Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 2 of 2 for:    r. mucosa eczema

Study to Assess the Efficacy and Long-term Safety of Dupilumab (REGN668/SAR231893) in Adult Participants With Moderate-to-Severe Atopic Dermatitis (CHRONOS)

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: NCT02260986
Recruitment Status : Completed
First Posted : October 9, 2014
Results First Posted : October 17, 2017
Last Update Posted : October 17, 2017
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
Regeneron Pharmaceuticals

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Atopic Dermatitis
Interventions Drug: Dupilumab
Drug: Placebo (for Dupilumab)
Other: Topical Corticosteroid (TCS)
Enrollment 740
Recruitment Details The study was conducted in 14 countries between 16 Sep 2014 and 19 Oct 2016. A total of 957 participants were screened in the study.
Pre-assignment Details Out of 957 participants, 740 participants were randomized and treated in the study. Participants were randomized in 3:1:3 ratio to receive Dupilumab 300 mg once weekly (qw) or Dupilumab 300 mg every 2 weeks (q2w) or placebo (for Dupilumab) qw.
Arm/Group Title Placebo qw Dupilumab 300 mg q2w Dupilumab 300 mg qw
Hide Arm/Group Description Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51. Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo. Two 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 of Dupilumab qw from Week 1 to Week 51.
Period Title: Overall Study
Started 315 106 319
Safety Population 315 110 [1] 315 [2]
Completed 225 93 278
Not Completed 90 13 41
Reason Not Completed
Adverse Event             24             0             11
Lack of Efficacy             27             3             0
Protocol Violation             14             5             16
Car accident             0             0             1
Withdrawal by Subject             17             4             9
Incorrect randomization             0             1             0
Lack of investigation product supply             2             0             1
Lost to Follow-up             4             0             3
Pregnancy             2             0             0
[1]
4 participants from Dupilumab 300 mg qw arm analyzed in Dupilumab 300 mg q2w arm
[2]
4 participants received fewer injections of Dupilumab 300 mg (analyzed in Dupilumab 300 mg q2w arm)
Arm/Group Title Placebo qw Dupilumab 300 mg q2w Dupilumab 300 mg qw Total
Hide Arm/Group Description Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51. Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo. Two 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 of Dupilumab qw from Week 1 to Week 51. Total of all reporting groups
Overall Number of Baseline Participants 315 106 319 740
Hide Baseline Analysis Population Description
Baseline population included all randomized participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 315 participants 106 participants 319 participants 740 participants
36.6  (13.01) 39.6  (13.98) 36.9  (13.67) 37.1  (13.46)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 315 participants 106 participants 319 participants 740 participants
Female
122
  38.7%
44
  41.5%
128
  40.1%
294
  39.7%
Male
193
  61.3%
62
  58.5%
191
  59.9%
446
  60.3%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 315 participants 106 participants 319 participants 740 participants
Hispanic or Latino
10
   3.2%
2
   1.9%
5
   1.6%
17
   2.3%
Not Hispanic or Latino
299
  94.9%
103
  97.2%
309
  96.9%
711
  96.1%
Unknown or Not Reported
6
   1.9%
1
   0.9%
5
   1.6%
12
   1.6%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 315 participants 106 participants 319 participants 740 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
83
  26.3%
29
  27.4%
89
  27.9%
201
  27.2%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
19
   6.0%
2
   1.9%
13
   4.1%
34
   4.6%
White
208
  66.0%
74
  69.8%
208
  65.2%
490
  66.2%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
5
   1.6%
1
   0.9%
9
   2.8%
15
   2.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Romania Number Analyzed 315 participants 106 participants 319 participants 740 participants
2 0 2 4
Hungary Number Analyzed 315 participants 106 participants 319 participants 740 participants
11 5 11 27
United States Number Analyzed 315 participants 106 participants 319 participants 740 participants
61 19 59 139
Japan Number Analyzed 315 participants 106 participants 319 participants 740 participants
54 16 47 117
United Kingdom Number Analyzed 315 participants 106 participants 319 participants 740 participants
17 4 15 36
Spain Number Analyzed 315 participants 106 participants 319 participants 740 participants
4 2 4 10
New Zealand Number Analyzed 315 participants 106 participants 319 participants 740 participants
1 1 3 5
Canada Number Analyzed 315 participants 106 participants 319 participants 740 participants
47 17 51 115
Czech Republic Number Analyzed 315 participants 106 participants 319 participants 740 participants
7 7 6 20
Netherlands Number Analyzed 315 participants 106 participants 319 participants 740 participants
17 7 19 43
Korea, Republic of Number Analyzed 315 participants 106 participants 319 participants 740 participants
8 4 14 26
Poland Number Analyzed 315 participants 106 participants 319 participants 740 participants
63 17 64 144
Italy Number Analyzed 315 participants 106 participants 319 participants 740 participants
5 1 7 13
Australia Number Analyzed 315 participants 106 participants 319 participants 740 participants
18 6 17 41
Eczema Area and Severity Index (EASI) Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 315 participants 106 participants 319 participants 740 participants
32.6  (12.93) 33.6  (13.30) 32.1  (12.76) 32.5  (12.90)
[1]
Measure Description: The EASI score was used to measure the severity and extent of atopic dermatitis (AD) and measures erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD.
Investigator Global Assessment (IGA) Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 315 participants 106 participants 319 participants 740 participants
3.5  (0.50) 3.5  (0.50) 3.5  (0.50) 3.5  (0.50)
[1]
Measure Description: IGA was an assessment scale used to determine severity of AD and clinical response to treatment on a 5-point scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe) based on erythema and papulation/infiltration. Therapeutic response was an IGA score of 0 (clear) or 1 (almost clear).
Weekly Peak Averaged Pruritus Numeric Rating Scale (NRS)   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 315 participants 106 participants 319 participants 740 participants
7.3  (1.84) 7.4  (1.66) 7.1  (1.90) 7.3  (1.84)
[1]
Measure Description: Pruritus NRS was an assessment tool that was used to report the intensity of participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at worst moment during previous 24 hours (for maximum itch intensity on a scale of 0-10 [0=no itch;10=worst itch imaginable]).
Body Surface Area (BSA) Involvement with Atopic Dermatitis   [1] 
Mean (Standard Deviation)
Unit of measure:  Percentage of body surface area
Number Analyzed 315 participants 106 participants 319 participants 740 participants
56.9  (21.69) 59.5  (20.84) 54.1  (21.76) 56.1  (21.66)
[1]
Measure Description: Body surface area affected by AD was assessed for each section of the body (the possible highest score for each region was: head and neck [9%], anterior trunk [18%], back [18%], upper limbs [18%], lower limbs [36%], and genitals [1%]). It was reported as a percentage of all major body sections combined.
SCORing Atopic Dermatitis (SCORAD) Score   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 313 participants 105 participants 316 participants 734 participants
66.0  (13.53) 69.3  (15.24) 65.9  (13.63) 66.4  (13.86)
[1]
Measure Description: SCORAD is a clinical tool for assessing the severity of atopic dermatitis developed by the European Task Force on Atopic Dermatitis (Severity scoring of atopic dermatitis: the SCORAD index). Consensus Report of the European Task Force on Atopic Dermatitis. Dermatology (Basel) 186 (1): 23-31. 1993. Extent and intensity of eczema as well as subjective signs (insomnia, etc.) are assessed and scored. Total score ranges from 0 (absent disease) to 103 (severe disease).
[2]
Measure Analysis Population Description: Number of participants analyzed = participants with available data for this baseline parameter.
Dermatology Life Quality Index (DLQI) Total Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 315 participants 106 participants 319 participants 740 participants
14.7  (7.37) 14.5  (7.31) 14.4  (7.17) 14.5  (7.27)
[1]
Measure Description: DLQI is a 10-item, validated questionnaire used in clinical practice and clinical trials to assess the impact of AD disease symptoms and treatment on quality of life (QOL). The 10 questions assessed QOL over the past week, with an overall scoring of 0 (absent disease) to 30 (severe disease); a high score was indicative of a poor QOL.
Patient Oriented Eczema Measure (POEM)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 314 participants 106 participants 319 participants 739 participants
20.0  (5.99) 20.3  (5.68) 20.1  (6.05) 20.1  (5.95)
[1]
Measure Description: The POEM was a 7-item questionnaire that assessed disease symptoms (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) with a scoring system of 0 (absent disease) to 28 (severe disease) (high score indicative of poor quality of life [QOL]).
[2]
Measure Analysis Population Description: Number of participants analyzed = participants with available data for this baseline parameter.
Global Individual Signs Score (GISS)   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 315 participants 106 participants 319 participants 740 participants
8.7  (1.84) 8.9  (2.04) 8.9  (1.80) 8.8  (1.85)
[1]
Measure Description: Individual components of the AD lesions (erythema, infiltration/ papulation, excoriations, and lichenification) were rated globally (each assessed for the whole body, not by anatomical region) on a 4-point scale (0 = none, 1 = mild, 2 = moderate and 3 = severe) using the EASI severity grading criteria. Total score ranges from 0 (absent disease) to 12 (severe disease).
Total Hospital Anxiety Depression Scale (HADS)   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 315 participants 106 participants 319 participants 740 participants
12.6  (8.06) 12.9  (7.73) 12.8  (8.01) 12.7  (7.98)
[1]
Measure Description: The HADS is a fourteen item scale. Seven of the items relate to anxiety and seven relate to depression. Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 (no symptoms) and 21 (severe symptoms) for either anxiety or depression. Cut-offs for identifying psychiatric distress has been reported as 7 to 8 for possible presence, 10 to 11 for probable presence, and 14 to 15 for severe anxiety or depression.
1.Primary Outcome
Title Percentage of Participants With Investigator's Global Assessment (IGA) Score of "0" or "1" and Reduction From Baseline of ≥2 Points at Week 16
Hide Description IGA is an assessment scale used to determine severity of AD and clinical response to treatment on a 5-point scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe) based on erythema and papulation/infiltration. Therapeutic response is an IGA score of 0 (clear) or 1 (almost clear). Participants with IGA score "0" or "1" and a reduction from baseline of ≥2 points at Week 16 were reported.
Time Frame Baseline to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
All efficacy analyses were performed on the Full Analysis Set (FAS), which included all randomized participants. Efficacy analyses were based on the treatment allocated by interactive voice response system/ interactive web response system (IVRS/IWRS) at randomization (as randomized).
Arm/Group Title Placebo qw Dupilumab 300 mg q2w Dupilumab 300 mg qw
Hide Arm/Group Description:
Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51
Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.
Two 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 of Dupilumab qw from Week 1 to Week 51.
Overall Number of Participants Analyzed 315 106 319
Measure Type: Number
Unit of Measure: percentage of participants
12.4 38.7 39.2
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo qw, Dupilumab 300 mg q2w
Comments Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity (IGA baseline values: IGA=3 vs IGA=4). Values after first rescue treatment were set to missing and participants with missing IGA scores at Week 16 were considered as non-responders.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.025 level.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in percentages
Estimated Value 26.3
Confidence Interval (2-Sided) 95%
16.34 to 36.26
Estimation Comments Dupilumab 300 mg q2w v Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo qw, Dupilumab 300 mg qw
Comments Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity (IGA baseline values: IGA=3 vs IGA=4). Values after first rescue treatment were set to missing and participants with missing IGA scores at Week 16 were considered as non-responders.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.025 level.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in percentages
Estimated Value 26.8
Confidence Interval (2-Sided) 95%
20.33 to 33.28
Estimation Comments Dupilumab 300 mg qw v Placebo
2.Secondary Outcome
Title Percentage of Participants With Eczema Area and Severity Index-75 (EASI-75) (≥75% Improvement From Baseline) at Week 16
Hide Description The EASI score was used to measure the severity and extent of atopic dermatitis (AD) and measures erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI-75 responders were the participants who achieved ≥75% overall improvement in EASI score from baseline to Week 16.
Time Frame Baseline to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).
Arm/Group Title Placebo qw Dupilumab 300 mg q2w Dupilumab 300 mg qw
Hide Arm/Group Description:
Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51.
Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51.
Two 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 of Dupilumab qw from Week 1 to Week 51.
Overall Number of Participants Analyzed 315 106 319
Measure Type: Number
Unit of Measure: percentage of participants
23.2 68.9 63.9
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo qw, Dupilumab 300 mg q2w
Comments A hierarchical testing procedure was used to control type I error and handle multiple secondary endpoint analyses. Testing was then performed sequentially in the order the endpoints are reported. The hierarchical testing sequence continued only when the previous endpoint was statistically significant at 0.025 level for both comparisons.
Type of Statistical Test Superiority
Comments Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity (IGA baseline values: IGA=3 vs IGA=4). Values after first rescue treatment use were set to missing and participants with missing EASI score at Week 16 were considered as non-responders.
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.025 level.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in percentages
Estimated Value 45.7
Confidence Interval (2-Sided) 95%
35.72 to 55.66
Estimation Comments Dupilumab 300 mg q2w v Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo qw, Dupilumab 300 mg qw
Comments A hierarchical testing procedure was used to control type I error and handle multiple secondary endpoint analyses. Testing was then performed sequentially in the order the endpoints are reported. The hierarchical testing sequence continued only when previous endpoint was statistically significant at 0.025 level for both comparisons.
Type of Statistical Test Superiority
Comments Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity (IGA baseline values: IGA=3 vs IGA=4). Values after first rescue treatment use were set to missing and participants with missing EASI score at Week 16 were considered as non-responders.
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.025 level.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in percentages
Estimated Value 40.8
Confidence Interval (2-Sided) 95%
33.74 to 47.81
Estimation Comments Dupilumab 300 mg qw v Placebo
3.Secondary Outcome
Title Percentage of Participants With Improvement (Reduction ≥4 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 16
Hide Description Pruritus NRS was an assessment tool that was used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 [0 = no itch; 10 = worst itch imaginable]). Participants achieving a reduction of ≥4 points from baseline in weekly average of peak daily pruritus NRS score at Week 16 were reported.
Time Frame Baseline to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of participants analyzed = participants with baseline peak pruritus NRS score ≥4.
Arm/Group Title Placebo qw Dupilumab 300 mg q2w Dupilumab 300 mg qw
Hide Arm/Group Description:
Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51.
Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.
Two 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 of Dupilumab qw from Week 1 to Week 51.
Overall Number of Participants Analyzed 299 102 295
Measure Type: Number
Unit of Measure: percentage of participants
19.7 58.8 50.8
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo qw, Dupilumab 300 mg q2w
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity (IGA baseline values: IGA=3 vs IGA=4). Values after first rescue treatment use were set to missing and participants with missing peak NRS at Week 16 were considered as non-responders.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.025 level.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in percentages
Estimated Value 39.1
Confidence Interval (2-Sided) 95%
28.53 to 49.65
Estimation Comments Dupilumab 300 mg q2w v Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo qw, Dupilumab 300 mg qw
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity (IGA baseline values: IGA=3 vs IGA=4). Values after first rescue treatment use were set to missing and participants with missing peak NRS at Week 16 were considered as non-responders.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.025 level.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in percentages
Estimated Value 31.1
Confidence Interval (2-Sided) 95%
23.84 to 38.39
Estimation Comments Dupilumab 300 mg qw v Placebo
4.Secondary Outcome
Title Percentage of Participants With Improvement (Reduction ≥3 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 16
Hide Description Pruritus NRS was an assessment tool that was used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 [0 = no itch; 10 = worst itch imaginable]). Participants achieving a reduction of ≥3 points from baseline in weekly average of peak daily pruritus NRS score at Week 16 were reported.
Time Frame Baseline to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of participants analyzed = participants with baseline peak pruritus NRS score ≥3.
Arm/Group Title Placebo qw Dupilumab 300 mg q2w Dupilumab 300 mg qw
Hide Arm/Group Description:
Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51.
Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.
Two 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 of Dupilumab qw from Week 1 to Week 51.
Overall Number of Participants Analyzed 306 105 309
Measure Type: Number
Unit of Measure: percentage of participants
27.8 65.7 62.5
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo qw, Dupilumab 300 mg q2w
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity (IGA baseline values: IGA=3 vs IGA=4). Values after first rescue treatment use were set to missing and participants with missing peak NRS at Week 16 were considered as non-responders.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.025 level.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in percentages
Estimated Value 37.9
Confidence Interval (2-Sided) 95%
27.56 to 48.31
Estimation Comments Dupilumab 300 mg q2w v Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo qw, Dupilumab 300 mg qw
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity (IGA baseline values: IGA=3 vs IGA=4). Values after first rescue treatment use were set to missing and participants with missing peak NRS at Week 16 were considered as non-responders.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.025 level.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in percentages
Estimated Value 34.7
Confidence Interval (2-Sided) 95%
27.31 to 42.05
Estimation Comments Dupilumab 300 mg qw v Placebo
5.Secondary Outcome
Title Percentage of Participants With Investigator's Global Assessment (IGA) Score of "0" or "1" and Reduction From Baseline of ≥2 Points at Week 52
Hide Description IGA is an assessment scale used to determine severity of AD and clinical response to treatment on a 5-point scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe) based on erythema and papulation/infiltration. Therapeutic response is an IGA score of 0 (clear) or 1 (almost clear). Participants with IGA score of "0" or "1" and a reduction from baseline of ≥2 points at Week 52 were reported.
Time Frame Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of participants analyzed = participants with available data for this endpoint.
Arm/Group Title Placebo qw Dupilumab 300 mg q2w Dupilumab 300 mg qw
Hide Arm/Group Description:
Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51.
Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.
Two 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 of Dupilumab qw from Week 1 to Week 51.
Overall Number of Participants Analyzed 264 89 270
Measure Type: Number
Unit of Measure: percentage of participants
12.5 36.0 40.0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo qw, Dupilumab 300 mg q2w
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity (IGA baseline values: IGA=3 vs IGA=4). Values after first rescue treatment were set to missing and participants with missing IGA scores at Week 52 were considered as non-responders.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.025 level.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in percentages
Estimated Value 23.5
Confidence Interval (2-Sided) 95%
12.72 to 34.19
Estimation Comments Dupilumab 300 mg q2w v Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo qw, Dupilumab 300 mg qw
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity (IGA baseline values: IGA=3 vs IGA=4). Values after first rescue treatment were set to missing and participants with missing IGA scores at Week 52 were considered as non-responders.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.025 level.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in percentages
Estimated Value 27.5
Confidence Interval (2-Sided) 95%
20.42 to 34.58
Estimation Comments Dupilumab 300 mg qw v Placebo
6.Secondary Outcome
Title Percentage of Participants With Eczema Area and Severity Index-75 (EASI-75) (≥75% Improvement From Baseline) at Week 52
Hide Description The EASI score was used to measure the severity and extent of AD and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI-75 responders were the participants who achieved ≥75% overall improvement in EASI score from baseline to Week 52.
Time Frame Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of participants analyzed = participants with available data for this endpoint.
Arm/Group Title Placebo qw Dupilumab 300 mg q2w Dupilumab 300 mg qw
Hide Arm/Group Description:
Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51.
Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.
Two 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 of Dupilumab qw from Week 1 to Week 51.
Overall Number of Participants Analyzed 264 89 270
Measure Type: Number
Unit of Measure: percentage of participants
21.6 65.2 64.1
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo qw, Dupilumab 300 mg q2w
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity (IGA baseline values: IGA=3 vs IGA=4). Values after first rescue treatment use were set to missing and participants with missing EASI score at Week 52 were considered as non-responders.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.025 level.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in percentages
Estimated Value 43.6
Confidence Interval (2-Sided) 95%
32.50 to 54.65
Estimation Comments Dupilumab 300 mg q2w v Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo qw, Dupilumab 300 mg qw
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity (IGA baseline values: IGA=3 vs IGA=4). Values after first rescue treatment use were set to missing and participants with missing EASI score at Week 52 were considered as non-responders.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.025 level.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in percentages
Estimated Value 42.5
Confidence Interval (2-Sided) 95%
34.91 to 50.06
Estimation Comments Dupilumab 300 mg qw v Placebo
7.Secondary Outcome
Title Percent Change From Baseline in Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score to Week 16
Hide Description Pruritus NRS was an assessment tool that was used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 [0 = no itch; 10 = worst itch imaginable]).
Time Frame Baseline to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).
Arm/Group Title Placebo qw Dupilumab 300 mg q2w Dupilumab 300 mg qw
Hide Arm/Group Description:
Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51.
Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.
Two 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 of Dupilumab qw from Week 1 to Week 51.
Overall Number of Participants Analyzed 315 106 319
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-30.3  (2.36) -56.6  (3.95) -57.1  (2.11)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo qw, Dupilumab 300 mg q2w
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using ANCOVA model with baseline measurements as covariate and the treatment, region and baseline IGA strata as fixed factors.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.025 level.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least square (LS) mean difference
Estimated Value -26.2
Confidence Interval (2-Sided) 95%
-35.04 to -17.43
Estimation Comments Dupilumab 300 mg q2w v Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo qw, Dupilumab 300 mg qw
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using ANCOVA model with baseline measurements as covariate and the treatment, region and baseline IGA strata as fixed factors.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.025 level.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -26.8
Confidence Interval (2-Sided) 95%
-32.83 to -20.73
Estimation Comments Dupilumab 300 mg qw v Placebo
8.Secondary Outcome
Title Percentage of Participants With Improvement (Reduction ≥4 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 52
Hide Description Pruritus NRS was an assessment tool that was used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 [0 = no itch; 10 = worst itch imaginable]). Participants achieving a reduction of ≥4 points from baseline in weekly average of peak daily pruritus NRS score at Week 52 were reported.
Time Frame Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of participants analyzed = participants with baseline peak pruritus NRS score ≥4.
Arm/Group Title Placebo qw Dupilumab 300 mg q2w Dupilumab 300 mg qw
Hide Arm/Group Description:
Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51.
Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.
Two 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 of Dupilumab qw from Week 1 to Week 51.
Overall Number of Participants Analyzed 249 86 249
Measure Type: Number
Unit of Measure: percentage of participants
12.9 51.2 39.0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo qw, Dupilumab 300 mg q2w
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity (IGA baseline values: IGA=3 vs IGA=4). Values after first rescue treatment were set to missing and participants with missing peak NRS at Week 52 were considered as non-responders.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.025 level.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in percentages
Estimated Value 38.3
Confidence Interval (2-Sided) 95%
26.96 to 49.66
Estimation Comments Dupilumab 300 mg q2w v Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo qw, Dupilumab 300 mg qw
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity (IGA baseline values: IGA=3 vs IGA=4). Values after first rescue treatment were set to missing and participants with missing peak NRS at Week 52 were considered as non-responders.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.025 level.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in percentages
Estimated Value 26.1
Confidence Interval (2-Sided) 95%
18.76 to 33.45
Estimation Comments Dupilumab 300 mg qw v Placebo
9.Secondary Outcome
Title Percentage of Participants With Improvement (Reduction ≥3 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 52
Hide Description Pruritus NRS was an assessment tool that was used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 [0 = no itch; 10 = worst itch imaginable]). Participants achieving a reduction of ≥3 points from baseline in weekly average of peak daily pruritus NRS score at Week 52 were reported.
Time Frame Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of participants analyzed = participants with baseline peak pruritus NRS score ≥3.
Arm/Group Title Placebo qw Dupilumab 300 mg q2w Dupilumab 300 mg qw
Hide Arm/Group Description:
Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51.
Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.
Two 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 of Dupilumab qw from Week 1 to Week 51.
Overall Number of Participants Analyzed 256 88 261
Measure Type: Number
Unit of Measure: percentage of participants
15.6 55.7 42.9
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo qw, Dupilumab 300 mg q2w
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity (IGA baseline values: IGA=3 vs IGA=4). Values after first rescue treatment were set to missing and participants with missing peak NRS at Week 52 were considered as non-responders.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.025 level.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in percentages
Estimated Value 40.1
Confidence Interval (2-Sided) 95%
28.76 to 51.35
Estimation Comments Dupilumab 300 mg q2w v Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo qw, Dupilumab 300 mg qw
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity (IGA baseline values: IGA=3 vs IGA=4). Values after first rescue treatment were set to missing and participants with missing peak NRS at Week 52 were considered as non-responders.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.025 level.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in percentages
Estimated Value 27.3
Confidence Interval (2-Sided) 95%
19.81 to 34.76
Estimation Comments Dupilumab 300 mg qw v Placebo
10.Secondary Outcome
Title Percentage of Participants With Improvement (Reduction ≥4 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 24
Hide Description Pruritus NRS was an assessment tool that was used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 [0 = no itch; 10 = worst itch imaginable]). Participants achieving a reduction of ≥4 points from baseline in weekly average of peak daily pruritus NRS score at Week 24 were reported.
Time Frame Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of participants analyzed = participants with baseline peak pruritus NRS score ≥4.
Arm/Group Title Placebo qw Dupilumab 300 mg q2w Dupilumab 300 mg qw
Hide Arm/Group Description:
Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51.
Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.
Two 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 of Dupilumab qw from Week 1 to Week 51.
Overall Number of Participants Analyzed 299 102 295
Measure Type: Number
Unit of Measure: percentage of participants
16.1 53.9 43.7
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo qw, Dupilumab 300 mg q2w
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity (IGA baseline values: IGA=3 vs IGA=4). Values after first rescue treatment were set to missing and participants with missing peak NRS at Week 24 were considered as non-responders.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.025 level.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in percentages
Estimated Value 37.9
Confidence Interval (2-Sided) 95%
27.34 to 48.40
Estimation Comments Dupilumab 300 mg q2w v Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo qw, Dupilumab 300 mg qw
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity (IGA baseline values: IGA=3 vs IGA=4). Values after first rescue treatment were set to missing and participants with missing peak NRS at Week 24 were considered as non-responders.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.025 level.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in percentages
Estimated Value 27.7
Confidence Interval (2-Sided) 95%
20.65 to 34.70
Estimation Comments Dupilumab 300 mg qw v Placebo
11.Secondary Outcome
Title Percentage of Participants With Improvement (Reduction ≥4 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 4
Hide Description Pruritus NRS was an assessment tool that was used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 [0 = no itch; 10 = worst itch imaginable]). Participants achieving a reduction of ≥4 points from baseline in weekly average of peak daily pruritus NRS score at Week 4 were reported.
Time Frame Baseline to Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of participants analyzed = participants with baseline peak pruritus NRS score ≥4.
Arm/Group Title Placebo qw Dupilumab 300 mg q2w Dupilumab 300 mg qw
Hide Arm/Group Description:
Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51.
Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.
Two 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 of Dupilumab qw from Week 1 to Week 51.
Overall Number of Participants Analyzed 299 102 295
Measure Type: Number
Unit of Measure: percentage of participants
16.4 37.3 27.1
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo qw, Dupilumab 300 mg q2w
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity (IGA baseline values: IGA=3 vs IGA=4). Values after first rescue treatment were set to missing and participants with missing peak NRS at Week 4 were considered as non-responders.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.025 level.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in percentages
Estimated Value 20.9
Confidence Interval (2-Sided) 95%
10.59 to 31.15
Estimation Comments Dupilumab 300 mg q2w v Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo qw, Dupilumab 300 mg qw
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity (IGA baseline values: IGA=3 vs IGA=4). Values after first rescue treatment were set to missing and participants with missing peak NRS at Week 4 were considered as non-responders.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0021
Comments Threshold for significance at 0.025 level.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in percentages
Estimated Value 10.7
Confidence Interval (2-Sided) 95%
4.15 to 17.31
Estimation Comments Dupilumab 300 mg qw v Placebo
12.Secondary Outcome
Title Percentage of Participants With Improvement (Reduction ≥4 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 2
Hide Description Pruritus NRS was an assessment tool that was used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 [0 = no itch; 10 = worst itch imaginable]). Participants achieving a reduction of ≥4 points from baseline in weekly average of peak daily pruritus NRS score at Week 2 were reported.
Time Frame Baseline to Week 2
Hide Outcome Measure Data
Hide Analysis Population Description
All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of participants analyzed = participants with baseline peak pruritus NRS score ≥4.
Arm/Group Title Placebo qw Dupilumab 300 mg q2w Dupilumab 300 mg qw
Hide Arm/Group Description:
Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51.
Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.
Two 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 of Dupilumab qw from Week 1 to Week 51.
Overall Number of Participants Analyzed 299 102 295
Measure Type: Number
Unit of Measure: percentage of participants
8.0 17.6 13.6
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo qw, Dupilumab 300 mg q2w
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity (IGA baseline values: IGA=3 vs IGA=4). Values after first rescue treatment were set to missing and participants with missing peak NRS at Week 2 were considered as non-responders.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0062
Comments Threshold for significance at 0.025 level.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in percentages
Estimated Value 9.6
Confidence Interval (2-Sided) 95%
1.61 to 17.63
Estimation Comments Dupilumab 300 mg q2w v Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo qw, Dupilumab 300 mg qw
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity (IGA baseline values: IGA=3 vs IGA=4). Values after first rescue treatment were set to missing and participants with missing peak NRS at Week 2 were considered as non-responders.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0344
Comments Threshold for significance at 0.025 level.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in percentages
Estimated Value 5.5
Confidence Interval (2-Sided) 95%
0.56 to 10.51
Estimation Comments Dupilumab 300 mg qw v Placebo
13.Secondary Outcome
Title Change From Baseline in Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score to Week 16
Hide Description Pruritus NRS was an assessment tool that was used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 [0 = no itch; 10 = worst itch imaginable]).
Time Frame Baseline to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).
Arm/Group Title Placebo qw Dupilumab 300 mg q2w Dupilumab 300 mg qw
Hide Arm/Group Description:
Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51.
Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.
Two 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 of Dupilumab qw from Week 1 to Week 51.
Overall Number of Participants Analyzed 315 106 319
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-2.36  (0.138) -4.17  (0.207) -4.27  (0.126)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo qw, Dupilumab 300 mg q2w
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using ANCOVA model with baseline measurements as covariate and the treatment, region and baseline IGA strata as fixed factors.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.025 level.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -1.81
Confidence Interval (2-Sided) 95%
-2.297 to -1.322
Estimation Comments Dupilumab 300 mg q2w v Placebo
14.Secondary Outcome
Title Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score to Week 16
Hide Description The EASI score was used to measure the severity and extent of AD and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD.
Time Frame Baseline to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).
Arm/Group Title Placebo qw Dupilumab 300 mg q2w Dupilumab 300 mg qw
Hide Arm/Group Description:
Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51.
Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.
Two 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 of Dupilumab qw from Week 1 to Week 51.
Overall Number of Participants Analyzed 188 92 269
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-48.4  (3.82) -80.5  (6.34) -81.5  (5.78)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo qw, Dupilumab 300 mg q2w
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using ANCOVA model with baseline measurements as covariate and the treatment, region and baseline IGA strata as fixed factors.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.025 level.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -32.1
Confidence Interval (2-Sided) 95%
-46.37 to -17.82
Estimation Comments Dupilumab 300 mg q2w v Placebo
15.Secondary Outcome
Title Change From Baseline in Percent Body Surface Area (BSA) Affected by Atopic Dermatitis to Week 16
Hide Description BSA affected by AD was assessed for each section of the body (the possible highest score for each region was: head and neck [9%], anterior trunk [18%], back [18%], upper limbs [18%], lower limbs [36%], and genitals [1%]). It was reported as a percentage of all major body sections combined.
Time Frame Baseline to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).
Arm/Group Title Placebo qw Dupilumab 300 mg q2w Dupilumab 300 mg qw
Hide Arm/Group Description:
Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51.
Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.
Two 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 of Dupilumab qw from Week 1 to Week 51.
Overall Number of Participants Analyzed 315 106 319
Least Squares Mean (Standard Error)
Unit of Measure: Percentage of BSA
-22.01  (1.158) -40.39  (1.844) -39.58  (1.065)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo qw, Dupilumab 300 mg q2w
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using ANCOVA model with baseline measurements as covariate and the treatment, region and baseline IGA strata as fixed factors.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.025 level.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -18.38
Confidence Interval (2-Sided) 95%
-22.583 to -14.187
Estimation Comments Dupilumab 300 mg q2w v Placebo
16.Secondary Outcome
Title Percent Change From Baseline in the SCORing Atopic Dermatitis (SCORAD) Score to Week 16
Hide Description SCORAD was a clinical tool for assessing the severity of AD developed by the European Task Force on Atopic Dermatitis (Severity scoring of atopic dermatitis: the SCORAD index). Consensus Report of the European Task Force on Atopic Dermatitis. Dermatology (Basel) 186 (1): 23-31. 1993. Extent and intensity of eczema as well as subjective signs (insomnia, etc.) were assessed and scored. Total score ranges from 0 (absent disease) to 103 (severe disease).
Time Frame Baseline to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).
Arm/Group Title Placebo qw Dupilumab 300 mg q2w Dupilumab 300 mg qw
Hide Arm/Group Description:
Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51.
Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.
Two 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 of Dupilumab qw from Week 1 to Week 51.
Overall Number of Participants Analyzed 315 106 319
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-36.2  (1.66) -63.9  (2.52) -65.9  (1.49)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo qw, Dupilumab 300 mg q2w
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using ANCOVA model with baseline measurements as covariate and the treatment, region and baseline IGA strata as fixed factors.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.025 level.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -27.7
Confidence Interval (2-Sided) 95%
-33.46 to -21.9
Estimation Comments Dupilumab 300 mg q2w v Placebo
17.Secondary Outcome
Title Change From Baseline in Dermatology Life Quality Index (DLQI) to Week 16
Hide Description The DLQI was a 10-item, validated questionnaire used in clinical practice and clinical trials to assess the impact of AD disease symptoms and treatment on quality of life (QOL). The 10 questions assessed QOL over the past week, with an overall scoring of 0 (absent disease) to 30 (severe disease); a high score was indicative of a poor QOL.
Time Frame Baseline to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).
Arm/Group Title Placebo qw Dupilumab 300 mg q2w Dupilumab 300 mg qw
Hide Arm/Group Description:
Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51.
Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.
Two 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 of Dupilumab qw from Week 1 to Week 51.
Overall Number of Participants Analyzed 315 106 319
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-5.8  (0.34) -10.0  (0.5) -10.7  (0.31)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo qw, Dupilumab 300 mg q2w
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using ANCOVA model with baseline measurements as covariate and the treatment, region and baseline IGA strata as fixed factors.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.025 level.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -4.2
Confidence Interval (2-Sided) 95%
-5.31 to -3.02
Estimation Comments Dupilumab 300 mg q2w v Placebo
18.Secondary Outcome
Title Change From Baseline in Patient Oriented Eczema Measure (POEM) to Week 16
Hide Description The POEM was a 7-item questionnaire that assessed disease symptoms (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) with a scoring system of 0 (absent disease) to 28 (severe disease) (high score indicative of poor quality of life [QOL]).
Time Frame Baseline to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).
Arm/Group Title Placebo qw Dupilumab 300 mg q2w Dupilumab 300 mg qw
Hide Arm/Group Description:
Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51.
Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.
Two 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 of Dupilumab qw from Week 1 to Week 51.
Overall Number of Participants Analyzed 315 106 319
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-5.3  (0.41) -12.7  (0.64) -12.9  (0.37)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo qw, Dupilumab 300 mg q2w
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using ANCOVA model with baseline measurements as covariate and the treatment, region and baseline IGA strata as fixed factors.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.025 level.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -7.4
Confidence Interval (2-Sided) 95%
-8.85 to -5.93
Estimation Comments Dupilumab 300 mg q2w v Placebo
19.Secondary Outcome
Title Change From Baseline in Hospital Anxiety Depression Scale (HADS) to Week 16
Hide Description HADS is a fourteen item scale. Seven of the items relate to anxiety and seven items relate to depression. Each item on the questionnaire scored from 0 (minimum score) - 3 (maximum score) and this means that a person can score between 0 (no symptoms) and 21 (severe symptoms) for either anxiety or depression. Cut-offs for identifying psychiatric distress has been reported as 7 to 8 for possible presence, 10 to 11 for probable presence, and 14 to 15 for severe anxiety or depression.
Time Frame Baseline to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).
Arm/Group Title Placebo qw Dupilumab 300 mg q2w Dupilumab 300 mg qw
Hide Arm/Group Description:
Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51.
Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.
Two 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 of Dupilumab qw from Week 1 to Week 51.
Overall Number of Participants Analyzed 315 106 319
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-4.0  (0.37) -4.9  (0.58) -5.4  (0.35)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo qw, Dupilumab 300 mg q2w
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using ANCOVA model with baseline measurements as covariate and the treatment, region and baseline IGA strata as fixed factors.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1596
Comments Threshold for significance at 0.025 level.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -1.00
Confidence Interval (2-Sided) 95%
-2.27 to 0.37
Estimation Comments Dupilumab 300 mg q2w v Placebo
20.Secondary Outcome
Title Percent Change From Baseline in Total Global Individual Signs Score (GISS) to Week 16
Hide Description Individual components of the AD lesions (erythema, infiltration/ papulation, excoriations, and lichenification) were rated globally (each assessed for the whole body, not by anatomical region) on a 4-point scale (0= none, 1= mild, 2= moderate and 3= severe) using the EASI severity grading criteria. Total score ranges from 0 (absent disease) to 12 (severe disease).
Time Frame Baseline to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).
Arm/Group Title Placebo qw Dupilumab 300 mg q2w Dupilumab 300 mg qw
Hide Arm/Group Description:
Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51.
Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.
Two 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 of Dupilumab qw from Week 1 to Week 51.
Overall Number of Participants Analyzed 315 106 319
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-33.3  (1.89) -55.4  (2.69) -59.3  (1.64)
21.Secondary Outcome
Title Proportion of Topical Atopic Dermatitis Medication-Free Days Through Week 52
Hide Description Proportion of topical AD medication-free days through Week 52 was calculated as the number of days that a participant used neither topical corticosteroid (TCS)/ topical calcineurin inhibitors (TCI) nor system rescue therapy divided by the study days of each period.
Time Frame Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).
Arm/Group Title Placebo qw Dupilumab 300 mg q2w Dupilumab 300 mg qw
Hide Arm/Group Description:
Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51.
Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.
Two 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 of Dupilumab qw from Week 1 to Week 51.
Overall Number of Participants Analyzed 315 106 319
Mean (Standard Deviation)
Unit of Measure: days
10.5  (23.68) 16.6  (30.08) 22.5  (33.69)
22.Secondary Outcome
Title Percent Change From Baseline in Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score to Week 2
Hide Description Pruritus NRS was an assessment tool that was used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 [0 = no itch; 10 = worst itch imaginable]).
Time Frame Baseline to Week 2
Hide Outcome Measure Data
Hide Analysis Population Description
All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).
Arm/Group Title Placebo qw Dupilumab 300 mg q2w Dupilumab 300 mg qw
Hide Arm/Group Description:
Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51.
Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.
Two 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 of Dupilumab qw from Week 1 to Week 51.
Overall Number of Participants Analyzed 315 106 319
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-19.7  (1.58) -27.3  (2.67) -25.7  (1.57)
23.Secondary Outcome
Title Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score to Week 52
Hide Description The EASI score was used to measure the severity and extent of AD and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD.
Time Frame Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of participants analyzed = participants with available data for this endpoint.
Arm/Group Title Placebo qw Dupilumab 300 mg q2w Dupilumab 300 mg qw
Hide Arm/Group Description:
Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51.
Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.
Two 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 of Dupilumab qw from Week 1 to Week 51.
Overall Number of Participants Analyzed 264 89 270
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-60.9  (4.29) -84.9  (6.73) -87.8  (6.19)
24.Secondary Outcome
Title Change From Baseline in Percent Body Surface Area (BSA) Affected by Atopic Dermatitis to Week 52
Hide Description BSA affected by AD was assessed for each section of the body (the possible highest score for each region was: head and neck [9%], anterior trunk [18%], back [18%], upper limbs [18%], lower limbs [36%], and genitals [1%]). It was reported as a percentage of all major body sections combined.
Time Frame Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of participants analyzed = participants with available data for this endpoint.
Arm/Group Title Placebo qw Dupilumab 300 mg q2w Dupilumab 300 mg qw
Hide Arm/Group Description:
Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51.
Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.
Two 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 of Dupilumab qw from Week 1 to Week 51.
Overall Number of Participants Analyzed 264 89 270
Least Squares Mean (Standard Error)
Unit of Measure: Percentage of BSA
-29.41  (1.443) -43.75  (1.874) -43.67  (1.143)
25.Secondary Outcome
Title Percent Change From Baseline in the SCORing Atopic Dermatitis (SCORAD) Score to Week 52
Hide Description SCORAD was a clinical tool for assessing the severity of AD developed by the European Task Force on Atopic Dermatitis (Severity scoring of atopic dermatitis: the SCORAD index). Consensus Report of the European Task Force on Atopic Dermatitis. Dermatology (Basel) 186 (1): 23-31. 1993. Extent and intensity of eczema as well as subjective signs (insomnia, etc.) were assessed and scored. Total score ranges from 0 (absent disease) to 103 (severe disease).
Time Frame Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of participants analyzed = participants with available data for this endpoint.
Arm/Group Title Placebo qw Dupilumab 300 mg q2w Dupilumab 300 mg qw
Hide Arm/Group Description:
Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51.
Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.
Two 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 of Dupilumab qw from Week 1 to Week 51.
Overall Number of Participants Analyzed 264 89 270
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-47.3  (2.18) -69.7  (3.06) -70.4  (1.72)
26.Secondary Outcome
Title Percent Change From Baseline in Global Individual Signs Score (GISS) to Week 52
Hide Description Individual components of the AD lesions (erythema, infiltration/ papulation, excoriations, and lichenification) were rated globally (each assessed for the whole body, not by anatomical region) on a 4-point scale (0= none, 1= mild, 2= moderate and 3= severe) using the EASI severity grading criteria. Total score ranges from 0 (absent disease) to 12 (severe disease).
Time Frame Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of participants analyzed = participants with available data for this endpoint.
Arm/Group Title Placebo qw Dupilumab 300 mg q2w Dupilumab 300 mg qw
Hide Arm/Group Description:
Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51.
Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.
Two 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 of Dupilumab qw from Week 1 to Week 51.
Overall Number of Participants Analyzed 264 89 270
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-40.8  (2.72) -62.8  (3.35) -64.4  (2.13)
27.Secondary Outcome
Title Change From Baseline in Dermatology Life Quality Index (DLQI) to Week 52
Hide Description The DLQI was a 10-item, validated questionnaire used in clinical practice and clinical trials to assess the impact of AD disease symptoms and treatment on quality of life (QOL). The 10 questions assessed QOL over the past week, with an overall scoring of 0 (absent disease) to 30 (severe disease); a high score was indicative of a poor QOL.
Time Frame Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of participants analyzed = participants with available data for this endpoint.
Arm/Group Title Placebo qw Dupilumab 300 mg q2w Dupilumab 300 mg qw
Hide Arm/Group Description:
Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51.
Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.
Two 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 of Dupilumab qw from Week 1 to Week 51.
Overall Number of Participants Analyzed 264 89 270
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-7.2  (0.4) -11.4  (0.57) -11.1  (0.36)
28.Secondary Outcome
Title Change From Baseline in Patient Oriented Eczema Measure (POEM) to Week 52
Hide Description The POEM was a 7-item questionnaire that assesses disease symptoms (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) with a scoring system of 0 (absent disease) to 28 (severe disease) (high score indicative of poor quality of life [QOL]).
Time Frame Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of participants analyzed = participants with available data for this endpoint.
Arm/Group Title Placebo qw Dupilumab 300 mg q2w Dupilumab 300 mg qw
Hide Arm/Group Description:
Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51.
Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.
Two 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 of Dupilumab qw from Week 1 to Week 51.
Overall Number of Participants Analyzed 264 89 270
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-7.0  (0.57) -14.2  (0.78) -13.2  (0.45)
29.Secondary Outcome
Title Change From Baseline in Hospital Anxiety Depression Scale (HADS) to Week 52
Hide Description HADS is a fourteen item scale. Seven of the items relate to anxiety and seven items relate to depression. Each item on the questionnaire is scored from 0 (minimum score) - 3 (maximum score) and this means that a person can score between 0 (no symptoms) and 21 (severe symptoms) for either anxiety or depression. Cut-offs for identifying psychiatric distress has been reported as 7 to 8 for possible presence, 10 to 11 for probable presence, and 14 to 15 for severe anxiety or depression.
Time Frame Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of participants analyzed = participants with available data for this endpoint.
Arm/Group Title Placebo qw Dupilumab 300 mg q2w Dupilumab 300 mg qw
Hide Arm/Group Description:
Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51.
Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.
Two 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 of Dupilumab qw from Week 1 to Week 51.
Overall Number of Participants Analyzed 264 89 270
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-3.8  (0.47) -5.5  (0.71) -5.9  (0.42)
30.Secondary Outcome
Title Number of Flares Through Week 52
Hide Description Atopic dermatitis (AD) flares were defined as worsening of the disease that required escalation/intensification of AD treatment. Number of flares occurred in the participants starting from first dose through Week 52 were reported.
Time Frame Baseline up to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
All safety analysis were performed on safety analysis set (SAF) that included all randomized participants who received any study drug, and were analyzed as-treated.
Arm/Group Title Placebo qw Dupilumab 300 mg q2w Dupilumab 300 mg qw
Hide Arm/Group Description:
Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51.
Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo. Four participants received fewer injections of Dupilumab 300 mg in Dupilumab 300 qw arm, were analyzed in Dupilumab 300 mg q2w arm.
Two 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 of Dupilumab qw from Week 1 to Week 51. Four participants received fewer injections of Dupilumab 300 mg in Dupilumab 300 qw arm, were analyzed in Dupilumab 300 mg q2w arm.
Overall Number of Participants Analyzed 315 110 315
Measure Type: Number
Unit of Measure: flares
216 20 51
31.Secondary Outcome
Title Number of Serious Treatment Emergent Adverse Events (TEAEs) Leading to Study Drug Discontinuation Through Week 52
Hide Description Any untoward medical occurrence in a participant who received investigational medicinal product (IMP) was considered an AE without regard to possibility of causal relationship with this treatment. A 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 participants with both serious and non-serious AEs.
Time Frame Baseline up to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
All safety analysis were performed on SAF that included all randomized participants who received any study drug, and was analyzed as-treated.
Arm/Group Title Placebo qw Dupilumab 300 mg q2w Dupilumab 300 mg qw
Hide Arm/Group Description:
Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51.
Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo. Four participants received fewer injections of Dupilumab 300 mg in Dupilumab 300 qw arm, were analyzed in Dupilumab 300 mg q2w arm.
Two 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 of Dupilumab qw from Week 1 to Week 51. Four participants received fewer injections of Dupilumab 300 mg in Dupilumab 300 qw arm, were analyzed in Dupilumab 300 mg q2w arm.
Overall Number of Participants Analyzed 315 110 315
Measure Type: Number
Unit of Measure: events
28 2 10
32.Secondary Outcome
Title Percentage of Participants With Skin Infection Treatment Emergent Adverse Events (TEAEs) (Excluding Herpetic Infections) From Baseline Through Week 52
Hide Description Any untoward medical occurrence in a participants who received IMP was considered an AE without regard to possibility of causal relationship with this treatment. TEAEs were defined as AEs that developed or worsened or became serious during on-treatment period (time from the first dose of study drug up to end of treatment at Week 52). Any TEAE included participants with both serious and non-serious AEs. Skin infection TEAEs were identified based on blinded adjudication of all reported TEAEs under the 2 primary System Organ Classes (SOC): SOC = "Infection and Infestations" or SOC = "Skin and Subcutaneous Tissue Disorders". Blinded adjudication was performed and finalized by the study medical monitor before database lock.
Time Frame Baseline up to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
All safety analysis were performed on SAF that included all randomized participants who received any study drug, and was analyzed as-treated.
Arm/Group Title Placebo qw Dupilumab 300 mg q2w Dupilumab 300 mg qw
Hide Arm/Group Description:
Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51.
Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo. Four participants received fewer injections of Dupilumab 300 mg in Dupilumab 300 qw arm, were analyzed in Dupilumab 300 mg q2w arm.
Two 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 of Dupilumab qw from Week 1 to Week 51. Four participants received fewer injections of Dupilumab 300 mg in Dupilumab 300 qw arm, were analyzed in Dupilumab 300 mg q2w arm.
Overall Number of Participants Analyzed 315 110 315
Measure Type: Number
Unit of Measure: percentage of participants
17.8 10.9 8.3
33.Secondary Outcome
Title Number of Skin Infection TEAEs (Excluding Herpetic Infections) From Baseline Through Week 52
Hide Description Any untoward medical occurrence in a participant who received IMP was considered an AE without regard to possibility of causal relationship with this treatment. TEAEs were defined as AEs that developed or worsened or became serious during on-treatment period (time from the first dose of study drug up to end of treatment at Week 52). Any TEAE included participants with both serious and non-serious AEs. Skin infection TEAEs were identified based on blinded adjudication of all reported TEAEs under the 2 primary System Organ Classes (SOC): SOC = "Infection and Infestations" or SOC = "Skin and Subcutaneous Tissue Disorders". Blinded adjudication was performed and finalized by the study medical monitor before database lock.
Time Frame Baseline up to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
All safety analysis were performed on SAF that included all randomized participants who received any study drug, and was analyzed as-treated.
Arm/Group Title Placebo qw Dupilumab 300 mg q2w Dupilumab 300 mg qw
Hide Arm/Group Description:
Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51.
Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo. Four participants received fewer injections of Dupilumab 300 mg in Dupilumab 300 qw arm, were analyzed in Dupilumab 300 mg q2w arm.
Two 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 of Dupilumab qw from Week 1 to Week 51. Four participants received fewer injections of Dupilumab 300 mg in Dupilumab 300 qw arm, were analyzed in Dupilumab 300 mg q2w arm.
Overall Number of Participants Analyzed 315 110 315
Measure Type: Number
Unit of Measure: events
80 15 29
34.Secondary Outcome
Title Percentage of Participants With Skin Infection Treatment Emergent Adverse Events (TEAEs) (Excluding Herpetic Infections) Requiring Systemic Treatment From Baseline Through Week 52
Hide Description Any untoward medical occurrence in a participant who received IMP was considered an AE without regard to possibility of causal relationship with this treatment. TEAEs were defined as AEs that developed or worsened or became serious during on-treatment period (time from the first dose of study drug up to end of treatment at Week 52). Any TEAE included participants with both serious and non-serious AEs. Skin infection TEAEs were identified based on blinded adjudication of all reported TEAEs under the 2 primary System Organ Classes (SOC): SOC = "Infection and Infestations" or SOC = "Skin and Subcutaneous Tissue Disorders". Blinded adjudication was performed and finalized by the study medical monitor before database lock.
Time Frame Baseline up to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
All safety analysis were performed on SAF that included all randomized participants who received any study drug, and was analyzed as-treated.
Arm/Group Title Placebo qw Dupilumab 300 mg q2w Dupilumab 300 mg qw
Hide Arm/Group Description:
Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51.
Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo. Four participants received fewer injections of Dupilumab 300 mg in Dupilumab 300 qw arm, were analyzed in Dupilumab 300 mg q2w arm.
Two 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 of Dupilumab qw from Week 1 to Week 51. Four participants received fewer injections of Dupilumab 300 mg in Dupilumab 300 qw arm, were analyzed in Dupilumab 300 mg q2w arm.
Overall Number of Participants Analyzed 315 110 315
Measure Type: Number
Unit of Measure: percentage of participants
9.5 5.5 3.8
35.Secondary Outcome
Title Number of Skin Infection Treatment Emergent Adverse Events (TEAEs) (Excluding Herpetic Infections) Requiring Systemic Treatment From Baseline Through Week 52
Hide Description Any untoward medical occurrence in a participant who received IMP was considered an AE without regard to possibility of causal relationship with this treatment. TEAEs were defined as AEs that developed or worsened or became serious during on-treatment period (time from the first dose of study drug up to end of treatment at Week 52). Any TEAE included participants with both serious and non-serious AEs. Skin infection TEAEs were identified based on blinded adjudication of all reported TEAEs under the 2 primary System Organ Classes (SOC): SOC = "Infection and Infestations" or SOC = "Skin and Subcutaneous Tissue Disorders". Blinded adjudication was performed and finalized by the study medical monitor before database lock.
Time Frame Baseline up to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
All safety analysis were performed on SAF that included all randomized participants who received any study drug, and was analyzed as-treated.
Arm/Group Title Placebo qw Dupilumab 300 mg q2w Dupilumab 300 mg qw
Hide Arm/Group Description:
Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51.
Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.Four participants received fewer injections of Dupilumab 300 mg in Dupilumab 300 qw arm, were analyzed in Dupilumab 300 mg q2w arm.
Two 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 of Dupilumab qw from Week 1 to Week 51. Four participants received fewer injections of Dupilumab 300 mg in Dupilumab 300 qw arm, were analyzed in Dupilumab 300 mg q2w arm.
Overall Number of Participants Analyzed 315 110 315
Measure Type: Number
Unit of Measure: events
44 7 13
36.Other Pre-specified Outcome
Title Change From Baseline in Sinonasal Outcome Test (SNOT-22) Score to Week 16
Hide Description The SNOT 22 was a validated measure of health related quality of life in sinonasal disease. It was 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). The SNOT-22 was administered only to participants with chronic inflammatory conditions of the nasal mucosa and/or paranasal sinuses.
Time Frame Baseline to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of participants analyzed = participants with available data for this endpoint.
Arm/Group Title Placebo qw Dupilumab 300 mg q2w Dupilumab 300 mg qw
Hide Arm/Group Description:
Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51.
Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.
Two 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 of Dupilumab qw from Week 1 to Week 51.
Overall Number of Participants Analyzed 99 45 99
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-4.77  (1.903) -6.38  (2.445) -10.39  (1.63)
37.Other Pre-specified Outcome
Title Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score to Week 16
Hide Description ACQ-5 questionnaire was a validated questionnaire comprising of 5 questions for asthma symptoms: woken at night by symptoms, wake in the mornings with symptoms, limitation of daily activities, shortness of breath, and wheeze. Participants were asked to rate their asthma symptoms during the previous week on a 7-point scale as 0=no impairment, 6=maximum impairment. ACQ-5 score was the mean of the 5 questions and range between 0 (totally controlled) and 6 (severely uncontrolled) (a higher score indicated lower asthma control). The ACQ-5 questionnaire was administered only to the participants with a medical history of asthma.
Time Frame Baseline to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of participants analyzed = participants with ACQ-5 value at baseline.
Arm/Group Title Placebo qw Dupilumab 300 mg q2w Dupilumab 300 mg qw
Hide Arm/Group Description:
Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51.
Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.
Two 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 of Dupilumab qw from Week 1 to Week 51.
Overall Number of Participants Analyzed 154 48 145
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.12  (0.082) -0.19  (0.113) -0.36  (0.068)
Time Frame Time-frame was 'On treatment (Week 52) period' defined time from administration of first dose of study drug to study completion date of Week 52 visit (365 days starting from first dose of study drug if the date of Week 52 visit was unavailable).
Adverse Event Reporting Description All Adverse Events (AEs) were collected from signature of informed consent form up to study completion date of the Week 52 visit regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment-emergent that is AEs that developed/worsened and deaths that occurred during 'On treatment (Week 52) period'. Analysis was performed on SAF.
 
Arm/Group Title Placebo qw Dupilumab 300 mg q2w Dupilumab 300 mg qw
Hide Arm/Group Description Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51. Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo. Four participants received fewer injections of Dupilumab 300 mg in Dupilumab 300 qw arm, were analyzed in Dupilumab 300 mg q2w arm. Two 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 of Dupilumab qw from Week 1 to Week 51. Four participants received fewer injections of Dupilumab 300 mg in Dupilumab 300 qw arm, were analyzed in Dupilumab 300 mg q2w arm.
All-Cause Mortality
Placebo qw Dupilumab 300 mg q2w Dupilumab 300 mg qw
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/315 (0.00%)      0/110 (0.00%)      1/315 (0.32%)    
Hide Serious Adverse Events
Placebo qw Dupilumab 300 mg q2w Dupilumab 300 mg qw
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   20/315 (6.35%)      4/110 (3.64%)      12/315 (3.81%)    
Cardiac disorders       
Acute myocardial infarction  1  1/315 (0.32%)  1 0/110 (0.00%)  0 0/315 (0.00%)  0
Eye disorders       
Cataract  1  1/315 (0.32%)  1 0/110 (0.00%)  0 0/315 (0.00%)  0
Cystoid macular oedema  1  0/315 (0.00%)  0 0/110 (0.00%)  0 1/315 (0.32%)  1
Glaucoma  1  1/315 (0.32%)  1 0/110 (0.00%)  0 0/315 (0.00%)  0
Gastrointestinal disorders       
Pancreatitis  1  1/315 (0.32%)  1 0/110 (0.00%)  0 0/315 (0.00%)  0
General disorders       
Soft tissue inflammation  1  1/315 (0.32%)  1 0/110 (0.00%)  0 0/315 (0.00%)  0
Hepatobiliary disorders       
Cholelithiasis  1  0/315 (0.00%)  0 0/110 (0.00%)  0 1/315 (0.32%)  1
Infections and infestations       
Abdominal wall abscess  1  1/315 (0.32%)  1 0/110 (0.00%)  0 0/315 (0.00%)  0
Appendicitis  1  0/315 (0.00%)  0 0/110 (0.00%)  0 1/315 (0.32%)  1
Bronchitis  1  1/315 (0.32%)  1 0/110 (0.00%)  0 0/315 (0.00%)  0
Eczema herpeticum  1  1/315 (0.32%)  1 0/110 (0.00%)  0 0/315 (0.00%)  0
Pneumonia  1  1/315 (0.32%)  1 0/110 (0.00%)  0 0/315 (0.00%)  0
Superinfection bacterial  1  0/315 (0.00%)  0 1/110 (0.91%)  1 0/315 (0.00%)  0
Injury, poisoning and procedural complications       
Clavicle fracture  1  1/315 (0.32%)  1 0/110 (0.00%)  0 0/315 (0.00%)  0
Concussion  1  1/315 (0.32%)  1 0/110 (0.00%)  0 0/315 (0.00%)  0
Contusion  1  1/315 (0.32%)  1 0/110 (0.00%)  0 0/315 (0.00%)  0
Ligament rupture  1  1/315 (0.32%)  1 0/110 (0.00%)  0 0/315 (0.00%)  0
Limb traumatic amputation  1  1/315 (0.32%)  1 0/110 (0.00%)  0 0/315 (0.00%)  0
Road traffic accident  1  0/315 (0.00%)  0 0/110 (0.00%)  0 1/315 (0.32%)  1
Spinal compression fracture  1  0/315 (0.00%)  0 0/110 (0.00%)  0 1/315 (0.32%)  1
Investigations       
Liver function test abnormal  1  1/315 (0.32%)  1 0/110 (0.00%)  0 0/315 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Pseudarthrosis  1  1/315 (0.32%)  1 0/110 (0.00%)  0 0/315 (0.00%)  0
Osteoarthritis  1  0/315 (0.00%)  0 0/110 (0.00%)  0 1/315 (0.32%)  1
Spondylolisthesis  1  0/315 (0.00%)  0 0/110 (0.00%)  0 1/315 (0.32%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Cervix carcinoma  1  1/315 (0.32%)  1 0/110 (0.00%)  0 0/315 (0.00%)  0
Penile squamous cell carcinoma  1  1/315 (0.32%)  1 0/110 (0.00%)  0 0/315 (0.00%)  0
Squamous cell carcinoma  1  1/315 (0.32%)  1 0/110 (0.00%)  0 1/315 (0.32%)  1
Squamous cell carcinoma of skin  1  0/315 (0.00%)  0 1/110 (0.91%)  1 1/315 (0.32%)  1
Squamous cell carcinoma of the tongue  1  0/315 (0.00%)  0 0/110 (0.00%)  0 1/315 (0.32%)  1
Uterine leiomyoma  1  1/315 (0.32%)  1 0/110 (0.00%)  0 0/315 (0.00%)  0
Nervous system disorders       
Carotid artery stenosis  1  1/315 (0.32%)  1 0/110 (0.00%)  0 0/315 (0.00%)  0
Cerebral infarction  1  0/315 (0.00%)  0 1/110 (0.91%)  1 0/315 (0.00%)  0
Cerebrovascular accident  1  1/315 (0.32%)  1 0/110 (0.00%)  0 0/315 (0.00%)  0
Psychiatric disorders       
Anxiety  1  0/315 (0.00%)  0 1/110 (0.91%)  2 0/315 (0.00%)  0
Skin and subcutaneous tissue disorders       
Dermatitis atopic  1  1/315 (0.32%)  1 1/110 (0.91%)  1 1/315 (0.32%)  2
Rash maculo-papular  1  0/315 (0.00%)  0 0/110 (0.00%)  0 1/315 (0.32%)  1
Urticaria  1  1/315 (0.32%)  1 0/110 (0.00%)  0 0/315 (0.00%)  0
Vascular disorders       
Hypertension  1  1/315 (0.32%)  1 0/110 (0.00%)  0 0/315 (0.00%)  0
Venous thrombosis limb  1  1/315 (0.32%)  1 0/110 (0.00%)  0 0/315 (0.00%)  0
1
Term from vocabulary, meddra (18.0)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo qw Dupilumab 300 mg q2w Dupilumab 300 mg qw
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   216/315 (68.57%)      74/110 (67.27%)      228/315 (72.38%)    
Eye disorders       
Blepharitis  1  3/315 (0.95%)  3 6/110 (5.45%)  7 11/315 (3.49%)  14
Conjunctivitis allergic  1  19/315 (6.03%)  22 13/110 (11.82%)  20 54/315 (17.14%)  74
General disorders       
Injection site reaction  1  24/315 (7.62%)  102 16/110 (14.55%)  34 60/315 (19.05%)  224
Infections and infestations       
Influenza  1  17/315 (5.40%)  25 4/110 (3.64%)  4 9/315 (2.86%)  13
Nasopharyngitis  1  62/315 (19.68%)  89 26/110 (23.64%)  40 63/315 (20.00%)  88
Oral herpes  1  10/315 (3.17%)  15 4/110 (3.64%)  9 17/315 (5.40%)  31
Sinusitis  1  9/315 (2.86%)  11 2/110 (1.82%)  2 18/315 (5.71%)  20
Upper respiratory tract infection  1  34/315 (10.79%)  52 11/110 (10.00%)  21 46/315 (14.60%)  78
Urinary tract infection  1  14/315 (4.44%)  16 2/110 (1.82%)  3 16/315 (5.08%)  22
Nervous system disorders       
Headache  1  19/315 (6.03%)  30 5/110 (4.55%)  5 24/315 (7.62%)  48
Respiratory, thoracic and mediastinal disorders       
Asthma  1  19/315 (6.03%)  23 5/110 (4.55%)  5 7/315 (2.22%)  7
Skin and subcutaneous tissue disorders       
Dermatitis atopic  1  161/315 (51.11%)  278 40/110 (36.36%)  52 91/315 (28.89%)  133
1
Term from vocabulary, meddra (18.0)
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.
Not less than 45 days prior to submission for publication or presentation, the Institution shall, or cause the Principal Investigator to, provide the Sponsor with a copy of the Manuscript. The Institution shall consider in good faith any comments from the Sponsor regarding the content, and shall delete Confidential Information upon written request of the Sponsor. At the Sponsor's request, the Institution shall delay publication for an additional 60 days to allow patent applications to be filed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Clinical Trial Management
Organization: Regeneron Pharmaceuticals, Inc.
EMail: clinicaltrials@regeneron.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02260986    
Other Study ID Numbers: R668-AD-1224
First Submitted: October 6, 2014
First Posted: October 9, 2014
Results First Submitted: April 30, 2017
Results First Posted: October 17, 2017
Last Update Posted: October 17, 2017