Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Evaluation of Dupilumab in Patients With Severe Steroid Dependent Asthma (VENTURE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02528214
Recruitment Status : Completed
First Posted : August 19, 2015
Results First Posted : October 23, 2018
Last Update Posted : October 1, 2019
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Asthma
Interventions Drug: Dupilumab
Drug: Placebo
Drug: Oral corticosteroid therapy (prednisone/prednisolone)
Drug: Inhaled corticosteroid (ICS) therapy
Drug: Albuterol/Salbutamol
Drug: Levalbuterol/Levosalbutamol
Enrollment 210
Recruitment Details The study was conducted at 68 centers in 17 countries. A total of 390 participants were screened between October 2015 & April 2017, of which,210 were randomized & treated. 180 participants were screen failures mainly due to exclusion criteria met & inclusion criteria not met. Assignment was done by Interactive Voice/Web Response System(IVRS/IWRS).
Pre-assignment Details Screening period included an OCS optimization phase (up to 10 weeks) where participants using OCS other than prednisone/prednisolone switched to these OCS. At the end of period, participants were randomized in 1:1 ratio (dupilumab:placebo).Randomization was stratified by optimized OCS dose (=<10 & >10 mg/day) at randomization visit & by country.
Arm/Group Title Placebo q2w Dupilumab 300 mg q2w
Hide Arm/Group Description 2 subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1, followed by a single injection every 2 weeks (q2w) for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20. 2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.
Period Title: Overall Study
Started 107 103
Treated 107 103
Completed 107 100
Not Completed 0 3
Reason Not Completed
Protocol Violation             0             1
Adverse Event             0             1
Other than specified above             0             1
Arm/Group Title Placebo q2w Dupilumab 300 mg q2w Total
Hide Arm/Group Description 2 subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1, followed by a single injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20. 2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20. Total of all reporting groups
Overall Number of Baseline Participants 107 103 210
Hide Baseline Analysis Population Description
Baseline population included all randomized participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 107 participants 103 participants 210 participants
50.7  (12.8) 51.9  (12.5) 51.3  (12.6)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 107 participants 103 participants 210 participants
<18 years
2
   1.9%
1
   1.0%
3
   1.4%
Between 18 and 64 years
88
  82.2%
91
  88.3%
179
  85.2%
>=65 years
17
  15.9%
11
  10.7%
28
  13.3%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 107 participants 103 participants 210 participants
Female
65
  60.7%
62
  60.2%
127
  60.5%
Male
42
  39.3%
41
  39.8%
83
  39.5%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 107 participants 103 participants 210 participants
Hispanic or Latino
22
  20.6%
23
  22.3%
45
  21.4%
Not Hispanic or Latino
85
  79.4%
80
  77.7%
165
  78.6%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 107 participants 103 participants 210 participants
Caucasian/White
100
  93.5%
97
  94.2%
197
  93.8%
Black/of African descent
1
   0.9%
4
   3.9%
5
   2.4%
Asian/Oriental
2
   1.9%
0
   0.0%
2
   1.0%
American Indian or Alaska Native
2
   1.9%
0
   0.0%
2
   1.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
1
   1.0%
1
   0.5%
Other
2
   1.9%
1
   1.0%
3
   1.4%
Baseline Blood Eosinophil Count  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 107 participants 103 participants 210 participants
<0.15 Giga/L
38
  35.5%
22
  21.4%
60
  28.6%
>=0.15 - <0.3 Giga/L
28
  26.2%
33
  32.0%
61
  29.0%
>=0.3 Giga/L
41
  38.3%
48
  46.6%
89
  42.4%
Baseline Optimized Daily OCS Dose   [1] 
Mean (Standard Deviation)
Unit of measure:  Mg/day
Number Analyzed 107 participants 103 participants 210 participants
11.75  (6.31) 10.75  (5.9) 11.26  (6.12)
[1]
Measure Description: During screening period and before randomization, OCS dose was adjusted in each participant to achieve the lowest OCS dose, also known as optimized dose, required for management of participant's asthma.Participants using OCS medications other than prednisone/prednisolone were switched to either of these corticosteroids at a dose clinically comparable to their current stable OCS dose. To optimize the OCS dose, investigators were instructed to adjust the OCS dose weekly according to a pre-specified titration schedule, based on changes in participant's asthma control, and their clinical judgment.
Daily OCS Dose at Visit 1 (i.e. preoptimization)  
Mean (Standard Deviation)
Unit of measure:  Mg/day
Number Analyzed 107 participants 103 participants 210 participants
11.83  (6.02) 11.79  (6.4) 11.81  (6.20)
1.Primary Outcome
Title Percentage Reduction From Baseline in Oral Corticosteroids (OCS) Dose at Week 24 While Maintaining Asthma Control
Hide Description Percentage reduction of OCS dose was calculated as (optimized OCS dose [mg/day] at baseline - final OCS dose at Week 24)/optimized OCS dose at baseline x 100. Result is presented as Least Squares Mean (Standard Error) percentage reduction from baseline derived from ANCOVA model with missing data multiply imputed.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on intent-to-treat (ITT) population which included randomized population analysed according to the treatment group allocated by randomization regardless of whether the treatment kit was used or not.
Arm/Group Title Placebo q2w Dupilumab 300 mg q2w
Hide Arm/Group Description:
2 subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1, followed by a single injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.
Overall Number of Participants Analyzed 107 103
Least Squares Mean (Standard Error)
Unit of Measure: Percentage reduction from baseline
41.85  (4.57) 70.09  (4.90)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo q2w, Dupilumab 300 mg q2w
Comments The outcome measure was analyzed using analysis of covariance (ANCOVA) model which included percentage reduction of OCS dose at Week 24 as the response variable, and treatment group, baseline eosinophil level, optimized OCS dose at baseline, region as covariates. Missing data was imputed using a pattern mixture model by multiple imputation approach.
Type of Statistical Test Superiority
Comments A hierarchical testing procedure was used to control the overall type I error. Testing was then performed sequentially in order the outcome measure are reported and continued when previous outcome measure was statistically significant at two-sided 0.05. Only the primary and the first 4 secondary outcome measures were included in the procedure.
Statistical Test of Hypothesis P-Value < 0.0001
Comments Threshold for significance at two-sided 0.05 level.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square (LS) Mean Difference
Estimated Value 28.24
Confidence Interval (2-Sided) 95%
15.81 to 40.67
Estimation Comments LS mean difference represents reduction difference i.e. dupilumab - placebo.
2.Primary Outcome
Title Supplementary Presentation of Primary Outcome Measure Data: Median Percentage Reduction From Baseline in Oral Corticosteroids Dose at Week 24 While Maintaining Asthma Control
Hide Description The Primary Outcome Measure (Percentage Reduction From Baseline in Oral Corticosteroids Dose at Week 24 While Maintaining Asthma Control) is summarized above, as LS Mean (SE). Table below provides a supplementary presentation of the Primary Outcome Measure data; result is presented as median (inter-quartile range). Percentage reduction of OCS dose was calculated as (optimized OCS dose [mg/day] at baseline - final OCS dose at Week 24)/optimized OCS dose at baseline x 100.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population included ITT patients with available data.
Arm/Group Title Placebo q2w Dupilumab 300 mg q2w
Hide Arm/Group Description:
2 subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1, followed by a single injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.
Overall Number of Participants Analyzed 106 101
Median (Inter-Quartile Range)
Unit of Measure: percentage reduction from baseline
50.0
(0 to 100.0)
100.0
(62.5 to 100.0)
3.Secondary Outcome
Title Percentage of Participants Achieving >= 50% Reduction in Oral Corticosteroids Dose at Week 24 While Maintaining Asthma Control
Hide Description Participants were classified according to the binary status of whether or not the 50% OCS dose reduction criterion was achieved at week 24.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population.
Arm/Group Title Placebo q2w Dupilumab 300 mg q2w
Hide Arm/Group Description:
2 subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1, followed by a single injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.
Overall Number of Participants Analyzed 107 103
Measure Type: Number
Unit of Measure: percentage of participants
53.3 79.6
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo q2w, Dupilumab 300 mg q2w
Comments The outcome measure was analyzed using a logistic regression model. The model included the binary status of whether or not a participant achieved the 50% OCS dose reduction criterion as the response variable, and treatment groups, optimized OCS dose at baseline, regions, and baseline eosinophil level subgroups as covariates. Missing data was imputed by using a pattern mixture model by multiple imputation approach.
Type of Statistical Test Superiority
Comments Testing was performed according to the hierarchical testing procedure (continued only if previous endpoints were statistically significant).
Statistical Test of Hypothesis P-Value < 0.0001
Comments Threshold for significance at 0.05.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.98
Confidence Interval (2-Sided) 95%
2.06 to 7.67
Estimation Comments Dupilumab 300 mg q2w v Placebo q2w
4.Secondary Outcome
Title Percentage of Participants Achieving a Reduction in Oral Corticosteroids Dose to <5 mg/Day at Week 24 While Maintaining Asthma Control
Hide Description Participants were classified according to the binary status of whether or not the reduction of OCS dose to <5 mg/day was achieved at Week 24.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population.
Arm/Group Title Placebo q2w Dupilumab 300 mg q2w
Hide Arm/Group Description:
2 subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1, followed by a single injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.
Overall Number of Participants Analyzed 107 103
Measure Type: Number
Unit of Measure: percentage of participants
37.4 71.8
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo q2w, Dupilumab 300 mg q2w
Comments The outcome measure was analyzed using a logistic regression model. The model included the binary status of whether or not a participant achieved a reduction of OCS dose to <5 mg/day at Week 24 as the response variable, treatment groups, optimized OCS dose at baseline, regions, and baseline eosinophil level subgroups as covariates. Missing data was imputed by using a pattern mixture model by multiple imputation approach.
Type of Statistical Test Superiority
Comments Testing was performed according to the hierarchical testing procedure (continued only if previous endpoints were statistically significant).
Statistical Test of Hypothesis P-Value < 0.0001
Comments Threshold for significance at 0.05.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.48
Confidence Interval (2-Sided) 95%
2.39 to 8.39
Estimation Comments Dupilumab 300 mg q2w v Placebo q2w
5.Secondary Outcome
Title Percentage of Participants Achieving Maximum Possible Reduction in Oral Corticosteroids Dose Per Protocol at Week 24 While Maintaining Asthma Control
Hide Description For all participants except those with baseline OCS dose at 35 mg/day, the maximum possible reduction corresponds to reduction to 0 mg/day (no longer requiring OCS). For participants starting with 35 mg/day at baseline, the maximum possible reduction is 32.5 mg/day (i.e. minimum dose per protocol is 2.5 mg).
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population.
Arm/Group Title Placebo q2w Dupilumab 300 mg q2w
Hide Arm/Group Description:
2 subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1, followed by a single injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.
Overall Number of Participants Analyzed 107 103
Measure Type: Number
Unit of Measure: percentage of participants
29.9 52.4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo q2w, Dupilumab 300 mg q2w
Comments The outcome was analyzed using a logistic regression model. The model included binary status of whether or not a participant achieved their maximum possible reduction of OCS dose per protocol at Week 24 as the response variable, treatment groups, optimized OCS dose at baseline, regions, and baseline eosinophil level subgroups as covariates. Missing data was imputed by using a pattern mixture model by multiple imputation approach.
Type of Statistical Test Superiority
Comments Testing was performed according to the hierarchical testing procedure (continued only if previous endpoints were statistically significant).
Statistical Test of Hypothesis P-Value 0.0024
Comments Threshold for significance at 0.05.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.57
Confidence Interval (2-Sided) 95%
1.4 to 4.73
Estimation Comments Dupilumab 300 mg q2w v Placebo q2w
6.Secondary Outcome
Title Percentage of Participants Who No Longer Required Oral Corticosteroids Dose at Week 24 While Maintaining Asthma Control
Hide Description Participants were classified according to the binary status of whether or not the participant still required OCS at Week 24 while maintaining asthma control.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population with baseline OCS dose less than or equal to 30 mg/day.
Arm/Group Title Placebo q2w Dupilumab 300 mg q2w
Hide Arm/Group Description:
2 subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1, followed by a single injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until week 20.
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.
Overall Number of Participants Analyzed 106 103
Measure Type: Number
Unit of Measure: percentage of participants
29.2 52.4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo q2w, Dupilumab 300 mg q2w
Comments The outcome measure was analyzed using a logistic regression model. The model included the binary status of whether or not a participant no longer required OCS at Week 24 as the response variable, and treatment groups, optimized OCS dose at baseline, regions, and baseline eosinophil level subgroups as covariates. Missing data was imputed using a pattern mixture model by multiple imputation approach.
Type of Statistical Test Superiority
Comments Testing was performed according to the hierarchical testing procedure (continued only if previous endpoints were statistically significant).
Statistical Test of Hypothesis P-Value 0.0015
Comments Threshold for significance at 0.05.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.74
Confidence Interval (2-Sided) 95%
1.47 to 5.1
Estimation Comments Dupilumab 300 mg q2w v Placebo q2w
7.Secondary Outcome
Title Absolute Reduction From Baseline in Oral Corticosteroids Dose at Week 24 While Maintaining Asthma Control
Hide Description Absolute reduction was calculated by subtracting Week 24 value from baseline value.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population but not included in the hierarchical testing procedure. Here, "number analyzed"= participants with available data for specified categories.
Arm/Group Title Placebo q2w Dupilumab 300 mg q2w
Hide Arm/Group Description:
2 subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1, followed by a single injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.
Overall Number of Participants Analyzed 107 103
Mean (Standard Deviation)
Unit of Measure: mg/day
Baseline Number Analyzed 107 participants 103 participants
11.75  (6.31) 10.75  (5.90)
Week 24 Number Analyzed 106 participants 101 participants
6.32  (6.75) 3.13  (5.44)
Absolute reduction at Week 24 Number Analyzed 106 participants 101 participants
5.45  (6.80) 7.66  (6.10)
8.Other Pre-specified Outcome
Title Annualized Rate of Severe Exacerbation Events During The 24-Week Treatment Period
Hide Description A severe asthma exacerbation event was defined as a deterioration of asthma during the 24-week treatment period requiring: use of systemic corticosteroids for >=3 days (at least double the dose currently used); and/or hospitalization related to asthma symptoms or emergency room visit because of asthma requiring intervention with a systemic corticosteroid treatment. Annualized event rate was the total number of exacerbations that occurred during the treatment period divided by the total number of participant-years treated.
Time Frame Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed ITT population.
Arm/Group Title Placebo q2w Dupilumab 300 mg q2w
Hide Arm/Group Description:
2 subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1, followed by a single injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.
Overall Number of Participants Analyzed 107 103
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Exacerbation per participant-year
1.597
(1.248 to 2.043)
0.649
(0.442 to 0.955)
9.Other Pre-specified Outcome
Title Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) at Weeks 12 and 24
Hide Description FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer.
Time Frame Baseline, Week 12 and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population. Here, "number analyzed"= participants with available data for specified categories.
Arm/Group Title Placebo q2w Dupilumab 300 mg q2w
Hide Arm/Group Description:
2 subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1, followed by a single injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.
Overall Number of Participants Analyzed 107 103
Mean (Standard Deviation)
Unit of Measure: liter
Baseline Number Analyzed 107 participants 103 participants
1.63  (0.61) 1.53  (0.53)
Week 12 Number Analyzed 105 participants 99 participants
1.68  (0.61) 1.82  (0.63)
Change at Week 12 Number Analyzed 105 participants 99 participants
0.06  (0.50) 0.29  (0.43)
Week 24 Number Analyzed 104 participants 97 participants
1.63  (0.65) 1.84  (0.60)
Change at Week 24 Number Analyzed 104 participants 97 participants
0.00  (0.51) 0.29  (0.46)
10.Other Pre-specified Outcome
Title Change From Baseline in Asthma Control Questionnaire 5-Question Version (ACQ-5) Score at Weeks 2, 4, 8, 12, 16, 20, and 24
Hide Description The ACQ-5 has 5 questions, reflecting top-scoring 5 asthma symptoms: woken at night by symptoms, wake in mornings with symptoms, limitation of daily activities, shortness of breath and wheeze. Participants were asked to recall how their asthma had been during previous week and to respond to each of 5 symptom questions on a 7-point scale ranged from 0 (no impairment) to 6 (maximum impairment). ACQ-5 total score was mean of scores of all 5 questions and, therefore, ranged from 0 (totally controlled) to 6 (severely uncontrolled). Higher score indicated lower asthma control.
Time Frame Baseline and at Weeks 2, 4, 8, 12, 16, 20, and 24
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population. Here, number analyzed = participants with available data for specified categories.
Arm/Group Title Placebo q2w Dupilumab 300 mg q2w
Hide Arm/Group Description:
2 subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1, followed by a single injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.
Overall Number of Participants Analyzed 107 103
Mean (Standard Deviation)
Unit of Measure: score on a scale
Change at Week 2 Number Analyzed 102 participants 95 participants
-0.18  (0.67) -0.49  (0.86)
Change at Week 4 Number Analyzed 103 participants 93 participants
-0.36  (0.81) -0.61  (1.01)
Change at Week 8 Number Analyzed 104 participants 96 participants
-0.39  (1.13) -0.68  (1.06)
Change at Week 12 Number Analyzed 101 participants 96 participants
-0.54  (1.17) -0.92  (1.09)
Change at Week 16 Number Analyzed 104 participants 95 participants
-0.57  (1.05) -0.87  (1.18)
Change at Week 20 Number Analyzed 102 participants 97 participants
-0.53  (1.09) -0.83  (1.19)
Change at Week 24 Number Analyzed 99 participants 96 participants
-0.57  (1.19) -0.94  (1.22)
11.Other Pre-specified Outcome
Title Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Global Score at Week 12 and Week 24
Hide Description AQLQ is a disease-specific, self-administered quality of life questionnaire designed to measure functional impairments that were most important to participants with asthma. AQLQ comprised of 32 items in 4 domains: symptoms (12 items), activity limitation (11 items), emotional function (5 items), environmental stimuli (4 items). Each item was scored on a 7-point likert scale (1=maximal impairment, 7=no impairment). The 32 items of the questionnaire were averaged to produce one overall quality of life score ranging from 1 (severely impaired) to 7 (not impaired at all). Higher scores indicate better quality of life.
Time Frame Baseline, Week 12 and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population. Here, number analyzed = participants with available data for specified categories.
Arm/Group Title Placebo q2w Dupilumab 300 mg q2w
Hide Arm/Group Description:
2 subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1, followed by a single injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.
Overall Number of Participants Analyzed 107 103
Mean (Standard Deviation)
Unit of Measure: score on a scale
Change at Week 12 Number Analyzed 105 participants 98 participants
0.56  (1.08) 0.78  (1.09)
Change at Week 24 Number Analyzed 100 participants 98 participants
0.56  (0.97) 0.94  (1.17)
12.Other Pre-specified Outcome
Title Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions, 5 Levels (EQ-5D-5L) Scores at Week 12 and Week 24
Hide Description EQ-5D-5L is a standardized health-related quality of life questionnaire developed by EuroQol Group in order to provide a simple, generic measure of health for clinical and economic appraisal. EQ-5D consists of EQ-5D descriptive system and EQ visual analogue scale (VAS). EQ-5D descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The 5D-5L systems are converted into a single index utility score between 0 to 1, where higher score indicates a better health state. EQ-5D-5L-VAS records participant's self-rated health on a vertical VAS that allows them to indicate their health state that can range from 0 (worst imaginable) to 100 (best imaginable).
Time Frame Baseline, Week 12 and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population. Here, number analyzed = participants with available data for specified categories
Arm/Group Title Placebo q2w Dupilumab 300 mg q2w
Hide Arm/Group Description:
2 subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1, followed by a single injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.
Overall Number of Participants Analyzed 107 103
Median (Standard Deviation)
Unit of Measure: score on a scale
Single Index: Change at Week 12 Number Analyzed 105 participants 98 participants
0.04  (0.20) 0.03  (0.17)
Single Index: Change at Week 24 Number Analyzed 100 participants 98 participants
0.05  (0.18) 0.05  (0.18)
VAS Score: Change at Week 12 Number Analyzed 105 participants 98 participants
5.99  (16.85) 9.34  (18.20)
VAS Score: Change at Week 24 Number Analyzed 100 participants 98 participants
4.16  (16.74) 11.06  (17.60)
13.Other Pre-specified Outcome
Title Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Total Score at Week 12 and Week 24
Hide Description The HADS is a general scale to detect states of anxiety and depression already used and validated in asthma, which includes HADS-A and HADS-D subscales. The instrument is comprised of 14 items: 7 related to anxiety (HADS-A) and 7 to depression (HADS-D). Each item on the questionnaire is scored from 0-3. And, the total score is the sum of the scores of the 14 items ranging from 0 (no symptoms) to 42 (severe symptoms), with higher scores indicating higher anxiety/depression complains.
Time Frame Baseline, Week 12 and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population. Here, number analyzed = participants with available data for specified categories.
Arm/Group Title Placebo q2w Dupilumab 300 mg q2w
Hide Arm/Group Description:
2 subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1, followed by a single injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.
Overall Number of Participants Analyzed 107 103
Mean (Standard Deviation)
Unit of Measure: score on a scale
Change at Week 12 Number Analyzed 105 participants 98 participants
-0.75  (5.50) -2.13  (5.32)
Change at Week 24 Number Analyzed 100 participants 98 participants
-0.99  (5.36) -2.53  (5.98)
14.Other Pre-specified Outcome
Title Change From Baseline in Sino Nasal Outcome Test-22 (SNOT-22) Global Score at Week 12 and Week 24
Hide Description The SNOT-22 is a validated measure of health related quality of life in sino nasal disease. It is a 22 item questionnaire with each item assigned a score ranging from 0-5. The total score may range from 0 (no disease) -110 (worst disease), lower scores represent better health related quality of life.
Time Frame Baseline, Week 12 and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population with bilateral nasal polyposis/chronic rhinosinusitis. Here, number analyzed = participants with available data for specified categories.
Arm/Group Title Placebo q2w Dupilumab 300 mg q2w
Hide Arm/Group Description:
2 subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1, followed by a single injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.
Overall Number of Participants Analyzed 41 31
Mean (Standard Deviation)
Unit of Measure: score on a scale
Change at Week 12 Number Analyzed 38 participants 29 participants
-3.79  (21.34) -12.45  (17.10)
Change at Week 24 Number Analyzed 37 participants 27 participants
-2.46  (19.11) -14.56  (15.89)
Time Frame All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 36) regardless of seriousness or relationship to investigational product.
Adverse Event Reporting Description Reported AEs were treatment emergent AEs developed/worsened occurred during 'treatment-emergent period' (from first dose of study drug injection until 98 days after last dose of drug) or entry in the LTS12551 study (NCT02134028). Analysis was performed on safety population which included all participants who actually received at least 1 dose or part of a dose of the IMP and analyzed according to the treatment that participants actually received.
 
Arm/Group Title Placebo q2w Dupilumab 300mg q2w
Hide Arm/Group Description Participants who received Placebo (for Dupilumab) in combination with OCS and stable ICS (mean exposure of 24 weeks). Participants who received Dupilumab 300 mg q2w in combination with OCS and stable ICS (mean exposure of 24 weeks).
All-Cause Mortality
Placebo q2w Dupilumab 300mg q2w
Affected / at Risk (%) Affected / at Risk (%)
Total   0/107 (0.00%)   0/103 (0.00%) 
Hide Serious Adverse Events
Placebo q2w Dupilumab 300mg q2w
Affected / at Risk (%) Affected / at Risk (%)
Total   6/107 (5.61%)   9/103 (8.74%) 
Blood and lymphatic system disorders     
Eosinophilia  1  0/107 (0.00%)  2/103 (1.94%) 
Infections and infestations     
Pneumonia  1  0/107 (0.00%)  1/103 (0.97%) 
Respiratory tract infection  1  0/107 (0.00%)  1/103 (0.97%) 
Injury, poisoning and procedural complications     
Acetabulum fracture  1  0/107 (0.00%)  1/103 (0.97%) 
Foreign body aspiration  1  0/107 (0.00%)  1/103 (0.97%) 
Metabolism and nutrition disorders     
Type 2 diabetes mellitus  1  1/107 (0.93%)  0/103 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Gastrointestinal stromal tumour  1  1/107 (0.93%)  0/103 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Asthma  1  3/107 (2.80%)  3/103 (2.91%) 
Asthmatic crisis  1  1/107 (0.93%)  0/103 (0.00%) 
Chylothorax  1  0/107 (0.00%)  1/103 (0.97%) 
Pneumonia aspiration  1  0/107 (0.00%)  1/103 (0.97%) 
Pneumothorax  1  0/107 (0.00%)  1/103 (0.97%) 
Pulmonary mass  1  0/107 (0.00%)  1/103 (0.97%) 
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo q2w Dupilumab 300mg q2w
Affected / at Risk (%) Affected / at Risk (%)
Total   30/107 (28.04%)   29/103 (28.16%) 
Infections and infestations     
Bronchitis  1  6/107 (5.61%)  7/103 (6.80%) 
Influenza  1  6/107 (5.61%)  3/103 (2.91%) 
Sinusitis  1  4/107 (3.74%)  7/103 (6.80%) 
Viral upper respiratory tract infection  1  19/107 (17.76%)  9/103 (8.74%) 
Investigations     
Eosinophil count increased  1  0/107 (0.00%)  7/103 (6.80%) 
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Trial Transparency Team
Organization: Sanofi
Phone: 800-633-1610 ext 1#
EMail: Contact-US@sanofi.com
Layout table for additonal information
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT02528214    
Other Study ID Numbers: EFC13691
2015-001573-40 ( EudraCT Number )
U1111-1170-7152 ( Other Identifier: UTN )
First Submitted: August 18, 2015
First Posted: August 19, 2015
Results First Submitted: July 27, 2018
Results First Posted: October 23, 2018
Last Update Posted: October 1, 2019