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Safety, Pharmacokinetics and Efficacy of Dupilumab in Patients ≥6 Months to <6 Years With Moderate-to-Severe Atopic Dermatitis (Liberty AD PRESCHOOL) (Liberty AD)

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: NCT03346434
Recruitment Status : Completed
First Posted : November 17, 2017
Results First Posted : July 28, 2022
Last Update Posted : July 28, 2022
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
Regeneron Pharmaceuticals

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Dermatitis, Atopic
Interventions Drug: Dupilumab
Drug: Matching placebo
Enrollment 202
Recruitment Details This study was conducted in 2 parts: Part A and Part B; Participants who enrolled in Part A of study were not eligible to participate in Part B.
Pre-assignment Details Participants in Part A enrolled in 2 sequential age cohorts: Cohort 1 (≥2 to <6 yrs) and Cohort 2 (≥6 months to <2 yrs). Each age cohort received dupilumab in 1 of 2 doses: 3 milligrams per kilogram (mg/kg) or 6 mg/kg. Participants in Part B were randomized to 1 of 2 treatment groups: placebo + topical corticosteroids (TCS) or dupilumab 200/300 mg every four weeks (Q4W) + TCS.
Arm/Group Title Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg Part B: Placebo + TCS Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
Hide Arm/Group Description Participants received a single subcutaneous (SC) injection of dupilumab at a dose of 3 mg/kg at Day 1. At week 4, participants could roll over into an open-label extension (OLE) study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety. Participants received a single SC injection of dupilumab at a dose of 6 mg/kg at Day 1. At week 4, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety. Participants received a single SC injection of dupilumab at a dose of 3 mg/kg at Day 1. At week 4, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety. Participants received a single SC injection of dupilumab at a dose of 6 mg/kg at Day 1. At week 4, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety. Participants received SC injection of placebo matched to dupilumab Q4W for 16 weeks along with low potency TCS applied once daily to areas with active lesions. At week 16, participants could roll over into an OLE study (R668-AD-1434/ NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (Week 28, end of study [EOS] period). Participants with baseline weight of ≥ 5 to < 15 kilogram (kg) received SC injections of 200 mg or participants with baseline weight ≥ 15 to < 30 kg received SC injections of 300 mg of dupilumab at Day 1 and Q4W from week 4 to week 12. Participants applied low potency TCS once daily to areas with active lesions for 16 weeks. At week 16, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (Week 28, EOS period).
Period Title: Overall Study
Started 10 10 10 10 79 83
Completed Part A 10 10 9 10 0 0
Completed Part B (Week 16) 0 0 0 0 76 83
Completed Part B (Week 28) [1] 0 0 0 0 1 1
Completed 10 10 9 10 1 1
Not Completed 0 0 1 0 78 82
Reason Not Completed
Randomized in Error             0             0             0             0             1             0
Withdrawal by Subject             0             0             1             0             1             0
Lost to Follow-up             0             0             0             0             1             1
Transitioned to OLE study at Week 16 (NCT02612454)             0             0             0             0             75             81
[1]
End of Study
Arm/Group Title Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg Part B: Placebo + TCS Part B: Dupilumab 200 mg or 300 mg Q4W + TCS Total
Hide Arm/Group Description Participants received a single subcutaneous (SC) injection of dupilumab at a dose of 3 mg/kg at Day 1. At week 4, participants could roll over into an open-label extension (OLE) study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety. Participants received a single SC injection of dupilumab at a dose of 6 mg/kg at Day 1. At week 4, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety. Participants received a single SC injection of dupilumab at a dose of 3 mg/kg at Day 1. At week 4, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety. Participants received a single SC injection of dupilumab at a dose of 6 mg/kg at Day 1. At week 4, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety. Participants received SC injection of placebo matched to dupilumab Q4W for 16 weeks along with low potency TCS applied once daily to areas with active lesions. At week 16, participants could roll over into an OLE study (R668-AD-1434/ NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (Week 28, end of study [EOS] period). Participants with baseline weight of ≥ 5 to < 15 kilogram (kg) received SC injections of 200 mg or participants with baseline weight ≥ 15 to < 30 kg received SC injections of 300 mg of dupilumab at Day 1 and Q4W from week 4 to week 12. Participants applied low potency TCS once daily to areas with active lesions for 16 weeks. At week 16, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (Week 28, EOS period). Total of all reporting groups
Overall Number of Baseline Participants 10 10 10 10 79 83 202
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 10 participants 10 participants 10 participants 10 participants 79 participants 83 participants 202 participants
6 months - <2 years 0 0 10 10 5 6 31
≥2 years and <6 years 10 10 0 0 74 77 171
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 10 participants 10 participants 10 participants 79 participants 83 participants 202 participants
Female
4
  40.0%
3
  30.0%
1
  10.0%
2
  20.0%
24
  30.4%
39
  47.0%
73
  36.1%
Male
6
  60.0%
7
  70.0%
9
  90.0%
8
  80.0%
55
  69.6%
44
  53.0%
129
  63.9%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 10 participants 10 participants 10 participants 79 participants 83 participants 202 participants
Hispanic or Latino
3
  30.0%
2
  20.0%
2
  20.0%
2
  20.0%
9
  11.4%
11
  13.3%
29
  14.4%
Not Hispanic or Latino
7
  70.0%
8
  80.0%
8
  80.0%
8
  80.0%
70
  88.6%
72
  86.7%
173
  85.6%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Investigator Global Assessment (IGA)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 10 participants 10 participants 10 participants 79 participants 83 participants 202 participants
IGA=3 (moderate)
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
17
  21.5%
20
  24.1%
37
  18.3%
IGA=4 (severe)
10
 100.0%
10
 100.0%
10
 100.0%
10
 100.0%
62
  78.5%
63
  75.9%
165
  81.7%
[1]
Measure Description: The IGA is an assessment scale used in clinical studies to rate the severity of atopic dermatitis (AD) globally, based on a 5-point scale ranging from 0 to 4 where 0=clear; 1=almost clear; 2=mild; 3=moderate; 4=severe.
1.Primary Outcome
Title Part A: Maximum Observed Serum Concentration (Cmax) of Functional Dupilumab
Hide Description Serum concentration of functional dupilumab was reported.
Time Frame Post-dose on Days 1, 3, 8, 18, and 29
Hide Outcome Measure Data
Hide Analysis Population Description
The Pharmacokinetic Analysis Set (PKAS) included all treated participants who received any study drug (safety analysis set) and who had at least 1 non-missing functional dupilumab measurement following the administration of the first dose of study drug.
Arm/Group Title Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg
Hide Arm/Group Description:
Participants received a single subcutaneous (SC) injection of dupilumab at a dose of 3 mg/kg at Day 1. At week 4, participants could roll over into an open-label extension (OLE) study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Participants received a single SC injection of dupilumab at a dose of 6 mg/kg at Day 1. At week 4, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Participants received a single SC injection of dupilumab at a dose of 3 mg/kg at Day 1. At week 4, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Participants received a single SC injection of dupilumab at a dose of 6 mg/kg at Day 1. At week 4, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Overall Number of Participants Analyzed 9 10 10 10
Mean (Standard Deviation)
Unit of Measure: Milligrams per Liter (mg/L)
25.2  (7.44) 49.8  (11.3) 20.1  (6.81) 46.1  (11.1)
2.Primary Outcome
Title Part A: Dose Normalized Maximum Observed Serum Concentration (Cmax/Dose) of Dupilumab
Hide Description Dose normalized was calculated as Cmax obtained directly from the concentration versus time curve divided by dose. Cmax/dose was measured in Milligrams per Liter/Milligrams per Kilogram ([mg/L]/[mg/kg]).
Time Frame Post-dose on Days 1, 3, 8, 18, and 29
Hide Outcome Measure Data
Hide Analysis Population Description
The PKAS included all treated participants who received any study drug (safety analysis set) and who had at least 1 non-missing functional dupilumab measurement following the administration of the first dose of study drug.
Arm/Group Title Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg
Hide Arm/Group Description:
Participants received a single subcutaneous (SC) injection of dupilumab at a dose of 3 mg/kg at Day 1. At week 4, participants could roll over into an open-label extension (OLE) study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Participants received a single SC injection of dupilumab at a dose of 6 mg/kg at Day 1. At week 4, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Participants received a single SC injection of dupilumab at a dose of 3 mg/kg at Day 1. At week 4, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Participants received a single SC injection of dupilumab at a dose of 6 mg/kg at Day 1. At week 4, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Overall Number of Participants Analyzed 9 10 10 10
Mean (Standard Deviation)
Unit of Measure: [mg/L]/[mg/kg]
8.39  (2.48) 8.30  (1.89) 6.70  (2.27) 7.68  (1.86)
3.Primary Outcome
Title Part A: Time to Reach the Maximum Serum Concentration (Tmax) of Dupilumab
Hide Description Tmax was obtained directly from the concentration versus time curve.
Time Frame Post-dose on Days 1, 3, 8, 18, and 29
Hide Outcome Measure Data
Hide Analysis Population Description
The PKAS included all treated participants who received any study drug (safety analysis set) and who had at least 1 non-missing functional dupilumab measurement following the administration of the first dose of study drug.
Arm/Group Title Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg
Hide Arm/Group Description:
Participants received a single SC injection of dupilumab at a dose of 6 mg/kg at Day 1. At week 4, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Participants received a single SC injection of dupilumab at a dose of 3 mg/kg at Day 1. At week 4, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Participants received a single SC injection of dupilumab at a dose of 6 mg/kg at Day 1. At week 4, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Participants received a single subcutaneous (SC) injection of dupilumab at a dose of 3 mg/kg at Day 1. At week 4, participants could roll over into an open-label extension (OLE) study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Overall Number of Participants Analyzed 10 10 10 9
Median (Full Range)
Unit of Measure: Days
1.97
(1.87 to 7.82)
1.95
(1.75 to 3.08)
2.10
(1.80 to 7.99)
1.92
(1.72 to 3.02)
4.Primary Outcome
Title Part A: Last Quantifiable Serum Concentration (Clast) of Dupilumab
Hide Description Clast is the last measurable serum concentration of dupilumab.
Time Frame Post-dose on Days 1, 3, 8, 18, and 29
Hide Outcome Measure Data
Hide Analysis Population Description
The PKAS included all treated participants who received any study drug (safety analysis set) and who had at least 1 non-missing functional dupilumab measurement following the administration of the first dose of study drug.
Arm/Group Title Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg
Hide Arm/Group Description:
Participants received a single subcutaneous (SC) injection of dupilumab at a dose of 3 mg/kg at Day 1. At week 4, participants could roll over into an open-label extension (OLE) study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Participants received a single SC injection of dupilumab at a dose of 6 mg/kg at Day 1. At week 4, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Participants received a single SC injection of dupilumab at a dose of 3 mg/kg at Day 1. At week 4, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Participants received a single SC injection of dupilumab at a dose of 6 mg/kg at Day 1. At week 4, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Overall Number of Participants Analyzed 9 10 10 10
Mean (Standard Deviation)
Unit of Measure: mg/L
6.64  (6.16) 6.14  (4.69) 5.64  (4.52) 15.1  (9.48)
5.Primary Outcome
Title Part A: Time of the Last Quantifiable Serum Concentration (Tlast) of Dupilumab
Hide Description Tlast was defined as the last time point with a measurable serum concentration of dupilumab.
Time Frame Post-dose on Days 1, 3, 8, 18, and 29
Hide Outcome Measure Data
Hide Analysis Population Description
The PKAS included all treated participants who received any study drug (safety analysis set) and who had at least 1 non-missing functional dupilumab measurement following the administration of the first dose of study drug.
Arm/Group Title Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg
Hide Arm/Group Description:
Participants received a single subcutaneous (SC) injection of dupilumab at a dose of 3 mg/kg at Day 1. At week 4, participants could roll over into an open-label extension (OLE) study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Participants received a single SC injection of dupilumab at a dose of 6 mg/kg at Day 1. At week 4, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Participants received a single SC injection of dupilumab at a dose of 3 mg/kg at Day 1. At week 4, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Participants received a single SC injection of dupilumab at a dose of 6 mg/kg at Day 1. At week 4, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Overall Number of Participants Analyzed 9 10 10 10
Median (Full Range)
Unit of Measure: Days
14.8
(6.79 to 28.0)
26.5
(15.0 to 32.0)
8.56
(6.88 to 16.9)
16.0
(6.95 to 28.0)
6.Primary Outcome
Title Part A: Area Under the Serum Concentration-Time Curve From Time Zero to the Time of the Last Measurable Concentration (AUClast) of Dupilumab
Hide Description AUClast was defined as area under the serum concentration time-curve from zero to the last measured concentration.
Time Frame Post-dose on Days 1, 3, 8, 18, and 29
Hide Outcome Measure Data
Hide Analysis Population Description
The PKAS included all treated participants who received any study drug (safety analysis set) and who had at least 1 non-missing functional dupilumab measurement following the administration of the first dose of study drug.
Arm/Group Title Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg
Hide Arm/Group Description:
Participants received a single subcutaneous (SC) injection of dupilumab at a dose of 3 mg/kg at Day 1. At week 4, participants could roll over into an open-label extension (OLE) study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Participants received a single SC injection of dupilumab at a dose of 6 mg/kg at Day 1. At week 4, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Participants received a single SC injection of dupilumab at a dose of 3 mg/kg at Day 1. At week 4, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Participants received a single SC injection of dupilumab at a dose of 6 mg/kg at Day 1. At week 4, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Overall Number of Participants Analyzed 9 10 10 10
Mean (Standard Deviation)
Unit of Measure: Days*Milligrams per Liter (day*mg/L)
198  (125) 622  (184) 123  (86.0) 493  (294)
7.Primary Outcome
Title Part A: Dose Normalized Area Under the Serum Concentration-Time Curve From Time Zero to the Time of the Last Measurable Concentration (AUClast/Dose) of Dupilumab
Hide Description Dose normalized AUClast was calculated by AUClast/dose.
Time Frame Post-dose on Days 1, 3, 8, 18, and 29
Hide Outcome Measure Data
Hide Analysis Population Description
The PKAS included all treated participants who received any study drug (safety analysis set) and who had at least 1 non-missing functional dupilumab measurement following the administration of the first dose of study drug.
Arm/Group Title Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg
Hide Arm/Group Description:
Participants received a single subcutaneous (SC) injection of dupilumab at a dose of 3 mg/kg at Day 1. At week 4, participants could roll over into an open-label extension (OLE) study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Participants received a single SC injection of dupilumab at a dose of 6 mg/kg at Day 1. At week 4, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Participants received a single SC injection of dupilumab at a dose of 3 mg/kg at Day 1. At week 4, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Participants received a single SC injection of dupilumab at a dose of 6 mg/kg at Day 1. At week 4, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Overall Number of Participants Analyzed 9 10 10 10
Mean (Standard Deviation)
Unit of Measure: [day*mg/L]/[mg/kg]
66.0  (41.6) 104  (30.6) 41.0  (28.7) 82.1  (48.9)
8.Primary Outcome
Title Part A: Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE)
Hide Description Adverse Event (AE) was defined as any untoward medical occurrence in a participant administered a study drug which may/may not have a causal relationship with study drug. Serious AE (SAE) was defined as any untoward medical occurrence that resulted in any of following outcomes: death, life-threatening, required initial/prolonged in-participant hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect/considered as medically important event. TEAE was defined as AE starting/worsening after first intake of study drug. TEAEs included participants with both SAEs and non-SAEs. Number of participants with TEAEs is reported.
Time Frame Baseline up to Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set (SAF) included all participants who received any study drug and were analyzed based on the actual treatment received.
Arm/Group Title Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg
Hide Arm/Group Description:
Participants received a single subcutaneous (SC) injection of dupilumab at a dose of 3 mg/kg at Day 1. At week 4, participants could roll over into an open-label extension (OLE) study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Participants received a single SC injection of dupilumab at a dose of 6 mg/kg at Day 1. At week 4, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Participants received a single SC injection of dupilumab at a dose of 3 mg/kg at Day 1. At week 4, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Participants received a single SC injection of dupilumab at a dose of 6 mg/kg at Day 1. At week 4, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Overall Number of Participants Analyzed 10 10 10 10
Measure Type: Count of Participants
Unit of Measure: Participants
3
  30.0%
2
  20.0%
7
  70.0%
7
  70.0%
9.Primary Outcome
Title Part A: Number of Participants With TEAEs by Severity According to Qualitative Toxicity Scale
Hide Description Severity of TEAEs were graded using Qualitative Toxicity Scale, as follows: Mild: Participant is aware of the event or symptom, but the event or symptom is easily tolerated; Moderate: Participant experiences sufficient discomfort to interfere with or reduce his or her usual level of activity; Severe: Significant impairment of functioning: the participant is unable to carry out his or her usual activities. Number of participants with TEAEs by severity were reported.
Time Frame Baseline up to Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
The SAF included all participants who received any study drug and were analyzed based on the actual treatment received.
Arm/Group Title Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg
Hide Arm/Group Description:
Participants received a single subcutaneous (SC) injection of dupilumab at a dose of 3 mg/kg at Day 1. At week 4, participants could roll over into an open-label extension (OLE) study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Participants received a single SC injection of dupilumab at a dose of 6 mg/kg at Day 1. At week 4, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Participants received a single SC injection of dupilumab at a dose of 3 mg/kg at Day 1. At week 4, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Participants received a single SC injection of dupilumab at a dose of 6 mg/kg at Day 1. At week 4, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Overall Number of Participants Analyzed 10 10 10 10
Measure Type: Count of Participants
Unit of Measure: Participants
Mild
1
  10.0%
2
  20.0%
4
  40.0%
5
  50.0%
Moderate
2
  20.0%
0
   0.0%
2
  20.0%
2
  20.0%
Severe
0
   0.0%
0
   0.0%
1
  10.0%
0
   0.0%
10.Primary Outcome
Title Part B: Percentage of Participants With Investigator's Global Assessment (IGA) Score 0 or 1 at Week 16
Hide Description The IGA is an assessment scale used in clinical studies to rate the severity of AD globally, based on a 5-point scale ranging from 0 to 4 where 0 = clear; 1=almost clear; 2=mild; 3=moderate; 4=severe. A negative change from baseline indicated improvement. Percentage of participants with IGA score of '0' or '1' is reported.
Time Frame Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized participants. Efficacy analyses were based on the treatment allocated at randomization (as randomized). Missing data due to withdrawn consent, adverse event (AE), lack of efficacy were imputed as non responder. Missing data due to any other reason including COVID-19 were imputed using multiple imputation (MI). Participants were considered as non-responders after initiation of rescue treatment.
Arm/Group Title Part B: Placebo + TCS Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
Hide Arm/Group Description:
Participants received SC injection of placebo matched to dupilumab Q4W for 16 weeks along with low potency TCS applied once daily to areas with active lesions. At week 16, participants could roll over into an OLE study (R668-AD-1434/ NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (Week 28, end of study [EOS] period).
Participants with baseline weight of ≥ 5 to < 15 kilogram (kg) received SC injections of 200 mg or participants with baseline weight ≥ 15 to < 30 kg received SC injections of 300 mg of dupilumab at Day 1 and Q4W from week 4 to week 12. Participants applied low potency TCS once daily to areas with active lesions for 16 weeks. At week 16, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (Week 28, EOS period).
Overall Number of Participants Analyzed 79 83
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
3.9
(-0.42 to 8.21)
27.7
(18.45 to 38.62)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part B: Placebo + TCS, Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
Comments [Not Specified]
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 23.8
Confidence Interval (2-Sided) 95%
13.27 to 34.37
Estimation Comments [Not Specified]
11.Primary Outcome
Title Part B: Percentage of Participants With Eczema Area and Severity Index (EASI) -75 (EASI-75) (≥75% Improvement From Baseline) at Week 16
Hide Description The EASI score is 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 indicating the worse severity of AD. EASI-75 responders were the participants who achieved ≥75% overall improvement in EASI score from baseline at Week 16.
Time Frame Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized participants. Efficacy analyses were based on the treatment allocated at randomization (as randomized). Missing data due to withdrawn consent, AE, lack of efficacy were imputed as non responder. Missing data due to any other reason including COVID-19 were imputed using MI. Participants were considered as non-responders after initiation of rescue treatment.
Arm/Group Title Part B: Placebo + TCS Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
Hide Arm/Group Description:
Participants received SC injection of placebo matched to dupilumab Q4W for 16 weeks along with low potency TCS applied once daily to areas with active lesions. At week 16, participants could roll over into an OLE study (R668-AD-1434/ NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (Week 28, end of study [EOS] period).
Participants with baseline weight of ≥ 5 to < 15 kilogram (kg) received SC injections of 200 mg or participants with baseline weight ≥ 15 to < 30 kg received SC injections of 300 mg of dupilumab at Day 1 and Q4W from week 4 to week 12. Participants applied low potency TCS once daily to areas with active lesions for 16 weeks. At week 16, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (Week 28, EOS period).
Overall Number of Participants Analyzed 79 83
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
10.7
(3.65 to 17.74)
53.0
(41.74 to 64.07)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part B: Placebo + TCS, Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
Comments [Not Specified]
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 42.3
Confidence Interval (2-Sided) 95%
29.47 to 55.16
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Part A: Number of Participants With Serious TEAEs and Severe TEAEs
Hide Description Adverse Event (AE) was defined as any untoward medical occurrence in a participant administered a study drug which may/may not have a causal relationship with study drug. A serious TEAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. Severe TEAE: significant impairment of functioning the participant is unable to carry out his or her usual activities.
Time Frame Baseline up to Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
The SAF included all participants who received any study drug and was analyzed based on the actual treatment received.
Arm/Group Title Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg
Hide Arm/Group Description:
Participants received a single subcutaneous (SC) injection of dupilumab at a dose of 3 mg/kg at Day 1. At week 4, participants could roll over into an open-label extension (OLE) study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Participants received a single SC injection of dupilumab at a dose of 6 mg/kg at Day 1. At week 4, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Participants received a single SC injection of dupilumab at a dose of 3 mg/kg at Day 1. At week 4, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Participants received a single SC injection of dupilumab at a dose of 6 mg/kg at Day 1. At week 4, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Overall Number of Participants Analyzed 10 10 10 10
Measure Type: Count of Participants
Unit of Measure: Participants
Participants with serious TEAEs
1
  10.0%
0
   0.0%
1
  10.0%
0
   0.0%
Participants with severe TEAEs
0
   0.0%
0
   0.0%
1
  10.0%
0
   0.0%
13.Secondary Outcome
Title Part A: Percent Change From Baseline in EASI Score at Week 4
Hide Description The EASI score is 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 indicated the worse severity of AD. A negative change from baseline indicated improvement.
Time Frame Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
The SAF included all participants who received any study drug and was analyzed based on the actual treatment received.
Arm/Group Title Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg
Hide Arm/Group Description:
Participants received a single subcutaneous (SC) injection of dupilumab at a dose of 3 mg/kg at Day 1. At week 4, participants could roll over into an open-label extension (OLE) study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Participants received a single SC injection of dupilumab at a dose of 6 mg/kg at Day 1. At week 4, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Participants received a single SC injection of dupilumab at a dose of 3 mg/kg at Day 1. At week 4, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Participants received a single SC injection of dupilumab at a dose of 6 mg/kg at Day 1. At week 4, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Overall Number of Participants Analyzed 10 10 10 10
Mean (Standard Deviation)
Unit of Measure: Percent Change
-26.6  (47.37) -48.7  (28.89) -22.4  (42.52) -43.2  (35.55)
14.Secondary Outcome
Title Part A: Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score at Week 4
Hide Description The SCORAD is used to assess the extent and severity of AD. Extent and severity of eczema as well as subjective symptoms (insomnia, etc) were assessed and scored. SCORAD total score ranges from 0 (absent disease) to 103 (severe disease). A negative change from baseline indicated improvement.
Time Frame Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
SAF included all participants who received any study drug and was analyzed based on the actual treatment received.
Arm/Group Title Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg
Hide Arm/Group Description:
Participants received a single subcutaneous (SC) injection of dupilumab at a dose of 3 mg/kg at Day 1. At week 4, participants could roll over into an open-label extension (OLE) study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Participants received a single SC injection of dupilumab at a dose of 6 mg/kg at Day 1. At week 4, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Participants received a single SC injection of dupilumab at a dose of 3 mg/kg at Day 1. At week 4, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Participants received a single SC injection of dupilumab at a dose of 6 mg/kg at Day 1. At week 4, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Overall Number of Participants Analyzed 10 10 10 10
Mean (Standard Deviation)
Unit of Measure: Percent Change
-18.6  (26.18) -31.9  (17.45) -22.4  (26.44) -28.1  (27.84)
15.Secondary Outcome
Title Part A: Percentage of Participants With IGA Score 0 or 1 at Week 4
Hide Description The IGA is an assessment scale used in clinical studies to rate the severity of AD globally, based on a 5-point scale ranging from 0 to 4 where 0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe. Percentage of participants with IGA score of '0' or '1' were reported.
Time Frame Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
SAF included all participants who received any study drug and was analyzed based on the actual treatment received.
Arm/Group Title Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg
Hide Arm/Group Description:
Participants received a single subcutaneous (SC) injection of dupilumab at a dose of 3 mg/kg at Day 1. At week 4, participants could roll over into an open-label extension (OLE) study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Participants received a single SC injection of dupilumab at a dose of 6 mg/kg at Day 1. At week 4, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Participants received a single SC injection of dupilumab at a dose of 3 mg/kg at Day 1. At week 4, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Participants received a single SC injection of dupilumab at a dose of 6 mg/kg at Day 1. At week 4, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Overall Number of Participants Analyzed 10 10 10 10
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
10.0
(0.25 to 44.50)
0.0
(0.00 to 30.85)
10.0
(0.25 to 44.50)
10.0
(0.25 to 44.50)
16.Secondary Outcome
Title Part A: Number of Participants With at Least One Positive Treatment-Emergent Anti-Drug Antibodies (ADA)
Hide Description Treatment boosted (TB) Response: Any post-dose positive result at least 9-fold over the baseline level when baseline is positive; Treatment emergent (TE) Response: Post-dose positive result when baseline results were negative.
Time Frame Baseline up to Day 57
Hide Outcome Measure Data
Hide Analysis Population Description
The ADA Analysis Set (AAS) included all treated participants who received any study drug and who had at least 1 non-missing ADA result following the first dose of study drug.
Arm/Group Title Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg
Hide Arm/Group Description:
Participants received a single subcutaneous (SC) injection of dupilumab at a dose of 3 mg/kg at Day 1. At week 4, participants could roll over into an open-label extension (OLE) study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Participants received a single SC injection of dupilumab at a dose of 6 mg/kg at Day 1. At week 4, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Participants received a single SC injection of dupilumab at a dose of 3 mg/kg at Day 1. At week 4, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Participants received a single SC injection of dupilumab at a dose of 6 mg/kg at Day 1. At week 4, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
Overall Number of Participants Analyzed 10 10 10 10
Measure Type: Count of Participants
Unit of Measure: Participants
TB Response
0
   0.0%
0
   0.0%
1
  10.0%
0
   0.0%
TE Response
5
  50.0%
4
  40.0%
5
  50.0%
5
  50.0%
17.Secondary Outcome
Title Part B: Number of Participants With at Least One Serious Adverse Event (SAE) Through Week 16
Hide Description [Not Specified]
Time Frame Baseline through Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
SAF included all randomized participants who received at least one dose of study drug and was analysed as treated.
Arm/Group Title Part B: Placebo + TCS Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
Hide Arm/Group Description:
Participants received SC injection of placebo matched to dupilumab Q4W for 16 weeks along with low potency TCS applied once daily to areas with active lesions. At week 16, participants could roll over into an OLE study (R668-AD-1434/ NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (Week 28, end of study [EOS] period).
Participants with baseline weight of ≥ 5 to < 15 kilogram (kg) received SC injections of 200 mg or participants with baseline weight ≥ 15 to < 30 kg received SC injections of 300 mg of dupilumab at Day 1 and Q4W from week 4 to week 12. Participants applied low potency TCS once daily to areas with active lesions for 16 weeks. At week 16, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (Week 28, EOS period).
Overall Number of Participants Analyzed 78 83
Measure Type: Count of Participants
Unit of Measure: Participants
4
   5.1%
0
   0.0%
18.Secondary Outcome
Title Part B: Number of Participants With at Least One Skin Infection Treatment Emergent Adverse Event (TEAE) (Excluding Herpetic Infection) Through Week 16
Hide Description [Not Specified]
Time Frame Baseline through Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
SAF included all randomized participants who received at least one dose of study drug and was analysed as treated.
Arm/Group Title Part B: Placebo + TCS Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
Hide Arm/Group Description:
Participants received SC injection of placebo matched to dupilumab Q4W for 16 weeks along with low potency TCS applied once daily to areas with active lesions. At week 16, participants could roll over into an OLE study (R668-AD-1434/ NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (Week 28, end of study [EOS] period).
Participants with baseline weight of ≥ 5 to < 15 kilogram (kg) received SC injections of 200 mg or participants with baseline weight ≥ 15 to < 30 kg received SC injections of 300 mg of dupilumab at Day 1 and Q4W from week 4 to week 12. Participants applied low potency TCS once daily to areas with active lesions for 16 weeks. At week 16, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (Week 28, EOS period).
Overall Number of Participants Analyzed 78 83
Measure Type: Count of Participants
Unit of Measure: Participants
19
  24.4%
10
  12.0%
19.Secondary Outcome
Title Part B: Number of Participants With at Least One Positive Treatment-Emergent ADA
Hide Description Treatment emergent (TE): Post-dose positive result when baseline results were negative.
Time Frame Baseline up to Day 197
Hide Outcome Measure Data
Hide Analysis Population Description
AAS included all participants who received any study drug and who had at least one non-missing ADA result after the first dose of the study drug.
Arm/Group Title Part B: Placebo + TCS Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
Hide Arm/Group Description:
Participants received SC injection of placebo matched to dupilumab Q4W for 16 weeks along with low potency TCS applied once daily to areas with active lesions. At week 16, participants could roll over into an OLE study (R668-AD-1434/ NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (Week 28, end of study [EOS] period).
Participants with baseline weight of ≥ 5 to < 15 kilogram (kg) received SC injections of 200 mg or participants with baseline weight ≥ 15 to < 30 kg received SC injections of 300 mg of dupilumab at Day 1 and Q4W from week 4 to week 12. Participants applied low potency TCS once daily to areas with active lesions for 16 weeks. At week 16, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (Week 28, EOS period).
Overall Number of Participants Analyzed 69 74
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
1
   1.4%
20.Secondary Outcome
Title Part B: Percent Change From Baseline in EASI Score at Week 16
Hide Description The EASI score is 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 indicating the worse severity of AD. A negative change from baseline indicated improvement.
Time Frame Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants. Efficacy analyses were based on the treatment allocated at randomisation (as randomised). Missing data due to withdrawn consent, AE, or lack of efficacy and data after rescue were imputed by post baseline worst observation carried forward (WOCF). If there was no post baseline assessment, the baseline value was used. Missing values due to other reasons including COVID-19 were imputed by MI approach.
Arm/Group Title Part B: Placebo + TCS Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
Hide Arm/Group Description:
Participants received SC injection of placebo matched to dupilumab Q4W for 16 weeks along with low potency TCS applied once daily to areas with active lesions. At week 16, participants could roll over into an OLE study (R668-AD-1434/ NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (Week 28, end of study [EOS] period).
Participants with baseline weight of ≥ 5 to < 15 kilogram (kg) received SC injections of 200 mg or participants with baseline weight ≥ 15 to < 30 kg received SC injections of 300 mg of dupilumab at Day 1 and Q4W from week 4 to week 12. Participants applied low potency TCS once daily to areas with active lesions for 16 weeks. At week 16, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (Week 28, EOS period).
Overall Number of Participants Analyzed 79 83
Least Squares Mean (Standard Error)
Unit of Measure: Percent Change
-19.6  (5.13) -70.0  (4.85)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part B: Placebo + TCS, Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
Comments [Not Specified]
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 -50.4
Confidence Interval (2-Sided) 95%
-62.38 to -38.40
Estimation Comments [Not Specified]
21.Secondary Outcome
Title Part B: Percent Change From Baseline in Weekly Average of Daily Worst Scratch/Itch/Numerical Rating Scale (NRS) at Week 16
Hide Description Pruritus NRS is an assessment tool used to report intensity of participant's pruritus (itch), both average & maximum intensity, during 24-hr recall period. Participants were asked two questions: 1) For average itch intensity: how would you rate your itch overall (on average) during the previous 24 hrs; 2) For maximum itch intensity: How would you rate your itch at the worst moment during the previous 24 hrs? Both questions were rated on a scale: 0-10 with 0=no itch & 10=worst itch imaginable. A negative change from baseline indicated improvement.
Time Frame Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized participants. Efficacy analyses were based on the treatment allocated at randomization (as randomized). Missing data due to withdrawn consent, AE, or lack of efficacy and data after rescue were imputed by post baseline WOCF. If there was no post baseline assessment, the baseline value was used. Missing values due to other reasons including COVID-19 were imputed by MI approach.
Arm/Group Title Part B: Placebo + TCS Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
Hide Arm/Group Description:
Participants received SC injection of placebo matched to dupilumab Q4W for 16 weeks along with low potency TCS applied once daily to areas with active lesions. At week 16, participants could roll over into an OLE study (R668-AD-1434/ NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (Week 28, end of study [EOS] period).
Participants with baseline weight of ≥ 5 to < 15 kilogram (kg) received SC injections of 200 mg or participants with baseline weight ≥ 15 to < 30 kg received SC injections of 300 mg of dupilumab at Day 1 and Q4W from week 4 to week 12. Participants applied low potency TCS once daily to areas with active lesions for 16 weeks. At week 16, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (Week 28, EOS period).
Overall Number of Participants Analyzed 79 83
Least Squares Mean (Standard Error)
Unit of Measure: Percent Change
-2.2  (5.22) -49.4  (5.03)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part B: Placebo + TCS, Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
Comments [Not Specified]
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 -47.1
Confidence Interval (2-Sided) 95%
-59.47 to -34.79
Estimation Comments [Not Specified]
22.Secondary Outcome
Title Part B: Percentage of Participants With Improvement (Reduction From Baseline) of Weekly Average of Daily Worst Scratch/Itch/NRS ≥4 Points at Week 16
Hide Description Pruritus NRS is an assessment tool used to report intensity of subject's pruritus (itch), both average & maximum intensity, during 24-hr recall period. Subjects were asked two questions: 1) For average itch intensity: how would you rate your itch overall (on average) during the previous 24 hrs; & 2) For maximum itch intensity: How would you rate your itch at the worst moment during the previous 24 hrs? Both questions were rated on a scale: 0-10 with 0=no itch & 10=worst itch imaginable.
Time Frame Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized participants. Efficacy analyses were based on the treatment allocated at randomization (as randomized). Missing data due to withdrawn consent, AE, lack of efficacy were imputed as non responder. Missing data due to any other reason including COVID-19 were imputed using MI. Participants were considered as non-responders after initiation of rescue treatment.
Arm/Group Title Part B: Placebo + TCS Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
Hide Arm/Group Description:
Participants received SC injection of placebo matched to dupilumab Q4W for 16 weeks along with low potency TCS applied once daily to areas with active lesions. At week 16, participants could roll over into an OLE study (R668-AD-1434/ NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (Week 28, end of study [EOS] period).
Participants with baseline weight of ≥ 5 to < 15 kilogram (kg) received SC injections of 200 mg or participants with baseline weight ≥ 15 to < 30 kg received SC injections of 300 mg of dupilumab at Day 1 and Q4W from week 4 to week 12. Participants applied low potency TCS once daily to areas with active lesions for 16 weeks. At week 16, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (Week 28, EOS period).
Overall Number of Participants Analyzed 78 83
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
8.9
(2.25 to 15.51)
48.1
(37.05 to 59.15)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part B: Placebo + TCS, Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
Comments [Not Specified]
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 39.2
Confidence Interval (2-Sided) 95%
26.18 to 52.27
Estimation Comments [Not Specified]
23.Secondary Outcome
Title Part B: Percentage of Participants With Improvement (Reduction From Baseline) of Weekly Average of Daily Worst Scratch/Itch/NRS ≥3 Points at Week 16
Hide Description Pruritus NRS is an assessment tool used to report intensity of participant's pruritus (itch), both average & maximum intensity, during 24-hr recall period. Participants were asked two questions: 1) For average itch intensity: how would you rate your itch overall (on average) during the previous 24 hrs; & 2) For maximum itch intensity: How would you rate your itch at the worst moment during the previous 24 hrs? Both questions were rated on a scale: 0-10 with 0=no itch & 10=worst itch imaginable.
Time Frame Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized participants. Efficacy analyses were based on the treatment allocated at randomization (as randomized). Missing data due to withdrawn consent, AE, lack of efficacy were imputed as non responder. Missing data due to any other reason including COVID-19 were imputed using MI. Participants were considered as non-responders after initiation of rescue treatment.
Arm/Group Title Part B: Placebo + TCS Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
Hide Arm/Group Description:
Participants received SC injection of placebo matched to dupilumab Q4W for 16 weeks along with low potency TCS applied once daily to areas with active lesions. At week 16, participants could roll over into an OLE study (R668-AD-1434/ NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (Week 28, end of study [EOS] period).
Participants with baseline weight of ≥ 5 to < 15 kilogram (kg) received SC injections of 200 mg or participants with baseline weight ≥ 15 to < 30 kg received SC injections of 300 mg of dupilumab at Day 1 and Q4W from week 4 to week 12. Participants applied low potency TCS once daily to areas with active lesions for 16 weeks. At week 16, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (Week 28, EOS period).
Overall Number of Participants Analyzed 78 83
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
9.9
(2.59 to 17.22)
53.3
(42.29 to 64.22)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part B: Placebo + TCS, Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
Comments [Not Specified]
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 43.3
Confidence Interval (2-Sided) 95%
30.03 to 56.67
Estimation Comments [Not Specified]
24.Secondary Outcome
Title Part B: Percentage of Participants Who Achieved EASI-50 (≥50% Improvement From Baseline) at Week 16
Hide Description The EASI score is 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 indicating the worse severity of AD. EASI-50 responders were the participants who achieved ≥50% overall improvement in EASI score from baseline at Week 16.
Time Frame Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized participants. Efficacy analyses were based on the treatment allocated at randomization (as randomized). Missing data due to withdrawn consent, AE, lack of efficacy were imputed as non responder. Missing data due to any other reason including COVID-19 were imputed using MI. Participants were considered as non-responders after initiation of rescue treatment.
Arm/Group Title Part B: Placebo + TCS Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
Hide Arm/Group Description:
Participants received SC injection of placebo matched to dupilumab Q4W for 16 weeks along with low potency TCS applied once daily to areas with active lesions. At week 16, participants could roll over into an OLE study (R668-AD-1434/ NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (Week 28, end of study [EOS] period).
Participants with baseline weight of ≥ 5 to < 15 kilogram (kg) received SC injections of 200 mg or participants with baseline weight ≥ 15 to < 30 kg received SC injections of 300 mg of dupilumab at Day 1 and Q4W from week 4 to week 12. Participants applied low potency TCS once daily to areas with active lesions for 16 weeks. At week 16, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (Week 28, EOS period).
Overall Number of Participants Analyzed 79 83
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
20.2
(11.09 to 29.23)
68.7
(57.56 to 78.41)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part B: Placebo + TCS, Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
Comments [Not Specified]
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 48.5
Confidence Interval (2-Sided) 95%
35.03 to 62.00
Estimation Comments [Not Specified]
25.Secondary Outcome
Title Part B: Percentage of Participants Who Achieved EASI-90 (≥90% Improvement From Baseline) at Week 16
Hide Description The EASI score is 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 indicating the worse severity of AD. EASI-90 responders were the participant who achieved ≥90% overall improvement in EASI score from baseline at Week 16.
Time Frame Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized participants. Efficacy analyses were based on the treatment allocated at randomization (as randomized). Missing data due to withdrawn consent, AE, lack of efficacy were imputed as non responder. Missing data due to any other reason including COVID-19 were imputed using MI. Participants were considered as non-responders after initiation of rescue treatment.
Arm/Group Title Part B: Placebo + TCS Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
Hide Arm/Group Description:
Participants received SC injection of placebo matched to dupilumab Q4W for 16 weeks along with low potency TCS applied once daily to areas with active lesions. At week 16, participants could roll over into an OLE study (R668-AD-1434/ NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (Week 28, end of study [EOS] period).
Participants with baseline weight of ≥ 5 to < 15 kilogram (kg) received SC injections of 200 mg or participants with baseline weight ≥ 15 to < 30 kg received SC injections of 300 mg of dupilumab at Day 1 and Q4W from week 4 to week 12. Participants applied low potency TCS once daily to areas with active lesions for 16 weeks. At week 16, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (Week 28, EOS period).
Overall Number of Participants Analyzed 79 83
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
2.8
(-1.02 to 6.66)
25.3
(16.39 to 36.04)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part B: Placebo + TCS, Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
Comments [Not Specified]
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 22.5
Confidence Interval (2-Sided) 95%
12.37 to 32.60
Estimation Comments [Not Specified]
26.Secondary Outcome
Title Part B: Change From Baseline in Percent Body Surface Area (BSA) Affected by Atopic Dermatitis (AD) 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. A negative change from baseline indicated improvement.
Time Frame Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized participant. Efficacy analyses were based on the treatment allocated at randomization (as randomized). Missing data due to withdrawn consent, AE, or lack of efficacy and data after rescue were imputed by post baseline WOCF. If there was no post baseline assessment, the baseline value was used. Missing values due to other reasons including COVID-19 were imputed by MI approach.
Arm/Group Title Part B: Placebo + TCS Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
Hide Arm/Group Description:
Participants received SC injection of placebo matched to dupilumab Q4W for 16 weeks along with low potency TCS applied once daily to areas with active lesions. At week 16, participants could roll over into an OLE study (R668-AD-1434/ NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (Week 28, end of study [EOS] period).
Participants with baseline weight of ≥ 5 to < 15 kilogram (kg) received SC injections of 200 mg or participants with baseline weight ≥ 15 to < 30 kg received SC injections of 300 mg of dupilumab at Day 1 and Q4W from week 4 to week 12. Participants applied low potency TCS once daily to areas with active lesions for 16 weeks. At week 16, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (Week 28, EOS period).
Overall Number of Participants Analyzed 79 83
Least Squares Mean (Standard Error)
Unit of Measure: Percentage of Body Surface Area (BSA)
-10.74  (2.926) -35.00  (2.815)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part B: Placebo + TCS, Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
Comments [Not Specified]
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 -24.27
Confidence Interval (2-Sided) 95%
-31.204 to -17.329
Estimation Comments [Not Specified]
27.Secondary Outcome
Title Part B: Change From Baseline in Patient Oriented Eczema Measure (POEM) at Week 16
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]). A negative change from baseline indicated improvement.
Time Frame Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized participants. Efficacy analyses were based on the treatment allocated at randomization (as randomized). Missing data due to withdrawn consent, AE, or lack of efficacy and data after rescue were imputed by post baseline WOCF. If there was no post baseline assessment, the baseline value was used. Missing values due to other reasons including COVID-19 were imputed by MI approach.
Arm/Group Title Part B: Placebo + TCS Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
Hide Arm/Group Description:
Participants received SC injection of placebo matched to dupilumab Q4W for 16 weeks along with low potency TCS applied once daily to areas with active lesions. At week 16, participants could roll over into an OLE study (R668-AD-1434/ NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (Week 28, end of study [EOS] period).
Participants with baseline weight of ≥ 5 to < 15 kilogram (kg) received SC injections of 200 mg or participants with baseline weight ≥ 15 to < 30 kg received SC injections of 300 mg of dupilumab at Day 1 and Q4W from week 4 to week 12. Participants applied low potency TCS once daily to areas with active lesions for 16 weeks. At week 16, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (Week 28, EOS period).
Overall Number of Participants Analyzed 79 83
Least Squares Mean (Standard Error)
Unit of Measure: Score on a Scale
-3.8  (0.92) -12.9  (0.89)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part B: Placebo + TCS, Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
Comments [Not Specified]
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 -9.1
Confidence Interval (2-Sided) 95%
-11.26 to -6.89
Estimation Comments [Not Specified]
28.Secondary Outcome
Title Part B: Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) at Week 16
Hide Description The SCORAD index is a clinical tool for assessing the severity of atopic dermatitis (AD). 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). A negative change from baseline indicated improvement.
Time Frame Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized participant. Efficacy analyses were based on the treatment allocated at randomization (as randomized). Missing data due to withdrawn consent, AE, or lack of efficacy and data after rescue were imputed by post baseline WOCF. If there was no post baseline assessment, the baseline value was used. Missing values due to other reasons including COVID-19 were imputed by MI approach.
Arm/Group Title Part B: Placebo + TCS Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
Hide Arm/Group Description:
Participants received SC injection of placebo matched to dupilumab Q4W for 16 weeks along with low potency TCS applied once daily to areas with active lesions. At week 16, participants could roll over into an OLE study (R668-AD-1434/ NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (Week 28, end of study [EOS] period).
Participants with baseline weight of ≥ 5 to < 15 kilogram (kg) received SC injections of 200 mg or participants with baseline weight ≥ 15 to < 30 kg received SC injections of 300 mg of dupilumab at Day 1 and Q4W from week 4 to week 12. Participants applied low potency TCS once daily to areas with active lesions for 16 weeks. At week 16, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (Week 28, EOS period).
Overall Number of Participants Analyzed 79 83
Least Squares Mean (Standard Error)
Unit of Measure: Percent Change
-16.2  (3.54) -54.7  (3.39)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part B: Placebo + TCS, Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
Comments [Not Specified]
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 -38.4
Confidence Interval (2-Sided) 95%
-46.65 to -30.21
Estimation Comments [Not Specified]
29.Secondary Outcome
Title Part B: Change From Baseline in Participant's Sleep Quality NRS at Week 16
Hide Description A sleep diary is completed by the parent/caregiver, included 2 questions assessing the caregiver's sleep, and 6 questions assessing the child's sleep based on caregiver observation. Sleep diary items, either alone or in combination serve as subjective measures of sleep quality, difficulty falling asleep, nighttime awakenings, and sleep duration. Sleep quality is measured using an 11-point NRS (0 to 10) in which 0 indicates worst possible sleep while 10 indicates best possible sleep.
Time Frame Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized participants. Efficacy analyses were based on the treatment allocated at randomization (as randomized). Missing data due to withdrawn consent, AE, or lack of efficacy and data after rescue were imputed by post baseline WOCF. If there was no post baseline assessment, the baseline value was used. Missing values due to other reasons including COVID-19 were imputed by MI approach.
Arm/Group Title Part B: Placebo + TCS Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
Hide Arm/Group Description:
Participants received SC injection of placebo matched to dupilumab Q4W for 16 weeks along with low potency TCS applied once daily to areas with active lesions. At week 16, participants could roll over into an OLE study (R668-AD-1434/ NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (Week 28, end of study [EOS] period).
Participants with baseline weight of ≥ 5 to < 15 kilogram (kg) received SC injections of 200 mg or participants with baseline weight ≥ 15 to < 30 kg received SC injections of 300 mg of dupilumab at Day 1 and Q4W from week 4 to week 12. Participants applied low potency TCS once daily to areas with active lesions for 16 weeks. At week 16, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (Week 28, EOS period).
Overall Number of Participants Analyzed 79 83
Least Squares Mean (Standard Error)
Unit of Measure: Score on a Scale
0.34  (0.256) 2.04  (0.251)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part B: Placebo + TCS, Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Threshold significance was at 0.05 level.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 1.70
Confidence Interval (2-Sided) 95%
1.093 to 2.317
Estimation Comments [Not Specified]
30.Secondary Outcome
Title Part B: Change From Baseline in Participant's Skin Pain NRS at Week 16
Hide Description Skin pain was assessed by the parent/caregiver and measured using a 11-point scale (0 to 10) in which 0 indicated no pain while 10 indicated worst pain possible. A negative change from baseline indicated improvement.
Time Frame Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized participants. Efficacy analyses were based on the treatment allocated at randomization (as randomized). Missing data due to withdrawn consent, AE, or lack of efficacy and data after rescue were imputed by post baseline WOCF. If there was no post baseline assessment, the baseline value was used. Missing values due to other reasons including COVID-19 were imputed by MI approach.
Arm/Group Title Part B: Placebo + TCS Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
Hide Arm/Group Description:
Participants received SC injection of placebo matched to dupilumab Q4W for 16 weeks along with low potency TCS applied once daily to areas with active lesions. At week 16, participants could roll over into an OLE study (R668-AD-1434/ NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (Week 28, end of study [EOS] period).
Participants with baseline weight of ≥ 5 to < 15 kilogram (kg) received SC injections of 200 mg or participants with baseline weight ≥ 15 to < 30 kg received SC injections of 300 mg of dupilumab at Day 1 and Q4W from week 4 to week 12. Participants applied low potency TCS once daily to areas with active lesions for 16 weeks. At week 16, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (Week 28, EOS period).
Overall Number of Participants Analyzed 79 83
Least Squares Mean (Standard Error)
Unit of Measure: Score on a Scale
-0.62  (0.302) -3.93  (0.295)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part B: Placebo + TCS, Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Threshold significance at 0.05 level.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -3.31
Confidence Interval (2-Sided) 95%
-4.029 to -2.600
Estimation Comments [Not Specified]
31.Secondary Outcome
Title Part B: Change From Baseline in Dermatitis Family Index (DFI) at Week 16
Hide Description DFI is a 10-item questionnaire with items inquiring about housework, food preparation, sleep, family leisure activity, shopping, expenditure, tiredness, emotional distress, relationships, and impact of helping with treatment on the primary caregiver's life. DFI questions were scored on a four-point Likert scale ranging from 0 to 3, so that the total DFI score ranges from 0 to 30. Timeframe of reference was the past week. A higher DFI score indicated greater impairment in family Quality of life (QOL) as affected by atopic dermatitis. A negative change from baseline indicated improvement.
Time Frame Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized participants. Efficacy analyses were based on the treatment allocated at randomization (as randomized). Missing data due to withdrawn consent, AE, or lack of efficacy and data after rescue were imputed by post baseline WOCF. If there was no post baseline assessment, the baseline value was used. Missing values due to other reasons including COVID-19 were imputed by MI approach.
Arm/Group Title Part B: Placebo + TCS Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
Hide Arm/Group Description:
Participants received SC injection of placebo matched to dupilumab Q4W for 16 weeks along with low potency TCS applied once daily to areas with active lesions. At week 16, participants could roll over into an OLE study (R668-AD-1434/ NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (Week 28, end of study [EOS] period).
Participants with baseline weight of ≥ 5 to < 15 kilogram (kg) received SC injections of 200 mg or participants with baseline weight ≥ 15 to < 30 kg received SC injections of 300 mg of dupilumab at Day 1 and Q4W from week 4 to week 12. Participants applied low potency TCS once daily to areas with active lesions for 16 weeks. At week 16, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (Week 28, EOS period).
Overall Number of Participants Analyzed 79 83
Least Squares Mean (Standard Error)
Unit of Measure: Score on a Scale
-2.68  (0.839) -10.48  (0.806)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part B: Placebo + TCS, Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Threshold significance at 0.05 level.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -7.80
Confidence Interval (2-Sided) 95%
-9.789 to -5.814
Estimation Comments [Not Specified]
32.Secondary Outcome
Title Part B: Change From Baseline in Children's Dermatology Life Quality Index (CDLQI) at Week 16
Hide Description CDLQI is a validated 10 question tool to measure impact of skin disease on QOL in children by assessing how much the skin problem has affected the subjects over past week. Nine questions were scored as follows: Very much = 3, Quite a lot = 2, Only a little = 1, Not at all or unanswered = 0. Question 7 has an added possible response, which was scored as 3. CDLQI equals the sum of the score of each question (max. = 30, min. = 0). Higher the score, the greater the impact on QOL. A negative change from baseline indicated improvement.
Time Frame Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized participants. Efficacy analyses were based on the treatment allocated at randomization (as randomized). Missing data due to withdrawn consent, AE, or lack of efficacy and data after rescue were imputed by post baseline WOCF. If there was no post baseline assessment, the baseline value was used. Missing values due to other reasons including COVID-19 were imputed by MI approach.
Arm/Group Title Part B: Placebo + TCS Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
Hide Arm/Group Description:
Participants received SC injection of placebo matched to dupilumab Q4W for 16 weeks along with low potency TCS applied once daily to areas with active lesions. At week 16, participants could roll over into an OLE study (R668-AD-1434/ NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (Week 28, end of study [EOS] period).
Participants with baseline weight of ≥ 5 to < 15 kilogram (kg) received SC injections of 200 mg or participants with baseline weight ≥ 15 to < 30 kg received SC injections of 300 mg of dupilumab at Day 1 and Q4W from week 4 to week 12. Participants applied low potency TCS once daily to areas with active lesions for 16 weeks. At week 16, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (Week 28, EOS period).
Overall Number of Participants Analyzed 38 47
Least Squares Mean (Standard Error)
Unit of Measure: Score on a Scale
-2.5  (1.66) -10.0  (1.56)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part B: Placebo + TCS, Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Threshold significance at 0.05 level.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -7.5
Confidence Interval (2-Sided) 95%
-10.29 to -4.75
Estimation Comments [Not Specified]
33.Secondary Outcome
Title Part B: Change From Baseline in Infants' Dermatology Quality of Life Index (IDQOL) at Week 16
Hide Description Infants' Dermatitis Quality of Life Index (IDQOL) is used to evaluate quality of life for subjects of age less than 4 years. IDQOL questionnaires were designed for infants (below the age of 4 years) with atopic dermatitis. The IDQOL was calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score in each questionnaire, the more quality of life is impaired. A negative change from baseline indicated improvement.
Time Frame Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized participants. Efficacy analyses were based on the treatment allocated at randomization (as randomized). Missing data due to withdrawn consent, AE, or lack of efficacy and data after rescue were imputed by post baseline WOCF. If there was no post baseline assessment, the baseline value was used. Missing values due to other reasons including COVID-19 were imputed by MI approach.
Arm/Group Title Part B: Placebo + TCS Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
Hide Arm/Group Description:
Participants received SC injection of placebo matched to dupilumab Q4W for 16 weeks along with low potency TCS applied once daily to areas with active lesions. At week 16, participants could roll over into an OLE study (R668-AD-1434/ NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (Week 28, end of study [EOS] period).
Participants with baseline weight of ≥ 5 to < 15 kilogram (kg) received SC injections of 200 mg or participants with baseline weight ≥ 15 to < 30 kg received SC injections of 300 mg of dupilumab at Day 1 and Q4W from week 4 to week 12. Participants applied low potency TCS once daily to areas with active lesions for 16 weeks. At week 16, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (Week 28, EOS period).
Overall Number of Participants Analyzed 41 36
Least Squares Mean (Standard Error)
Unit of Measure: Score on a Scale
-1.95  (1.078) -10.91  (1.159)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part B: Placebo + TCS, Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Threshold significance at 0.05 level.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -8.96
Confidence Interval (2-Sided) 95%
-11.711 to -6.202
Estimation Comments [Not Specified]
34.Secondary Outcome
Title Part B: Percentage of Topical Corticosteroid (TCS) Medication-free Days From Baseline to Week 16
Hide Description Percentage of TCS medication-free days was calculated as the number of days that a subject used neither TCS/TCI nor system rescue therapy divided by the study days.
Time Frame Baseline up to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized participants. Efficacy analyses were based on the treatment allocated at randomization (as randomized).
Arm/Group Title Part B: Placebo + TCS Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
Hide Arm/Group Description:
Participants received SC injection of placebo matched to dupilumab Q4W for 16 weeks along with low potency TCS applied once daily to areas with active lesions. At week 16, participants could roll over into an OLE study (R668-AD-1434/ NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (Week 28, end of study [EOS] period).
Participants with baseline weight of ≥ 5 to < 15 kilogram (kg) received SC injections of 200 mg or participants with baseline weight ≥ 15 to < 30 kg received SC injections of 300 mg of dupilumab at Day 1 and Q4W from week 4 to week 12. Participants applied low potency TCS once daily to areas with active lesions for 16 weeks. At week 16, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (Week 28, EOS period).
Overall Number of Participants Analyzed 77 82
Median (Full Range)
Unit of Measure: Percentage of Days
0.04
(0.0 to 0.9)
0.21
(0.0 to 1.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part B: Placebo + TCS, Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0015
Comments Threshold significance is at 0.05 level.
Method ANCOVA
Comments [Not Specified]
35.Secondary Outcome
Title Part B: Mean Weekly Dose of Low Potency TCS in Grams From Baseline to Week 16
Hide Description Mean weekly dose of TCS in grams/week for low potency TCS from baseline to Week 16 is reported.
Time Frame Baseline up to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized participants. Efficacy analyses were based on the treatment allocated at randomization (as randomized).
Arm/Group Title Part B: Placebo + TCS Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
Hide Arm/Group Description:
Participants received SC injection of placebo matched to dupilumab Q4W for 16 weeks along with low potency TCS applied once daily to areas with active lesions. At week 16, participants could roll over into an OLE study (R668-AD-1434/ NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (Week 28, end of study [EOS] period).
Participants with baseline weight of ≥ 5 to < 15 kilogram (kg) received SC injections of 200 mg or participants with baseline weight ≥ 15 to < 30 kg received SC injections of 300 mg of dupilumab at Day 1 and Q4W from week 4 to week 12. Participants applied low potency TCS once daily to areas with active lesions for 16 weeks. At week 16, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (Week 28, EOS period).
Overall Number of Participants Analyzed 78 81
Least Squares Mean (Standard Error)
Unit of Measure: Grams per Week
13.4  (1.44) 10.5  (1.39)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part B: Placebo + TCS, Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0997
Comments Threshold significance at 0.05 level.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -2.9
Confidence Interval (2-Sided) 95%
-6.35 to 0.56
Estimation Comments [Not Specified]
36.Secondary Outcome
Title Part B: Mean Weekly Dose of TCS in Grams for Medium or High Potency TCS From Baseline to Week 16
Hide Description Mean weekly dose of TCS in grams/week for medium or high potency TCS from baseline to Week 16 is reported.
Time Frame Baseline up to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized participants. Efficacy analyses were based on the treatment allocated at randomization (as randomized).
Arm/Group Title Part B: Placebo + TCS Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
Hide Arm/Group Description:
Participants received SC injection of placebo matched to dupilumab Q4W for 16 weeks along with low potency TCS applied once daily to areas with active lesions. At week 16, participants could roll over into an OLE study (R668-AD-1434/ NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (Week 28, end of study [EOS] period).
Participants with baseline weight of ≥ 5 to < 15 kilogram (kg) received SC injections of 200 mg or participants with baseline weight ≥ 15 to < 30 kg received SC injections of 300 mg of dupilumab at Day 1 and Q4W from week 4 to week 12. Participants applied low potency TCS once daily to areas with active lesions for 16 weeks. At week 16, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (Week 28, EOS period).
Overall Number of Participants Analyzed 43 24
Least Squares Mean (Standard Error)
Unit of Measure: Grams per Week
6.1  (1.70) 3.0  (1.54)
37.Secondary Outcome
Title Part B: Mean Number of Caregiver Missed Work Days Through Week 16
Hide Description Mean of number of caregiver missed work days through Week 16 is reported.
Time Frame Baseline through Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized participants. Efficacy analyses were based on the treatment allocated at randomization (as randomized).
Arm/Group Title Part B: Placebo + TCS Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
Hide Arm/Group Description:
Participants received SC injection of placebo matched to dupilumab Q4W for 16 weeks along with low potency TCS applied once daily to areas with active lesions. At week 16, participants could roll over into an OLE study (R668-AD-1434/ NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (Week 28, end of study [EOS] period).
Participants with baseline weight of ≥ 5 to < 15 kilogram (kg) received SC injections of 200 mg or participants with baseline weight ≥ 15 to < 30 kg received SC injections of 300 mg of dupilumab at Day 1 and Q4W from week 4 to week 12. Participants applied low potency TCS once daily to areas with active lesions for 16 weeks. At week 16, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (Week 28, EOS period).
Overall Number of Participants Analyzed 57 57
Mean (Standard Deviation)
Unit of Measure: Days
5.05  (8.975) 2.49  (5.524)
Time Frame From day of first treatment up to Week 28 (end of study)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg Part B: Placebo + TCS Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
Hide Arm/Group Description Participants received a single subcutaneous (SC) injection of dupilumab at a dose of 3 mg/kg at Day 1. At week 4, participants could roll over into an open-label extension (OLE) study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety. Participants received a single SC injection of dupilumab at a dose of 6 mg/kg at Day 1. At week 4, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety. Participants received a single SC injection of dupilumab at a dose of 3 mg/kg at Day 1. At week 4, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety. Participants received a single SC injection of dupilumab at a dose of 6 mg/kg at Day 1. At week 4, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 4 weeks for safety. Participants received SC injection of placebo matched to dupilumab Q4W for 16 weeks along with low potency TCS applied once daily to areas with active lesions. At week 16, participants could roll over into an OLE study (R668-AD-1434/ NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (Week 28, end of study [EOS] period). Participants with baseline weight of ≥ 5 to < 15 kilogram (kg) received SC injections of 200 mg or participants with baseline weight ≥ 15 to < 30 kg received SC injections of 300 mg of dupilumab at Day 1 and Q4W from week 4 to week 12. Participants applied low potency TCS once daily to areas with active lesions for 16 weeks. At week 16, participants could roll over into an OLE study (R668-AD-1434/NCT02612454), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (Week 28, EOS period).
All-Cause Mortality
Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg Part B: Placebo + TCS Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/10 (0.00%)      0/10 (0.00%)      0/10 (0.00%)      0/10 (0.00%)      0/78 (0.00%)      0/83 (0.00%)    
Hide Serious Adverse Events
Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg Part B: Placebo + TCS Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/10 (10.00%)      0/10 (0.00%)      1/10 (10.00%)      0/10 (0.00%)      4/78 (5.13%)      0/83 (0.00%)    
Immune system disorders             
Anaphylactic reaction † 1  1/10 (10.00%)  1 0/10 (0.00%)  0 1/10 (10.00%)  1 0/10 (0.00%)  0 0/78 (0.00%)  0 0/83 (0.00%)  0
Hypersensitivity † 2  0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 1/78 (1.28%)  1 0/83 (0.00%)  0
Infections and infestations             
Cellulitis staphylococcal † 2  0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 1/78 (1.28%)  1 0/83 (0.00%)  0
Dermatitis infected † 2  0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 1/78 (1.28%)  1 0/83 (0.00%)  0
Staphylococcal bacteraemia † 2  0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 1/78 (1.28%)  1 0/83 (0.00%)  0
Skin and subcutaneous tissue disorders             
Dermatitis atopic † 2  0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 1/78 (1.28%)  1 0/83 (0.00%)  0
1
Term from vocabulary, MedDRA 21.1 (Part A)
2
Term from vocabulary, MedDRA 23.1 (Part B)
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg Part B: Placebo + TCS Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   7/10 (70.00%)      7/10 (70.00%)      3/10 (30.00%)      2/10 (20.00%)      45/78 (57.69%)      29/83 (34.94%)    
Blood and lymphatic system disorders             
Lymphadenopathy † 3  0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 6/78 (7.69%)  9 3/83 (3.61%)  3
Thrombocytosis † 2  0/10 (0.00%)  0 1/10 (10.00%)  1 0/10 (0.00%)  0 0/10 (0.00%)  0 0/78 (0.00%)  0 0/83 (0.00%)  0
Eye disorders             
Lacrimation increased † 2  0/10 (0.00%)  0 1/10 (10.00%)  1 0/10 (0.00%)  0 0/10 (0.00%)  0 0/78 (0.00%)  0 0/83 (0.00%)  0
Gastrointestinal disorders             
Constipation † 1  1/10 (10.00%)  1 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 0/78 (0.00%)  0 2/83 (2.41%)  3
Diarrhoea † 1  1/10 (10.00%)  1 1/10 (10.00%)  1 0/10 (0.00%)  0 0/10 (0.00%)  0 2/78 (2.56%)  2 1/83 (1.20%)  1
Teething † 2  1/10 (10.00%)  1 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 0/78 (0.00%)  0 0/83 (0.00%)  0
General disorders             
Injection site erythema † 1  0/10 (0.00%)  0 1/10 (10.00%)  1 0/10 (0.00%)  0 0/10 (0.00%)  0 0/78 (0.00%)  0 1/83 (1.20%)  1
Pyrexia † 1  2/10 (20.00%)  2 0/10 (0.00%)  0 1/10 (10.00%)  1 0/10 (0.00%)  0 7/78 (8.97%)  9 1/83 (1.20%)  1
Infections and infestations             
Nasopharyngitis † 1  1/10 (10.00%)  1 2/10 (20.00%)  2 1/10 (10.00%)  1 1/10 (10.00%)  1 7/78 (8.97%)  8 7/83 (8.43%)  8
Upper respiratory tract infection † 1  1/10 (10.00%)  1 1/10 (10.00%)  1 0/10 (0.00%)  0 0/10 (0.00%)  0 7/78 (8.97%)  9 5/83 (6.02%)  5
Impetigo † 1  1/10 (10.00%)  1 1/10 (10.00%)  1 1/10 (10.00%)  1 0/10 (0.00%)  0 6/78 (7.69%)  7 3/83 (3.61%)  3
Folliculitis † 2  1/10 (10.00%)  1 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 0/78 (0.00%)  0 0/83 (0.00%)  0
Injury, poisoning and procedural complications             
Skin abrasion † 2  0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 1/10 (10.00%)  1 0/78 (0.00%)  0 0/83 (0.00%)  0
Musculoskeletal and connective tissue disorders             
Joint swelling † 2  1/10 (10.00%)  1 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 0/78 (0.00%)  0 0/83 (0.00%)  0
Respiratory, thoracic and mediastinal disorders             
Asthma † 3  0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 5/78 (6.41%)  8 3/83 (3.61%)  3
Cough † 1  1/10 (10.00%)  1 1/10 (10.00%)  1 0/10 (0.00%)  0 1/10 (10.00%)  1 5/78 (6.41%)  6 0/83 (0.00%)  0
Skin and subcutaneous tissue disorders             
Dermatitis atopic † 1  0/10 (0.00%)  0 1/10 (10.00%)  1 1/10 (10.00%)  1 0/10 (0.00%)  0 24/78 (30.77%)  46 12/83 (14.46%)  17
Urticaria † 1  1/10 (10.00%)  1 1/10 (10.00%)  1 0/10 (0.00%)  0 0/10 (0.00%)  0 4/78 (5.13%)  4 1/83 (1.20%)  1
1
Term from vocabulary, MedDRA 21.1; 23.1
2
Term from vocabulary, MedDRA 21.1 (Part A)
3
Term from vocabulary, MedDRA 23.1 (Part B)
†
Indicates events were collected by systematic assessment
[Not Specified]
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 Trials Administrator
Organization: Regeneron Pharmaceuticals, Inc.
Phone: 844-734-6643
EMail: clinicaltrials@regeneron.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03346434    
Other Study ID Numbers: R668-AD-1539
2016-000955-28 ( EudraCT Number )
First Submitted: February 6, 2017
First Posted: November 17, 2017
Results First Submitted: June 14, 2022
Results First Posted: July 28, 2022
Last Update Posted: July 28, 2022