Trial Outcomes & Findings for Efficacy and Safety of Dupilumab in Participants ≥12 to <18 Years of Age, With Moderate-to-severe Atopic Dermatitis (NCT NCT03054428)

NCT ID: NCT03054428

Last Updated: 2019-07-23

Results Overview

IGA is an assessment scale used to determine severity of atopic dermatitis (AD) and clinical response to treatment on a 5-point scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe) based on erythema and papulation/infiltration. Therapeutic response was an IGA score of 0 (clear) or 1 (almost clear). Participants with IGA "0" or "1" and a reduction from baseline of ≥2 points at Week 16 were reported. \[Values after first rescue treatment used were set to missing. Participants with missing score at week 16 were considered as a non-responder. Participant considered non-responder after rescue treatment use. Efficacy analyses were based on the treatment allocated at randomization (as randomized).\]

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 251 participants
• Primary outcome timeframe: Baseline and Week 16
• Results posted on: 2019-07-23

Participant Flow

The study was conducted at 45 sites in the United States and Canada between 21 Mar 2017 and 05 Jun 2018. A total of 295 participants were screened, of which, 251 were eligible. The most common causes for screening failures were lack of adequate disease severity and lack of willingness to comply with study visits and procedures.

Eligible participants were randomized (1:1:1) & stratified by baseline Investigator's Global Assessment (IGA) score (3 vs 4) & body weight (<60 kg vs ≥60 kg) to 16 wks treatment with dupilumab every 2 wks (q2w) or q4w,or placebo q2w.

Participant milestones

Measure	Placebo Participants received placebo matching dupilumab once every 2 weeks (Q2W) (including doubling the amount of placebo on day 1 to match the loading dose). Participants in the \<60-kilogram (kg) weight stratum received, in a 1:1 ratio, either placebo matching 200 milligram (mg) or placebo matching 300 milligram (mg). In the ≥60 kg weight stratum, the participants randomized to the placebo group received placebo matching 300 mg dupilumab.	Dupilumab 300 mg Q4W Participants received once every 4 weeks (Q4W) subcutaneous (SC) injections of 300 milligrams (mg) dupilumab following a loading dose of 600 mg on day 1. To maintain blinding, all participants received an injection once every 2 weeks (Q2W) from day 1 to week 14. Participants received placebo 2 millilitre (mL) injection at the weeks dupilumab was not given.	Dupilumab 200 mg or 300 mg Q2W Participants with baseline weight \<60 kg received once every 2 weeks (Q2W) subcutaneous (SC) injections of 200 milligrams (mg) dupilumab following a loading dose of 400 mg on day 1. Participants with baseline weight ≥60 kg received Q2W SC injections of 300 mg dupilumab following a loading dose of 600 mg on day 1.
Overall Study STARTED	85	84	82
Overall Study Completed Wk 16 End of Treatment (EOT)	80	81	79
Overall Study Completed Week 28 (End of Study)	2	4	3
Overall Study COMPLETED	2	4	3
Overall Study NOT COMPLETED	83	80	79

Reasons for withdrawal

Measure	Placebo Participants received placebo matching dupilumab once every 2 weeks (Q2W) (including doubling the amount of placebo on day 1 to match the loading dose). Participants in the \<60-kilogram (kg) weight stratum received, in a 1:1 ratio, either placebo matching 200 milligram (mg) or placebo matching 300 milligram (mg). In the ≥60 kg weight stratum, the participants randomized to the placebo group received placebo matching 300 mg dupilumab.	Dupilumab 300 mg Q4W Participants received once every 4 weeks (Q4W) subcutaneous (SC) injections of 300 milligrams (mg) dupilumab following a loading dose of 600 mg on day 1. To maintain blinding, all participants received an injection once every 2 weeks (Q2W) from day 1 to week 14. Participants received placebo 2 millilitre (mL) injection at the weeks dupilumab was not given.	Dupilumab 200 mg or 300 mg Q2W Participants with baseline weight \<60 kg received once every 2 weeks (Q2W) subcutaneous (SC) injections of 200 milligrams (mg) dupilumab following a loading dose of 400 mg on day 1. Participants with baseline weight ≥60 kg received Q2W SC injections of 300 mg dupilumab following a loading dose of 600 mg on day 1.
Overall Study Physician Decision	0	1	1
Overall Study Lack of Efficacy	3	1	0
Overall Study Discontinued to enroll in OLE: enrolled	0	0	1
Overall Study Discont'd to enroll in OLE: not enrolled	1	0	0
Overall Study Transitioned to OLE study	76	76	73
Overall Study Withdrawal by Subject	3	2	3
Overall Study Lost to Follow-up	0	0	1

Baseline Characteristics

Efficacy and Safety of Dupilumab in Participants ≥12 to <18 Years of Age, With Moderate-to-severe Atopic Dermatitis

Baseline characteristics by cohort

Measure	Placebo n=85 Participants Participants received placebo matching dupilumab once every 2 weeks (Q2W) (including doubling the amount of placebo on day 1 to match the loading dose). Participants in the \<60-kilogram (kg) weight stratum received, in a 1:1 ratio, either placebo matching 200 milligram (mg) or placebo matching 300 milligram (mg). In the ≥60 kg weight stratum, the participants randomized to the placebo group received placebo matching 300 mg dupilumab.	Dupilumab 300 mg Q4W n=84 Participants Participants received once every 4 weeks (Q4W) subcutaneous (SC) injections of 300 milligrams (mg) dupilumab following a loading dose of 600 mg on day 1. To maintain blinding, all participants received an injection once every 2 weeks (Q2W) from day 1 to week 14. Participants received placebo 2 millilitre (mL) injection at the weeks dupilumab was not given.	Dupilumab 200 mg or 300 mg Q2W n=82 Participants Participants with baseline weight \<60 kg received once every 2 weeks (Q2W) subcutaneous (SC) injections of 200 milligrams (mg) dupilumab following a loading dose of 400 mg on day 1. Participants with baseline weight ≥60 kg received Q2W SC injections of 300 mg dupilumab following a loading dose of 600 mg on day 1.	Total n=251 Participants Total of all reporting groups
Age, Continuous	14.5 years STANDARD_DEVIATION 1.78 • n=5 Participants	14.4 years STANDARD_DEVIATION 1.59 • n=7 Participants	14.5 years STANDARD_DEVIATION 1.74 • n=5 Participants	14.5 years STANDARD_DEVIATION 1.70 • n=4 Participants
Age, Customized ≥12 to <15 years of age	41 Participants n=5 Participants	45 Participants n=7 Participants	43 Participants n=5 Participants	129 Participants n=4 Participants
Age, Customized ≥15 to <18 years of age	44 Participants n=5 Participants	39 Participants n=7 Participants	39 Participants n=5 Participants	122 Participants n=4 Participants
Sex: Female, Male Female	32 Participants n=5 Participants	32 Participants n=7 Participants	39 Participants n=5 Participants	103 Participants n=4 Participants
Sex: Female, Male Male	53 Participants n=5 Participants	52 Participants n=7 Participants	43 Participants n=5 Participants	148 Participants n=4 Participants
Race/Ethnicity, Customized White	48 Participants n=5 Participants	55 Participants n=7 Participants	54 Participants n=5 Participants	157 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	15 Participants n=5 Participants	8 Participants n=7 Participants	7 Participants n=5 Participants	30 Participants n=4 Participants
Race/Ethnicity, Customized Asian	13 Participants n=5 Participants	13 Participants n=7 Participants	12 Participants n=5 Participants	38 Participants n=4 Participants
Race/Ethnicity, Customized Other	6 Participants n=5 Participants	8 Participants n=7 Participants	7 Participants n=5 Participants	21 Participants n=4 Participants
Race/Ethnicity, Customized Not Reported/ Missing	3 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	72 Participants n=5 Participants	64 Participants n=7 Participants	69 Participants n=5 Participants	205 Participants n=4 Participants
Race/Ethnicity, Customized Hispanic or Latino	13 Participants n=5 Participants	20 Participants n=7 Participants	13 Participants n=5 Participants	46 Participants n=4 Participants
Duration of Atopic Dermatitis (AD)	12.3 Years STANDARD_DEVIATION 3.44 • n=5 Participants	11.9 Years STANDARD_DEVIATION 3.18 • n=7 Participants	12.5 Years STANDARD_DEVIATION 2.97 • n=5 Participants	12.2 Years STANDARD_DEVIATION 3.20 • n=4 Participants
Eczema Area and Severity Index (EASI) Score	35.5 Scores on a scale STANDARD_DEVIATION 13.97 • n=5 Participants	35.8 Scores on a scale STANDARD_DEVIATION 14.82 • n=7 Participants	35.3 Scores on a scale STANDARD_DEVIATION 13.84 • n=5 Participants	35.5 Scores on a scale STANDARD_DEVIATION 14.16 • n=4 Participants
Investigator's Global Assessment (IGA) Score IGA score = 3 (moderate)	39 Participants n=5 Participants	38 Participants n=7 Participants	39 Participants n=5 Participants	116 Participants n=4 Participants
Investigator's Global Assessment (IGA) Score IGA score = 4 (severe)	46 Participants n=5 Participants	46 Participants n=7 Participants	43 Participants n=5 Participants	135 Participants n=4 Participants
Peak Weekly Averaged Pruritus Numerical Rating Scale (NRS) Score	7.7 Peak weekly average score STANDARD_DEVIATION 1.62 • n=5 Participants	7.5 Peak weekly average score STANDARD_DEVIATION 1.84 • n=7 Participants	7.5 Peak weekly average score STANDARD_DEVIATION 1.52 • n=5 Participants	7.6 Peak weekly average score STANDARD_DEVIATION 1.66 • n=4 Participants
Body Surface Area (BSA) of Atopic Dermatitis (AD)	56.4 Percentage of BSA STANDARD_DEVIATION 24.13 • n=5 Participants	56.9 Percentage of BSA STANDARD_DEVIATION 23.51 • n=7 Participants	56.0 Percentage of BSA STANDARD_DEVIATION 21.40 • n=5 Participants	56.5 Percentage of BSA STANDARD_DEVIATION 22.97 • n=4 Participants
Scoring Atopic Dermatitis (SCORAD) Score	70.4 Scores on a scale STANDARD_DEVIATION 13.25 • n=5 Participants	69.8 Scores on a scale STANDARD_DEVIATION 14.12 • n=7 Participants	70.6 Scores on a scale STANDARD_DEVIATION 13.89 • n=5 Participants	70.3 Scores on a scale STANDARD_DEVIATION 13.70 • n=4 Participants
Patient Oriented Eczema Measure (POEM)	21.1 Scores on a scale STANDARD_DEVIATION 5.38 • n=5 Participants	21.1 Scores on a scale STANDARD_DEVIATION 5.47 • n=7 Participants	21.0 Scores on a scale STANDARD_DEVIATION 5.01 • n=5 Participants	21.0 Scores on a scale STANDARD_DEVIATION 5.27 • n=4 Participants
Children's Dermatology Life Quality Index (CDLQI) Total Score	13.1 Scores on a scale STANDARD_DEVIATION 6.72 • n=5 Participants	14.8 Scores on a scale STANDARD_DEVIATION 7.38 • n=7 Participants	13.0 Scores on a scale STANDARD_DEVIATION 6.21 • n=5 Participants	13.6 Scores on a scale STANDARD_DEVIATION 6.82 • n=4 Participants
Total Hospital Anxiety and Depression Scale (HADS)	11.6 Scores on a scale STANDARD_DEVIATION 7.76 • n=5 Participants	13.3 Scores on a scale STANDARD_DEVIATION 8.17 • n=7 Participants	12.6 Scores on a scale STANDARD_DEVIATION 8.04 • n=5 Participants	12.5 Scores on a scale STANDARD_DEVIATION 7.99 • n=4 Participants

PRIMARY outcome

Timeframe: Baseline and Week 16

Population: Analysis was performed on Full Analysis Set (FAS) population (all randomized participants).

IGA is an assessment scale used to determine severity of atopic dermatitis (AD) and clinical response to treatment on a 5-point scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe) based on erythema and papulation/infiltration. Therapeutic response was an IGA score of 0 (clear) or 1 (almost clear). Participants with IGA "0" or "1" and a reduction from baseline of ≥2 points at Week 16 were reported. [Values after first rescue treatment used were set to missing. Participants with missing score at week 16 were considered as a non-responder. Participant considered non-responder after rescue treatment use. Efficacy analyses were based on the treatment allocated at randomization (as randomized).]

Outcome measures

Measure	Placebo n=85 Participants Participants received placebo matching dupilumab once every 2 weeks (Q2W) (including doubling the amount of placebo on day 1 to match the loading dose). Participants in the \<60-kilogram (kg) weight stratum received, in a 1:1 ratio, either placebo matching 200 milligram (mg) or placebo matching 300 milligram (mg). In the ≥60 kg weight stratum, the participants randomized to the placebo group received placebo matching 300 mg dupilumab.	Dupilumab 300 mg Q4W n=84 Participants Participants received once every 4 weeks (Q4W) subcutaneous (SC) injections of 300 milligrams (mg) dupilumab following a loading dose of 600 mg on day 1. To maintain blinding, all participants received an injection once every 2 weeks (Q2W) from day 1 to week 14. Participants received placebo 2 millilitre (mL) injection at the weeks dupilumab was not given.	Dupilumab 200 mg or 300 mg Q2W n=82 Participants Participants with baseline weight \<60 kg received once every 2 weeks (Q2W) subcutaneous (SC) injections of 200 milligrams (mg) dupilumab following a loading dose of 400 mg on day 1. Participants with baseline weight ≥60 kg received Q2W SC injections of 300 mg dupilumab following a loading dose of 600 mg on day 1.
Percentage of Participants With Investigator's Global Assessment (IGA) 0 or 1 (and Reduction From Baseline of ≥2 Points) at Week 16	2.4 Percentage of participants	17.9 Percentage of participants	24.4 Percentage of participants

PRIMARY outcome

Timeframe: Baseline and Week 16

Population: Analysis was performed on Full Analysis Set (FAS) population (all randomized participants).

The EASI score was used to measure the severity and extent of AD and measures erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI--75 responders were the participants who achieved ≥75% overall improvement in EASI score from baseline to Week 16. [Values after first rescue treatment used were set to missing. Participants with missing score at week 16 were considered as a non-responder. Participant considered nonresponder after rescue treatment use. Efficacy analyses were based on the treatment allocated at randomization (as randomized).]

Outcome measures

Measure	Placebo n=85 Participants Participants received placebo matching dupilumab once every 2 weeks (Q2W) (including doubling the amount of placebo on day 1 to match the loading dose). Participants in the \<60-kilogram (kg) weight stratum received, in a 1:1 ratio, either placebo matching 200 milligram (mg) or placebo matching 300 milligram (mg). In the ≥60 kg weight stratum, the participants randomized to the placebo group received placebo matching 300 mg dupilumab.	Dupilumab 300 mg Q4W n=84 Participants Participants received once every 4 weeks (Q4W) subcutaneous (SC) injections of 300 milligrams (mg) dupilumab following a loading dose of 600 mg on day 1. To maintain blinding, all participants received an injection once every 2 weeks (Q2W) from day 1 to week 14. Participants received placebo 2 millilitre (mL) injection at the weeks dupilumab was not given.	Dupilumab 200 mg or 300 mg Q2W n=82 Participants Participants with baseline weight \<60 kg received once every 2 weeks (Q2W) subcutaneous (SC) injections of 200 milligrams (mg) dupilumab following a loading dose of 400 mg on day 1. Participants with baseline weight ≥60 kg received Q2W SC injections of 300 mg dupilumab following a loading dose of 600 mg on day 1.
Percentage of Participants With Eczema Area and Severity Index (EASI)-75 (≥75% Improvement From Baseline) at Week 16	8.2 Percentage of participants	38.1 Percentage of participants	41.5 Percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Analysis was performed on FAS population (all randomized participants).

The Eczema Area and Severity Index (EASI) score was used to measure the severity and extent of AD and measures erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. [Values after first rescue treatment use were set to missing and participants with missing EASI score at Week 16 were considered as non-responders.]

Outcome measures

Measure	Placebo n=85 Participants Participants received placebo matching dupilumab once every 2 weeks (Q2W) (including doubling the amount of placebo on day 1 to match the loading dose). Participants in the \<60-kilogram (kg) weight stratum received, in a 1:1 ratio, either placebo matching 200 milligram (mg) or placebo matching 300 milligram (mg). In the ≥60 kg weight stratum, the participants randomized to the placebo group received placebo matching 300 mg dupilumab.	Dupilumab 300 mg Q4W n=84 Participants Participants received once every 4 weeks (Q4W) subcutaneous (SC) injections of 300 milligrams (mg) dupilumab following a loading dose of 600 mg on day 1. To maintain blinding, all participants received an injection once every 2 weeks (Q2W) from day 1 to week 14. Participants received placebo 2 millilitre (mL) injection at the weeks dupilumab was not given.	Dupilumab 200 mg or 300 mg Q2W n=82 Participants Participants with baseline weight \<60 kg received once every 2 weeks (Q2W) subcutaneous (SC) injections of 200 milligrams (mg) dupilumab following a loading dose of 400 mg on day 1. Participants with baseline weight ≥60 kg received Q2W SC injections of 300 mg dupilumab following a loading dose of 600 mg on day 1.
Percent Change From Baseline in EASI Score at Week 16	-23.6 Percent change Standard Error 5.49 • Interval 5.49 to	-64.8 Percent change Standard Error 4.51 • Interval 4.51 to	-65.9 Percent change Standard Error 3.99 • Interval 3.99 to

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Analysis was performed on FAS population (all randomized participants).

Peak Pruritus NRS is an assessment tool used by subjects to report intensity of pruritus (itch) during a 24-hour recall period. Participants were asked the following question: For maximum itch intensity: "On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable,' how would you rate your itch at the worst moment during the previous 24 hours?" For post-baseline NRS, the mean weekly NRS was calculated as the prorated average of the reported daily NRS within the week. For example, if there were 3 scores in a week, the prorated average = (score1 + score2 + score3) /3. [Values after first rescue treatment were set to missing and participants with missing peak NRS at Week 16 were counted as non-responders.]

Outcome measures

Measure	Placebo n=85 Participants Participants received placebo matching dupilumab once every 2 weeks (Q2W) (including doubling the amount of placebo on day 1 to match the loading dose). Participants in the \<60-kilogram (kg) weight stratum received, in a 1:1 ratio, either placebo matching 200 milligram (mg) or placebo matching 300 milligram (mg). In the ≥60 kg weight stratum, the participants randomized to the placebo group received placebo matching 300 mg dupilumab.	Dupilumab 300 mg Q4W n=84 Participants Participants received once every 4 weeks (Q4W) subcutaneous (SC) injections of 300 milligrams (mg) dupilumab following a loading dose of 600 mg on day 1. To maintain blinding, all participants received an injection once every 2 weeks (Q2W) from day 1 to week 14. Participants received placebo 2 millilitre (mL) injection at the weeks dupilumab was not given.	Dupilumab 200 mg or 300 mg Q2W n=82 Participants Participants with baseline weight \<60 kg received once every 2 weeks (Q2W) subcutaneous (SC) injections of 200 milligrams (mg) dupilumab following a loading dose of 400 mg on day 1. Participants with baseline weight ≥60 kg received Q2W SC injections of 300 mg dupilumab following a loading dose of 600 mg on day 1.
Percent Change From Baseline in Weekly Average of Daily Peak Pruritus Numerical Rating Scale (NRS) Score at Week 16	-19.0 Percent change Standard Error 4.09 • Interval 4.09 to	-45.5 Percent change Standard Error 3.54 • Interval 3.54 to	-47.9 Percent change Standard Error 3.43 • Interval 3.43 to

SECONDARY outcome

Timeframe: Baseline to Week 16

Population: Analysis was performed on FAS population (all randomized participants). Here, number of participants analyzed = participants with baseline peak pruritus NRS ≥3.

Peak Pruritus NRS is an assessment tool used by participants to report intensity of pruritus (itch) during a 24-hour recall period. Participants were asked the following question: For maximum itch intensity: "On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable,' how would you rate your itch at the worst moment during the previous 24 hours?" [For this endpoint, participants achieving a reduction of ≥3 points from baseline in weekly average of peak daily pruritus NRS score at Week 16 were reported. Values after first rescue treatment were set to missing and participants with missing peak NRS at Week 16 were counted as non-responders.]

Outcome measures

Measure	Placebo n=85 Participants Participants received placebo matching dupilumab once every 2 weeks (Q2W) (including doubling the amount of placebo on day 1 to match the loading dose). Participants in the \<60-kilogram (kg) weight stratum received, in a 1:1 ratio, either placebo matching 200 milligram (mg) or placebo matching 300 milligram (mg). In the ≥60 kg weight stratum, the participants randomized to the placebo group received placebo matching 300 mg dupilumab.	Dupilumab 300 mg Q4W n=83 Participants Participants received once every 4 weeks (Q4W) subcutaneous (SC) injections of 300 milligrams (mg) dupilumab following a loading dose of 600 mg on day 1. To maintain blinding, all participants received an injection once every 2 weeks (Q2W) from day 1 to week 14. Participants received placebo 2 millilitre (mL) injection at the weeks dupilumab was not given.	Dupilumab 200 mg or 300 mg Q2W n=82 Participants Participants with baseline weight \<60 kg received once every 2 weeks (Q2W) subcutaneous (SC) injections of 200 milligrams (mg) dupilumab following a loading dose of 400 mg on day 1. Participants with baseline weight ≥60 kg received Q2W SC injections of 300 mg dupilumab following a loading dose of 600 mg on day 1.
Percentage of Participants With Improvement (Reduction ≥3 Points) of Weekly Average of Daily Peak Pruritus NRS From Baseline to Week 16	9.4 Percentage of participants	38.6 Percentage of participants	48.8 Percentage of participants

SECONDARY outcome

Timeframe: Baseline to Week 16

Population: Analysis was performed on FAS population (all randomized participants). Here, number of participants analyzed = participants with baseline peak pruritus NRS ≥4.

Peak Pruritus NRS is an assessment tool used by participants to report intensity of pruritus (itch) during a 24-hour recall period. Participants were asked the following question: For maximum itch intensity: "On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable,' how would you rate your itch at the worst moment during the previous 24 hours?" [For this endpoint, participants achieving a reduction of ≥4 points from baseline in weekly average of peak daily pruritus NRS score at Week 16 were reported. Values after first rescue treatment were set to missing and participants with missing peak NRS at Week 16 were counted as non-responders.]

Outcome measures

Measure	Placebo n=84 Participants Participants received placebo matching dupilumab once every 2 weeks (Q2W) (including doubling the amount of placebo on day 1 to match the loading dose). Participants in the \<60-kilogram (kg) weight stratum received, in a 1:1 ratio, either placebo matching 200 milligram (mg) or placebo matching 300 milligram (mg). In the ≥60 kg weight stratum, the participants randomized to the placebo group received placebo matching 300 mg dupilumab.	Dupilumab 300 mg Q4W n=83 Participants Participants received once every 4 weeks (Q4W) subcutaneous (SC) injections of 300 milligrams (mg) dupilumab following a loading dose of 600 mg on day 1. To maintain blinding, all participants received an injection once every 2 weeks (Q2W) from day 1 to week 14. Participants received placebo 2 millilitre (mL) injection at the weeks dupilumab was not given.	Dupilumab 200 mg or 300 mg Q2W n=82 Participants Participants with baseline weight \<60 kg received once every 2 weeks (Q2W) subcutaneous (SC) injections of 200 milligrams (mg) dupilumab following a loading dose of 400 mg on day 1. Participants with baseline weight ≥60 kg received Q2W SC injections of 300 mg dupilumab following a loading dose of 600 mg on day 1.
Percentage of Participants With Improvement (Reduction ≥4 Points) of Weekly Average of Daily Peak Pruritus NRS From Baseline to Week 16	4.8 Percentage of participants	26.5 Percentage of participants	36.6 Percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Analysis was performed on FAS population (all randomized participants).

The EASI score was used to measure the severity and extent of AD and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI-50 responders were the participants who achieved ≥50% overall improvement in EASI score at Week 16. [Values after first rescue treatment used were set to missing. Participants with missing value at Week 16 were considered as a non-responder].

Outcome measures

Measure	Placebo n=85 Participants Participants received placebo matching dupilumab once every 2 weeks (Q2W) (including doubling the amount of placebo on day 1 to match the loading dose). Participants in the \<60-kilogram (kg) weight stratum received, in a 1:1 ratio, either placebo matching 200 milligram (mg) or placebo matching 300 milligram (mg). In the ≥60 kg weight stratum, the participants randomized to the placebo group received placebo matching 300 mg dupilumab.	Dupilumab 300 mg Q4W n=84 Participants Participants received once every 4 weeks (Q4W) subcutaneous (SC) injections of 300 milligrams (mg) dupilumab following a loading dose of 600 mg on day 1. To maintain blinding, all participants received an injection once every 2 weeks (Q2W) from day 1 to week 14. Participants received placebo 2 millilitre (mL) injection at the weeks dupilumab was not given.	Dupilumab 200 mg or 300 mg Q2W n=82 Participants Participants with baseline weight \<60 kg received once every 2 weeks (Q2W) subcutaneous (SC) injections of 200 milligrams (mg) dupilumab following a loading dose of 400 mg on day 1. Participants with baseline weight ≥60 kg received Q2W SC injections of 300 mg dupilumab following a loading dose of 600 mg on day 1.
Percentage of Participants With EASI-50 (≥50% Improvement From Baseline) at Week 16	12.9 Percentage of participants	54.8 Percentage of participants	61.0 Percentage of participants

SECONDARY outcome

Timeframe: Baeline and Week 16

Population: Analysis was performed on FAS population (all randomized participants).

The EASI score was used to measure the severity and extent of AD and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI-90 responders were the participants who achieved ≥90% overall improvement in EASI score at Week 16. [Values after first rescue treatment used were set to missing. Participants with missing value at week 16 were considered as a non-responder.]

Outcome measures

Measure	Placebo n=85 Participants Participants received placebo matching dupilumab once every 2 weeks (Q2W) (including doubling the amount of placebo on day 1 to match the loading dose). Participants in the \<60-kilogram (kg) weight stratum received, in a 1:1 ratio, either placebo matching 200 milligram (mg) or placebo matching 300 milligram (mg). In the ≥60 kg weight stratum, the participants randomized to the placebo group received placebo matching 300 mg dupilumab.	Dupilumab 300 mg Q4W n=84 Participants Participants received once every 4 weeks (Q4W) subcutaneous (SC) injections of 300 milligrams (mg) dupilumab following a loading dose of 600 mg on day 1. To maintain blinding, all participants received an injection once every 2 weeks (Q2W) from day 1 to week 14. Participants received placebo 2 millilitre (mL) injection at the weeks dupilumab was not given.	Dupilumab 200 mg or 300 mg Q2W n=82 Participants Participants with baseline weight \<60 kg received once every 2 weeks (Q2W) subcutaneous (SC) injections of 200 milligrams (mg) dupilumab following a loading dose of 400 mg on day 1. Participants with baseline weight ≥60 kg received Q2W SC injections of 300 mg dupilumab following a loading dose of 600 mg on day 1.
Percentage of Participants With EASI-90 (≥90% Improvement From Baseline) at Week 16	2.4 Percentage of participants	19.0 Percentage of participants	23.2 Percentage of participants

SECONDARY outcome

Timeframe: Baseline up to week 16

Population: Analysis was performed on FAS population (all randomized participants). Here, number of participants analyzed = participants with baseline peak pruritus NRS ≥3.

Peak Pruritus NRS is an assessment tool used by participants to report intensity of pruritus (itch) during a 24-hour recall period. Participants were asked the following question: For maximum itch intensity: "On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable,' how would you rate your itch at the worst moment during the previous 24 hours?" [For this endpoint, participants achieving a reduction of ≥3 points from baseline in weekly average of peak daily pruritus NRS score at Week 16 were reported. Values after first rescue treatment were set to missing and participants with missing peak NRS at Week 16 were counted as non-responders.]

Outcome measures

Measure	Placebo n=85 Participants Participants received placebo matching dupilumab once every 2 weeks (Q2W) (including doubling the amount of placebo on day 1 to match the loading dose). Participants in the \<60-kilogram (kg) weight stratum received, in a 1:1 ratio, either placebo matching 200 milligram (mg) or placebo matching 300 milligram (mg). In the ≥60 kg weight stratum, the participants randomized to the placebo group received placebo matching 300 mg dupilumab.	Dupilumab 300 mg Q4W n=83 Participants Participants received once every 4 weeks (Q4W) subcutaneous (SC) injections of 300 milligrams (mg) dupilumab following a loading dose of 600 mg on day 1. To maintain blinding, all participants received an injection once every 2 weeks (Q2W) from day 1 to week 14. Participants received placebo 2 millilitre (mL) injection at the weeks dupilumab was not given.	Dupilumab 200 mg or 300 mg Q2W n=82 Participants Participants with baseline weight \<60 kg received once every 2 weeks (Q2W) subcutaneous (SC) injections of 200 milligrams (mg) dupilumab following a loading dose of 400 mg on day 1. Participants with baseline weight ≥60 kg received Q2W SC injections of 300 mg dupilumab following a loading dose of 600 mg on day 1.
Time to Onset of Effect on Pruritus as Measured by Percentage of Participants With Improvement (Reduction ≥3 Points) of Weekly Average of Daily Peak Pruritus NRS From Baseline	11.4 Percentage of participants Standard Deviation 5.63 • Interval 5.63 to	8.4 Percentage of participants Standard Deviation 5.92 • Interval 5.92 to	7.7 Percentage of participants Standard Deviation 5.57 • Interval 5.57 to

SECONDARY outcome

Timeframe: Baseline up to Week 16

Population: Analysis was performed on FAS population (all randomized participants). Here, number of participants analyzed = participants with baseline peak pruritus NRS ≥4.

Peak Pruritus NRS is an assessment tool used by participants to report intensity of pruritus (itch) during a 24-hour recall period. Participants were asked the following question: For maximum itch intensity: "On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable,' how would you rate your itch at the worst moment during the previous 24 hours?" [For this endpoint, subjects achieving a reduction of ≥4 points from baseline in weekly average of peak daily pruritus NRS score at Week 16 were reported. Values after first rescue treatment were set to missing and participants with missing peak NRS at Week 16 were counted as non-responders.]

Outcome measures

Measure	Placebo n=84 Participants Participants received placebo matching dupilumab once every 2 weeks (Q2W) (including doubling the amount of placebo on day 1 to match the loading dose). Participants in the \<60-kilogram (kg) weight stratum received, in a 1:1 ratio, either placebo matching 200 milligram (mg) or placebo matching 300 milligram (mg). In the ≥60 kg weight stratum, the participants randomized to the placebo group received placebo matching 300 mg dupilumab.	Dupilumab 300 mg Q4W n=83 Participants Participants received once every 4 weeks (Q4W) subcutaneous (SC) injections of 300 milligrams (mg) dupilumab following a loading dose of 600 mg on day 1. To maintain blinding, all participants received an injection once every 2 weeks (Q2W) from day 1 to week 14. Participants received placebo 2 millilitre (mL) injection at the weeks dupilumab was not given.	Dupilumab 200 mg or 300 mg Q2W n=82 Participants Participants with baseline weight \<60 kg received once every 2 weeks (Q2W) subcutaneous (SC) injections of 200 milligrams (mg) dupilumab following a loading dose of 400 mg on day 1. Participants with baseline weight ≥60 kg received Q2W SC injections of 300 mg dupilumab following a loading dose of 600 mg on day 1.
Time to Onset of Effect on Pruritus as Measured by Percentage of Participants With Improvement (Reduction ≥4 Points) of Weekly Average of Daily Peak Pruritus NRS From Baseline	12.8 Percentage of participants Standard Deviation 4.90 • Interval 4.9 to	9.9 Percentage of participants Standard Deviation 5.87 • Interval 5.87 to	10.6 Percentage of participants Standard Deviation 5.50 • Interval 5.5 to

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Analysis was performed on FAS population (all randomized participants).

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.

Outcome measures

Measure	Placebo n=85 Participants Participants received placebo matching dupilumab once every 2 weeks (Q2W) (including doubling the amount of placebo on day 1 to match the loading dose). Participants in the \<60-kilogram (kg) weight stratum received, in a 1:1 ratio, either placebo matching 200 milligram (mg) or placebo matching 300 milligram (mg). In the ≥60 kg weight stratum, the participants randomized to the placebo group received placebo matching 300 mg dupilumab.	Dupilumab 300 mg Q4W n=84 Participants Participants received once every 4 weeks (Q4W) subcutaneous (SC) injections of 300 milligrams (mg) dupilumab following a loading dose of 600 mg on day 1. To maintain blinding, all participants received an injection once every 2 weeks (Q2W) from day 1 to week 14. Participants received placebo 2 millilitre (mL) injection at the weeks dupilumab was not given.	Dupilumab 200 mg or 300 mg Q2W n=82 Participants Participants with baseline weight \<60 kg received once every 2 weeks (Q2W) subcutaneous (SC) injections of 200 milligrams (mg) dupilumab following a loading dose of 400 mg on day 1. Participants with baseline weight ≥60 kg received Q2W SC injections of 300 mg dupilumab following a loading dose of 600 mg on day 1.
Change From Baseline in Percent Body Surface Area (BSA) at Week 16	-11.66 Percentage of body surface area Standard Error 2.720 • Interval 2.72 to	-33.41 Percentage of body surface area Standard Error 2.330 • Interval 2.33 to	-30.11 Percentage of body surface area Standard Error 2.337 • Interval 2.337 to

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Analysis was performed on FAS population (all randomized participants).

The SCORAD index is a clinical tool for assessing the severity of atopic dermatitis. Extent and intensity of eczema as well as subjective signs (insomnia, etc.) are assessed and scored. Total score ranges from 0 (absent disease) to 103 (severe disease).

Outcome measures

Measure	Placebo n=85 Participants Participants received placebo matching dupilumab once every 2 weeks (Q2W) (including doubling the amount of placebo on day 1 to match the loading dose). Participants in the \<60-kilogram (kg) weight stratum received, in a 1:1 ratio, either placebo matching 200 milligram (mg) or placebo matching 300 milligram (mg). In the ≥60 kg weight stratum, the participants randomized to the placebo group received placebo matching 300 mg dupilumab.	Dupilumab 300 mg Q4W n=84 Participants Participants received once every 4 weeks (Q4W) subcutaneous (SC) injections of 300 milligrams (mg) dupilumab following a loading dose of 600 mg on day 1. To maintain blinding, all participants received an injection once every 2 weeks (Q2W) from day 1 to week 14. Participants received placebo 2 millilitre (mL) injection at the weeks dupilumab was not given.	Dupilumab 200 mg or 300 mg Q2W n=82 Participants Participants with baseline weight \<60 kg received once every 2 weeks (Q2W) subcutaneous (SC) injections of 200 milligrams (mg) dupilumab following a loading dose of 400 mg on day 1. Participants with baseline weight ≥60 kg received Q2W SC injections of 300 mg dupilumab following a loading dose of 600 mg on day 1.
Percent Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Score at Week 16	-17.6 Percent change Standard Error 3.76 • Interval 3.76 to	-47.5 Percent change Standard Error 3.21 • Interval 3.21 to	-51.6 Percent change Standard Error 3.23 • Interval 3.23 to

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Analysis was performed on FAS population (all randomized participants).

The CDLQI is a 10-item questionnaire used to measure how much a participant's skin problem had affected the participant's quality of life (QOL) over a recall period of the past week. The questionnaire consists of 10 items. For each item the scale is rated as follows: 0 = Not at all = Not relevant; 1 = Only a little; 2 = Quite a lot; 3 = Very much = Yes = Prevents school. The CDLQI total score is the sum of the score of each question with a maximum of 30 and a minimum of 0. The higher the score, the greater the impact is on the QOL.

Outcome measures

Measure	Placebo n=85 Participants Participants received placebo matching dupilumab once every 2 weeks (Q2W) (including doubling the amount of placebo on day 1 to match the loading dose). Participants in the \<60-kilogram (kg) weight stratum received, in a 1:1 ratio, either placebo matching 200 milligram (mg) or placebo matching 300 milligram (mg). In the ≥60 kg weight stratum, the participants randomized to the placebo group received placebo matching 300 mg dupilumab.	Dupilumab 300 mg Q4W n=84 Participants Participants received once every 4 weeks (Q4W) subcutaneous (SC) injections of 300 milligrams (mg) dupilumab following a loading dose of 600 mg on day 1. To maintain blinding, all participants received an injection once every 2 weeks (Q2W) from day 1 to week 14. Participants received placebo 2 millilitre (mL) injection at the weeks dupilumab was not given.	Dupilumab 200 mg or 300 mg Q2W n=82 Participants Participants with baseline weight \<60 kg received once every 2 weeks (Q2W) subcutaneous (SC) injections of 200 milligrams (mg) dupilumab following a loading dose of 400 mg on day 1. Participants with baseline weight ≥60 kg received Q2W SC injections of 300 mg dupilumab following a loading dose of 600 mg on day 1.
Change From Baseline in Children's Dermatology Life Quality Index (CDLQI) Total Score at Week 16	-5.1 Scores on a scale Standard Error 0.62 • Interval 0.62 to	-8.8 Scores on a scale Standard Error 0.53 • Interval 0.53 to	-8.5 Scores on a scale Standard Error 0.50 • Interval 0.5 to

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Analysis was performed on FAS population (all randomized participants).

The POEM is a 7-item, validated questionnaire used in clinical practice and clinical trials to assess disease symptoms in children and adults with atopic eczema. The format is subject response to 7 items (dryness, itching, flaking, cracking, sleep loss, bleeding, and weeping) based on symptom frequency during the past week (ie, 0 = 'no days', 1 = '1 to 2 days', 2 = '3 to 4 days', 3 = '5 to 6' days, and 4 = 'every day'). The total score is the sum of the 7 items which is ranged from 0 to 28; a high score is indicative of a poor quality of life (QOL).

Outcome measures

Measure	Placebo n=85 Participants Participants received placebo matching dupilumab once every 2 weeks (Q2W) (including doubling the amount of placebo on day 1 to match the loading dose). Participants in the \<60-kilogram (kg) weight stratum received, in a 1:1 ratio, either placebo matching 200 milligram (mg) or placebo matching 300 milligram (mg). In the ≥60 kg weight stratum, the participants randomized to the placebo group received placebo matching 300 mg dupilumab.	Dupilumab 300 mg Q4W n=84 Participants Participants received once every 4 weeks (Q4W) subcutaneous (SC) injections of 300 milligrams (mg) dupilumab following a loading dose of 600 mg on day 1. To maintain blinding, all participants received an injection once every 2 weeks (Q2W) from day 1 to week 14. Participants received placebo 2 millilitre (mL) injection at the weeks dupilumab was not given.	Dupilumab 200 mg or 300 mg Q2W n=82 Participants Participants with baseline weight \<60 kg received once every 2 weeks (Q2W) subcutaneous (SC) injections of 200 milligrams (mg) dupilumab following a loading dose of 400 mg on day 1. Participants with baseline weight ≥60 kg received Q2W SC injections of 300 mg dupilumab following a loading dose of 600 mg on day 1.
Change From Baseline in Patient Oriented Eczema Measure (POEM) at Week 16	-3.8 Scores on a scale Standard Error 0.96 • Interval 0.96 to	-9.5 Scores on a scale Standard Error 0.86 • Interval 0.86 to	-10.1 Scores on a scale Standard Error 0.76 • Interval 0.76 to

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Analysis was performed on FAS population (all randomized participants).

Peak Pruritus NRS is an assessment tool used by participants to report intensity of pruritus (itch) during a 24-hour recall period. Particpants were asked the following question for maximum itch intensity: "On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable,' how would you rate your itch at the worst moment during the previous 24 hours?" For post-baseline NRS, the mean weekly NRS was calculated as the prorated average of the reported daily NRS within the week. For example, if there were 3 scores in a week, the prorated average = (score1 + score2 + score3)/ 3.

Outcome measures

Measure	Placebo n=85 Participants Participants received placebo matching dupilumab once every 2 weeks (Q2W) (including doubling the amount of placebo on day 1 to match the loading dose). Participants in the \<60-kilogram (kg) weight stratum received, in a 1:1 ratio, either placebo matching 200 milligram (mg) or placebo matching 300 milligram (mg). In the ≥60 kg weight stratum, the participants randomized to the placebo group received placebo matching 300 mg dupilumab.	Dupilumab 300 mg Q4W n=84 Participants Participants received once every 4 weeks (Q4W) subcutaneous (SC) injections of 300 milligrams (mg) dupilumab following a loading dose of 600 mg on day 1. To maintain blinding, all participants received an injection once every 2 weeks (Q2W) from day 1 to week 14. Participants received placebo 2 millilitre (mL) injection at the weeks dupilumab was not given.	Dupilumab 200 mg or 300 mg Q2W n=82 Participants Participants with baseline weight \<60 kg received once every 2 weeks (Q2W) subcutaneous (SC) injections of 200 milligrams (mg) dupilumab following a loading dose of 400 mg on day 1. Participants with baseline weight ≥60 kg received Q2W SC injections of 300 mg dupilumab following a loading dose of 600 mg on day 1.
Change From Baseline in Weekly Average of Daily Peak Pruritus NRS at Week 16	-1.54 Scores on a scale Standard Error 0.303 • Interval 0.303 to	-3.44 Scores on a scale Standard Error 0.260 • Interval 0.26 to	-3.70 Scores on a scale Standard Error 0.250 • Interval 0.25 to

SECONDARY outcome

Timeframe: Baseline and Week 4

Population: Analysis was performed on FAS population (all randomized participants).

Peak Pruritus NRS is an assessment tool used by participants to report intensity of pruritus (itch) during a 24-hour recall period. Participants were asked the following question for maximum itch intensity: "On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable,' how would you rate your itch at the worst moment during the previous 24 hours?" For post-baseline NRS, the mean weekly NRS was calculated as the prorated average of the reported daily NRS within the week. For example, if there were 3 scores in a week, the prorated average = (score1 + score2 + score3)/ 3.

Outcome measures

Measure	Placebo n=85 Participants Participants received placebo matching dupilumab once every 2 weeks (Q2W) (including doubling the amount of placebo on day 1 to match the loading dose). Participants in the \<60-kilogram (kg) weight stratum received, in a 1:1 ratio, either placebo matching 200 milligram (mg) or placebo matching 300 milligram (mg). In the ≥60 kg weight stratum, the participants randomized to the placebo group received placebo matching 300 mg dupilumab.	Dupilumab 300 mg Q4W n=84 Participants Participants received once every 4 weeks (Q4W) subcutaneous (SC) injections of 300 milligrams (mg) dupilumab following a loading dose of 600 mg on day 1. To maintain blinding, all participants received an injection once every 2 weeks (Q2W) from day 1 to week 14. Participants received placebo 2 millilitre (mL) injection at the weeks dupilumab was not given.	Dupilumab 200 mg or 300 mg Q2W n=82 Participants Participants with baseline weight \<60 kg received once every 2 weeks (Q2W) subcutaneous (SC) injections of 200 milligrams (mg) dupilumab following a loading dose of 400 mg on day 1. Participants with baseline weight ≥60 kg received Q2W SC injections of 300 mg dupilumab following a loading dose of 600 mg on day 1.
Percent Change From Baseline in Weekly Average of Daily Peak Pruritus NRS at Week 4	-12.5 Percent change Standard Error 3.06 • Interval 3.06 to	-33.1 Percent change Standard Error 3.05 • Interval 3.05 to	-34.7 Percent change Standard Error 2.99 • Interval 2.99 to

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Analysis was performed on FAS population (all randomized participants).

The HADS is 14-item questionnaire with two subscales: anxiety & depression. Each item is rated on a 4-point scale (0-3). A person could score between 0 & 21 for each subscale (anxiety & depression). A high score is indicative of a poor state. Scores of 11 or more on either subscale are considered a 'definite case' of psychological morbidity, while scores of 8 to 10 represents 'probable case' & 0 to 7 'not a case'. The total score was the sum of the 2 sub-scores; therefore, the full range of possible values for the reported data is 0-42.

Outcome measures

Measure	Placebo n=85 Participants Participants received placebo matching dupilumab once every 2 weeks (Q2W) (including doubling the amount of placebo on day 1 to match the loading dose). Participants in the \<60-kilogram (kg) weight stratum received, in a 1:1 ratio, either placebo matching 200 milligram (mg) or placebo matching 300 milligram (mg). In the ≥60 kg weight stratum, the participants randomized to the placebo group received placebo matching 300 mg dupilumab.	Dupilumab 300 mg Q4W n=84 Participants Participants received once every 4 weeks (Q4W) subcutaneous (SC) injections of 300 milligrams (mg) dupilumab following a loading dose of 600 mg on day 1. To maintain blinding, all participants received an injection once every 2 weeks (Q2W) from day 1 to week 14. Participants received placebo 2 millilitre (mL) injection at the weeks dupilumab was not given.	Dupilumab 200 mg or 300 mg Q2W n=82 Participants Participants with baseline weight \<60 kg received once every 2 weeks (Q2W) subcutaneous (SC) injections of 200 milligrams (mg) dupilumab following a loading dose of 400 mg on day 1. Participants with baseline weight ≥60 kg received Q2W SC injections of 300 mg dupilumab following a loading dose of 600 mg on day 1.
Change From Baseline in Total Hospital Anxiety and Depression Scale (HADS) at Week 16	-2.5 Scores on a scale Standard Error 0.80 • Interval 0.8 to	-5.2 Scores on a scale Standard Error 0.73 • Interval 0.73 to	-3.8 Scores on a scale Standard Error 0.68 • Interval 0.68 to

SECONDARY outcome

Timeframe: Baseline and Week 4

Population: Analysis was performed on FAS population (all randomized participants).

Peak Pruritus NRS is an assessment tool used by participants to report intensity of pruritus (itch) during a 24-hour recall period. Participants were asked the following question for maximum itch intensity: "On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable,' how would you rate your itch at the worst moment during the previous 24 hours?" For post-baseline NRS, the mean weekly NRS was calculated as the prorated average of the reported daily NRS within the week. For example, if there were 3 scores in a week, the prorated average = (score1 + score2 + score3)/ 3.

Outcome measures

Measure	Placebo n=85 Participants Participants received placebo matching dupilumab once every 2 weeks (Q2W) (including doubling the amount of placebo on day 1 to match the loading dose). Participants in the \<60-kilogram (kg) weight stratum received, in a 1:1 ratio, either placebo matching 200 milligram (mg) or placebo matching 300 milligram (mg). In the ≥60 kg weight stratum, the participants randomized to the placebo group received placebo matching 300 mg dupilumab.	Dupilumab 300 mg Q4W n=84 Participants Participants received once every 4 weeks (Q4W) subcutaneous (SC) injections of 300 milligrams (mg) dupilumab following a loading dose of 600 mg on day 1. To maintain blinding, all participants received an injection once every 2 weeks (Q2W) from day 1 to week 14. Participants received placebo 2 millilitre (mL) injection at the weeks dupilumab was not given.	Dupilumab 200 mg or 300 mg Q2W n=82 Participants Participants with baseline weight \<60 kg received once every 2 weeks (Q2W) subcutaneous (SC) injections of 200 milligrams (mg) dupilumab following a loading dose of 400 mg on day 1. Participants with baseline weight ≥60 kg received Q2W SC injections of 300 mg dupilumab following a loading dose of 600 mg on day 1.
Percentage of Participants With Improvement (Reduction ≥4 Points) of Weekly Average of Daily Peak Pruritus NRS From Baseline at Week 4	4.8 Percentage of participants	20.5 Percentage of participants	22.0 Percentage of participants

SECONDARY outcome

Timeframe: Baseline through Week 16

Population: Analysis was performed on FAS population (all randomized participants). Here, number of participants analyzed = participants with available data for this endpoint.

Any untoward medical occurrence in a subject who received investigational medicinal product (IMP) was considered an AE without regard to possibility of causal relationship with this treatment. Treatment-emergent adverse events (TEAEs) were defined as AEs that developed or worsened or became serious during on-treatment period (time from the first dose of study drug up to the end of study (Week 16)). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs.

Outcome measures

Measure	Placebo n=85 Participants Participants received placebo matching dupilumab once every 2 weeks (Q2W) (including doubling the amount of placebo on day 1 to match the loading dose). Participants in the \<60-kilogram (kg) weight stratum received, in a 1:1 ratio, either placebo matching 200 milligram (mg) or placebo matching 300 milligram (mg). In the ≥60 kg weight stratum, the participants randomized to the placebo group received placebo matching 300 mg dupilumab.	Dupilumab 300 mg Q4W n=83 Participants Participants received once every 4 weeks (Q4W) subcutaneous (SC) injections of 300 milligrams (mg) dupilumab following a loading dose of 600 mg on day 1. To maintain blinding, all participants received an injection once every 2 weeks (Q2W) from day 1 to week 14. Participants received placebo 2 millilitre (mL) injection at the weeks dupilumab was not given.	Dupilumab 200 mg or 300 mg Q2W n=82 Participants Participants with baseline weight \<60 kg received once every 2 weeks (Q2W) subcutaneous (SC) injections of 200 milligrams (mg) dupilumab following a loading dose of 400 mg on day 1. Participants with baseline weight ≥60 kg received Q2W SC injections of 300 mg dupilumab following a loading dose of 600 mg on day 1.
Percentage of Participants With Skin-infection Treatment Emergent Adverse Events (TEAEs) (Excluding Herpetic Infections) Through Week 16	18.8 Percentage of participants	9.6 Percentage of participants	9.8 Percentage of participants

SECONDARY outcome

Timeframe: Baseline through Week 16

Population: Analysis was performed on FAS population (all randomized participants). Here, number of participants analyzed = participants with available data for this endpoint.

Any untoward medical occurrence in a participant who received investigational medicinal product (IMP) was considered an AE without regard to possibility of causal relationship with this treatment. Treatment-emergent adverse events (TEAEs) were defined as AEs that developed or worsened or became serious during on-treatment period (time from the first dose of study drug up to the end of study (Week 28)). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs.

Outcome measures

Measure	Placebo n=85 Participants Participants received placebo matching dupilumab once every 2 weeks (Q2W) (including doubling the amount of placebo on day 1 to match the loading dose). Participants in the \<60-kilogram (kg) weight stratum received, in a 1:1 ratio, either placebo matching 200 milligram (mg) or placebo matching 300 milligram (mg). In the ≥60 kg weight stratum, the participants randomized to the placebo group received placebo matching 300 mg dupilumab.	Dupilumab 300 mg Q4W n=83 Participants Participants received once every 4 weeks (Q4W) subcutaneous (SC) injections of 300 milligrams (mg) dupilumab following a loading dose of 600 mg on day 1. To maintain blinding, all participants received an injection once every 2 weeks (Q2W) from day 1 to week 14. Participants received placebo 2 millilitre (mL) injection at the weeks dupilumab was not given.	Dupilumab 200 mg or 300 mg Q2W n=82 Participants Participants with baseline weight \<60 kg received once every 2 weeks (Q2W) subcutaneous (SC) injections of 200 milligrams (mg) dupilumab following a loading dose of 400 mg on day 1. Participants with baseline weight ≥60 kg received Q2W SC injections of 300 mg dupilumab following a loading dose of 600 mg on day 1.
Percentage of Participants With Serious TEAEs Through Week 16	1.2 Percentage of participants	0 Percentage of participants	0 Percentage of participants

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 40 other events

Deaths: 0 deaths

Dupilumab 300 mg Q4W

Serious events: 0 serious events

Other events: 34 other events

Deaths: 0 deaths

Dupilumab 200 mg or 300 mg

Serious events: 0 serious events

Other events: 39 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=85 participants at risk Participants received placebo matching dupilumab once every 2 weeks (Q2W) (including doubling the amount of placebo on day 1 to match the loading dose). Participants in the \<60-kilogram (kg) weight stratum received, in a 1:1 ratio, either placebo matching 200 milligram (mg) or placebo matching 300 milligram (mg). In the ≥60 kg weight stratum, the participants randomized to the placebo group received placebo matching 300 mg dupilumab.	Dupilumab 300 mg Q4W n=83 participants at risk Participants received once every 4 weeks (Q4W) subcutaneous (SC) injections of 300 milligrams (mg) dupilumab following a loading dose of 600 mg on day 1. To maintain blinding, all participants received an injection once every 2 weeks (Q2W) from day 1 to week 14. Participants received placebo 2 millilitre (mL) injection at the weeks dupilumab was not given.	Dupilumab 200 mg or 300 mg n=82 participants at risk Participants with baseline weight \<60 kg received once every 2 weeks (Q2W) subcutaneous (SC) injections of 200 milligrams (mg) dupilumab following a loading dose of 400 mg on day 1. Participants with baseline weight ≥60 kgreceived Q2W SC injections of 300 mg dupilumab following a loading dose of 600 mg on day 1.
Infections and infestations Appendicitis	1.2% 1/85 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product (IP). Of 251 participants randomized, 250 were included in Safety Analysis Set (SAF) reported here. (One participant in dupilumab Q4W arm was not dosed \& was excluded from SAF). SAF analyzed as treated. Reported AEs are treatment-emergent AEs (TEAEs): developed/worsened during 'on treatment period' (from 1st dose of IP up to Day 113). TEAEs were collected for the 16-week treatment \& follow-up period up to 12 weeks. After completing the treatment period, all were offered to enroll in study NCT02612454.	0.00% 0/83 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product (IP). Of 251 participants randomized, 250 were included in Safety Analysis Set (SAF) reported here. (One participant in dupilumab Q4W arm was not dosed \& was excluded from SAF). SAF analyzed as treated. Reported AEs are treatment-emergent AEs (TEAEs): developed/worsened during 'on treatment period' (from 1st dose of IP up to Day 113). TEAEs were collected for the 16-week treatment \& follow-up period up to 12 weeks. After completing the treatment period, all were offered to enroll in study NCT02612454.	0.00% 0/82 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product (IP). Of 251 participants randomized, 250 were included in Safety Analysis Set (SAF) reported here. (One participant in dupilumab Q4W arm was not dosed \& was excluded from SAF). SAF analyzed as treated. Reported AEs are treatment-emergent AEs (TEAEs): developed/worsened during 'on treatment period' (from 1st dose of IP up to Day 113). TEAEs were collected for the 16-week treatment \& follow-up period up to 12 weeks. After completing the treatment period, all were offered to enroll in study NCT02612454.

Other adverse events

Measure	Placebo n=85 participants at risk Participants received placebo matching dupilumab once every 2 weeks (Q2W) (including doubling the amount of placebo on day 1 to match the loading dose). Participants in the \<60-kilogram (kg) weight stratum received, in a 1:1 ratio, either placebo matching 200 milligram (mg) or placebo matching 300 milligram (mg). In the ≥60 kg weight stratum, the participants randomized to the placebo group received placebo matching 300 mg dupilumab.	Dupilumab 300 mg Q4W n=83 participants at risk Participants received once every 4 weeks (Q4W) subcutaneous (SC) injections of 300 milligrams (mg) dupilumab following a loading dose of 600 mg on day 1. To maintain blinding, all participants received an injection once every 2 weeks (Q2W) from day 1 to week 14. Participants received placebo 2 millilitre (mL) injection at the weeks dupilumab was not given.	Dupilumab 200 mg or 300 mg n=82 participants at risk Participants with baseline weight \<60 kg received once every 2 weeks (Q2W) subcutaneous (SC) injections of 200 milligrams (mg) dupilumab following a loading dose of 400 mg on day 1. Participants with baseline weight ≥60 kgreceived Q2W SC injections of 300 mg dupilumab following a loading dose of 600 mg on day 1.
Infections and infestations Influenza	4.7% 4/85 • Number of events 4 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product (IP). Of 251 participants randomized, 250 were included in Safety Analysis Set (SAF) reported here. (One participant in dupilumab Q4W arm was not dosed \& was excluded from SAF). SAF analyzed as treated. Reported AEs are treatment-emergent AEs (TEAEs): developed/worsened during 'on treatment period' (from 1st dose of IP up to Day 113). TEAEs were collected for the 16-week treatment \& follow-up period up to 12 weeks. After completing the treatment period, all were offered to enroll in study NCT02612454.	0.00% 0/83 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product (IP). Of 251 participants randomized, 250 were included in Safety Analysis Set (SAF) reported here. (One participant in dupilumab Q4W arm was not dosed \& was excluded from SAF). SAF analyzed as treated. Reported AEs are treatment-emergent AEs (TEAEs): developed/worsened during 'on treatment period' (from 1st dose of IP up to Day 113). TEAEs were collected for the 16-week treatment \& follow-up period up to 12 weeks. After completing the treatment period, all were offered to enroll in study NCT02612454.	6.1% 5/82 • Number of events 6 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product (IP). Of 251 participants randomized, 250 were included in Safety Analysis Set (SAF) reported here. (One participant in dupilumab Q4W arm was not dosed \& was excluded from SAF). SAF analyzed as treated. Reported AEs are treatment-emergent AEs (TEAEs): developed/worsened during 'on treatment period' (from 1st dose of IP up to Day 113). TEAEs were collected for the 16-week treatment \& follow-up period up to 12 weeks. After completing the treatment period, all were offered to enroll in study NCT02612454.
Infections and infestations Nasopharyngitis	4.7% 4/85 • Number of events 5 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product (IP). Of 251 participants randomized, 250 were included in Safety Analysis Set (SAF) reported here. (One participant in dupilumab Q4W arm was not dosed \& was excluded from SAF). SAF analyzed as treated. Reported AEs are treatment-emergent AEs (TEAEs): developed/worsened during 'on treatment period' (from 1st dose of IP up to Day 113). TEAEs were collected for the 16-week treatment \& follow-up period up to 12 weeks. After completing the treatment period, all were offered to enroll in study NCT02612454.	12.0% 10/83 • Number of events 16 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product (IP). Of 251 participants randomized, 250 were included in Safety Analysis Set (SAF) reported here. (One participant in dupilumab Q4W arm was not dosed \& was excluded from SAF). SAF analyzed as treated. Reported AEs are treatment-emergent AEs (TEAEs): developed/worsened during 'on treatment period' (from 1st dose of IP up to Day 113). TEAEs were collected for the 16-week treatment \& follow-up period up to 12 weeks. After completing the treatment period, all were offered to enroll in study NCT02612454.	6.1% 5/82 • Number of events 8 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product (IP). Of 251 participants randomized, 250 were included in Safety Analysis Set (SAF) reported here. (One participant in dupilumab Q4W arm was not dosed \& was excluded from SAF). SAF analyzed as treated. Reported AEs are treatment-emergent AEs (TEAEs): developed/worsened during 'on treatment period' (from 1st dose of IP up to Day 113). TEAEs were collected for the 16-week treatment \& follow-up period up to 12 weeks. After completing the treatment period, all were offered to enroll in study NCT02612454.
Infections and infestations Pharyngitis streptococcal	0.00% 0/85 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product (IP). Of 251 participants randomized, 250 were included in Safety Analysis Set (SAF) reported here. (One participant in dupilumab Q4W arm was not dosed \& was excluded from SAF). SAF analyzed as treated. Reported AEs are treatment-emergent AEs (TEAEs): developed/worsened during 'on treatment period' (from 1st dose of IP up to Day 113). TEAEs were collected for the 16-week treatment \& follow-up period up to 12 weeks. After completing the treatment period, all were offered to enroll in study NCT02612454.	6.0% 5/83 • Number of events 5 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product (IP). Of 251 participants randomized, 250 were included in Safety Analysis Set (SAF) reported here. (One participant in dupilumab Q4W arm was not dosed \& was excluded from SAF). SAF analyzed as treated. Reported AEs are treatment-emergent AEs (TEAEs): developed/worsened during 'on treatment period' (from 1st dose of IP up to Day 113). TEAEs were collected for the 16-week treatment \& follow-up period up to 12 weeks. After completing the treatment period, all were offered to enroll in study NCT02612454.	2.4% 2/82 • Number of events 2 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product (IP). Of 251 participants randomized, 250 were included in Safety Analysis Set (SAF) reported here. (One participant in dupilumab Q4W arm was not dosed \& was excluded from SAF). SAF analyzed as treated. Reported AEs are treatment-emergent AEs (TEAEs): developed/worsened during 'on treatment period' (from 1st dose of IP up to Day 113). TEAEs were collected for the 16-week treatment \& follow-up period up to 12 weeks. After completing the treatment period, all were offered to enroll in study NCT02612454.
Infections and infestations Upper respiratory tract infection	17.6% 15/85 • Number of events 23 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product (IP). Of 251 participants randomized, 250 were included in Safety Analysis Set (SAF) reported here. (One participant in dupilumab Q4W arm was not dosed \& was excluded from SAF). SAF analyzed as treated. Reported AEs are treatment-emergent AEs (TEAEs): developed/worsened during 'on treatment period' (from 1st dose of IP up to Day 113). TEAEs were collected for the 16-week treatment \& follow-up period up to 12 weeks. After completing the treatment period, all were offered to enroll in study NCT02612454.	8.4% 7/83 • Number of events 9 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product (IP). Of 251 participants randomized, 250 were included in Safety Analysis Set (SAF) reported here. (One participant in dupilumab Q4W arm was not dosed \& was excluded from SAF). SAF analyzed as treated. Reported AEs are treatment-emergent AEs (TEAEs): developed/worsened during 'on treatment period' (from 1st dose of IP up to Day 113). TEAEs were collected for the 16-week treatment \& follow-up period up to 12 weeks. After completing the treatment period, all were offered to enroll in study NCT02612454.	12.2% 10/82 • Number of events 13 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product (IP). Of 251 participants randomized, 250 were included in Safety Analysis Set (SAF) reported here. (One participant in dupilumab Q4W arm was not dosed \& was excluded from SAF). SAF analyzed as treated. Reported AEs are treatment-emergent AEs (TEAEs): developed/worsened during 'on treatment period' (from 1st dose of IP up to Day 113). TEAEs were collected for the 16-week treatment \& follow-up period up to 12 weeks. After completing the treatment period, all were offered to enroll in study NCT02612454.
Nervous system disorders Headache	10.6% 9/85 • Number of events 14 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product (IP). Of 251 participants randomized, 250 were included in Safety Analysis Set (SAF) reported here. (One participant in dupilumab Q4W arm was not dosed \& was excluded from SAF). SAF analyzed as treated. Reported AEs are treatment-emergent AEs (TEAEs): developed/worsened during 'on treatment period' (from 1st dose of IP up to Day 113). TEAEs were collected for the 16-week treatment \& follow-up period up to 12 weeks. After completing the treatment period, all were offered to enroll in study NCT02612454.	4.8% 4/83 • Number of events 5 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product (IP). Of 251 participants randomized, 250 were included in Safety Analysis Set (SAF) reported here. (One participant in dupilumab Q4W arm was not dosed \& was excluded from SAF). SAF analyzed as treated. Reported AEs are treatment-emergent AEs (TEAEs): developed/worsened during 'on treatment period' (from 1st dose of IP up to Day 113). TEAEs were collected for the 16-week treatment \& follow-up period up to 12 weeks. After completing the treatment period, all were offered to enroll in study NCT02612454.	11.0% 9/82 • Number of events 11 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product (IP). Of 251 participants randomized, 250 were included in Safety Analysis Set (SAF) reported here. (One participant in dupilumab Q4W arm was not dosed \& was excluded from SAF). SAF analyzed as treated. Reported AEs are treatment-emergent AEs (TEAEs): developed/worsened during 'on treatment period' (from 1st dose of IP up to Day 113). TEAEs were collected for the 16-week treatment \& follow-up period up to 12 weeks. After completing the treatment period, all were offered to enroll in study NCT02612454.
Skin and subcutaneous tissue disorders Dermatitis atopic	24.7% 21/85 • Number of events 29 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product (IP). Of 251 participants randomized, 250 were included in Safety Analysis Set (SAF) reported here. (One participant in dupilumab Q4W arm was not dosed \& was excluded from SAF). SAF analyzed as treated. Reported AEs are treatment-emergent AEs (TEAEs): developed/worsened during 'on treatment period' (from 1st dose of IP up to Day 113). TEAEs were collected for the 16-week treatment \& follow-up period up to 12 weeks. After completing the treatment period, all were offered to enroll in study NCT02612454.	19.3% 16/83 • Number of events 27 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product (IP). Of 251 participants randomized, 250 were included in Safety Analysis Set (SAF) reported here. (One participant in dupilumab Q4W arm was not dosed \& was excluded from SAF). SAF analyzed as treated. Reported AEs are treatment-emergent AEs (TEAEs): developed/worsened during 'on treatment period' (from 1st dose of IP up to Day 113). TEAEs were collected for the 16-week treatment \& follow-up period up to 12 weeks. After completing the treatment period, all were offered to enroll in study NCT02612454.	18.3% 15/82 • Number of events 21 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Day 197) regardless of seriousness or relationship to investigational product (IP). Of 251 participants randomized, 250 were included in Safety Analysis Set (SAF) reported here. (One participant in dupilumab Q4W arm was not dosed \& was excluded from SAF). SAF analyzed as treated. Reported AEs are treatment-emergent AEs (TEAEs): developed/worsened during 'on treatment period' (from 1st dose of IP up to Day 113). TEAEs were collected for the 16-week treatment \& follow-up period up to 12 weeks. After completing the treatment period, all were offered to enroll in study NCT02612454.

Additional Information

Clinical Trial Management

Regeneron Pharmaceuticals, Inc.

Phone: 844-734-6643

Email: clinicaltrials@regeneron.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER