Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Evaluation of Dupilumab's Effects on Airway Inflammation in Patients With Asthma (EXPEDITION)

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: NCT02573233
Recruitment Status : Completed
First Posted : October 9, 2015
Results First Posted : January 28, 2019
Last Update Posted : January 28, 2019
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double;   Primary Purpose: Treatment
Condition Asthma
Interventions Drug: Placebo
Drug: Dupilumab SAR231893/REGN668
Drug: fluticasone propionate and salmeterol
Drug: budesonide and formoterol
Drug: mometasone furoate and formoterol
Enrollment 42
Recruitment Details The study was conducted at 16 sites in 6 countries. A total of 133 participants were screened between January 2016 and January 2018. Of which, 42 participants were randomized. 91 participants were screen failures mainly due to exclusion criteria met and inclusion criteria not met.
Pre-assignment Details Participants were randomized in 1:1 ratio to receive dupilumab 300 mg every 2 weeks (q2w) and placebo q2w by using Interactive Voice/Web Response System (IVRS). Randomization was stratified by inhaled corticosteroids (ICS) dose (medium and high) and region (North America and Europe).
Arm/Group Title Placebo Dupilumab
Hide Arm/Group Description Placebo (for dupilumab), 2 subcutaneous injections on Day 1 (Week 1) as a loading dose followed by a single injection q2w from Week 2 to Week 14 added to stable inhaled corticosteroid/ long-acting beta-agonist (ICS/LABA) therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. Dupilumab, 2 subcutaneous injections on Day 1 as a loading dose for a total of 600 mg, followed by a single 300 mg injection q2w from Week 2 to Week 14 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
Period Title: Overall Study
Started 22 20
Completed 22 20
Not Completed 0 0
Arm/Group Title Placebo Dupilumab Total
Hide Arm/Group Description Placebo (for dupilumab), 2 subcutaneous injections on Day 1 (Week 1) as a loading dose followed by a single injection q2w from Week 2 to Week 14 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. Dupilumab, 2 subcutaneous injections on Day 1 as a loading dose for a total of 600 mg, followed by a single 300 mg injection q2w from Week 2 to Week 14 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. Total of all reporting groups
Overall Number of Baseline Participants 22 20 42
Hide Baseline Analysis Population Description
Baseline population included all randomized participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 22 participants 20 participants 42 participants
41.0  (10.3) 45.5  (10.6) 43.1  (10.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants 20 participants 42 participants
Female
8
  36.4%
13
  65.0%
21
  50.0%
Male
14
  63.6%
7
  35.0%
21
  50.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants 20 participants 42 participants
Hispanic or Latino
1
   4.5%
1
   5.0%
2
   4.8%
Not Hispanic or Latino
21
  95.5%
19
  95.0%
40
  95.2%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants 20 participants 42 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
1
   5.0%
1
   2.4%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
3
  13.6%
3
  15.0%
6
  14.3%
White
19
  86.4%
16
  80.0%
35
  83.3%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Baseline Eosinophils Count in Bronchial Tissue   [1] [2] 
Median (Inter-Quartile Range)
Unit of measure:  Cells/mm^2
Number Analyzed 21 participants 19 participants 40 participants
12.97
(9.91 to 21.24)
34.96
(10.07 to 263.75)
20.73
(9.99 to 68.87)
[1]
Measure Description: Inflammatory cells i.e. eosinophils were counted in the bronchial submucosa of biopsy thin sections using quantitative immunohistochemistry and reported as the number of cells per square millimeter.
[2]
Measure Analysis Population Description: Here, number analyzed = participants with available data at baseline.
Baseline Mucin-Stained Area in The Bronchial Tissue Specimen   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Cells/mm^2
Number Analyzed 22 participants 19 participants 41 participants
561.12  (289.00) 520.57  (511.69) 542.33  (402.61)
[1]
Measure Description: Mucin was identified by staining with Alcian-blue periodic acid-Schiff and/or immunostaining for MUC5AC and then the mucin-positive area was measured and expressed per square millimeter.
[2]
Measure Analysis Population Description: Here, number analyzed = participants with available data at baseline.
Baseline Mast Cells Count (Chymase Positive) in Bronchial Tissue   [1] 
Mean (Standard Deviation)
Unit of measure:  Cells/mm^2
Number Analyzed 22 participants 20 participants 42 participants
74.36  (58.63) 79.17  (68.07) 76.59  (62.42)
[1]
Measure Description: Inflammatory cells i.e. mast cells were counted in the bronchial submucosa of biopsy thin sections using quantitative immunohistochemistry and reported as the number of cells per square millimeter.
Baseline Mast Cells Count (Tryptase Positive) in Bronchial Tissue   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Cells/mm^2
Number Analyzed 22 participants 19 participants 41 participants
80.10  (64.92) 105.53  (104.68) 91.88  (85.49)
[1]
Measure Description: Inflammatory cells i.e. mast cells were counted in the bronchial submucosa of biopsy thin sections using quantitative immunohistochemistry and reported as the number of cells per square millimeter.
[2]
Measure Analysis Population Description: Here, number analyzed = participants with available data at baseline.
Baseline Total T-Lymphocytes Count in Bronchial Tissue   [1] [2] 
Median (Inter-Quartile Range)
Unit of measure:  Cells/mm^2
Number Analyzed 22 participants 19 participants 41 participants
301.09
(121.01 to 500.43)
153.33
(83.81 to 192.40)
181.50
(105.08 to 392.13)
[1]
Measure Description: T-Lymphocytes i.e. CD3 positive cells were counted in the bronchial submucosa of biopsy thin sections using quantitative immunohistochemistry and reported as the number of cells per square millimeter.
[2]
Measure Analysis Population Description: Here, number analyzed = participants with available data at baseline.
Baseline T-Helper Lymphocytes Count in Bronchial Tissue   [1] [2] 
Median (Inter-Quartile Range)
Unit of measure:  Cells/mm^2
Number Analyzed 22 participants 19 participants 41 participants
237.10
(190.17 to 511.48)
200.85
(102.49 to 398.08)
215.05
(147.29 to 467.90)
[1]
Measure Description: T-helper i.e. CD4 positive lymphocytes were counted in the bronchial submucosa of biopsy thin sections using quantitative immunohistochemistry and reported as the number of cells per square millimeter.
[2]
Measure Analysis Population Description: Here, number analyzed = participants with available data at baseline.
Baseline Fractional exhaled nitric oxide (FeNO)   [1] 
Mean (Standard Deviation)
Unit of measure:  Parts per billion (ppb)
Number Analyzed 22 participants 20 participants 42 participants
41.2  (31.5) 36.4  (22.8) 38.9  (27.5)
[1]
Measure Description: FeNO is a surrogate marker for airway inflammation. FeNO was analyzed using a NIOX instrument or similar analyzer using a flow rate of 50 mL/s, and reported in ppb.
1.Primary Outcome
Title Change From Baseline in Eosinophils Cells Count in the Bronchial Submucosa at Week 12
Hide Description Inflammatory cells i.e. eosinophils were counted in the bronchial submucosa of biopsy thin sections using quantitative immunohistochemistry and reported as the number of cells per square millimeter.
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on pharmacodynamic (PD) population which consisted of all randomized participants who underwent baseline and Week12/end of treatment (EOT) bronchoscopies and have adequate biopsies for analysis at both baseline and EOT. Here, overall number of participants analyzed = participants with available data for this outcome measure.
Arm/Group Title Placebo Dupilumab
Hide Arm/Group Description:
Placebo (for dupilumab), 2 subcutaneous injections on Day 1 (Week 1) as a loading dose followed by a single injection q2w from Week 2 to Week 14 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
Dupilumab, 2 subcutaneous injections on Day 1 as a loading dose for a total of 600 mg, followed by a single 300 mg injection q2w from Week 2 to Week 14 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
Overall Number of Participants Analyzed 20 17
Median (Inter-Quartile Range)
Unit of Measure: cells/mm^2
5.80
(-9.18 to 33.41)
-6.04
(-174.71 to 19.41)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Dupilumab
Comments Analysis was performed using a rank ANCOVA model stratified by ICS dose level and region.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8400
Comments Threshold for significance at 0.05 level
Method Rank ANCOVA
Comments Rank ANCOVA model stratified by ICS dose level and region
2.Primary Outcome
Title Change From Baseline in Mucin-Stained Area in the Bronchial Submucosa at Week 12
Hide Description Mucin was identified by staining with Alcian-blue periodic acid-Schiff and/or immunostaining for MUC5AC and then the mucin-positive area was measured and expressed per square millimeter.
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on PD population. Here, overall number of participants analyzed = participants with available data for this outcome measure.
Arm/Group Title Placebo Dupilumab
Hide Arm/Group Description:
Placebo (for dupilumab), 2 subcutaneous injections on Day 1 (Week 1) as a loading dose followed by a single injection q2w from Week 2 to Week 14 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
Dupilumab, 2 subcutaneous injections on Day 1 as a loading dose for a total of 600 mg, followed by a single 300 mg injection q2w from Week 2 to Week 14 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
Overall Number of Participants Analyzed 20 16
Mean (Standard Deviation)
Unit of Measure: cells/mm^2
64.09  (391.96) -142.74  (477.89)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Dupilumab
Comments Analysis was performed using a linear fixed-effect model with treatment, region and ICS dose level as fixed effects, and the baseline value as continuous covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0336
Comments Threshold for significance at 0.05 level
Method Linear fixed-effect model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -235.02
Confidence Interval (2-Sided) 90%
-414.19 to -55.84
Estimation Comments [Not Specified]
3.Primary Outcome
Title Change From Baseline in Mast Cells Count (Chymase Positive) in the Bronchial Submucosa at Week 12
Hide Description Inflammatory cells i.e. mast cells were counted in the bronchial submucosa of biopsy thin sections using quantitative immunohistochemistry and reported as the number of cells per square millimeter.
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on PD population. Here, overall number of participants analyzed = participants with available data for this outcome measure.
Arm/Group Title Placebo Dupilumab
Hide Arm/Group Description:
Placebo (for dupilumab), 2 subcutaneous injections on Day 1 (Week 1) as a loading dose followed by a single injection q2w from Week 2 to Week 14 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
Dupilumab, 2 subcutaneous injections on Day 1 as a loading dose for a total of 600 mg, followed by a single 300 mg injection q2w from Week 2 to Week 14 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
Overall Number of Participants Analyzed 20 17
Mean (Standard Deviation)
Unit of Measure: cells/mm^2
-14.80  (76.52) 1.76  (62.41)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Dupilumab
Comments Analysis was performed using a linear fixed-effect model with treatment, region and ICS dose level as fixed effects, and the baseline value as continuous covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4795
Comments Threshold for significance at 0.05 level.
Method Linear fixed-effect model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 13.89
Confidence Interval (2-Sided) 90%
-19.00 to 46.78
Estimation Comments [Not Specified]
4.Primary Outcome
Title Change From Baseline in Mast Cells Count (Tryptase Positive) in the Bronchial Submucosa at Week 12
Hide Description Inflammatory cells i.e. mast cells were counted in the bronchial submucosa of biopsy thin sections using quantitative immunohistochemistry and reported as the number of cells per square millimeter.
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on PD population. Here, overall number of participants analyzed = participants with available data for this outcome measure.
Arm/Group Title Placebo Dupilumab
Hide Arm/Group Description:
Placebo (for dupilumab), 2 subcutaneous injections on Day 1 (Week 1) as a loading dose followed by a single injection q2w from Week 2 to Week 14 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
Dupilumab, 2 subcutaneous injections on Day 1 as a loading dose for a total of 600 mg, followed by a single 300 mg injection q2w from Week 2 to Week 14 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
Overall Number of Participants Analyzed 21 17
Mean (Standard Deviation)
Unit of Measure: cells/mm^2
2.37  (90.20) -20.89  (59.09)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Dupilumab
Comments Analysis was performed using a linear fixed-effect model with treatment, region and ICS dose level as fixed effects, and the baseline value as continuous covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4494
Comments Threshold for significance at 0.05 level.
Method Linear fixed-effect model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -18.98
Confidence Interval (2-Sided) 90%
-60.92 to 22.97
Estimation Comments [Not Specified]
5.Primary Outcome
Title Change From Baseline in T-Lymphocytes Count in the Bronchial Submucosa at Week 12
Hide Description T-Lymphocytes i.e. CD3 positive cells were counted in the bronchial submucosa of biopsy thin sections using quantitative immunohistochemistry and reported as the number of cells per square millimeter.
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on PD population. Here, overall number of participants analyzed = participants with available data for this outcome measure.
Arm/Group Title Placebo Dupilumab
Hide Arm/Group Description:
Placebo (for dupilumab), 2 subcutaneous injections on Day 1 (Week 1) as a loading dose followed by a single injection q2w from Week 2 to Week 14 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
Dupilumab, 2 subcutaneous injections on Day 1 as a loading dose for a total of 600 mg, followed by a single 300 mg injection q2w from Week 2 to Week 14 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
Overall Number of Participants Analyzed 20 16
Median (Inter-Quartile Range)
Unit of Measure: cells/mm^2
-36.70
(-200.25 to 267.51)
34.21
(-95.08 to 232.99)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Dupilumab
Comments Analysis was performed using a rank ANCOVA model stratified by ICS dose level and region.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6865
Comments Threshold for significance at 0.05 level.
Method Rank ANCOVA
Comments Rank ANCOVA model stratified by ICS dose level and region
6.Primary Outcome
Title Change From Baseline in T-Helper Lymphocytes Count in the Bronchial Submucosa at Week 12
Hide Description T-helper i.e. CD4 positive lymphocytes were counted in the bronchial submucosa of biopsy thin sections using quantitative immunohistochemistry and reported as the number of cells per square millimeter.
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on PD population. Here, overall number of participants analyzed = participants with available data for this outcome measure.
Arm/Group Title Placebo Dupilumab
Hide Arm/Group Description:
Placebo (for dupilumab), 2 subcutaneous injections on Day 1 (Week 1) as a loading dose followed by a single injection q2w from Week 2 to Week 14 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
Dupilumab, 2 subcutaneous injections on Day 1 as a loading dose for a total of 600 mg, followed by a single 300 mg injection q2w from Week 2 to Week 14 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
Overall Number of Participants Analyzed 20 16
Median (Inter-Quartile Range)
Unit of Measure: cells/mm^2
7.26
(-179.43 to 224.96)
62.34
(-100.62 to 159.09)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Dupilumab
Comments Analysis was performed using a rank ANCOVA model stratified by ICS dose level and region.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7588
Comments Threshold for significance at 0.05 level
Method Rank ANCOVA
Comments Rank ANCOVA model stratified by ICS dose level and region
7.Secondary Outcome
Title Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) at Week 12
Hide Description FeNO is a surrogate marker for airway inflammation. FeNO was analyzed using a NIOX instrument or similar analyzer using a flow rate of 50 mL/second, and reported in ppb.
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on secondary PD population which consisted of all randomized and treated participants. Here, overall number of participants analyzed = participants with available data for this outcome measure.
Arm/Group Title Placebo Dupilumab
Hide Arm/Group Description:
Placebo (for dupilumab), 2 subcutaneous injections on Day 1 (Week 1) as a loading dose followed by a single injection q2w from Week 2 to Week 14 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
Dupilumab, 2 subcutaneous injections on Day 1 as a loading dose for a total of 600 mg, followed by a single 300 mg injection q2w from Week 2 to Week 14 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
Overall Number of Participants Analyzed 21 18
Mean (Standard Deviation)
Unit of Measure: ppb
3.9  (22.8) -15.1  (18.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Dupilumab
Comments Analysis was performed using a Mixed-effect Model with Repeated Measures (MRMM) with treatment, treatment-by-visit interaction, region, and ICS dose level as fixed effects, and baseline biomarker-by-visit interaction as fixed covariate, and assuming an unstructured covariance structure separately by treatment group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0012
Comments Threshold for significance at 0.05 level
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -22.4
Confidence Interval (2-Sided) 90%
-32.9 to -11.9
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Average Change in Fractional Exhaled Nitric Oxide (FeNO) From Baseline to Week 6 Through Week 12
Hide Description

FeNO is a surrogate marker for airway inflammation. FeNO was analyzed using a NIOX instrument or similar analyzer using a flow rate of 50 mL/s, and reported in ppb.

The average change in FeNO from baseline to Week 6 through Week 12 was calculated as follows: For each participant the change in FeNO from Baseline to Week 6, Week 8, Week 10 and Week 12 was calculated (value at Week X - value at baseline). Subsequently the weekly mean of these 4 "change from baseline" values was determined (Weeks 6, 8, 10 and 12). Using these weekly mean values the overall arithmetic mean and standard deviation of the average change in FeNO from baseline to Week 6 through Week 12 was calculated.

Time Frame From Baseline to Week 6 through Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on secondary PD population.
Arm/Group Title Placebo Dupilumab
Hide Arm/Group Description:
Placebo (for dupilumab), 2 subcutaneous injections on Day 1 (Week 1) as a loading dose followed by a single injection q2w from Week 2 to Week 14 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
Dupilumab, 2 subcutaneous injections on Day 1 as a loading dose for a total of 600 mg, followed by a single 300 mg injection q2w from Week 2 to Week 14 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
Overall Number of Participants Analyzed 22 20
Mean (Standard Deviation)
Unit of Measure: ppb
3.5  (18.0) -16.0  (21.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Dupilumab
Comments Analysis was performed using a Mixed-effect model with Repeated Measures (MMRM) with treatment, treatment-by-visit interaction, region, and ICS dose level as fixed effects, and baseline biomarker-by-visit interaction as fixed covariate, and assuming an unstructured covariance structure separately by treatment group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0005
Comments Threshold for significance at 0.05 level
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -22.0
Confidence Interval (2-Sided) 90%
-31.3 to -12.8
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Number of Participants With Antidrug Antibodies (ADA)
Hide Description Anti-drug antibodies were detected using a validated immunoassay. Incidence of ADA were classified as following: 1) Pre-existing immunoreactivity - an ADA positive response in the assay at baseline with all post treatment ADA results negative or an ADA positive response at baseline with all post treatment ADA responses less than 4-fold over baseline titer levels. 2) Treatment-emergent ADA: an ADA positive response in the assay post first dose, when baseline results were negative or missing. 3) Treatment-boosted ADA: an ADA positive response in the assay post first dose that was greater-than or equal to 4-fold over baseline titer levels, when baseline results were positive.
Time Frame From Baseline up to 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ADA population which consisted of all participants with at least one qualified ADA result in the ADA assay following the first dose of the study medication.
Arm/Group Title Placebo Dupilumab
Hide Arm/Group Description:
Placebo (for dupilumab), 2 subcutaneous injections on Day 1 (Week 1) as a loading dose followed by a single injection q2w from Week 2 to Week 14 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
Dupilumab, 2 subcutaneous injections on Day 1 as a loading dose for a total of 600 mg, followed by a single 300 mg injection q2w from Week 2 to Week 14 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
Overall Number of Participants Analyzed 21 19
Measure Type: Count of Participants
Unit of Measure: Participants
With pre-existing immunoreactivity
1
   4.8%
0
   0.0%
With treatment-emergent ADA
0
   0.0%
1
   5.3%
With treatment-boosted ADA
0
   0.0%
0
   0.0%
10.Secondary Outcome
Title Pharmacokinetics (PK) Assessment: Serum Functional Dupilumab Concentration
Hide Description Serum functional dupilumab concentrations were determined using an enzyme-linked immunosorbent assay (ELISA) method.
Time Frame Week 0, Week 2, 6, 8, 12, 18, End of study (Week 24)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on PK population which consisted of all participants with at least one non-missing and eligible post-baseline dupilumab serum concentration data. Data for this outcome measure was not planned to be analyzed for placebo arm. Here, "number analyzed" represents number of subjects with available data for specified time points.
Arm/Group Title Dupilumab
Hide Arm/Group Description:
Dupilumab, 2 subcutaneous injections on Day 1 as a loading dose for a total of 600 mg, followed by a single 300 mg injection q2w from Week 2 to Week 14 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
Overall Number of Participants Analyzed 20
Mean (Standard Deviation)
Unit of Measure: ng/mL
Week 0 Number Analyzed 20 participants
0.00  (0.00)
Week 2 Number Analyzed 20 participants
52675.00  (23107.55)
Week 6 Number Analyzed 20 participants
59969.00  (27422.27)
Week 8 Number Analyzed 20 participants
61097.95  (29775.23)
Week 12 Number Analyzed 20 participants
67387.00  (32800.44)
Week 18 Number Analyzed 6 participants
20728.17  (17718.93)
Week 24 Number Analyzed 5 participants
1851.20  (2796.78)
11.Secondary Outcome
Title Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Hide Description Adverse event (AE) was defined as any untoward medical occurrence in a participant who received investigational medicinal product (IMP) without regard to possibility of causal relationship with this treatment. TEAEs: AEs that developed or worsened or became serious during between the first administration of study medication to the end of the 12 week Post-treatment Period. Serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included both serious and non-serious AEs.
Time Frame Baseline up to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on safety population which consisted of all participants randomized and exposed to study medication, regardless of the amount of treatment administered.
Arm/Group Title Placebo Dupilumab
Hide Arm/Group Description:
Placebo (for dupilumab), 2 subcutaneous injections on Day 1 (Week 1) as a loading dose followed by a single injection q2w from Week 2 to Week 14 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
Dupilumab, 2 subcutaneous injections on Day 1 as a loading dose for a total of 600 mg, followed by a single 300 mg injection q2w from Week 2 to Week 14 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
Overall Number of Participants Analyzed 22 20
Measure Type: Count of Participants
Unit of Measure: Participants
Any TEAE
17
  77.3%
15
  75.0%
Any treatment emergent SAE
0
   0.0%
1
   5.0%
Any TEAE leading to death
0
   0.0%
0
   0.0%
Any TEAE leading to permanent discontinuation
0
   0.0%
0
   0.0%
Time Frame All AEs were collected from signature of the informed consent form up to the end of study (i.e. up to the end of Post-treatment period [Week 24]) regardless of seriousness or relationship to investigational medicinal product (IMP).
Adverse Event Reporting Description Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during 'treatment-emergent period' (from first dose of investigational product injection up to the end of Post-treatment period [Week 24]). Analysis was performed on safety population.
 
Arm/Group Title Placebo Dupilumab
Hide Arm/Group Description Placebo (for dupilumab), 2 subcutaneous injections on Day 1 (Week 1) as a loading dose followed by a single injection q2w from Week 2 to Week 14 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. Dupilumab, 2 subcutaneous injections on Day 1 as a loading dose for a total of 600 mg, followed by a single 300 mg injection q2w from Week 2 to Week 14 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
All-Cause Mortality
Placebo Dupilumab
Affected / at Risk (%) Affected / at Risk (%)
Total   0/22 (0.00%)      0/20 (0.00%)    
Hide Serious Adverse Events
Placebo Dupilumab
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/22 (0.00%)      1/20 (5.00%)    
Blood and lymphatic system disorders     
Neutropenia  1  0/22 (0.00%)  0 1/20 (5.00%)  1
1
Term from vocabulary, MedDra 20.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Dupilumab
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   11/22 (50.00%)      14/20 (70.00%)    
Gastrointestinal disorders     
Nausea  1  1/22 (4.55%)  1 3/20 (15.00%)  3
Vomiting  1  0/22 (0.00%)  0 2/20 (10.00%)  2
General disorders     
Injection Site Erythema  1  2/22 (9.09%)  8 3/20 (15.00%)  8
Injection Site Inflammation  1  2/22 (9.09%)  3 1/20 (5.00%)  3
Injection Site Pruritus  1  1/22 (4.55%)  1 2/20 (10.00%)  3
Infections and infestations     
Nasopharyngitis  1  4/22 (18.18%)  6 2/20 (10.00%)  2
Upper Respiratory Tract Infection  1  1/22 (4.55%)  1 3/20 (15.00%)  3
Injury, poisoning and procedural complications     
Accidental Overdose  1  1/22 (4.55%)  1 2/20 (10.00%)  3
Road Traffic Accident  1  0/22 (0.00%)  0 2/20 (10.00%)  2
Musculoskeletal and connective tissue disorders     
Back Pain  1  0/22 (0.00%)  0 3/20 (15.00%)  3
Nervous system disorders     
Headache  1  3/22 (13.64%)  9 5/20 (25.00%)  11
Respiratory, thoracic and mediastinal disorders     
Asthma  1  1/22 (4.55%)  1 2/20 (10.00%)  2
Cough  1  2/22 (9.09%)  2 1/20 (5.00%)  1
Wheezing  1  2/22 (9.09%)  2 0/20 (0.00%)  0
Vascular disorders     
Hypertension  1  2/22 (9.09%)  3 1/20 (5.00%)  1
1
Term from vocabulary, MedDra 20.1
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: NCT02573233    
Other Study ID Numbers: PDY14192
2015-001572-22 ( EudraCT Number )
U1111-1170-7168 ( Other Identifier: UTN )
First Submitted: October 8, 2015
First Posted: October 9, 2015
Results First Submitted: December 19, 2018
Results First Posted: January 28, 2019
Last Update Posted: January 28, 2019