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Trial record 1 of 1 for:    R668-AD-1526
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Efficacy and Safety of Dupilumab in Participants ≥12 to <18 Years of Age, With Moderate-to-severe Atopic Dermatitis

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: NCT03054428
Recruitment Status : Completed
First Posted : February 15, 2017
Results First Posted : July 23, 2019
Last Update Posted : July 23, 2019
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
Regeneron Pharmaceuticals

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Moderate-to-Severe Atopic Dermatitis
Dermatitis, Dermatitis Atopic
Eczema, Skin Diseases, Skin
Diseases Genetic, Genetic
Diseases Inborn, Skin
Disease, Eczematous Skin
Hypersensitivity, Immediate
Hypersensitivity, Immune System Diseases
Dermatitis, Atopic
Interventions Drug: Dupilumab
Drug: Placebo
Enrollment 251
Recruitment Details The study was conducted at 45 sites in the United States and Canada between 21 Mar 2017 and 05 Jun 2018. A total of 295 participants were screened, of which, 251 were eligible. The most common causes for screening failures were lack of adequate disease severity and lack of willingness to comply with study visits and procedures.
Pre-assignment Details Eligible participants were randomized (1:1:1) & stratified by baseline Investigator's Global Assessment (IGA) score (3 vs 4) & body weight (<60 kg vs ≥60 kg) to 16 wks treatment with dupilumab every 2 wks (q2w) or q4w,or placebo q2w.
Arm/Group Title Placebo Dupilumab 300 mg Q4W Dupilumab 200 mg or 300 mg Q2W
Hide Arm/Group Description Participants received placebo matching dupilumab once every 2 weeks (Q2W) (including doubling the amount of placebo on day 1 to match the loading dose). Participants in the <60-kilogram (kg) weight stratum received, in a 1:1 ratio, either placebo matching 200 milligram (mg) or placebo matching 300 milligram (mg). In the ≥60 kg weight stratum, the participants randomized to the placebo group received placebo matching 300 mg dupilumab. Participants received once every 4 weeks (Q4W) subcutaneous (SC) injections of 300 milligrams (mg) dupilumab following a loading dose of 600 mg on day 1. To maintain blinding, all participants received an injection once every 2 weeks (Q2W) from day 1 to week 14. Participants received placebo 2 millilitre (mL) injection at the weeks dupilumab was not given. Participants with baseline weight <60 kg received once every 2 weeks (Q2W) subcutaneous (SC) injections of 200 milligrams (mg) dupilumab following a loading dose of 400 mg on day 1. Participants with baseline weight ≥60 kg received Q2W SC injections of 300 mg dupilumab following a loading dose of 600 mg on day 1.
Period Title: Overall Study
Started 85 84 82
Completed Wk 16 End of Treatment (EOT) 80 81 79
Completed Week 28 (End of Study) 2 4 3
Completed 2 4 3
Not Completed 83 80 79
Reason Not Completed
Physician Decision             0             1             1
Lack of Efficacy             3             1             0
Discontinued to enroll in OLE: enrolled             0             0             1
Discont'd to enroll in OLE: not enrolled             1             0             0
Transitioned to OLE study             76             76             73
Withdrawal by Subject             3             2             3
Lost to Follow-up             0             0             1
Arm/Group Title Placebo Dupilumab 300 mg Q4W Dupilumab 200 mg or 300 mg Q2W Total
Hide Arm/Group Description Participants received placebo matching dupilumab once every 2 weeks (Q2W) (including doubling the amount of placebo on day 1 to match the loading dose). Participants in the <60-kilogram (kg) weight stratum received, in a 1:1 ratio, either placebo matching 200 milligram (mg) or placebo matching 300 milligram (mg). In the ≥60 kg weight stratum, the participants randomized to the placebo group received placebo matching 300 mg dupilumab. Participants received once every 4 weeks (Q4W) subcutaneous (SC) injections of 300 milligrams (mg) dupilumab following a loading dose of 600 mg on day 1. To maintain blinding, all participants received an injection once every 2 weeks (Q2W) from day 1 to week 14. Participants received placebo 2 millilitre (mL) injection at the weeks dupilumab was not given. Participants with baseline weight <60 kg received once every 2 weeks (Q2W) subcutaneous (SC) injections of 200 milligrams (mg) dupilumab following a loading dose of 400 mg on day 1. Participants with baseline weight ≥60 kg received Q2W SC injections of 300 mg dupilumab following a loading dose of 600 mg on day 1. Total of all reporting groups
Overall Number of Baseline Participants 85 84 82 251
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 85 participants 84 participants 82 participants 251 participants
14.5  (1.78) 14.4  (1.59) 14.5  (1.74) 14.5  (1.70)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 85 participants 84 participants 82 participants 251 participants
≥12 to <15 years of age 41 45 43 129
≥15 to <18 years of age 44 39 39 122
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 85 participants 84 participants 82 participants 251 participants
Female
32
  37.6%
32
  38.1%
39
  47.6%
103
  41.0%
Male
53
  62.4%
52
  61.9%
43
  52.4%
148
  59.0%
Race/Ethnicity, Customized   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 85 participants 84 participants 82 participants 251 participants
White 48 55 54 157
Black or African American 15 8 7 30
Asian 13 13 12 38
Other 6 8 7 21
Not Reported/ Missing 3 0 2 5
[1]
Measure Description: Race
Race/Ethnicity, Customized   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 85 participants 84 participants 82 participants 251 participants
Not Hispanic or Latino 72 64 69 205
Hispanic or Latino 13 20 13 46
[1]
Measure Description: Ethnicity
Duration of Atopic Dermatitis (AD)  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 85 participants 84 participants 82 participants 251 participants
12.3  (3.44) 11.9  (3.18) 12.5  (2.97) 12.2  (3.20)
Eczema Area and Severity Index (EASI) Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Scores on a scale
Number Analyzed 85 participants 84 participants 82 participants 251 participants
35.5  (13.97) 35.8  (14.82) 35.3  (13.84) 35.5  (14.16)
[1]
Measure Description: The EASI score was used to measure the severity and extent of 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's Global Assessment (IGA) Score   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 85 participants 84 participants 82 participants 251 participants
IGA score = 3 (moderate)
39
  45.9%
38
  45.2%
39
  47.6%
116
  46.2%
IGA score = 4 (severe)
46
  54.1%
46
  54.8%
43
  52.4%
135
  53.8%
[1]
Measure Description: IGA is an assessment scale used to determine severity of atopic dermatitis (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).
Peak Weekly Averaged Pruritus Numerical Rating Scale (NRS) Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Peak weekly average score
Number Analyzed 85 participants 84 participants 82 participants 251 participants
7.7  (1.62) 7.5  (1.84) 7.5  (1.52) 7.6  (1.66)
[1]
Measure Description: Peak Pruritus NRS is an assessment tool used by participants to report intensity of pruritus (itch) during a 24-hour recall period. Participants were asked the following question for maximum itch intensity: "On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable,' how would you rate your itch at the worst moment during the previous 24 hours?" Baseline NRS was the prorated average of NRSs reported continuously for 7 days right before and on the baseline visit (i.e., study day -6 to day 1).
Body Surface Area (BSA) of Atopic Dermatitis (AD)   [1] 
Mean (Standard Deviation)
Unit of measure:  Percentage of BSA
Number Analyzed 85 participants 84 participants 82 participants 251 participants
56.4  (24.13) 56.9  (23.51) 56.0  (21.40) 56.5  (22.97)
[1]
Measure 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.
Scoring Atopic Dermatitis (SCORAD) Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Scores on a scale
Number Analyzed 85 participants 84 participants 82 participants 251 participants
70.4  (13.25) 69.8  (14.12) 70.6  (13.89) 70.3  (13.70)
[1]
Measure Description: The SCORAD index is a clinical tool for assessing the severity of atopic dermatitis. 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).
Patient Oriented Eczema Measure (POEM)   [1] 
Mean (Standard Deviation)
Unit of measure:  Scores on a scale
Number Analyzed 85 participants 84 participants 82 participants 251 participants
21.1  (5.38) 21.1  (5.47) 21.0  (5.01) 21.0  (5.27)
[1]
Measure Description: The POEM is a 7-item, validated questionnaire used in clinical practice and clinical trials to assess disease symptoms in children and adults with atopic eczema. The format is participant response to 7 items (dryness, itching, flaking, cracking, sleep loss, bleeding, and weeping) based on symptom frequency during the past week (ie, 0 = 'no days', 1 = '1 to 2 days', 2 = '3 to 4 days', 3 = '5 to 6' days, and 4 = 'every day'). The total score is the sum of the 7 items which is ranged from 0 to 28; a high score is indicative of a poor quality of life (QOL).
Children's Dermatology Life Quality Index (CDLQI) Total Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Scores on a scale
Number Analyzed 85 participants 84 participants 82 participants 251 participants
13.1  (6.72) 14.8  (7.38) 13.0  (6.21) 13.6  (6.82)
[1]
Measure Description: The CDLQI is a 10-item questionnaire used to measure how much a participant's skin problem had affected the participant's quality of life (QOL) over a recall period of the past week. The questionnaire consists of 10 items. For each item the scale is rated as follows: 0 = Not at all = Not relevant; 1 = Only a little; 2 = Quite a lot; 3 = Very much = Yes = Prevents school. The CDLQI total score is the sum of the score of each question with a maximum of 30 and a minimum of 0. The higher the score, the greater the impact is on the QOL.
Total Hospital Anxiety and Depression Scale (HADS)   [1] 
Mean (Standard Deviation)
Unit of measure:  Scores on a scale
Number Analyzed 85 participants 84 participants 82 participants 251 participants
11.6  (7.76) 13.3  (8.17) 12.6  (8.04) 12.5  (7.99)
[1]
Measure Description: The HADS is 14-item questionnaire with two subscales: anxiety & depression. Each item is rated on a 4-point scale (0-3). A person could score between 0 & 21 for each subscale (anxiety & depression). A high score is indicative of a poor state. Scores of 11 or more on either subscale are considered a 'definite case' of psychological morbidity, while scores of 8 to 10 represents 'probable case' & 0 to 7 'not a case'. The total score was the sum of the 2 sub-scores; therefore, the full range of possible values for the reported data is 0-42.
1.Primary Outcome
Title Percentage of Participants With Investigator's Global Assessment (IGA) 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 atopic dermatitis (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). Participants with IGA "0" or "1" and a reduction from baseline of ≥2 points at Week 16 were reported. [Values after first rescue treatment used were set to missing. Participants with missing score at week 16 were considered as a non-responder. Participant considered non-responder after rescue treatment use. Efficacy analyses were based on the treatment allocated at randomization (as randomized).]
Time Frame Baseline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on Full Analysis Set (FAS) population (all randomized participants).
Arm/Group Title Placebo Dupilumab 300 mg Q4W Dupilumab 200 mg or 300 mg Q2W
Hide Arm/Group Description:
Participants received placebo matching dupilumab once every 2 weeks (Q2W) (including doubling the amount of placebo on day 1 to match the loading dose). Participants in the <60-kilogram (kg) weight stratum received, in a 1:1 ratio, either placebo matching 200 milligram (mg) or placebo matching 300 milligram (mg). In the ≥60 kg weight stratum, the participants randomized to the placebo group received placebo matching 300 mg dupilumab.
Participants received once every 4 weeks (Q4W) subcutaneous (SC) injections of 300 milligrams (mg) dupilumab following a loading dose of 600 mg on day 1. To maintain blinding, all participants received an injection once every 2 weeks (Q2W) from day 1 to week 14. Participants received placebo 2 millilitre (mL) injection at the weeks dupilumab was not given.
Participants with baseline weight <60 kg received once every 2 weeks (Q2W) subcutaneous (SC) injections of 200 milligrams (mg) dupilumab following a loading dose of 400 mg on day 1. Participants with baseline weight ≥60 kg received Q2W SC injections of 300 mg dupilumab following a loading dose of 600 mg on day 1.
Overall Number of Participants Analyzed 85 84 82
Measure Type: Number
Unit of Measure: Percentage of participants
2.4 17.9 24.4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Dupilumab 200 mg or 300 mg Q2W
Comments A hierarchical testing procedure was used to control type I error. Analysis was performed using Cochran-Mantel-Haenszel (CMH) test stratified by baseline disease severity (IGA=3 vs IGA=4) and baseline weight group (less than [<] 60 kilogram [kg] vs greater than or equal to [≥] 60 kg).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Threshold for significance at 0.05 level.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter percentage difference
Estimated Value 22
Confidence Interval (2-Sided) 95%
12.2 to 31.87
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Dupilumab 300 mg Q4W
Comments A hierarchical testing procedure was used to control type I error. Analysis was performed using CMH test stratified by baseline disease severity (IGA=3 vs IGA=4) and baseline weight group (<60 kg vs ≥60 kg).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0007
Comments Threshold for significance at 0.05 level.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter percentage difference
Estimated Value 15.5
Confidence Interval (2-Sided) 95%
6.7 to 24.31
Estimation Comments [Not Specified]
2.Primary Outcome
Title Percentage of Participants With Eczema Area and Severity Index (EASI)-75 (≥75% Improvement From Baseline) at Week 16
Hide Description The EASI score was used to measure the severity and extent of 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. [Values after first rescue treatment used were set to missing. Participants with missing score at week 16 were considered as a non-responder. Participant considered nonresponder after rescue treatment use. Efficacy analyses were based on the treatment allocated at randomization (as randomized).]
Time Frame Baseline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on Full Analysis Set (FAS) population (all randomized participants).
Arm/Group Title Placebo Dupilumab 300 mg Q4W Dupilumab 200 mg or 300 mg Q2W
Hide Arm/Group Description:
Participants received placebo matching dupilumab once every 2 weeks (Q2W) (including doubling the amount of placebo on day 1 to match the loading dose). Participants in the <60-kilogram (kg) weight stratum received, in a 1:1 ratio, either placebo matching 200 milligram (mg) or placebo matching 300 milligram (mg). In the ≥60 kg weight stratum, the participants randomized to the placebo group received placebo matching 300 mg dupilumab.
Participants received once every 4 weeks (Q4W) subcutaneous (SC) injections of 300 milligrams (mg) dupilumab following a loading dose of 600 mg on day 1. To maintain blinding, all participants received an injection once every 2 weeks (Q2W) from day 1 to week 14. Participants received placebo 2 millilitre (mL) injection at the weeks dupilumab was not given.
Participants with baseline weight <60 kg received once every 2 weeks (Q2W) subcutaneous (SC) injections of 200 milligrams (mg) dupilumab following a loading dose of 400 mg on day 1. Participants with baseline weight ≥60 kg received Q2W SC injections of 300 mg dupilumab following a loading dose of 600 mg on day 1.
Overall Number of Participants Analyzed 85 84 82
Measure Type: Number
Unit of Measure: Percentage of participants
8.2 38.1 41.5
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Dupilumab 200 mg or 300 mg Q2W
Comments A hierarchical testing procedure was used to control type I error. Analysis was performed using CMH test stratified by baseline disease severity (IGA=3 vs IGA=4) and baseline weight group (<60 kg vs ≥60 kg).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Threshold for significance at 0.05 level.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter percentage difference
Estimated Value 33.2
Confidence Interval (2-Sided) 95%
21.07 to 45.39
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Dupilumab 300 mg Q4W
Comments A hierarchical testing procedure was used to control type I error. Analysis was performed using CMH test stratified by baseline disease severity (IGA=3 vs IGA=4) and baseline weight group (<60 kg vs ≥60 kg).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Threshold for significance at 0.05 level.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter percentage difference
Estimated Value 29.9
Confidence Interval (2-Sided) 95%
17.94 to 41.78
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percent Change From Baseline in EASI Score at Week 16
Hide Description The Eczema Area and Severity Index (EASI) score was used to measure the severity and extent of 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. [Values after first rescue treatment use were set to missing and participants with missing EASI score at Week 16 were considered as non-responders.]
Time Frame Baseline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on FAS population (all randomized participants).
Arm/Group Title Placebo Dupilumab 300 mg Q4W Dupilumab 200 mg or 300 mg Q2W
Hide Arm/Group Description:
Participants received placebo matching dupilumab once every 2 weeks (Q2W) (including doubling the amount of placebo on day 1 to match the loading dose). Participants in the <60-kilogram (kg) weight stratum received, in a 1:1 ratio, either placebo matching 200 milligram (mg) or placebo matching 300 milligram (mg). In the ≥60 kg weight stratum, the participants randomized to the placebo group received placebo matching 300 mg dupilumab.
Participants received once every 4 weeks (Q4W) subcutaneous (SC) injections of 300 milligrams (mg) dupilumab following a loading dose of 600 mg on day 1. To maintain blinding, all participants received an injection once every 2 weeks (Q2W) from day 1 to week 14. Participants received placebo 2 millilitre (mL) injection at the weeks dupilumab was not given.
Participants with baseline weight <60 kg received once every 2 weeks (Q2W) subcutaneous (SC) injections of 200 milligrams (mg) dupilumab following a loading dose of 400 mg on day 1. Participants with baseline weight ≥60 kg received Q2W SC injections of 300 mg dupilumab following a loading dose of 600 mg on day 1.
Overall Number of Participants Analyzed 85 84 82
Least Squares Mean (Standard Error)
Unit of Measure: Percent change
-23.6  (5.49) -64.8  (4.51) -65.9  (3.99)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Dupilumab 200 mg or 300 mg Q2W
Comments A hierarchical testing procedure was used to control type I error. The confidence interval (CI) with p-value is based on treatment difference (Dupilumab group vs. Placebo) of the LS mean percent change using analysis of covariance (ANCOVA) model with baseline measurement as covariate and the treatment, randomization strata (baseline disease severity [IGA=3 vs IGA=4] and baseline weight group [<60 kg vs ≥60 kg]) as fixed factors.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Threshold for significance at 0.05 level.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square (LS) Mean difference
Estimated Value -42.3
Confidence Interval (2-Sided) 95%
-55.6 to -29.04
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Dupilumab 300 mg Q4W
Comments A hierarchical testing procedure was used to control type I error. The confidence interval (CI) with p-value is based on treatment difference (Dupilumab group vs. Placebo) of the LS mean percent change using ANCOVA model with baseline measurement as covariate and the treatment, randomization strata (baseline disease severity [IGA=3 vs IGA=4] and baseline weight group [<60 kg vs ≥60 kg]) as fixed factors.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Threshold for significance at 0.05 level.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -41.2
Confidence Interval (2-Sided) 95%
-54.44 to -28.02
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Percent Change From Baseline in Weekly Average of Daily Peak Pruritus Numerical Rating Scale (NRS) Score at Week 16
Hide Description Peak Pruritus NRS is an assessment tool used by subjects to report intensity of pruritus (itch) during a 24-hour recall period. Participants were asked the following question: For maximum itch intensity: "On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable,' how would you rate your itch at the worst moment during the previous 24 hours?" For post-baseline NRS, the mean weekly NRS was calculated as the prorated average of the reported daily NRS within the week. For example, if there were 3 scores in a week, the prorated average = (score1 + score2 + score3) /3. [Values after first rescue treatment were set to missing and participants with missing peak NRS at Week 16 were counted as non-responders.]
Time Frame Baseline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on FAS population (all randomized participants).
Arm/Group Title Placebo Dupilumab 300 mg Q4W Dupilumab 200 mg or 300 mg Q2W
Hide Arm/Group Description:
Participants received placebo matching dupilumab once every 2 weeks (Q2W) (including doubling the amount of placebo on day 1 to match the loading dose). Participants in the <60-kilogram (kg) weight stratum received, in a 1:1 ratio, either placebo matching 200 milligram (mg) or placebo matching 300 milligram (mg). In the ≥60 kg weight stratum, the participants randomized to the placebo group received placebo matching 300 mg dupilumab.
Participants received once every 4 weeks (Q4W) subcutaneous (SC) injections of 300 milligrams (mg) dupilumab following a loading dose of 600 mg on day 1. To maintain blinding, all participants received an injection once every 2 weeks (Q2W) from day 1 to week 14. Participants received placebo 2 millilitre (mL) injection at the weeks dupilumab was not given.
Participants with baseline weight <60 kg received once every 2 weeks (Q2W) subcutaneous (SC) injections of 200 milligrams (mg) dupilumab following a loading dose of 400 mg on day 1. Participants with baseline weight ≥60 kg received Q2W SC injections of 300 mg dupilumab following a loading dose of 600 mg on day 1.
Overall Number of Participants Analyzed 85 84 82
Least Squares Mean (Standard Error)
Unit of Measure: Percent change
-19.0  (4.09) -45.5  (3.54) -47.9  (3.43)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Dupilumab 200 mg or 300 mg Q2W
Comments A hierarchical testing procedure was used to control type I error. The confidence interval (CI) with p-value is based on treatment difference (Dupilumab group vs. Placebo) of the LS mean percent change using ANCOVA model with baseline measurement as covariate and the treatment, randomization strata (baseline disease severity [IGA=3 vs IGA=4] and baseline weight group [<60 kg vs ≥60 kg]) as fixed factors.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Threshold for significance at 0.05 level.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -29
Confidence Interval (2-Sided) 95%
-39.54 to -18.38
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Dupilumab 300 mg Q4W
Comments A hierarchical testing procedure was used to control type I error. The confidence interval (CI) with p-value is based on treatment difference (Dupilumab group vs. Placebo) of the LS mean percent change using ANCOVA model with baseline measurement as covariate and the treatment, randomization strata (baseline disease severity [IGA=3 vs IGA=4] and baseline weight group [<60 kg vs ≥60 kg]) as fixed factors.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Threshold for significance at 0.05 level.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -26.5
Confidence Interval (2-Sided) 95%
-37.45 to 15.63
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Percentage of Participants With Improvement (Reduction ≥3 Points) of Weekly Average of Daily Peak Pruritus NRS From Baseline to Week 16
Hide Description Peak Pruritus NRS is an assessment tool used by participants to report intensity of pruritus (itch) during a 24-hour recall period. Participants were asked the following question: For maximum itch intensity: "On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable,' how would you rate your itch at the worst moment during the previous 24 hours?" [For this endpoint, participants achieving a reduction of ≥3 points from baseline in weekly average of peak daily pruritus NRS score at Week 16 were reported. Values after first rescue treatment were set to missing and participants with missing peak NRS at Week 16 were counted as non-responders.]
Time Frame Baseline to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on FAS population (all randomized participants). Here, number of participants analyzed = participants with baseline peak pruritus NRS ≥3.
Arm/Group Title Placebo Dupilumab 300 mg Q4W Dupilumab 200 mg or 300 mg Q2W
Hide Arm/Group Description:
Participants received placebo matching dupilumab once every 2 weeks (Q2W) (including doubling the amount of placebo on day 1 to match the loading dose). Participants in the <60-kilogram (kg) weight stratum received, in a 1:1 ratio, either placebo matching 200 milligram (mg) or placebo matching 300 milligram (mg). In the ≥60 kg weight stratum, the participants randomized to the placebo group received placebo matching 300 mg dupilumab.
Participants received once every 4 weeks (Q4W) subcutaneous (SC) injections of 300 milligrams (mg) dupilumab following a loading dose of 600 mg on day 1. To maintain blinding, all participants received an injection once every 2 weeks (Q2W) from day 1 to week 14. Participants received placebo 2 millilitre (mL) injection at the weeks dupilumab was not given.
Participants with baseline weight <60 kg received once every 2 weeks (Q2W) subcutaneous (SC) injections of 200 milligrams (mg) dupilumab following a loading dose of 400 mg on day 1. Participants with baseline weight ≥60 kg received Q2W SC injections of 300 mg dupilumab following a loading dose of 600 mg on day 1.
Overall Number of Participants Analyzed 85 83 82
Measure Type: Number
Unit of Measure: Percentage of participants
9.4 38.6 48.8
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Dupilumab 200 mg or 300 mg Q2W
Comments A hierarchical testing procedure was used to control type I error. Difference is Dupilumab minus Placebo. C.I. = Confidence interval calculated using normal approximation. P-values were derived by CMH test stratified by baseline disease severity [IGA=3 vs IGA=4] and baseline weight group [<60 kg vs ≥60 kg].
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Threshold for significance at 0.05 level.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter percentage difference
Estimated Value 39.4
Confidence Interval (2-Sided) 95%
26.9 to 51.84
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Dupilumab 300 mg Q4W
Comments A hierarchical testing procedure was used to control type I error. Difference is Dupilumab minus Placebo. C.I. = Confidence interval calculated using normal approximation. P-values were derived by Cochran-Mantel-Haenszel (CMH) test stratified by baseline disease severity [IGA=3 vs IGA=4] and baseline weight group [<60 kg vs ≥60 kg].
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Threshold for significance at 0.05 level.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter percentage difference
Estimated Value 29.1
Confidence Interval (2-Sided) 95%
16.97 to 41.32
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Percentage of Participants With Improvement (Reduction ≥4 Points) of Weekly Average of Daily Peak Pruritus NRS From Baseline to Week 16
Hide Description Peak Pruritus NRS is an assessment tool used by participants to report intensity of pruritus (itch) during a 24-hour recall period. Participants were asked the following question: For maximum itch intensity: "On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable,' how would you rate your itch at the worst moment during the previous 24 hours?" [For this endpoint, participants achieving a reduction of ≥4 points from baseline in weekly average of peak daily pruritus NRS score at Week 16 were reported. Values after first rescue treatment were set to missing and participants with missing peak NRS at Week 16 were counted as non-responders.]
Time Frame Baseline to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on FAS population (all randomized participants). Here, number of participants analyzed = participants with baseline peak pruritus NRS ≥4.
Arm/Group Title Placebo Dupilumab 300 mg Q4W Dupilumab 200 mg or 300 mg Q2W
Hide Arm/Group Description:
Participants received placebo matching dupilumab once every 2 weeks (Q2W) (including doubling the amount of placebo on day 1 to match the loading dose). Participants in the <60-kilogram (kg) weight stratum received, in a 1:1 ratio, either placebo matching 200 milligram (mg) or placebo matching 300 milligram (mg). In the ≥60 kg weight stratum, the participants randomized to the placebo group received placebo matching 300 mg dupilumab.
Participants received once every 4 weeks (Q4W) subcutaneous (SC) injections of 300 milligrams (mg) dupilumab following a loading dose of 600 mg on day 1. To maintain blinding, all participants received an injection once every 2 weeks (Q2W) from day 1 to week 14. Participants received placebo 2 millilitre (mL) injection at the weeks dupilumab was not given.
Participants with baseline weight <60 kg received once every 2 weeks (Q2W) subcutaneous (SC) injections of 200 milligrams (mg) dupilumab following a loading dose of 400 mg on day 1. Participants with baseline weight ≥60 kg received Q2W SC injections of 300 mg dupilumab following a loading dose of 600 mg on day 1.
Overall Number of Participants Analyzed 84 83 82
Measure Type: Number
Unit of Measure: Percentage of participants
4.8 26.5 36.6
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Dupilumab 200 mg or 300 mg Q2W
Comments A hierarchical testing procedure was used to control type I error. Difference is Dupilumab minus Placebo. C.I. = Confidence interval calculated using normal approximation. P-values were derived by Cochran-Mantel-Haenszel (CMH) test stratified by baseline disease severity [IGA=3 vs IGA=4] and baseline weight group [<60 kg vs ≥60 kg].
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Threshold for significance at 0.05 level.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage difference
Estimated Value 31.8
Confidence Interval (2-Sided) 95%
20.45 to 43.2
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Dupilumab 300 mg Q4W
Comments A hierarchical testing procedure was used to control type I error. Difference is Dupilumab minus Placebo. C.I. = Confidence interval calculated using normal approximation. P-values were derived by Cochran-Mantel-Haenszel (CMH) test stratified by baseline disease severity [IGA=3 vs IGA=4] and baseline weight group [<60 kg vs ≥60 kg].
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0001
Comments Threshold for significance at 0.05 level.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage difference
Estimated Value 21.7
Confidence Interval (2-Sided) 95%
11.21 to 32.28
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Percentage of Participants With EASI-50 (≥50% Improvement From Baseline) at 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. EASI-50 responders were the participants who achieved ≥50% overall improvement in EASI score at Week 16. [Values after first rescue treatment used were set to missing. Participants with missing value at Week 16 were considered as a non-responder].
Time Frame Baseline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on FAS population (all randomized participants).
Arm/Group Title Placebo Dupilumab 300 mg Q4W Dupilumab 200 mg or 300 mg Q2W
Hide Arm/Group Description:
Participants received placebo matching dupilumab once every 2 weeks (Q2W) (including doubling the amount of placebo on day 1 to match the loading dose). Participants in the <60-kilogram (kg) weight stratum received, in a 1:1 ratio, either placebo matching 200 milligram (mg) or placebo matching 300 milligram (mg). In the ≥60 kg weight stratum, the participants randomized to the placebo group received placebo matching 300 mg dupilumab.
Participants received once every 4 weeks (Q4W) subcutaneous (SC) injections of 300 milligrams (mg) dupilumab following a loading dose of 600 mg on day 1. To maintain blinding, all participants received an injection once every 2 weeks (Q2W) from day 1 to week 14. Participants received placebo 2 millilitre (mL) injection at the weeks dupilumab was not given.
Participants with baseline weight <60 kg received once every 2 weeks (Q2W) subcutaneous (SC) injections of 200 milligrams (mg) dupilumab following a loading dose of 400 mg on day 1. Participants with baseline weight ≥60 kg received Q2W SC injections of 300 mg dupilumab following a loading dose of 600 mg on day 1.
Overall Number of Participants Analyzed 85 84 82
Measure Type: Number
Unit of Measure: Percentage of participants
12.9 54.8 61.0
8.Secondary Outcome
Title Percentage of Participants With EASI-90 (≥90% Improvement From Baseline) at 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. EASI-90 responders were the participants who achieved ≥90% overall improvement in EASI score at Week 16. [Values after first rescue treatment used were set to missing. Participants with missing value at week 16 were considered as a non-responder.]
Time Frame Baeline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on FAS population (all randomized participants).
Arm/Group Title Placebo Dupilumab 300 mg Q4W Dupilumab 200 mg or 300 mg Q2W
Hide Arm/Group Description:
Participants received placebo matching dupilumab once every 2 weeks (Q2W) (including doubling the amount of placebo on day 1 to match the loading dose). Participants in the <60-kilogram (kg) weight stratum received, in a 1:1 ratio, either placebo matching 200 milligram (mg) or placebo matching 300 milligram (mg). In the ≥60 kg weight stratum, the participants randomized to the placebo group received placebo matching 300 mg dupilumab.
Participants received once every 4 weeks (Q4W) subcutaneous (SC) injections of 300 milligrams (mg) dupilumab following a loading dose of 600 mg on day 1. To maintain blinding, all participants received an injection once every 2 weeks (Q2W) from day 1 to week 14. Participants received placebo 2 millilitre (mL) injection at the weeks dupilumab was not given.
Participants with baseline weight <60 kg received once every 2 weeks (Q2W) subcutaneous (SC) injections of 200 milligrams (mg) dupilumab following a loading dose of 400 mg on day 1. Participants with baseline weight ≥60 kg received Q2W SC injections of 300 mg dupilumab following a loading dose of 600 mg on day 1.
Overall Number of Participants Analyzed 85 84 82
Measure Type: Number
Unit of Measure: Percentage of participants
2.4 19.0 23.2
9.Secondary Outcome
Title Time to Onset of Effect on Pruritus as Measured by Percentage of Participants With Improvement (Reduction ≥3 Points) of Weekly Average of Daily Peak Pruritus NRS From Baseline
Hide Description Peak Pruritus NRS is an assessment tool used by participants to report intensity of pruritus (itch) during a 24-hour recall period. Participants were asked the following question: For maximum itch intensity: "On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable,' how would you rate your itch at the worst moment during the previous 24 hours?" [For this endpoint, participants achieving a reduction of ≥3 points from baseline in weekly average of peak daily pruritus NRS score at Week 16 were reported. Values after first rescue treatment were set to missing and participants with missing peak NRS at Week 16 were counted as non-responders.]
Time Frame Baseline up to week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on FAS population (all randomized participants). Here, number of participants analyzed = participants with baseline peak pruritus NRS ≥3.
Arm/Group Title Placebo Dupilumab 300 mg Q4W Dupilumab 200 mg or 300 mg Q2W
Hide Arm/Group Description:
Participants received placebo matching dupilumab once every 2 weeks (Q2W) (including doubling the amount of placebo on day 1 to match the loading dose). Participants in the <60-kilogram (kg) weight stratum received, in a 1:1 ratio, either placebo matching 200 milligram (mg) or placebo matching 300 milligram (mg). In the ≥60 kg weight stratum, the participants randomized to the placebo group received placebo matching 300 mg dupilumab.
Participants received once every 4 weeks (Q4W) subcutaneous (SC) injections of 300 milligrams (mg) dupilumab following a loading dose of 600 mg on day 1. To maintain blinding, all participants received an injection once every 2 weeks (Q2W) from day 1 to week 14. Participants received placebo 2 millilitre (mL) injection at the weeks dupilumab was not given.
Participants with baseline weight <60 kg received once every 2 weeks (Q2W) subcutaneous (SC) injections of 200 milligrams (mg) dupilumab following a loading dose of 400 mg on day 1. Participants with baseline weight ≥60 kg received Q2W SC injections of 300 mg dupilumab following a loading dose of 600 mg on day 1.
Overall Number of Participants Analyzed 85 83 82
Mean (Standard Deviation)
Unit of Measure: Percentage of participants
11.4  (5.63) 8.4  (5.92) 7.7  (5.57)
10.Secondary Outcome
Title Time to Onset of Effect on Pruritus as Measured by Percentage of Participants With Improvement (Reduction ≥4 Points) of Weekly Average of Daily Peak Pruritus NRS From Baseline
Hide Description Peak Pruritus NRS is an assessment tool used by participants to report intensity of pruritus (itch) during a 24-hour recall period. Participants were asked the following question: For maximum itch intensity: "On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable,' how would you rate your itch at the worst moment during the previous 24 hours?" [For this endpoint, subjects achieving a reduction of ≥4 points from baseline in weekly average of peak daily pruritus NRS score at Week 16 were reported. Values after first rescue treatment were set to missing and participants with missing peak NRS at Week 16 were counted as non-responders.]
Time Frame Baseline up to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on FAS population (all randomized participants). Here, number of participants analyzed = participants with baseline peak pruritus NRS ≥4.
Arm/Group Title Placebo Dupilumab 300 mg Q4W Dupilumab 200 mg or 300 mg Q2W
Hide Arm/Group Description:
Participants received placebo matching dupilumab once every 2 weeks (Q2W) (including doubling the amount of placebo on day 1 to match the loading dose). Participants in the <60-kilogram (kg) weight stratum received, in a 1:1 ratio, either placebo matching 200 milligram (mg) or placebo matching 300 milligram (mg). In the ≥60 kg weight stratum, the participants randomized to the placebo group received placebo matching 300 mg dupilumab.
Participants received once every 4 weeks (Q4W) subcutaneous (SC) injections of 300 milligrams (mg) dupilumab following a loading dose of 600 mg on day 1. To maintain blinding, all participants received an injection once every 2 weeks (Q2W) from day 1 to week 14. Participants received placebo 2 millilitre (mL) injection at the weeks dupilumab was not given.
Participants with baseline weight <60 kg received once every 2 weeks (Q2W) subcutaneous (SC) injections of 200 milligrams (mg) dupilumab following a loading dose of 400 mg on day 1. Participants with baseline weight ≥60 kg received Q2W SC injections of 300 mg dupilumab following a loading dose of 600 mg on day 1.
Overall Number of Participants Analyzed 84 83 82
Mean (Standard Deviation)
Unit of Measure: Percentage of participants
12.8  (4.90) 9.9  (5.87) 10.6  (5.50)
11.Secondary Outcome
Title Change From Baseline in Percent Body Surface Area (BSA) at 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 and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on FAS population (all randomized participants).
Arm/Group Title Placebo Dupilumab 300 mg Q4W Dupilumab 200 mg or 300 mg Q2W
Hide Arm/Group Description:
Participants received placebo matching dupilumab once every 2 weeks (Q2W) (including doubling the amount of placebo on day 1 to match the loading dose). Participants in the <60-kilogram (kg) weight stratum received, in a 1:1 ratio, either placebo matching 200 milligram (mg) or placebo matching 300 milligram (mg). In the ≥60 kg weight stratum, the participants randomized to the placebo group received placebo matching 300 mg dupilumab.
Participants received once every 4 weeks (Q4W) subcutaneous (SC) injections of 300 milligrams (mg) dupilumab following a loading dose of 600 mg on day 1. To maintain blinding, all participants received an injection once every 2 weeks (Q2W) from day 1 to week 14. Participants received placebo 2 millilitre (mL) injection at the weeks dupilumab was not given.
Participants with baseline weight <60 kg received once every 2 weeks (Q2W) subcutaneous (SC) injections of 200 milligrams (mg) dupilumab following a loading dose of 400 mg on day 1. Participants with baseline weight ≥60 kg received Q2W SC injections of 300 mg dupilumab following a loading dose of 600 mg on day 1.
Overall Number of Participants Analyzed 85 84 82
Least Squares Mean (Standard Error)
Unit of Measure: Percentage of body surface area
-11.66  (2.720) -33.41  (2.330) -30.11  (2.337)
12.Secondary Outcome
Title Percent Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Score at Week 16
Hide Description The SCORAD index is a clinical tool for assessing the severity of atopic dermatitis. 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).
Time Frame Baseline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on FAS population (all randomized participants).
Arm/Group Title Placebo Dupilumab 300 mg Q4W Dupilumab 200 mg or 300 mg Q2W
Hide Arm/Group Description:
Participants received placebo matching dupilumab once every 2 weeks (Q2W) (including doubling the amount of placebo on day 1 to match the loading dose). Participants in the <60-kilogram (kg) weight stratum received, in a 1:1 ratio, either placebo matching 200 milligram (mg) or placebo matching 300 milligram (mg). In the ≥60 kg weight stratum, the participants randomized to the placebo group received placebo matching 300 mg dupilumab.
Participants received once every 4 weeks (Q4W) subcutaneous (SC) injections of 300 milligrams (mg) dupilumab following a loading dose of 600 mg on day 1. To maintain blinding, all participants received an injection once every 2 weeks (Q2W) from day 1 to week 14. Participants received placebo 2 millilitre (mL) injection at the weeks dupilumab was not given.
Participants with baseline weight <60 kg received once every 2 weeks (Q2W) subcutaneous (SC) injections of 200 milligrams (mg) dupilumab following a loading dose of 400 mg on day 1. Participants with baseline weight ≥60 kg received Q2W SC injections of 300 mg dupilumab following a loading dose of 600 mg on day 1.
Overall Number of Participants Analyzed 85 84 82
Least Squares Mean (Standard Error)
Unit of Measure: Percent change
-17.6  (3.76) -47.5  (3.21) -51.6  (3.23)
13.Secondary Outcome
Title Change From Baseline in Children's Dermatology Life Quality Index (CDLQI) Total Score at Week 16
Hide Description The CDLQI is a 10-item questionnaire used to measure how much a participant's skin problem had affected the participant's quality of life (QOL) over a recall period of the past week. The questionnaire consists of 10 items. For each item the scale is rated as follows: 0 = Not at all = Not relevant; 1 = Only a little; 2 = Quite a lot; 3 = Very much = Yes = Prevents school. The CDLQI total score is the sum of the score of each question with a maximum of 30 and a minimum of 0. The higher the score, the greater the impact is on the QOL.
Time Frame Baseline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on FAS population (all randomized participants).
Arm/Group Title Placebo Dupilumab 300 mg Q4W Dupilumab 200 mg or 300 mg Q2W
Hide Arm/Group Description:
Participants received placebo matching dupilumab once every 2 weeks (Q2W) (including doubling the amount of placebo on day 1 to match the loading dose). Participants in the <60-kilogram (kg) weight stratum received, in a 1:1 ratio, either placebo matching 200 milligram (mg) or placebo matching 300 milligram (mg). In the ≥60 kg weight stratum, the participants randomized to the placebo group received placebo matching 300 mg dupilumab.
Participants received once every 4 weeks (Q4W) subcutaneous (SC) injections of 300 milligrams (mg) dupilumab following a loading dose of 600 mg on day 1. To maintain blinding, all participants received an injection once every 2 weeks (Q2W) from day 1 to week 14. Participants received placebo 2 millilitre (mL) injection at the weeks dupilumab was not given.
Participants with baseline weight <60 kg received once every 2 weeks (Q2W) subcutaneous (SC) injections of 200 milligrams (mg) dupilumab following a loading dose of 400 mg on day 1. Participants with baseline weight ≥60 kg received Q2W SC injections of 300 mg dupilumab following a loading dose of 600 mg on day 1.
Overall Number of Participants Analyzed 85 84 82
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
-5.1  (0.62) -8.8  (0.53) -8.5  (0.50)
14.Secondary Outcome
Title Change From Baseline in Patient Oriented Eczema Measure (POEM) at Week 16
Hide Description The POEM is a 7-item, validated questionnaire used in clinical practice and clinical trials to assess disease symptoms in children and adults with atopic eczema. The format is subject response to 7 items (dryness, itching, flaking, cracking, sleep loss, bleeding, and weeping) based on symptom frequency during the past week (ie, 0 = 'no days', 1 = '1 to 2 days', 2 = '3 to 4 days', 3 = '5 to 6' days, and 4 = 'every day'). The total score is the sum of the 7 items which is ranged from 0 to 28; a high score is indicative of a poor quality of life (QOL).
Time Frame Baseline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on FAS population (all randomized participants).
Arm/Group Title Placebo Dupilumab 300 mg Q4W Dupilumab 200 mg or 300 mg Q2W
Hide Arm/Group Description:
Participants received placebo matching dupilumab once every 2 weeks (Q2W) (including doubling the amount of placebo on day 1 to match the loading dose). Participants in the <60-kilogram (kg) weight stratum received, in a 1:1 ratio, either placebo matching 200 milligram (mg) or placebo matching 300 milligram (mg). In the ≥60 kg weight stratum, the participants randomized to the placebo group received placebo matching 300 mg dupilumab.
Participants received once every 4 weeks (Q4W) subcutaneous (SC) injections of 300 milligrams (mg) dupilumab following a loading dose of 600 mg on day 1. To maintain blinding, all participants received an injection once every 2 weeks (Q2W) from day 1 to week 14. Participants received placebo 2 millilitre (mL) injection at the weeks dupilumab was not given.
Participants with baseline weight <60 kg received once every 2 weeks (Q2W) subcutaneous (SC) injections of 200 milligrams (mg) dupilumab following a loading dose of 400 mg on day 1. Participants with baseline weight ≥60 kg received Q2W SC injections of 300 mg dupilumab following a loading dose of 600 mg on day 1.
Overall Number of Participants Analyzed 85 84 82
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
-3.8  (0.96) -9.5  (0.86) -10.1  (0.76)
15.Secondary Outcome
Title Change From Baseline in Weekly Average of Daily Peak Pruritus NRS at Week 16
Hide Description Peak Pruritus NRS is an assessment tool used by participants to report intensity of pruritus (itch) during a 24-hour recall period. Particpants were asked the following question for maximum itch intensity: "On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable,' how would you rate your itch at the worst moment during the previous 24 hours?" For post-baseline NRS, the mean weekly NRS was calculated as the prorated average of the reported daily NRS within the week. For example, if there were 3 scores in a week, the prorated average = (score1 + score2 + score3)/ 3.
Time Frame Baseline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on FAS population (all randomized participants).
Arm/Group Title Placebo Dupilumab 300 mg Q4W Dupilumab 200 mg or 300 mg Q2W
Hide Arm/Group Description:
Participants received placebo matching dupilumab once every 2 weeks (Q2W) (including doubling the amount of placebo on day 1 to match the loading dose). Participants in the <60-kilogram (kg) weight stratum received, in a 1:1 ratio, either placebo matching 200 milligram (mg) or placebo matching 300 milligram (mg). In the ≥60 kg weight stratum, the participants randomized to the placebo group received placebo matching 300 mg dupilumab.
Participants received once every 4 weeks (Q4W) subcutaneous (SC) injections of 300 milligrams (mg) dupilumab following a loading dose of 600 mg on day 1. To maintain blinding, all participants received an injection once every 2 weeks (Q2W) from day 1 to week 14. Participants received placebo 2 millilitre (mL) injection at the weeks dupilumab was not given.
Participants with baseline weight <60 kg received once every 2 weeks (Q2W) subcutaneous (SC) injections of 200 milligrams (mg) dupilumab following a loading dose of 400 mg on day 1. Participants with baseline weight ≥60 kg received Q2W SC injections of 300 mg dupilumab following a loading dose of 600 mg on day 1.
Overall Number of Participants Analyzed 85 84 82
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
-1.54  (0.303) -3.44  (0.260) -3.70  (0.250)
16.Secondary Outcome
Title Percent Change From Baseline in Weekly Average of Daily Peak Pruritus NRS at Week 4
Hide Description Peak Pruritus NRS is an assessment tool used by participants to report intensity of pruritus (itch) during a 24-hour recall period. Participants were asked the following question for maximum itch intensity: "On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable,' how would you rate your itch at the worst moment during the previous 24 hours?" For post-baseline NRS, the mean weekly NRS was calculated as the prorated average of the reported daily NRS within the week. For example, if there were 3 scores in a week, the prorated average = (score1 + score2 + score3)/ 3.
Time Frame Baseline and Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on FAS population (all randomized participants).
Arm/Group Title Placebo Dupilumab 300 mg Q4W Dupilumab 200 mg or 300 mg Q2W
Hide Arm/Group Description:
Participants received placebo matching dupilumab once every 2 weeks (Q2W) (including doubling the amount of placebo on day 1 to match the loading dose). Participants in the <60-kilogram (kg) weight stratum received, in a 1:1 ratio, either placebo matching 200 milligram (mg) or placebo matching 300 milligram (mg). In the ≥60 kg weight stratum, the participants randomized to the placebo group received placebo matching 300 mg dupilumab.
Participants received once every 4 weeks (Q4W) subcutaneous (SC) injections of 300 milligrams (mg) dupilumab following a loading dose of 600 mg on day 1. To maintain blinding, all participants received an injection once every 2 weeks (Q2W) from day 1 to week 14. Participants received placebo 2 millilitre (mL) injection at the weeks dupilumab was not given.
Participants with baseline weight <60 kg received once every 2 weeks (Q2W) subcutaneous (SC) injections of 200 milligrams (mg) dupilumab following a loading dose of 400 mg on day 1. Participants with baseline weight ≥60 kg received Q2W SC injections of 300 mg dupilumab following a loading dose of 600 mg on day 1.
Overall Number of Participants Analyzed 85 84 82
Least Squares Mean (Standard Error)
Unit of Measure: Percent change
-12.5  (3.06) -33.1  (3.05) -34.7  (2.99)
17.Secondary Outcome
Title Change From Baseline in Total Hospital Anxiety and Depression Scale (HADS) at Week 16
Hide Description The HADS is 14-item questionnaire with two subscales: anxiety & depression. Each item is rated on a 4-point scale (0-3). A person could score between 0 & 21 for each subscale (anxiety & depression). A high score is indicative of a poor state. Scores of 11 or more on either subscale are considered a 'definite case' of psychological morbidity, while scores of 8 to 10 represents 'probable case' & 0 to 7 'not a case'. The total score was the sum of the 2 sub-scores; therefore, the full range of possible values for the reported data is 0-42.
Time Frame Baseline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on FAS population (all randomized participants).
Arm/Group Title Placebo Dupilumab 300 mg Q4W Dupilumab 200 mg or 300 mg Q2W
Hide Arm/Group Description:
Participants received placebo matching dupilumab once every 2 weeks (Q2W) (including doubling the amount of placebo on day 1 to match the loading dose). Participants in the <60-kilogram (kg) weight stratum received, in a 1:1 ratio, either placebo matching 200 milligram (mg) or placebo matching 300 milligram (mg). In the ≥60 kg weight stratum, the participants randomized to the placebo group received placebo matching 300 mg dupilumab.
Participants received once every 4 weeks (Q4W) subcutaneous (SC) injections of 300 milligrams (mg) dupilumab following a loading dose of 600 mg on day 1. To maintain blinding, all participants received an injection once every 2 weeks (Q2W) from day 1 to week 14. Participants received placebo 2 millilitre (mL) injection at the weeks dupilumab was not given.
Participants with baseline weight <60 kg received once every 2 weeks (Q2W) subcutaneous (SC) injections of 200 milligrams (mg) dupilumab following a loading dose of 400 mg on day 1. Participants with baseline weight ≥60 kg received Q2W SC injections of 300 mg dupilumab following a loading dose of 600 mg on day 1.
Overall Number of Participants Analyzed 85 84 82
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
-2.5  (0.80) -5.2  (0.73) -3.8  (0.68)
18.Secondary Outcome
Title Percentage of Participants With Improvement (Reduction ≥4 Points) of Weekly Average of Daily Peak Pruritus NRS From Baseline at Week 4
Hide Description Peak Pruritus NRS is an assessment tool used by participants to report intensity of pruritus (itch) during a 24-hour recall period. Participants were asked the following question for maximum itch intensity: "On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable,' how would you rate your itch at the worst moment during the previous 24 hours?" For post-baseline NRS, the mean weekly NRS was calculated as the prorated average of the reported daily NRS within the week. For example, if there were 3 scores in a week, the prorated average = (score1 + score2 + score3)/ 3.
Time Frame Baseline and Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on FAS population (all randomized participants).
Arm/Group Title Placebo Dupilumab 300 mg Q4W Dupilumab 200 mg or 300 mg Q2W
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Participants received placebo matching dupilumab once every 2 weeks (Q2W) (including doubling the amount of placebo on day 1 to match the loading dose). Participants in the <60-kilogram (kg) weight stratum received, in a 1:1 ratio, either placebo matching 200 milligram (mg) or placebo matching 300 milligram (mg). In the ≥60 kg weight stratum, the participants randomized to the placebo group received placebo matching 300 mg dupilumab.
Participants received once every 4 weeks (Q4W) subcutaneous (SC) injections of 300 milligrams (mg) dupilumab following a loading dose of 600 mg on day 1. To maintain blinding, all participants received an injection once every 2 weeks (Q2W) from day 1 to week 14. Participants received placebo 2 millilitre (mL) injection at the weeks dupilumab was not given.
Participants with baseline weight <60 kg received once every 2 weeks (Q2W) subcutaneous (SC) injections of 200 milligrams (mg) dupilumab following a loading dose of 400 mg on day 1. Participants with baseline weight ≥60 kg received Q2W SC injections of 300 mg dupilumab following a loading dose of 600 mg on day 1.
Overall Number of Participants Analyzed 85 84 82
Measure Type: Number
Unit of Measure: Percentage of participants
4.8 20.5 22.0
19.Secondary Outcome
Title Percentage of Participants With Skin-infection Treatment Emergent Adverse Events (TEAEs) (Excluding Herpetic Infections) Through Week 16
Hide Description Any untoward medical occurrence in a subject who received investigational medicinal product (IMP) was considered an AE without regard to possibility of causal relationship with this treatment. Treatment-emergent adverse events (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 the end of study (Week 16)). 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 through Week 16
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Hide Analysis Population Description
Analysis was performed on FAS population (all randomized participants). Here, number of participants analyzed = participants with available data for this endpoint.
Arm/Group Title Placebo Dupilumab 300 mg Q4W Dupilumab 200 mg or 300 mg Q2W
Hide Arm/Group Description:
Participants received placebo matching dupilumab once every 2 weeks (Q2W) (including doubling the amount of placebo on day 1 to match the loading dose). Participants in the <60-kilogram (kg) weight stratum received, in a 1:1 ratio, either placebo matching 200 milligram (mg) or placebo matching 300 milligram (mg). In the ≥60 kg weight stratum, the participants randomized to the placebo group received placebo matching 300 mg dupilumab.
Participants received once every 4 weeks (Q4W) subcutaneous (SC) injections of 300 milligrams (mg) dupilumab following a loading dose of 600 mg on day 1. To maintain blinding, all participants received an injection once every 2 weeks (Q2W) from day 1 to week 14. Participants received placebo 2 millilitre (mL) injection at the weeks dupilumab was not given.
Participants with baseline weight <60 kg received once every 2 weeks (Q2W) subcutaneous (SC) injections of 200 milligrams (mg) dupilumab following a loading dose of 400 mg on day 1. Participants with baseline weight ≥60 kg received Q2W SC injections of 300 mg dupilumab following a loading dose of 600 mg on day 1.
Overall Number of Participants Analyzed 85 83 82
Measure Type: Number
Unit of Measure: Percentage of participants
18.8 9.6 9.8
20.Secondary Outcome
Title Percentage of Participants With Serious TEAEs Through Week 16
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. Treatment-emergent adverse events (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 the end of study (Week 28)). 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 through Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on FAS population (all randomized participants). Here, number of participants analyzed = participants with available data for this endpoint.
Arm/Group Title Placebo Dupilumab 300 mg Q4W Dupilumab 200 mg or 300 mg Q2W
Hide Arm/Group Description:
Participants received placebo matching dupilumab once every 2 weeks (Q2W) (including doubling the amount of placebo on day 1 to match the loading dose). Participants in the <60-kilogram (kg) weight stratum received, in a 1:1 ratio, either placebo matching 200 milligram (mg) or placebo matching 300 milligram (mg). In the ≥60 kg weight stratum, the participants randomized to the placebo group received placebo matching 300 mg dupilumab.
Participants received once every 4 weeks (Q4W) subcutaneous (SC) injections of 300 milligrams (mg) dupilumab following a loading dose of 600 mg on day 1. To maintain blinding, all participants received an injection once every 2 weeks (Q2W) from day 1 to week 14. Participants received placebo 2 millilitre (mL) injection at the weeks dupilumab was not given.
Participants with baseline weight <60 kg received once every 2 weeks (Q2W) subcutaneous (SC) injections of 200 milligrams (mg) dupilumab following a loading dose of 400 mg on day 1. Participants with baseline weight ≥60 kg received Q2W SC injections of 300 mg dupilumab following a loading dose of 600 mg on day 1.
Overall Number of Participants Analyzed 85 83 82
Measure Type: Number
Unit of Measure: Percentage of participants
1.2 0 0
Time Frame All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product (IP).
Adverse Event Reporting Description Of 251 participants randomized, 250 were included in Safety Analysis Set (SAF) reported here. (One participant in dupilumab Q4W arm was not dosed & was excluded from SAF). SAF analyzed as treated. Reported AEs are treatment-emergent AEs (TEAEs): developed/worsened during 'on treatment period' (from 1st dose of IP up to Day 113). TEAEs were collected for the 16-week treatment & follow-up period up to 12 weeks. After completing the treatment period, all were offered to enroll in study NCT02612454.
 
Arm/Group Title Placebo Dupilumab 300 mg Q4W Dupilumab 200 mg or 300 mg
Hide Arm/Group Description Participants received placebo matching dupilumab once every 2 weeks (Q2W) (including doubling the amount of placebo on day 1 to match the loading dose). Participants in the <60-kilogram (kg) weight stratum received, in a 1:1 ratio, either placebo matching 200 milligram (mg) or placebo matching 300 milligram (mg). In the ≥60 kg weight stratum, the participants randomized to the placebo group received placebo matching 300 mg dupilumab. Participants received once every 4 weeks (Q4W) subcutaneous (SC) injections of 300 milligrams (mg) dupilumab following a loading dose of 600 mg on day 1. To maintain blinding, all participants received an injection once every 2 weeks (Q2W) from day 1 to week 14. Participants received placebo 2 millilitre (mL) injection at the weeks dupilumab was not given. Participants with baseline weight <60 kg received once every 2 weeks (Q2W) subcutaneous (SC) injections of 200 milligrams (mg) dupilumab following a loading dose of 400 mg on day 1. Participants with baseline weight ≥60 kgreceived Q2W SC injections of 300 mg dupilumab following a loading dose of 600 mg on day 1.
All-Cause Mortality
Placebo Dupilumab 300 mg Q4W Dupilumab 200 mg or 300 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/85 (0.00%)      0/83 (0.00%)      0/82 (0.00%)    
Hide Serious Adverse Events
Placebo Dupilumab 300 mg Q4W Dupilumab 200 mg or 300 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/85 (1.18%)      0/83 (0.00%)      0/82 (0.00%)    
Infections and infestations       
Appendicitis  1  1/85 (1.18%)  1 0/83 (0.00%)  0 0/82 (0.00%)  0
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Dupilumab 300 mg Q4W Dupilumab 200 mg or 300 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   40/85 (47.06%)      34/83 (40.96%)      39/82 (47.56%)    
Infections and infestations       
Influenza  1  4/85 (4.71%)  4 0/83 (0.00%)  0 5/82 (6.10%)  6
Nasopharyngitis  1  4/85 (4.71%)  5 10/83 (12.05%)  16 5/82 (6.10%)  8
Pharyngitis streptococcal  1  0/85 (0.00%)  0 5/83 (6.02%)  5 2/82 (2.44%)  2
Upper respiratory tract infection  1  15/85 (17.65%)  23 7/83 (8.43%)  9 10/82 (12.20%)  13
Nervous system disorders       
Headache  1  9/85 (10.59%)  14 4/83 (4.82%)  5 9/82 (10.98%)  11
Skin and subcutaneous tissue disorders       
Dermatitis atopic  1  21/85 (24.71%)  29 16/83 (19.28%)  27 15/82 (18.29%)  21
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The investigator has the right to independently publish study results from the investigator's site after a multi-center publication, or a defined period after the completion of the study by all sites. The investigator must provide the sponsor a copy of any such publication derived from the study for review and comment in advance of any submission, and delay publication, if requested, to allow the Sponsor to preserve its proprietary rights.
Results Point of Contact
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Name/Title: Clinical Trial Management
Organization: Regeneron Pharmaceuticals, Inc.
Phone: 844-734-6643
EMail: clinicaltrials@regeneron.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03054428    
Other Study ID Numbers: R668-AD-1526
2015-004458-16 ( EudraCT Number )
First Submitted: February 13, 2017
First Posted: February 15, 2017
Results First Submitted: April 4, 2019
Results First Posted: July 23, 2019
Last Update Posted: July 23, 2019