Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 45 of 154 for:    Dermatitis, Atopic, 8

A Study to Confirm the Efficacy and Safety of Different Dupilumab Dose Regimens in Adults With Atopic Dermatitis (AD) (SOLO-CONTINUE)

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: NCT02395133
Recruitment Status : Completed
First Posted : March 20, 2015
Results First Posted : October 17, 2018
Last Update Posted : December 4, 2018
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
Enrollment 422
Recruitment Details The study was conducted in 15 countries between 25 March 2015 and 18 October 2016. A total of 422 participants were randomized in the study.
Pre-assignment Details Out of the 475 participants, 422 were randomized and received Dupilumab. Participants were randomized in 2:1:1:1 ratio to receive Dupilumab 300 milligram (mg) once weekly/twice weekly (QW/Q2W), Dupilumab 300 mg four times a week (Q4W), Dupilumab 300 mg eight times a week (Q8W) and Placebo.
Arm/Group Title Placebo QW Dupilumab 300 mg Q8W Dupilumab 300 mg Q4W Dupilumab 300 mg Q2W/QW
Hide Arm/Group Description Subcutaneous injection of Placebo (for Dupilumab) was administered weekly (QW) from Week 1 (Day 1) to Week 36. Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every eight week (Q8W) from Week 1 to Week 36. Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every four week (Q4W) from Week 1 to Week 36. Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every week (QW) or twice a week (Q2W) from Week 1 to Week 36.
Period Title: Overall Study
Started [1] 83 84 86 169
Completed 69 75 76 155
Not Completed 14 9 10 14
Reason Not Completed
Adverse Event             4             1             3             0
Lack of Efficacy             1             0             1             1
Protocol Violation             1             1             0             3
Lost to Follow-up             0             1             1             0
Pregnancy             0             0             3             0
Consent withdrawn with no reason given             1             3             0             2
Consent withdrawn with personal reason             0             1             0             3
Sponsor decision             2             0             0             1
Other than specified above             5             2             2             4
[1]
Full Analysis Set (FAS) included all randomized participants
Arm/Group Title Placebo QW Dupilumab 300 mg Q8W Dupilumab 300 mg Q4W Dupilumab 300 mg Q2W/QW Total
Hide Arm/Group Description Subcutaneous injection of Placebo (for Dupilumab) was administered weekly (QW) from Week 1 (Day 1) to Week 36. Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every eight week (Q8W) from Week 1 to Week 36. Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every four week (Q4W) from Week 1 to Week 36. Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every week (QW) or twice a week (Q2W) from Week 1 to Week 36. Total of all reporting groups
Overall Number of Baseline Participants 83 84 86 169 422
Hide Baseline Analysis Population Description
The full analysis set (FAS) included all randomized participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 83 participants 84 participants 86 participants 169 participants 422 participants
38.1  (13.64) 37.3  (13.98) 38.5  (16.76) 38.5  (13.94) 38.2  (14.46)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 83 participants 84 participants 86 participants 169 participants 422 participants
Female
32
  38.6%
33
  39.3%
43
  50.0%
87
  51.5%
195
  46.2%
Male
51
  61.4%
51
  60.7%
43
  50.0%
82
  48.5%
227
  53.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 83 participants 84 participants 86 participants 169 participants 422 participants
Hispanic or Latino
2
   2.4%
3
   3.6%
1
   1.2%
10
   5.9%
16
   3.8%
Not Hispanic or Latino
75
  90.4%
81
  96.4%
85
  98.8%
155
  91.7%
396
  93.8%
Unknown or Not Reported
6
   7.2%
0
   0.0%
0
   0.0%
4
   2.4%
10
   2.4%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 83 participants 84 participants 86 participants 169 participants 422 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
17
  20.5%
18
  21.4%
16
  18.6%
31
  18.3%
82
  19.4%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
7
   8.4%
8
   9.5%
4
   4.7%
7
   4.1%
26
   6.2%
White
54
  65.1%
56
  66.7%
64
  74.4%
124
  73.4%
298
  70.6%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
5
   6.0%
2
   2.4%
2
   2.3%
7
   4.1%
16
   3.8%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 83 participants 84 participants 86 participants 169 participants 422 participants
North America 38 39 38 77 192
Japan 12 11 12 23 58
Europe 33 34 36 69 172
Eczema Area and Severity Index (EASI) Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 83 participants 84 participants 86 participants 169 participants 422 participants
2.5  (2.31) 2.3  (2.33) 2.8  (3.31) 2.6  (2.92) 2.6  (2.78)
[1]
Measure Description: The EASI score was used to measure the severity and extent of atopic dermatitis (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 range from 0 (minimum) to 72 (maximum) points,with the higher scores reflecting the worse severity of AD.
Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS)   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 83 participants 84 participants 86 participants 169 participants 422 participants
2.8  (2.11) 2.7  (2.27) 3.1  (2.16) 2.8  (1.92) 2.8  (2.08)
[1]
Measure Description: Pruritus NRS scale is an assessment tool that is 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 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]).
Body Surface Area (BSA) Involvement with AD   [1] 
Mean (Standard Deviation)
Unit of measure:  Percentage of body surface area
Number Analyzed 83 participants 84 participants 86 participants 169 participants 422 participants
8.1  (8.21) 7.9  (9.04) 9.3  (10.51) 7.9  (9.02) 8.2  (9.18)
[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] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 83 participants 84 participants 86 participants 169 participants 422 participants
16.8  (10.03) 17.1  (9.41) 17.5  (10.59) 17.1  (10.49) 17.1  (10.18)
[1]
Measure 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).
Patient Oriented Eczema Measure (POEM)   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 83 participants 84 participants 86 participants 169 participants 422 participants
6.1  (5.43) 6.8  (5.88) 6.1  (5.11) 6.4  (5.30) 6.3  (5.40)
[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]).
Dermatology Life Quality Index (DLQI) Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 83 participants 84 participants 86 participants 169 participants 422 participants
3.4  (4.25) 3.0  (3.76) 3.2  (3.93) 3.4  (4.21) 3.3  (4.06)
[1]
Measure Description: The 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 indicative of a poor QOL.
Total Hospital Anxiety Depression Scale (HADS)   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 83 participants 84 participants 86 participants 169 participants 422 participants
5.9  (6.36) 7.1  (6.87) 7.3  (7.53) 6.4  (5.94) 6.6  (6.53)
[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 Difference Between Current Study Baseline and Week 36 in Percent Change in EASI From Parent Study Baseline (NCT02277743 and NCT02277769)
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. Difference of percent change in EASI between current study baseline and week 36 in from parent study baseline (NCT02277743 and NCT02277769) was reported. Values after first rescue treatment used were set to missing before multiple imputation (MI).
Time Frame Baseline (Parent Study), Baseline (Current Study) and Week 36 (Current study)
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) includes all randomized participants.
Arm/Group Title Placebo QW Dupilumab 300 mg Q8W Dupilumab 300 mg Q4W Dupilumab 300 mg Q2W/QW
Hide Arm/Group Description:
Subcutaneous injection of Placebo (for Dupilumab) was administered weekly (QW) from Week 1 (Day 1) to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every eight week (Q8W) from Week 1 to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every four week (Q4W) from Week 1 to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every week (QW) or twice a week (Q2W) from Week 1 to Week 36.
Overall Number of Participants Analyzed 83 84 86 169
Least Squares Mean (Standard Error)
Unit of Measure: percent change
21.67  (3.134) 6.84  (2.434) 3.84  (2.283) 0.06  (1.736)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo QW, Dupilumab 300 mg Q8W
Comments A 2-sided hierarchical testing procedure was used for the co-primary and key secondary efficacy endpoints in a pre-specified order. 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 0.05 level. Analysis was performed using ANCOVA method.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0001
Comments [Not Specified]
Method ANCOVA
Comments Threshold for significance at 0.05 level.
Method of Estimation Estimation Parameter Percent Change Difference
Estimated Value -14.83
Confidence Interval (2-Sided) 95%
-22.34 to -7.33
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo QW, Dupilumab 300 mg Q4W
Comments A 2-sided hierarchical testing procedure was used for the co-primary and key secondary efficacy endpoints in a pre-specified order. 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 0.05 level. Analysis was performed using ANCOVA method.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method ANCOVA
Comments Threshold for significance at 0.05 level.
Method of Estimation Estimation Parameter Percent Change Difference
Estimated Value -17.83
Confidence Interval (2-Sided) 95%
-25.33 to -10.34
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo QW, Dupilumab 300 mg Q2W/QW
Comments A 2-sided hierarchical testing procedure was used for the co-primary and key secondary efficacy endpoints in a pre-specified order. 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 0.05 level. Analysis was performed using ANCOVA method.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments Threshold for significance at 0.05 level.
Method of Estimation Estimation Parameter Percent Change Difference
Estimated Value -21.61
Confidence Interval (2-Sided) 95%
-28.36 to -14.87
Estimation Comments [Not Specified]
2.Primary Outcome
Title Percentage of Participants With Eczema Area and Severity Index >= 75% [EASI-75] at Baseline of Current Study Maintaining EASI-75 at Week 36
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 at Week 36. Values after first rescue treatment used were set to missing. Patients with missing value at week 36 were considered as a non-responder.
Time Frame Week 36
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population was used. Here, number of participants analyzed = participants with EASI-75 at baseline.
Arm/Group Title Placebo QW Dupilumab 300 mg Q8W Dupilumab 300 mg Q4W Dupilumab 300 mg Q2W/QW
Hide Arm/Group Description:
Subcutaneous injection of Placebo (for Dupilumab) was administered weekly (QW) from Week 1 (Day 1) to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every eight week (Q8W) from Week 1 to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every four week (Q4W) from Week 1 to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every week (QW) or twice a week (Q2W) from Week 1 to Week 36.
Overall Number of Participants Analyzed 79 82 84 162
Measure Type: Number
Unit of Measure: percentage of participants
30.4 54.9 58.3 71.6
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo QW, Dupilumab 300 mg Q8W
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, baseline disease severity and Dupilumab regimen received in parent studies.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0040
Comments Threshold for significance at 0.05 level.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage difference
Estimated Value 24.5
Confidence Interval (2-Sided) 95%
9.70 to 39.29
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo QW, Dupilumab 300 mg Q4W
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, baseline disease severity and Dupilumab regimen received in parent studies.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0004
Comments Threshold for significance at 0.05 level.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage difference
Estimated Value 28.0
Confidence Interval (2-Sided) 95%
13.32 to 42.58
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo QW, Dupilumab 300 mg Q2W/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, baseline disease severity and Dupilumab regimen received in parent studies.
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 41.2
Confidence Interval (2-Sided) 95%
28.93 to 53.52
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Participants Maintaining Investigator Global Assessment (IGA) Response Within 1 Point of Baseline at Week 36
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 at baseline and maintaining within 1 point of baseline were reported as responders. Values after first rescue treatment used were set to missing. Participants with missing value at a visit were considered as a non-responder.
Time Frame Baseline, Week 36
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population was used. Here, number of participants analyzed = participants with IGA 0 or 1 at Baseline from Interactive voice response system (IVRS).
Arm/Group Title Placebo QW Dupilumab 300 mg Q8W Dupilumab 300 mg Q4W Dupilumab 300 mg Q2W/QW
Hide Arm/Group Description:
Subcutaneous injection of Placebo (for Dupilumab) was administered weekly (QW) from Week 1 (Day 1) to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every eight week (Q8W) from Week 1 to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every four week (Q4W) from Week 1 to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every week (QW) or twice a week (Q2W) from Week 1 to Week 36.
Overall Number of Participants Analyzed 63 64 66 126
Measure Type: Number
Unit of Measure: percentage of participants
28.6 50.0 62.1 70.6
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo QW, Dupilumab 300 mg Q8W
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, baseline disease severity and Dupilumab regimen received in parent studies.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0130
Comments Threshold for significance at 0.05 level.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage difference
Estimated Value 21.4
Confidence Interval (2-Sided) 95%
4.86 to 38.00
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo QW, Dupilumab 300 mg Q4W
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, baseline disease severity and Dupilumab regimen received in parent studies.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0003
Comments Threshold for significance at 0.05 level.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage difference
Estimated Value 33.5
Confidence Interval (2-Sided) 95%
17.38 to 49.72
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo QW, Dupilumab 300 mg Q2W/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, baseline disease severity and Dupilumab regimen received in parent studies.
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 42.1
Confidence Interval (2-Sided) 95%
28.36 to 55.76
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Percentage of Participants Maintaining Investigator Global Assessment (IGA) Response at 0 or 1 Point at Week 36
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 at week 36 were reported as responders. Values after first rescue treatment were set to missing and participants with missing IGA scores at Week 36 were considered as non-responders.
Time Frame Week 36
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population was used. Here, number of participants analyzed = participants with IGA 0 or 1 at Baseline from IVRS.
Arm/Group Title Placebo QW Dupilumab 300 mg Q8W Dupilumab 300 mg Q4W Dupilumab 300 mg Q2W/QW
Hide Arm/Group Description:
Subcutaneous injection of Placebo (for Dupilumab) was administered weekly (QW) from Week 1 (Day 1) to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every eight week (Q8W) from Week 1 to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every four week (Q4W) from Week 1 to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every week (QW) or twice a week (Q2W) from Week 1 to Week 36.
Overall Number of Participants Analyzed 63 64 66 126
Measure Type: Number
Unit of Measure: percentage of participants
14.3 32.8 43.9 54.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo QW, Dupilumab 300 mg Q8W
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, baseline disease severity and Dupilumab regimen received in parent studies.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0209
Comments Threshold for significance at 0.05 level.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage difference
Estimated Value 18.5
Confidence Interval (2-Sided) 95%
4.14 to 32.91
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo QW, Dupilumab 300 mg Q4W
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, baseline disease severity and Dupilumab regimen received in parent studies.
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 29.7
Confidence Interval (2-Sided) 95%
14.89 to 44.42
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo QW, Dupilumab 300 mg Q2W/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, baseline disease severity and Dupilumab regimen received in parent studies.
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 39.7
Confidence Interval (2-Sided) 95%
27.42 to 51.95
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Percentage of Participants With Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score Increased by 3 or More Points From Baseline to Week 35
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]). Values after first rescue treatment were set to missing and participants with missing peak NRS at Week 35 were considered as non-responders.
Time Frame Baseline up to Week 35
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population was used. Here, number of participants analyzed = participants with NRS <= 7 at Baseline.
Arm/Group Title Placebo QW Dupilumab 300 mg Q8W Dupilumab 300 mg Q4W Dupilumab 300 mg Q2W/QW
Hide Arm/Group Description:
Subcutaneous injection of Placebo (for Dupilumab) was administered weekly (QW) from Week 1 (Day 1) to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every eight week (Q8W) from Week 1 to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every four week (Q4W) from Week 1 to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every week (QW) or twice a week (Q2W) from Week 1 to Week 36.
Overall Number of Participants Analyzed 80 81 83 168
Measure Type: Number
Unit of Measure: percentage of participants
70.0 55.6 49.4 33.9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo QW, Dupilumab 300 mg Q8W
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, baseline disease severity and Dupilumab regimen received in parent studies.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1048
Comments Threshold for significance at 0.05 level.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage difference
Estimated Value -14.4
Confidence Interval (2-Sided) 95%
-29.21 to 0.32
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo QW, Dupilumab 300 mg Q4W
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, baseline disease severity and Dupilumab regimen received in parent studies.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0107
Comments Threshold for significance at 0.05 level.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage difference
Estimated Value -20.6
Confidence Interval (2-Sided) 95%
-35.32 to -5.89
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo QW, Dupilumab 300 mg Q2W/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, baseline disease severity and Dupilumab regimen received in parent studies.
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 -36.1
Confidence Interval (2-Sided) 95%
-48.40 to -23.74
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Time to First Event of Investigator's Global Assessment (IGA) >= 2 for Participants With IGA 0 or 1 at Baseline
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).
Time Frame Baseline up to Week 36
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population was used. Here, number of participants analyzed = participants with IGA 0 or 1 at Baseline from IVRS.
Arm/Group Title Placebo QW Dupilumab 300 mg Q8W Dupilumab 300 mg Q4W Dupilumab 300 mg Q2W/QW
Hide Arm/Group Description:
Subcutaneous injection of Placebo (for Dupilumab) was administered weekly (QW) from Week 1 (Day 1) to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every eight week (Q8W) from Week 1 to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every four week (Q4W) from Week 1 to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every week (QW) or twice a week (Q2W) from Week 1 to Week 36.
Overall Number of Participants Analyzed 63 64 66 126
Median (95% Confidence Interval)
Unit of Measure: Days
57
(56 to 58)
85
(59 to 113)
80
(55 to 85)
114
(85 to 169)
7.Secondary Outcome
Title Percentage of Participants With Increased Investigator's Global Assessment (IGA) Score 3 or 4 at Week 36
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). Values after first rescue treatment were set to missing and participants with missing IGA scores at Week 36 were considered as responders (i.e. having a increase 3 or 4 of IGA value).
Time Frame Week 36
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population was used. Here, number of participants analyzed = participants with IGA 0 or 1 at Baseline from IVRS.
Arm/Group Title Placebo QW Dupilumab 300 mg Q8W Dupilumab 300 mg Q4W Dupilumab 300 mg Q2W/QW
Hide Arm/Group Description:
Subcutaneous injection of Placebo (for Dupilumab) was administered weekly (QW) from Week 1 (Day 1) to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every eight week (Q8W) from Week 1 to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every four week (Q4W) from Week 1 to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every week (QW) or twice a week (Q2W) from Week 1 to Week 36.
Overall Number of Participants Analyzed 63 64 66 126
Measure Type: Number
Unit of Measure: percentage of participants
66.7 48.4 34.8 26.2
8.Secondary Outcome
Title Percentage of Participants With Eczema Area and Severity Index-50 (EASI-50) (>= 50% Reduction in EASI Score) at Week 36
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 from baseline to Week 36. Values after first rescue treatment were set to missing and participants with missing EASI-50 scores at Week 36 were considered as non-responders.
Time Frame Week 36
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population was used.
Arm/Group Title Placebo QW Dupilumab 300 mg Q8W Dupilumab 300 mg Q4W Dupilumab 300 mg Q2W/QW
Hide Arm/Group Description:
Subcutaneous injection of Placebo (for Dupilumab) was administered weekly (QW) from Week 1 (Day 1) to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every eight week (Q8W) from Week 1 to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every four week (Q4W) from Week 1 to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every week (QW) or twice a week (Q2W) from Week 1 to Week 36.
Overall Number of Participants Analyzed 83 84 86 169
Measure Type: Number
Unit of Measure: percentage of participants
39.8 54.8 60.5 73.4
9.Secondary Outcome
Title Absolute Change From Baseline in Eczema Area and Severity Index (EASI) at Week 36
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. Values after first rescue treatment were set to missing and participants with missing Values at Week 36 were imputed by using multiple imputation method.
Time Frame Baseline, Week 36
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population was used.
Arm/Group Title Placebo QW Dupilumab 300 mg Q8W Dupilumab 300 mg Q4W Dupilumab 300 mg Q2W/QW
Hide Arm/Group Description:
Subcutaneous injection of Placebo (for Dupilumab) was administered weekly (QW) from Week 1 (Day 1) to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every eight week (Q8W) from Week 1 to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every four week (Q4W) from Week 1 to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every week (QW) or twice a week (Q2W) from Week 1 to Week 36.
Overall Number of Participants Analyzed 83 84 86 169
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
6.61  (0.799) 1.75  (0.738) 1.37  (0.735) 0.09  (0.511)
10.Secondary Outcome
Title Absolute Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score at Week 36
Hide Description SCORAD is 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.) are assessed and scored. Total score ranges from 0 (absent disease) to 103 (severe disease). Values after first rescue treatment used were set to missing (censoring) before MI.
Time Frame Baseline, Week 36
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population was used.
Arm/Group Title Placebo QW Dupilumab 300 mg Q8W Dupilumab 300 mg Q4W Dupilumab 300 mg Q2W/QW
Hide Arm/Group Description:
Subcutaneous injection of Placebo (for Dupilumab) was administered weekly (QW) from Week 1 (Day 1) to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every eight week (Q8W) from Week 1 to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every four week (Q4W) from Week 1 to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every week (QW) or twice a week (Q2W) from Week 1 to Week 36.
Overall Number of Participants Analyzed 83 84 86 169
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
18.61  (2.107) 6.62  (2.010) 2.25  (1.899) 0.99  (1.350)
11.Secondary Outcome
Title Absolute Change From Baseline in Peak Daily Pruritus Numerical Rating Scale (NRS) Score at Week 35
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]). Values after first rescue treatment used were set to missing before MI.
Time Frame Baseline, Week 35
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population was used.
Arm/Group Title Placebo QW Dupilumab 300 mg Q8W Dupilumab 300 mg Q4W Dupilumab 300 mg Q2W/QW
Hide Arm/Group Description:
Subcutaneous injection of Placebo (for Dupilumab) was administered weekly (QW) from Week 1 (Day 1) to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every eight week (Q8W) from Week 1 to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every four week (Q4W) from Week 1 to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every week (QW) or twice a week (Q2W) from Week 1 to Week 36.
Overall Number of Participants Analyzed 83 84 86 169
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
2.5  (0.29) 1.1  (0.27) 0.6  (0.25) -0.1  (0.20)
12.Secondary Outcome
Title Absolute Change From Baseline in Body Surface Area (BSA) Through Week 36
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. Values after first rescue treatment used were set to missing (censoring) before MI.
Time Frame Baseline through Week 36
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population was used.
Arm/Group Title Placebo QW Dupilumab 300 mg Q8W Dupilumab 300 mg Q4W Dupilumab 300 mg Q2W/QW
Hide Arm/Group Description:
Subcutaneous injection of Placebo (for Dupilumab) was administered weekly (QW) from Week 1 (Day 1) to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every eight week (Q8W) from Week 1 to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every four week (Q4W) from Week 1 to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every week (QW) or twice a week (Q2W) from Week 1 to Week 36.
Overall Number of Participants Analyzed 83 84 86 169
Least Squares Mean (Standard Error)
Unit of Measure: meter square
9.16  (1.642) 2.74  (1.530) 1.74  (1.457) -1.27  (1.044)
13.Secondary Outcome
Title Absolute Change From Baseline Through in Patient Oriented Eczema Measure (POEM) Through Week 36
Hide Description The POEM is 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]). Values after first rescue treatment used were set to missing (censoring) before MI.
Time Frame Baseline through Week 36
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population was used.
Arm/Group Title Placebo QW Dupilumab 300 mg Q8W Dupilumab 300 mg Q4W Dupilumab 300 mg Q2W/QW
Hide Arm/Group Description:
Subcutaneous injection of Placebo (for Dupilumab) was administered weekly (QW) from Week 1 (Day 1) to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every eight week (Q8W) from Week 1 to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every four week (Q4W) from Week 1 to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every week (QW) or twice a week (Q2W) from Week 1 to Week 36.
Overall Number of Participants Analyzed 83 84 86 169
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
7.0  (0.90) 2.8  (0.78) 0.8  (0.73) -0.3  (0.56)
14.Secondary Outcome
Title Absolute Change From Baseline in Dermatology Life Quality Index (DLQI) Through Week 36
Hide Description The 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. Values after first rescue treatment used were set to missing before MI.
Time Frame Baseline through Week 36
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population was used.
Arm/Group Title Placebo QW Dupilumab 300 mg Q8W Dupilumab 300 mg Q4W Dupilumab 300 mg Q2W/QW
Hide Arm/Group Description:
Subcutaneous injection of Placebo (for Dupilumab) was administered weekly (QW) from Week 1 (Day 1) to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every eight week (Q8W) from Week 1 to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every four week (Q4W) from Week 1 to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every week (QW) or twice a week (Q2W) from Week 1 to Week 36.
Overall Number of Participants Analyzed 83 84 86 169
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
3.1  (0.52) 1.5  (0.46) 0.3  (0.48) -0.2  (0.33)
15.Secondary Outcome
Title Absolute Change From Baseline in Hospital Anxiety Depression Scale (HADS) Through Week 36
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. Values after first rescue treatment used were set to missing before MI.
Time Frame Baseline through Week 36
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population was used.
Arm/Group Title Placebo QW Dupilumab 300 mg Q8W Dupilumab 300 mg Q4W Dupilumab 300 mg Q2W/QW
Hide Arm/Group Description:
Subcutaneous injection of Placebo (for Dupilumab) was administered weekly (QW) from Week 1 (Day 1) to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every eight week (Q8W) from Week 1 to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every four week (Q4W) from Week 1 to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every week (QW) or twice a week (Q2W) from Week 1 to Week 36.
Overall Number of Participants Analyzed 83 84 86 169
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
0.8  (0.60) 0.7  (0.52) 0.2  (0.54) -0.8  (0.39)
16.Secondary Outcome
Title Difference Between Current Study Baseline and Week 36 in Percent Change in SCORAD From Parent Study Baseline
Hide Description SCORAD is 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.) are assessed and scored. Total score ranges from 0 (absent disease) to 103 (severe disease). Values after first rescue treatment used were set to missing before MI.
Time Frame Baseline (Parent Study), Baseline (Current Study) and Week 36 (Current study)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population was used.
Arm/Group Title Placebo QW Dupilumab 300 mg Q8W Dupilumab 300 mg Q4W Dupilumab 300 mg Q2W/QW
Hide Arm/Group Description:
Subcutaneous injection of Placebo (for Dupilumab) was administered weekly (QW) from Week 1 (Day 1) to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every eight week (Q8W) from Week 1 to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every four week (Q4W) from Week 1 to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every week (QW) or twice a week (Q2W) from Week 1 to Week 36.
Overall Number of Participants Analyzed 83 84 86 169
Least Squares Mean (Standard Error)
Unit of Measure: Percent change
28.97  (3.683) 10.42  (2.988) 2.21  (2.743) 0.33  (2.092)
17.Secondary Outcome
Title Difference Between Current Study Baseline and Week 35 in Percent Change in Peak Weekly Pruritus NRS From Parent Study Baseline
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]). Values after first rescue treatment used were set to missing before MI.
Time Frame Baseline (Parent Study), Baseline (Current Study) and Week 35 (Current study)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population was used.
Arm/Group Title Placebo QW Dupilumab 300 mg Q8W Dupilumab 300 mg Q4W Dupilumab 300 mg Q2W/QW
Hide Arm/Group Description:
Subcutaneous injection of Placebo (for Dupilumab) was administered weekly (QW) from Week 1 (Day 1) to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every eight week (Q8W) from Week 1 to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every four week (Q4W) from Week 1 to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every week (QW) or twice a week (Q2W) from Week 1 to Week 36.
Overall Number of Participants Analyzed 83 84 86 169
Least Squares Mean (Standard Error)
Unit of Measure: percent change
35.6  (4.32) 16.7  (4.09) 8.6  (4.02) -0.1  (3.05)
18.Secondary Outcome
Title Annualized Event Rate of Skin Infection Treatment­ Emergent Adverse Events (TEAEs)
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 36]). 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 in­patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non­serious AEs.
Time Frame Baseline through Week 36
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population was used.
Arm/Group Title Placebo QW Dupilumab 300 mg Q8W Dupilumab 300 mg Q4W Dupilumab 300 mg Q2W/QW
Hide Arm/Group Description:
Subcutaneous injection of Placebo (for Dupilumab) was administered weekly (QW) from Week 1 (Day 1) to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every eight week (Q8W) from Week 1 to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every four week (Q4W) from Week 1 to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every week (QW) or twice a week (Q2W) from Week 1 to Week 36.
Overall Number of Participants Analyzed 83 84 86 169
Median (95% Confidence Interval)
Unit of Measure: events per year
0.12
(0.044 to 0.338)
0.07
(0.024 to 0.226)
0.02
(0.005 to 0.120)
0.02
(0.007 to 0.083)
19.Secondary Outcome
Title Annualized Event Rate of Flares
Hide Description Rate of Flares defined as worsening of disease requiring initiation or escalation of rescue treatment.
Time Frame Baseline through week 36
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population was used.
Arm/Group Title Placebo QW Dupilumab 300 mg Q8W Dupilumab 300 mg Q4W Dupilumab 300 mg Q2W/QW
Hide Arm/Group Description:
Subcutaneous injection of Placebo (for Dupilumab) was administered weekly (QW) from Week 1 (Day 1) to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every eight week (Q8W) from Week 1 to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every four week (Q4W) from Week 1 to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every week (QW) or twice a week (Q2W) from Week 1 to Week 36.
Overall Number of Participants Analyzed 83 84 86 169
Median (95% Confidence Interval)
Unit of Measure: events per year
0.75
(0.465 to 1.214)
0.60
(0.363 to 0.977)
0.39
(0.231 to 0.661)
0.24
(0.146 to 0.380)
20.Secondary Outcome
Title Percentage of Well-Controlled Weeks During the On-treatment Period
Hide Description Well-controlled weeks are those in which participants during their weekly IVRS call completion has their eczema been well-controlled over the last week during which no rescue treatments were administered. Percentage of well-controlled weeks during the on-treatment period were reported.
Time Frame Baseline through Week 36
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set (SAF) included all randomized participants who received any amount of study drug. Here, number of participants analyzed = participants with available data for this endpoint. One participant was randomized to Dupilumab Q2W/QW, but treated per Dupilumab Q4W arm and included in SAF.
Arm/Group Title Placebo QW Dupilumab 300 mg Q8W Dupilumab 300 mg Q4W Dupilumab 300 mg Q2W/QW
Hide Arm/Group Description:
Subcutaneous injection of Placebo (for Dupilumab) was administered weekly (QW) from Week 1 (Day 1) to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every eight week (Q8W) from Week 1 to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every four week (Q4W) from Week 1 to Week 36.
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every week (QW) or twice a week (Q2W) from Week 1 to Week 36.
Overall Number of Participants Analyzed 81 82 87 165
Mean (Standard Deviation)
Unit of Measure: percentage of weeks
40.9  (30.35) 53.2  (32.95) 52.3  (35.96) 63.6  (32.08)
Time Frame All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 36) regardless of seriousness or relationship to investigational product.
Adverse Event Reporting Description

Reported AEs are treatment-emergent adverse events that developed/worsened during the 'on-treatment period' (time from the first dose of study drug up to the end of study [Week 36]). The safety analysis set (SAF) included all randomized participants who received any amount of study drug.

Note: One participant was randomized to Dupilumab Q2W/QW, but treated per Dupilumab Q4W arm and included in the SAF

 
Arm/Group Title Placebo QW Dupilumab 300 mg Q8W Dupilumab 300 mg Q4W Dupilumab 300 mg Q2W/QW
Hide Arm/Group Description Subcutaneous injection of Placebo (for Dupilumab) was administered weekly (QW) from Week 1 (Day 1) to Week 36. Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every eight week (Q8W) from Week 1 to Week 36. Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every four week (Q4W) from Week 1 to Week 36. Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every week (QW) or twice a week (Q2W) from Week 1 to Week 36.
All-Cause Mortality
Placebo QW Dupilumab 300 mg Q8W Dupilumab 300 mg Q4W Dupilumab 300 mg Q2W/QW
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/82 (0.00%)      0/84 (0.00%)      1/87 (1.15%)      0/167 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Placebo QW Dupilumab 300 mg Q8W Dupilumab 300 mg Q4W Dupilumab 300 mg Q2W/QW
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/82 (1.22%)      3/84 (3.57%)      4/87 (4.60%)      6/167 (3.59%)    
Cardiac disorders         
Atrial fibrillation  1  0/82 (0.00%)  0 0/84 (0.00%)  0 1/87 (1.15%)  1 0/167 (0.00%)  0
Tachycardia induced cardiomyopathy  1  0/82 (0.00%)  0 0/84 (0.00%)  0 1/87 (1.15%)  1 0/167 (0.00%)  0
Immune system disorders         
Anaphylactic reaction  1  0/82 (0.00%)  0 0/84 (0.00%)  0 0/87 (0.00%)  0 1/167 (0.60%)  1
Injury, poisoning and procedural complications         
Gun shot wound  1  0/82 (0.00%)  0 0/84 (0.00%)  0 1/87 (1.15%)  1 0/167 (0.00%)  0
Muscle injury  1  0/82 (0.00%)  0 1/84 (1.19%)  1 0/87 (0.00%)  0 0/167 (0.00%)  0
Open fracture  1  0/82 (0.00%)  0 0/84 (0.00%)  0 0/87 (0.00%)  0 1/167 (0.60%)  1
Road traffic accident  1  0/82 (0.00%)  0 0/84 (0.00%)  0 0/87 (0.00%)  0 2/167 (1.20%)  2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Basal cell carcinoma  1  0/82 (0.00%)  0 2/84 (2.38%)  2 0/87 (0.00%)  0 0/167 (0.00%)  0
Glioblastoma  1  0/82 (0.00%)  0 0/84 (0.00%)  0 1/87 (1.15%)  1 0/167 (0.00%)  0
Squamous cell carcinoma of skin  1  0/82 (0.00%)  0 0/84 (0.00%)  0 0/87 (0.00%)  0 1/167 (0.60%)  1
Pregnancy, puerperium and perinatal conditions         
Biochemical pregnancy  1  0/82 (0.00%)  0 0/84 (0.00%)  0 0/87 (0.00%)  0 1/167 (0.60%)  1
Respiratory, thoracic and mediastinal disorders         
Pulmonary embolism  1  0/82 (0.00%)  0 0/84 (0.00%)  0 1/87 (1.15%)  1 0/167 (0.00%)  0
Skin and subcutaneous tissue disorders         
Dermatitis atopic  1  1/82 (1.22%)  1 0/84 (0.00%)  0 0/87 (0.00%)  0 0/167 (0.00%)  0
Surgical and medical procedures         
Abortion induced  1  0/82 (0.00%)  0 0/84 (0.00%)  0 1/87 (1.15%)  1 0/167 (0.00%)  0
Vascular disorders         
Deep vein thrombosis  1  0/82 (0.00%)  0 0/84 (0.00%)  0 1/87 (1.15%)  1 0/167 (0.00%)  0
Hypertension  1  0/82 (0.00%)  0 0/84 (0.00%)  0 0/87 (0.00%)  0 1/167 (0.60%)  1
1
Term from vocabulary, meddra (18.0)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo QW Dupilumab 300 mg Q8W Dupilumab 300 mg Q4W Dupilumab 300 mg Q2W/QW
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   55/82 (67.07%)      43/84 (51.19%)      47/87 (54.02%)      72/167 (43.11%)    
General disorders         
Injection site reaction  1  2/82 (2.44%)  22 3/84 (3.57%)  10 2/87 (2.30%)  8 10/167 (5.99%)  62
Infections and infestations         
Bronchitis  1  1/82 (1.22%)  1 0/84 (0.00%)  0 5/87 (5.75%)  6 3/167 (1.80%)  4
Influenza  1  1/82 (1.22%)  1 0/84 (0.00%)  0 5/87 (5.75%)  7 4/167 (2.40%)  4
Nasopharyngitis  1  11/82 (13.41%)  13 11/84 (13.10%)  14 11/87 (12.64%)  14 32/167 (19.16%)  41
Oral herpes  1  3/82 (3.66%)  4 5/84 (5.95%)  10 2/87 (2.30%)  5 3/167 (1.80%)  10
Upper respiratory tract infection  1  6/82 (7.32%)  6 7/84 (8.33%)  7 5/87 (5.75%)  6 13/167 (7.78%)  16
Nervous system disorders         
Headache  1  2/82 (2.44%)  6 3/84 (3.57%)  3 5/87 (5.75%)  7 8/167 (4.79%)  12
Skin and subcutaneous tissue disorders         
Dermatitis atopic  1  40/82 (48.78%)  60 27/84 (32.14%)  34 30/87 (34.48%)  43 34/167 (20.36%)  43
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.
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
Layout table for Results Point of Contact information
Name/Title: Clinical Trial Management
Organization: Regeneron Pharmaceuticals, Inc.
EMail: clinicaltrials@regeneron.com
Layout table for additonal information
Responsible Party: Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02395133     History of Changes
Other Study ID Numbers: R668-AD-1415
2014-003384-38 ( EudraCT Number )
First Submitted: March 16, 2015
First Posted: March 20, 2015
Results First Submitted: May 22, 2018
Results First Posted: October 17, 2018
Last Update Posted: December 4, 2018