parameter type 
Rate Ratio  
Point estimate 
0.95


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.64  
upper limit 
1.41  
Statistical analysis title 
Statistical analysis 12  
Statistical analysis description 
Baseline serum periostin < 75th Percentile


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.088  
Method 
Poisson regression  
Parameter type 
Rate Ratio  
Point estimate 
0.7


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.47  
upper limit 
1.05 


End point title 
Annual Asthma Exacerbation Rate (AER) by Thelper2 (Th2) Status ^{[34]}  
End point description 
Annualized AER was assessed based on AER data up to Week 53. An asthma exacerbation defined as a progressive increase of asthma symptoms that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 consecutive days as prescribed; or 2) participant initiation of systemic corticosteroids for a duration of at least 3 consecutive days. AER was evaluated by subgroup Th2 status. Th2high included those participants who had immunoglobulin E (IgE) >100 international unit per milliliter (IU/mL) and blood eosinophils >= 0.14 * 10 power 9 per Liter. Th2 low would include those participants who do not meet Th2 high status. Data were summarized together for ‘Placebo, Q2W’ and ‘Placebo, Q2/4W’ arms. Here "n" signifies evaluable participants for this measure for the specified time point for each arm, respectively.


End point type 
Secondary


End point timeframe 
Week 1 up to Week 53


Notes [34]  The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint was reporting data for total number of participants of both the placebo reporting group, hence not reporting statistics for all the arms in the baseline period. 



Notes [35]  ITT population [36]  ITT population [37]  ITT population 

Statistical analysis title 
Statistical analysis 1  
Statistical analysis description 
Th2 high


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.365  
Method 
Poisson regression  
Parameter type 
Rate Ratio  
Point estimate 
0.8


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.5  
upper limit 
1.29  
Statistical analysis title 
Statistical analysis 2  
Statistical analysis description 
Th2 high


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.922  
Method 
Poisson regression  
Parameter type 
Rate Ratio  
Point estimate 
0.97


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.56  
upper limit 
1.68  
Statistical analysis title 
Statistical analysis 3  
Statistical analysis description 
Th2 Low


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.685  
Method 
Poisson regression  
Parameter type 
Rate Ratio  
Point estimate 
1.11


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.67  
upper limit 
1.84  
Statistical analysis title 
Statistical analysis 4  
Statistical analysis description 
Th2 Low


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.813  
Method 
Poisson regression  
Parameter type 
Rate Ratio  
Point estimate 
1.06


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.66  
upper limit 
1.7 


End point title 
Annual Asthma Exacerbation Rate (AER) by Baseline Peripheral Blood Eosinophil Count ^{[38]}  
End point description 
Annualized AER was assessed based on AER data up to Week 53. An asthma exacerbation defined as a progressive increase of asthma symptoms that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 consecutive days as prescribed; or 2) participant initiation of systemic corticosteroids for a duration of at least 3 consecutive days. It was considered resolved 7 days after the last dose of OCS administered (10 days after an injectable corticosteroid). Courses of corticosteroids initiated after this time period were considered a separate new asthma exacerbation. AER evaluated by subgroups baseline peripheral blood eosinophil counts. Data were summarized together for ‘Placebo, Q2W’ and ‘Placebo, Q2/4W’ arms. Here "n" signifies evaluable participants for this measure.


End point type 
Secondary


End point timeframe 
Week 1 up to Week 53


Notes [38]  The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint was reporting data for total number of participants of both the placebo reporting group, hence not reporting statistics for all the arms in the baseline period. 



Notes [39]  ITT population [40]  ITT population [41]  ITT population 

Statistical analysis title 
Statistical analysis 1  
Statistical analysis description 
Baseline eosinophil count >=150 cells/mcgL


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.335  
Method 
Poisson regression  
Parameter type 
Rate Ratio  
Point estimate 
0.82


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.56  
upper limit 
1.22  
Statistical analysis title 
Statistical analysis 2  
Statistical analysis description 
Baseline eosinophil count >=150 cells/mcgL


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.586  
Method 
Poisson regression  
Parameter type 
Rate Ratio  
Point estimate 
0.88


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.54  
upper limit 
1.41  
Statistical analysis title 
Statistical Analysis 3  
Statistical analysis description 
Baseline eosinophil count <150 cells/mcgL


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.331  
Method 
Poisson regression  
Parameter type 
Rate Ratio  
Point estimate 
1.36


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.73  
upper limit 
2.52  
Statistical analysis title 
Statistical analysis 4  
Statistical analysis description 
Baseline eosinophil count <150 cells/mcgL


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.311  
Method 
Poisson regression  
Parameter type 
Rate Ratio  
Point estimate 
1.41


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.73  
upper limit 
2.71  
Statistical analysis title 
statistical analysis 5  
Statistical analysis description 
Baseline eosinophil count >=300 cells/mcgL


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.414  
Method 
Poisson regression  
Parameter type 
Rate Ratio  
Point estimate 
0.81


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.48  
upper limit 
1.35  
Statistical analysis title 
statistical analysis 6  
Statistical analysis description 
Baseline eosinophil count >=300 cells/mcgL


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.463  
Method 
Poisson regression  
Parameter type 
Rate Ratio  
Point estimate 
1.26


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.68  
upper limit 
2.36  
Statistical analysis title 
Statistical analysis 7  
Statistical analysis description 
Baseline eosinophil count <300 cells/mcgL


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.793  
Method 
Poisson regression  
Parameter type 
Rate Ratio  
Point estimate 
1.06


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.67  
upper limit 
1.68  
Statistical analysis title 
Statistical analysis 8  
Statistical analysis description 
Baseline eosinophil count <300 cells/mcgL


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.264  
Method 
Poisson regression  
Parameter type 
Rate Ratio  
Point estimate 
0.77


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.49  
upper limit 
1.22 


End point title 
Annual Asthma Exacerbation Rate (AER) by Baseline FEV1 Reversibility ^{[42]}  
End point description 
Annualized AER was assessed based on AER data up to Week 53. An asthma exacerbation defined as a progressive increase of asthma symptoms that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 consecutive days as prescribed; or 2) participant initiation of systemic corticosteroids for a duration of at least 3 consecutive days. It was considered resolved 7 days after the last dose of OCS administered (10 days after an injectable corticosteroid). Courses of corticosteroids initiated after this time period were considered a separate new asthma exacerbation. AER evaluated by subgroup baseline FEV1 reversibility >=12% and <12%. Data were summarized together for ‘Placebo, Q2W’ and ‘Placebo, Q2/4W’ arms. Here "n" signifies evaluable participants for this measure.


End point type 
Secondary


End point timeframe 
Week 1 up to Week 53


Notes [42]  The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint was reporting data for total number of participants of both the placebo reporting group, hence not reporting statistics for all the arms in the baseline period. 



Notes [43]  ITT population [44]  ITT population [45]  ITT population 

Statistical analysis title 
Statistical analysis 1  
Statistical analysis description 
Baseline FEV1 reversibility >=12%


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.245  
Method 
Poisson regression  
Parameter type 
Rate Ratio  
Point estimate 
0.66


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.33  
upper limit 
1.32  
Statistical analysis title 
Statistical analysis 2  
Statistical analysis description 
Baseline FEV1 reversibility >=12%


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.438  
Method 
Poisson regression  
Parameter type 
Rate Ratio  
Point estimate 
0.76


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.37  
upper limit 
1.54  
Statistical analysis title 
Statistical analysis 3  
Statistical analysis description 
Baseline FEV1 reversibility <12%


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.947  
Method 
Poisson regression  
Parameter type 
Rate Ratio  
Point estimate 
1.01


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.66  
upper limit 
1.57  
Statistical analysis title 
Statistical analysis 4  
Statistical analysis description 
Baseline FEV1 reversibility <12%


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.916  
Method 
Poisson regression  
Parameter type 
Rate Ratio  
Point estimate 
0.97


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.59  
upper limit 
1.59 


End point title 
Annual Asthma Exacerbation Rate (AER) by Baseline FEV1% Predicted ^{[46]}  
End point description 
Annualized AER was assessed based on AER data up to Week 53. An asthma exacerbation defined as a progressive increase of asthma symptoms that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 consecutive days as prescribed; or 2) participant initiation of systemic corticosteroids for a duration of at least 3 consecutive days. It was considered resolved 7 days after the last dose of OCS administered (10 days after an injectable corticosteroid). Courses of corticosteroids initiated after this time period were considered a separate new asthma exacerbation. AER was evaluated by subgroup baseline FEV1% predicaed. Data were summarized together for ‘Placebo, Q2W’ and ‘Placebo, Q2/4W’ arms. Here "n" signifies evaluable participants for this measure for the specified time point for each arm, respectively.


End point type 
Secondary


End point timeframe 
Week 1 up to Week 53


Notes [46]  The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint was reporting data for total number of participants of both the placebo reporting group, hence not reporting statistics for all the arms in the baseline period. 



Notes [47]  ITT population [48]  ITT population [49]  ITT population 

Statistical analysis title 
Statistical analysis 1  
Statistical analysis description 
Baseline FEV1% predicted <=60%


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.723  
Method 
Poisson regression  
Parameter type 
Rate Ratio  
Point estimate 
0.91


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.52  
upper limit 
1.56  
Statistical analysis title 
Statistical analysis 2  
Statistical analysis description 
Baseline FEV1% predicted <=60%


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.852  
Method 
Poisson regression  
Parameter type 
Rate Ratio  
Point estimate 
1.06


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.6  
upper limit 
1.86  
Statistical analysis title 
Statistical analysis 3  
Statistical analysis description 
Baseline FEV1% predicted <=80%


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.409  
Method 
Poisson regression  
Parameter type 
Rate Ratio  
Point estimate 
0.86


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.6  
upper limit 
1.23  
Statistical analysis title 
Statistical analysis 4  
Statistical analysis description 
Baseline FEV1% predicted <=80%


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.744  
Method 
Poisson regression  
Parameter type 
Rate Ratio  
Point estimate 
1.07


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.72  
upper limit 
1.58 


End point title 
Annual Asthma Exacerbation Rate (AER) by Asthma Exacerbations in the Past Year ^{[50]}  
End point description 
Annualized AER was assessed based on AER data up to Week 53. An asthma exacerbation defined as a progressive increase of asthma symptoms that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 consecutive days as prescribed; or 2) participant initiation of systemic corticosteroids for a duration of at least 3 consecutive days. It was considered resolved 7 days after the last dose of OCS administered (10 days after an injectable corticosteroid). Courses of corticosteroids initiated after this time period were considered a separate new asthma exacerbation. AER evaluated by subgroup as asthma exacerbations in the past year. Data were summarized together for ‘Placebo, Q2W’ and ‘Placebo, Q2/4W’ arms. Here "n" signifies evaluable participants for this measure at specified time points.


End point type 
Secondary


End point timeframe 
Week 1 up to Week 53


Notes [50]  The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint was reporting data for total number of participants of both the placebo reporting group, hence not reporting statistics for all the arms in the baseline period. 



Notes [51]  ITT population [52]  ITT population [53]  ITT population 

Statistical analysis title 
Statistical analysis 1  
Statistical analysis description 
2 asthma exacerbations in the past year


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.802  
Method 
Poisson regression  
Parameter type 
Rate Ratio  
Point estimate 
0.94


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.58  
upper limit 
1.52  
Statistical analysis title 
Statistical analysis 2  
Statistical analysis description 
2 asthma exacerbations in the past year


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.05  
Method 
Poisson regression  
Parameter type 
Rate Ratio  
Point estimate 
0.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.36  
upper limit 
1  
Statistical analysis title 
Statistical analysis 3  
Statistical analysis description 
> 2 but < 6 asthma exacerbations in the past year


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.792  
Method 
Poisson regression  
Parameter type 
Rate Ratio  
Point estimate 
0.93


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.56  
upper limit 
1.56  
Statistical analysis title 
Statistical analysis 4  
Statistical analysis description 
> 2 but < 6 asthma exacerbations in the past year


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.231  
Method 
Poisson regression  
Parameter type 
Rate Ratio  
Point estimate 
1.39


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.81  
upper limit 
2.38 


End point title 
Severe Asthma Exacerbation Rate (AER) by Baseline Serum Periostin ^{[54]}  
End point description 
Severe AER was assessed based on AER data up to Week 53. Annualized AER was assessed based on AER data up to Week 53. An asthma exacerbation defined as a progressive increase of asthma symptoms that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 consecutive days as prescribed; or 2) participant initiation of systemic corticosteroids for a duration of at least 3 consecutive days. It was considered resolved 7 days after the last dose of OCS (10 days after an injectable corticosteroid). Courses of corticosteroids initiated after this time period were considered a separate new asthma exacerbation. Severe AER evaluated by subgroup baseline serum periostin. Data were summarized together for ‘Placebo, Q2W’ and ‘Placebo, Q2/4W’ arms. Here "n" signifies evaluable participants for this measure.


End point type 
Secondary


End point timeframe 
Week 1 up to Week 53


Notes [54]  The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint was reporting data for total number of participants of both the placebo reporting group, hence not reporting statistics for all the arms in the baseline period. 



Notes [55]  ITT population [56]  ITT population [57]  ITT population 

Statistical analysis title 
Statistical analysis 1  
Statistical analysis description 
Baseline Serum Periostin >=Median


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.046  
Method 
Poisson regression  
Parameter type 
Rate Ratio  
Point estimate 
0.25


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.06  
upper limit 
0.98  
Statistical analysis title 
Statistical analysis 2  
Statistical analysis description 
Baseline Serum Periostin >=Median


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.197  
Method 
Poisson regression  
Parameter type 
Rate Ratio  
Point estimate 
0.47


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.15  
upper limit 
1.48  
Statistical analysis title 
Statistical analysis 3  
Statistical analysis description 
Baseline Serum Periostin < Median


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.708  
Method 
Poisson regression  
Parameter type 
Rate Ratio  
Point estimate 
1.18


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.5  
upper limit 
2.79  
Statistical analysis title 
Statistical analysis 4  
Statistical analysis description 
Baseline Serum Periostin < Median


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.594  
Method 
Poisson regression  
Parameter type 
Rate Ratio  
Point estimate 
1.31


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.48  
upper limit 
3.57 


End point title 
Severe Asthma Exacerbation Rate (AER) by Baseline FEV1 Reversibility ^{[58]}  
End point description 
Severe AER was assessed based on AER data up to Week 53. Annualized AER was assessed based on AER data up to Week 53. An asthma exacerbation defined as a progressive increase of asthma symptoms that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 consecutive days as prescribed; or 2) participant initiation of systemic corticosteroids for a duration of at least 3 consecutive days. It was considered resolved 7 days after the last dose of OCS administered (10 days after an injectable corticosteroid). Courses of corticosteroids initiated after this time period were considered a separate new asthma exacerbation. Severe AER was evaluated by subgroup FEV1 reversibility. Data were summarized together for ‘Placebo, Q2W’ and ‘Placebo, Q2/4W’ arms. Here "n" signifies evaluable participants for this measure.


End point type 
Secondary


End point timeframe 
Week 1 up to Week 53


Notes [58]  The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint was reporting data for total number of participants of both the placebo reporting group, hence not reporting statistics for all the arms in the baseline period. 



Notes [59]  ITT population [60]  ITT population [61]  ITT population 

Statistical analysis title 
Statistical analysis 1  
Statistical analysis description 
Baseline FEV1 reversibility >=12%


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.975  
Method 
Poisson regression  
Parameter type 
Rate Ratio  
Point estimate 
1.03


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.14  
upper limit 
7.67  
Statistical analysis title 
Statistical analysis 2  
Statistical analysis description 
Baseline FEV1 reversibility >=12%


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.473  
Method 
Poisson regression  
Parameter type 
Rate Ratio  
Point estimate 
1.66


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.41  
upper limit 
6.67  
Statistical analysis title 
Statistical analysis 3  
Statistical analysis description 
Baseline FEV1 reversibility <12%


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.099  
Method 
Poisson regression  
Parameter type 
Rate Ratio  
Point estimate 
0.49


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.21  
upper limit 
1.14  
Statistical analysis title 
Statistical analysis 4  
Statistical analysis description 
Baseline FEV1 reversibility <12%


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.148  
Method 
Poisson regression  
Parameter type 
Rate Ratio  
Point estimate 
0.42


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.13  
upper limit 
1.36 


End point title 
Severe Asthma Exacerbation Rate (AER) by Thelper2 (Th2) Status ^{[62]}  
End point description 
Severe AER was assessed based on AER data up to Week 53. An asthma exacerbation is a progressive increase of asthma symptoms that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 days as prescribed; or 2) participant initiation of systemic corticosteroids for a duration of at least 3 days. It was considered resolved 7 days after last dose of OCS (10 days after injectable corticosteroid). Corticosteroids initiated after this time period were considered separate new asthma exacerbation. Severe AER was evaluated by subgroup Th2 status. Th2high include who had IgE >100 IU/mL and blood eosinophils >=0.14*10^9/L. Th2 low would include who do not meet Th2 high status. Data were summarized together for ‘Placebo, Q2W’ and ‘Placebo, Q2/4W’ arms. Here "n" signifies evaluable participants for this measure.


End point type 
Secondary


End point timeframe 
Week 1 up to Week 53


Notes [62]  The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint was reporting data for total number of participants of both the placebo reporting group, hence not reporting statistics for all the arms in the baseline period. 



Notes [63]  ITT population [64]  ITT population [65]  ITT population 

Statistical analysis title 
Statistical analysis 1  
Statistical analysis description 
Th2 high


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.698  
Method 
Poisson regression  
Parameter type 
Rate Ratio  
Point estimate 
0.82


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.31  
upper limit 
2.19  
Statistical analysis title 
Statistical analysis 2  
Statistical analysis description 
Th2 high


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.299  
Method 
Poisson regression  
Parameter type 
Rate Ratio  
Point estimate 
0.55


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.18  
upper limit 
1.7  
Statistical analysis title 
Statistical analysis 3  
Statistical analysis description 
Th2 Low


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.105  
Method 
Poisson regression  
Parameter type 
Rate Ratio  
Point estimate 
0.25


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.05  
upper limit 
1.34  
Statistical analysis title 
Statistical analysis 4  
Statistical analysis description 
Th2 Low


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.576  
Method 
Poisson regression  
Parameter type 
Rate Ratio  
Point estimate 
0.7


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.2  
upper limit 
2.47 


End point title 
Severe Asthma Exacerbation Rate (AER) by Baseline Peripheral Blood Eosinophil Count ^{[66]}  
End point description 
Severe AER was assessed based on AER data up to Week 53. Annualized AER was assessed based on AER data up to Week 53. An asthma exacerbation defined as a progressive increase of asthma symptoms that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 consecutive days as prescribed; or 2) participant initiation of systemic corticosteroids for a duration of at least 3 consecutive days. It was considered resolved 7 days after the last dose of OCS (10 days after an injectable corticosteroid). Corticosteroids initiated after this time period were considered a separate new asthma exacerbation. Severe AER was evaluated by subgroup baseline peripheral blood eosinophil count. Data were summarized together for ‘Placebo, Q2W’ and ‘Placebo, Q2/4W’ arms. Here "n" signifies evaluable participants for this measure.


End point type 
Secondary


End point timeframe 
Week 1 up to Week 53


Notes [66]  The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint was reporting data for total number of participants of both the placebo reporting group, hence not reporting statistics for all the arms in the baseline period. 



Notes [67]  ITT population [68]  ITT population [69]  ITT population 

Statistical analysis title 
Statistical analysis 1  
Statistical analysis description 
Baseline eosinophil count >=300 cells/mcgL


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.133  
Method 
Poisson regression  
Parameter type 
Rate Ratio  
Point estimate 
0.48


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.19  
upper limit 
1.25  
Statistical analysis title 
Statistical analysis 2  
Statistical analysis description 
Baseline eosinophil count >=300 cells/mcgL


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.241  
Method 
Poisson regression  
Parameter type 
Rate Ratio  
Point estimate 
0.46


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.13  
upper limit 
1.67  
Statistical analysis title 
Statistical analysis 3  
Statistical analysis description 
Baseline eosinophil count <300 cells/mcgL


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.51  
Method 
Poisson regression  
Parameter type 
Rate Ratio  
Point estimate 
0.59


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.12  
upper limit 
2.84  
Statistical analysis title 
Statistical analysis 4  
Statistical analysis description 
Baseline eosinophil count <300 cells/mcgL


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.661  
Method 
Poisson regression  
Parameter type 
Rate Ratio  
Point estimate 
0.74


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.19  
upper limit 
2.85 


End point title 
Percent Change from Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups ^{[70]}  
End point description 
Prebronchodilator FEV1 was evaluated by subgroups. Data were summarized together for ‘Placebo, Q2W’ and ‘Placebo, Q2/4W’ arms. The ITT population included all participants who were randomized into the study. Here "n" signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.


End point type 
Secondary


End point timeframe 
Week 1 up to Week 53


Notes [70]  The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint was reporting data for total number of participants of both the placebo reporting group, hence not reporting statistics for all the arms in the baseline period. 



Statistical analysis title 
Statistical analysis 1  
Statistical analysis description 
Baseline serum periostin >= median


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.057  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
6.79


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.21  
upper limit 
13.79  
Statistical analysis title 
Statistical analysis 2  
Statistical analysis description 
Baseline serum periostin >= median


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.874  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.57


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
6.54  
upper limit 
7.68  
Statistical analysis title 
Statistical analysis 3  
Statistical analysis description 
Baseline serum periostin < median


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.028  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
7.37


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.8  
upper limit 
13.95  
Statistical analysis title 
Statistical analysis 4  
Statistical analysis description 
Baseline serum periostin < median


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.745  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
1.09


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
5.48  
upper limit 
7.66  
Statistical analysis title 
Statistical analysis 5  
Statistical analysis description 
Baseline serum periostin >= 25th percentile


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.011  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
7.12


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.66  
upper limit 
12.58  
Statistical analysis title 
Statistical analysis 6  
Statistical analysis description 
Baseline serum periostin >= 25th percentile


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.863  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.48


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
5.93  
upper limit 
4.97  
Statistical analysis title 
Statistical analysis 7  
Statistical analysis description 
Baseline serum periostin < 25th percentile


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.221  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
6.24


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.8  
upper limit 
16.27  
Statistical analysis title 
Statistical analysis 8  
Statistical analysis description 
Baseline serum periostin < 25th percentile


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.108  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
8.58


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.91  
upper limit 
19.07  
Statistical analysis title 
Statistical analysis 9  
Statistical analysis description 
Baseline serum periostin >= 75th percentile


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.09  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
9.89


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.57  
upper limit 
21.35  
Statistical analysis title 
Statistical analysis 10  
Statistical analysis description 
Baseline serum periostin >= 75th percentile


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.908  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.7


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
11.19  
upper limit 
12.59  
Statistical analysis title 
Statistical analysis 11  
Statistical analysis description 
Baseline serum periostin < 75th percentile


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.013  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
6.52


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.41  
upper limit 
11.64  
Statistical analysis title 
Statistical analysis 12  
Statistical analysis description 
Baseline serum periostin < 75th percentile


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.635  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
1.23


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.84  
upper limit 
6.29  
Statistical analysis title 
Statistical analysis 13  
Statistical analysis description 
Th2 high


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.014  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
8.89


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.84  
upper limit 
15.94  
Statistical analysis title 
Statistical analysis 14  
Statistical analysis description 
Th2 high


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.28  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
3.91


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.19  
upper limit 
11.02  
Statistical analysis title 
Statistical analysis 15  
Statistical analysis description 
Th2 low


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.292  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
3.22


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.78  
upper limit 
9.22  
Statistical analysis title 
Statistical analysis 16  
Statistical analysis description 
Th2 low


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.691  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
1.18


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
6.99  
upper limit 
4.64  
Statistical analysis title 
Statistical analysis 17  
Statistical analysis description 
Baseline peripheral blood eosinophil count >= 150 cells/μL


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.004  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
8.83


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.85  
upper limit 
14.81  
Statistical analysis title 
Statistical analysis 18  
Statistical analysis description 
Baseline peripheral blood eosinophil count >= 150 cells/μL


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.177  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
4.25


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.92  
upper limit 
10.43  
Statistical analysis title 
Statistical analysis 19  
Statistical analysis description 
Baseline peripheral blood eosinophil count < 150 cells/μL


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.159  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
6.05


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.39  
upper limit 
14.5  
Statistical analysis title 
Statistical analysis 20  
Statistical analysis description 
Baseline peripheral blood eosinophil count < 150 cells/μL


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.857  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.72


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
8.63  
upper limit 
7.18  
Statistical analysis title 
Statistical analysis 21  
Statistical analysis description 
Baseline peripheral blood eosinophil count >= 300 cells/μL


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.002  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
13.75


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
5.28  
upper limit 
22.22  
Statistical analysis title 
Statistical analysis 22  
Statistical analysis description 
Baseline peripheral blood eosinophil count >= 300 cells/μL


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.243  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
5.23


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.56  
upper limit 
14.02  
Statistical analysis title 
Statistical analysis 23  
Statistical analysis description 
Baseline peripheral blood eosinophil count < 300 cells/μL


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.144  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
4.37


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.5  
upper limit 
10.24  
Statistical analysis title 
Statistical analysis 24  
Statistical analysis description 
Baseline peripheral blood eosinophil count < 300 cells/μ


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.804  
Method 
Baseline peripheral blood eosinophil cou  
Parameter type 
Difference of LSmean  
Point estimate 
0.72


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
5.01  
upper limit 
6.46  
Statistical analysis title 
Statistical analysis 25  
Statistical analysis description 
Baseline FEV1 reversibility >= 12%


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.029  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
11.19


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.15  
upper limit 
21.23  
Statistical analysis title 
Statistical analysis 26  
Statistical analysis description 
Baseline FEV1 reversibility >= 12%


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.887  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.72


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
9.19  
upper limit 
10.62  
Statistical analysis title 
Statistical analysis 27  
Statistical analysis description 
Baseline FEV1 reversibility < 12%


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.002  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
7.67


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.76  
upper limit 
12.59  
Statistical analysis title 
Statistical analysis 28  
Statistical analysis description 
Baseline FEV1 reversibility < 12%


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.268  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
2.79


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.15  
upper limit 
7.74  
Statistical analysis title 
Statistical analysis 29  
Statistical analysis description 
2 asthma exacerbations in the past year


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.003  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
7.82


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.64  
upper limit 
13.01  
Statistical analysis title 
Statistical analysis 30  
Statistical analysis description 
2 asthma exacerbations in the past year


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.361  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
2.42


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.78  
upper limit 
7.62  
Statistical analysis title 
Statistical analysis 31  
Statistical analysis description 
> 2 but < 6 asthma exacerbations in the past year


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.185  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
6.34


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.06  
upper limit 
15.75  
Statistical analysis title 
Statistical analysis 32  
Statistical analysis description 
> 2 but < 6 asthma exacerbations in the past year


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.986  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.08


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
9.5  
upper limit 
9.34  
Statistical analysis title 
Statistical analysis 33  
Statistical analysis description 
Chronic OCS use


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.912  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.87


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
14.7  
upper limit 
16.44  
Statistical analysis title 
Statistical analysis 34  
Statistical analysis description 
Chronic OCS use


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.86  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
1.46


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
17.76  
upper limit 
14.84  
Statistical analysis title 
Statistical analysis 35  
Statistical analysis description 
Without chronic OCS use


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.002  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
7.56


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.76  
upper limit 
12.36  
Statistical analysis title 
Statistical analysis 36  
Statistical analysis description 
Without chronic OCS use


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.601  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
1.28


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.51  
upper limit 
6.06 


End point title 
Change from Baseline in Mean ACQ6 Scores at Week 53 in Subgroups ^{[71]}  
End point description 
Asthma Control Questionnaire (ACQ) is a participantreported questionnaire to assess the asthma control with 6 items assessing nighttime waking, symptoms on waking, activity limitation, shortness of breath, wheeze, and rescue shortacting beta agonist use. Each item was rated on a 7point Likert scale ranging from 0 (no impairment) to 6 (maximum impairment). Overall ACQ score was the mean of the 6 item scores with a score range of 0 (well controlled) to 6 (extremely poor controlled). Data collected on Day 1 prior to dosing was considered as baseline. Results were reported for overall ACQ score. Data were summarized together for ‘Placebo, Q2W’ and ‘Placebo, Q2/4W’ arms. The ITT population included all participants who were randomized into the study. Here "n" signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.


End point type 
Secondary


End point timeframe 
Week 1 up to Week 53


Notes [71]  The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint was reporting data for total number of participants of both the placebo reporting group, hence not reporting statistics for all the arms in the baseline period. 



Statistical analysis title 
Statistical analysis 1  
Statistical analysis description 
Baseline serum periostin >= median


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.145  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.24


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.57  
upper limit 
0.08  
Statistical analysis title 
Statistical analysis 2  
Statistical analysis description 
Baseline serum periostin >= median


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.759  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.05


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.28  
upper limit 
0.38  
Statistical analysis title 
Statistical analysis 3  
Statistical analysis description 
Baseline serum periostin < median


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.936  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.01


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.38  
upper limit 
0.35  
Statistical analysis title 
Statistical analysis 4  
Statistical analysis description 
Baseline serum periostin < median


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.127  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.28


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.64  
upper limit 
0.08  
Statistical analysis title 
Statistical analysis 5  
Statistical analysis description 
Baseline serum periostin>= 25th percentile


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.343  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.13


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.41  
upper limit 
0.14  
Statistical analysis title 
Statistical analysis 6  
Statistical analysis description 
Baseline serum periostin>= 25th percentile


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.928  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.01


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.29  
upper limit 
0.27  
Statistical analysis title 
Statistical analysis 7  
Statistical analysis description 
Baseline serum periostin < 25th percentile


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.374  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.23


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.74  
upper limit 
0.28  
Statistical analysis title 
Statistical analysis 8  
Statistical analysis description 
Baseline serum periostin < 25th percentile


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.259  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.29


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.81  
upper limit 
0.22  
Statistical analysis title 
Statistical analysis 9  
Statistical analysis description 
Baseline serum periostin >= 75th percentile


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.127  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.37


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.84  
upper limit 
0.11  
Statistical analysis title 
Statistical analysis 10  
Statistical analysis description 
Baseline serum periostin >= 75th percentile


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.775  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.07


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.56  
upper limit 
0.42  
Statistical analysis title 
Statistical analysis 11  
Statistical analysis description 
Baseline serum periostin < 75th percentile


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.512  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.38  
upper limit 
0.19  
Statistical analysis title 
Statistical analysis 12  
Statistical analysis description 
Baseline serum periostin < 75th percentile


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.404  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.12


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.4  
upper limit 
0.16  
Statistical analysis title 
Statistical analysis 13  
Statistical analysis description 
Th2 high


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.181  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.24


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.59  
upper limit 
0.11  
Statistical analysis title 
Statistical analysis 14  
Statistical analysis description 
Th2 high


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.161  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.25


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.6  
upper limit 
0.1  
Statistical analysis title 
Statistical analysis 15  
Statistical analysis description 
Th2 low


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.54  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.11


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.47  
upper limit 
0.25  
Statistical analysis title 
Statistical analysis 16  
Statistical analysis description 
Th2 low


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.674  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.07


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.42  
upper limit 
0.27  
Statistical analysis title 
Statistical analysis 17  
Statistical analysis description 
Baseline peripheral blood eosinophil count >= 150 cells/μL


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.154  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.22


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.52  
upper limit 
0.08  
Statistical analysis title 
Statistical analysis 18  
Statistical analysis description 
Baseline peripheral blood eosinophil count >= 150 cells/μ


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.271  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.17


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.48  
upper limit 
0.13  
Statistical analysis title 
Statistical analysis 19  
Statistical analysis description 
Baseline peripheral blood eosinophil count < 150 cells/μL


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.725  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.08


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.51  
upper limit 
0.36  
Statistical analysis title 
Statistical analysis 20  
Statistical analysis description 
Baseline peripheral blood eosinophil count < 150 cells/μL


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.559  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.12


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.53  
upper limit 
0.28  
Statistical analysis title 
Statistical analysis 21  
Statistical analysis description 
Baseline peripheral blood eosinophil count >= 300 cells/μL


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.019  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.47


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.87  
upper limit 
0.08  
Statistical analysis title 
Statistical analysis 22  
Statistical analysis description 
Baseline peripheral blood eosinophil count >= 300 cells/μL


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.348  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.61  
upper limit 
0.21  
Statistical analysis title 
Statistical analysis 23  
Statistical analysis description 
Baseline peripheral blood eosinophil count < 300 cells/μL


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.855  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.03


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.35  
upper limit 
0.29  
Statistical analysis title 
Statistical analysis 24  
Statistical analysis description 
Baseline peripheral blood eosinophil count < 300 cells/μL


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.203  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.5  
upper limit 
0.11  
Statistical analysis title 
Statistical analysis 25  
Statistical analysis description 
Baseline FEV1 reversibility >= 12%


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.055  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.44


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.89  
upper limit 
0.01  
Statistical analysis title 
Statistical analysis 26  
Statistical analysis description 
Baseline FEV1 reversibility >= 12%


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.104  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.37


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.82  
upper limit 
0.08  
Statistical analysis title 
Statistical analysis 27  
Statistical analysis description 
Baseline FEV1 reversibility < 12%


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.652  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.07


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.37  
upper limit 
0.23  
Statistical analysis title 
Statistical analysis 28  
Statistical analysis description 
Baseline FEV1 reversibility < 12%


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.905  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.02


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.28  
upper limit 
0.32  
Statistical analysis title 
Statistical analysis 29  
Statistical analysis description 
2 asthma exacerbations in the past year


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.198  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.19


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.49  
upper limit 
0.1  
Statistical analysis title 
Statistical analysis 30  
Statistical analysis description 
2 asthma exacerbations in the past year


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.226  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.18


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.47  
upper limit 
0.11  
Statistical analysis title 
Statistical analysis 31  
Statistical analysis description 
> 2 but < 6 asthma exacerbations in the past year


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.513  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.14


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.56  
upper limit 
0.28  
Statistical analysis title 
Statistical analysis 32  
Statistical analysis description 
> 2 but < 6 asthma exacerbations in the past year


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.974  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.01


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.43  
upper limit 
0.42  
Statistical analysis title 
Statistical analysis 33  
Statistical analysis description 
Chronic OCS use


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.226  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.37


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.97  
upper limit 
0.23  
Statistical analysis title 
Statistical analysis 34  
Statistical analysis description 
Chronic OCS use


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.613  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.15


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.44  
upper limit 
0.75  
Statistical analysis title 
Statistical analysis 35  
Statistical analysis description 
Without chronic OCS use


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.198  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.17


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.43  
upper limit 
0.09  
Statistical analysis title 
Statistical analysis 36  
Statistical analysis description 
Without chronic OCS use


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.165  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.19


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.45  
upper limit 
0.08 


End point title 
Change from Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups ^{[72]}  
End point description 
AQLQ: a 32item questionnaire evaluating quality of life of participants with asthma including 4 domains (symptoms, activity limitations, emotional function, and environmental stimuli). Participants were asked to recall their experiences during the previous 2 weeks and to score each of the 32 questions on a 7point scale ranging from 7 (no impairment) to 1 (severe impairment). The overall score was calculated as the mean response to all questions. The 4 domain scores were the means of the responses to the questions in each of the domains. Overall AQLQ score and 4 domain scores ranged from 7 (no impairment) to 1 (severe impairment). Data were summarized together for ‘Placebo, Q2W’ and ‘Placebo, Q2/4W’ arms. The ITT population included all participants who were randomized into the study. Here "n" signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.


End point type 
Secondary


End point timeframe 
Week 1 up to Week 53


Notes [72]  The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint was reporting data for total number of participants of both the placebo reporting group, hence not reporting statistics for all the arms in the baseline period. 



Statistical analysis title 
Statistical analysis 1  
Statistical analysis description 
Baseline serum periostin >= median


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.211  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.23


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.13  
upper limit 
0.6  
Statistical analysis title 
Statistical analysis 2  
Statistical analysis description 
Baseline serum periostin >= median


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.397  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.16


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.21  
upper limit 
0.53  
Statistical analysis title 
Statistical analysis 3  
Statistical analysis description 
Baseline serum periostin < median


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.315  
Method 
Repeated Measure Model  
Parameter type 
Difference of LSmean  
Point estimate 
0.19


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.18  
upper limit 
0.56  
Statistical analysis title 
Statistical analysis 4  
Statistical analysis description 
Baseline serum periostin < median


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.166  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.26


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.11  
upper limit 
0.63  
Statistical analysis title 
Statistical analysis 5  
Statistical analysis description 
Baseline serum periostin >= 25th percentile


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.262  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.17


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.13  
upper limit 
0.47  
Statistical analysis title 
Statistical analysis 6  
Statistical analysis description 
Baseline serum periostin >= 25th percentile


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.379  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.14


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.17  
upper limit 
0.44  
Statistical analysis title 
Statistical analysis 7  
Statistical analysis description 
Baseline serum periostin < 25th percentile


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.387  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.25


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.32  
upper limit 
0.81  
Statistical analysis title 
Statistical analysis 8  
Statistical analysis description 
Baseline serum periostin < 25th percentile


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.303  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.29


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.26  
upper limit 
0.84  
Statistical analysis title 
Statistical analysis 9  
Statistical analysis description 
Baseline serum periostin >=75th percentile


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.127  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.37


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.84  
upper limit 
0.11  
Statistical analysis title 
Statistical analysis 10  
Statistical analysis description 
Baseline serum periostin >=75th percentile


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.775  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.07


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.56  
upper limit 
0.42  
Statistical analysis title 
Statistical analysis 11  
Statistical analysis description 
Baseline serum periostin < 75th percentile


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.512  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.38  
upper limit 
0.19  
Statistical analysis title 
Statistical analysis 12  
Statistical analysis description 
Baseline serum periostin < 75th percentile


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.404  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.12


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.4  
upper limit 
0.16  
Statistical analysis title 
Statistical analysis 13  
Statistical analysis description 
Th2 high


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.102  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.31


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.06  
upper limit 
0.69  
Statistical analysis title 
Statistical analysis 14  
Statistical analysis description 
Th2 high


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.116  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.08  
upper limit 
0.68  
Statistical analysis title 
Statistical analysis 15  
Statistical analysis description 
Th2 low


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.54  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.11


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.47  
upper limit 
0.25  
Statistical analysis title 
Statistical analysis 16  
Statistical analysis description 
Th2 low


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.674  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.07


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.42  
upper limit 
0.27  
Statistical analysis title 
Statistical analysis 17  
Statistical analysis description 
Baseline peripheral blood eosinophil count >=150 cells/μL


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.295  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.17


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.15  
upper limit 
0.49  
Statistical analysis title 
Statistical analysis 18  
Statistical analysis description 
Baseline peripheral blood eosinophil count >=150 cells/μL


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.342  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.16


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.17  
upper limit 
0.49  
Statistical analysis title 
Statistical analysis 19  
Statistical analysis description 
Baseline peripheral blood eosinophil count < 150 cells/μL


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.406  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.18


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.24  
upper limit 
0.6  
Statistical analysis title 
Statistical analysis 20  
Statistical analysis description 
Baseline peripheral blood eosinophil count < 150 cells/μL


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.069  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.38


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.03  
upper limit 
0.79  
Statistical analysis title 
Statistical analysis 21  
Statistical analysis description 
Baseline peripheral blood eosinophil count >= 300 cells/μL


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.371  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.19


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.23  
upper limit 
0.62  
Statistical analysis title 
Statistical analysis 22  
Statistical analysis description 
Baseline peripheral blood eosinophil count >= 300 cells/μL


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.766  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.07


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.37  
upper limit 
0.51  
Statistical analysis title 
Statistical analysis 23  
Statistical analysis description 
Baseline peripheral blood eosinophil count < 300 cells/μL


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.147  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.24


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.09  
upper limit 
0.57  
Statistical analysis title 
Statistical analysis 24  
Statistical analysis description 
Baseline peripheral blood eosinophil count < 300 cells/μL


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.031  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.35


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.03  
upper limit 
0.68  
Statistical analysis title 
Statistical analysis 25  
Statistical analysis description 
Baseline FEV1 reversibility >= 12%


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.02  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.59


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.1  
upper limit 
1.09  
Statistical analysis title 
Statistical analysis 26  
Statistical analysis description 
Baseline FEV1 reversibility >= 12%


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.226  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.29


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.18  
upper limit 
0.77  
Statistical analysis title 
Statistical analysis 27  
Statistical analysis description 
Baseline FEV1 reversibility < 12%


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.964  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.01


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.31  
upper limit 
0.33  
Statistical analysis title 
Statistical analysis 28  
Statistical analysis description 
Baseline FEV1 reversibility < 12%


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.533  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.22  
upper limit 
0.42  
Statistical analysis title 
Statistical analysis 29  
Statistical analysis description 
2 asthma exacerbations in the past year


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.292  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.17


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.15  
upper limit 
0.5  
Statistical analysis title 
Statistical analysis 30  
Statistical analysis description 
2 asthma exacerbations in the past year


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.097  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.27


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.05  
upper limit 
0.59  
Statistical analysis title 
Statistical analysis 31  
Statistical analysis description 
> 2 but < 6 asthma exacerbations in the past year


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.26  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.24


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.18  
upper limit 
0.67  
Statistical analysis title 
Statistical analysis 32  
Statistical analysis description 
> 2 but < 6 asthma exacerbations in the past year


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.648  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.33  
upper limit 
0.53  
Statistical analysis title 
Statistical analysis 33  
Statistical analysis description 
Chronic OCS use


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.398  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.28


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.37  
upper limit 
0.93  
Statistical analysis title 
Statistical analysis 34  
Statistical analysis description 
Chronic OCS use


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.327  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.32


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.95  
upper limit 
0.32  
Statistical analysis title 
Statistical analysis 35  
Statistical analysis description 
Without chronic OCS use


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.105  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.23


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.05  
upper limit 
0.52  
Statistical analysis title 
Statistical analysis 36  
Statistical analysis description 
Without chronic OCS use


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.03  
Method 
Repeated measure model  
Parameter type 
Difference of LSmean  
Point estimate 
0.31


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.03  
upper limit 
0.6 


End point title 
Annual Asthma Exacerbation Rate (AER) by Atopic Asthma Status ^{[73]}  
End point description 
Annualized AER was assessed based on AER data up to Week 53. An asthma exacerbation defined as a progressive increase of asthma symptoms that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 consecutive days as prescribed; or 2) participant initiation of systemic corticosteroids for a duration of at least 3 consecutive days. AER was evaluated by subgroup Atopic and Nonatopic asthma status. Data were summarized together for ‘Placebo, Q2W’ and ‘Placebo, Q2/4W’ arms. The ITT population included all participants who were randomized into the study. Here "n" signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.


End point type 
Secondary


End point timeframe 
Week 1 up to Week 53


Notes [73]  The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint was reporting data for total number of participants of both the placebo reporting group, hence not reporting statistics for all the arms in the baseline period. 



Statistical analysis title 
Statistical analysis 1  
Statistical analysis description 
The 95% CI for rate ratio were estimated from the Poisson regression with treatment group, age, gender, number of exacerbations in past year (2 vs >2 but =<6), atopic asthma status, chronic OCS use and geographical region as the covariates.


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other ^{[74]}  
Pvalue 
= 0.803  
Method 
Poisson regression  
Parameter type 
Rate Ratio (RR)  
Point estimate 
0.95


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.62  
upper limit 
1.44  
Notes [74]  Placebo Total, Tralokinumab 300 mg, Q2W  Cohort 1  Atopic Asthma 

Statistical analysis title 
Statistical analysis 2  
Statistical analysis description 
The 95% CI for rate ratio were estimated from the Poisson regression with treatment group, age, gender, number of exacerbations in past year (2 vs >2 but =<6), atopic asthma status, chronic OCS use and geographical region as the covariates.


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other ^{[75]}  
Pvalue 
= 0.457  
Method 
Poisson regression  
Parameter type 
Rate Ratio (RR)  
Point estimate 
0.83


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.52  
upper limit 
1.35  
Notes [75]  Placebo Total, Tralokinumab 300 mg, Q2/4W  Cohort 2  Atopic Asthma 

Statistical analysis title 
Statistical analysis 3  
Statistical analysis description 
The 95% CI for rate ratio were estimated from the Poisson regression with treatment group, age, gender, number of exacerbations in past year (2 vs >2 but =<6), atopic asthma status, chronic OCS use and geographical region as the covariates.


Comparison groups 
Tralokinumab 300 mg, Q2W  Cohort 1 v Placebo Total


Number of subjects included in analysis 
301


Analysis specification 
Prespecified


Analysis type 
other ^{[76]}  
Pvalue 
= 0.25  
Method 
Poisson regression  
Parameter type 
Rate Ratio (RR)  
Point estimate 
0.71


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.4  
upper limit 
1.27  
Notes [76]  Placebo Total, Tralokinumab 300 mg, Q2W  Cohort 1  Nonatopic asthma 

Statistical analysis title 
Statistical analysis 4  
Statistical analysis description 
The 95% CI for rate ratio were estimated from the Poisson regression with treatment group, age, gender, number of exacerbations in past year (2 vs >2 but =<6), atopic asthma status, chronic OCS use and geographical region as the covariates.


Comparison groups 
Tralokinumab 300 mg, Q2/4W  Cohort 2 v Placebo Total


Number of subjects included in analysis 
302


Analysis specification 
Prespecified


Analysis type 
other ^{[77]}  
Pvalue 
= 0.794  
Method 
Poisson regression  
Parameter type 
Rate Ratio (RR)  
Point estimate 
1.07


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.66  
upper limit 
1.74  
Notes [77]  Placebo Total, Tralokinumab 300 mg, Q2/4W  Cohort 2  Nonatopic asthma 