Trial Outcomes & Findings for Safety, Pharmacokinetics and Efficacy of Dupilumab in Patients ≥6 Months to <6 Years With Moderate-to-Severe Atopic Dermatitis (Liberty AD PRESCHOOL) (NCT NCT03346434)

NCT ID: NCT03346434

Last Updated: 2022-07-28

Results Overview

Serum concentration of functional dupilumab was reported.

• Recruitment status: COMPLETED
• Study phase: PHASE2/PHASE3
• Target enrollment: 202 participants
• Primary outcome timeframe: Post-dose on Days 1, 3, 8, 18, and 29
• Results posted on: 2022-07-28

Participant Flow

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.

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.

Participant milestones

Measure	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg 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.	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg 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.	Part B: Placebo + TCS 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).	Part B: Dupilumab 200 mg or 300 mg Q4W + TCS 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 Study STARTED	10	10	10	10	79	83
Overall Study Completed Part A	10	10	9	10	0	0
Overall Study Completed Part B (Week 16)	0	0	0	0	76	83
Overall Study Completed Part B (Week 28)	0	0	0	0	1	1
Overall Study COMPLETED	10	10	9	10	1	1
Overall Study NOT COMPLETED	0	0	1	0	78	82

Reasons for withdrawal

Measure	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg 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.	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg 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.	Part B: Placebo + TCS 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).	Part B: Dupilumab 200 mg or 300 mg Q4W + TCS 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 Study Randomized in Error	0	0	0	0	1	0
Overall Study Withdrawal by Subject	0	0	1	0	1	0
Overall Study Lost to Follow-up	0	0	0	0	1	1
Overall Study Transitioned to OLE study at Week 16 (NCT02612454)	0	0	0	0	75	81

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg n=10 Participants 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.	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg n=10 Participants 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg n=10 Participants 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg n=10 Participants 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.	Part B: Placebo + TCS n=79 Participants 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).	Part B: Dupilumab 200 mg or 300 mg Q4W + TCS n=83 Participants 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 n=202 Participants Total of all reporting groups
Age, Customized 6 months - <2 years	0 Participants n=5 Participants	0 Participants n=7 Participants	10 Participants n=5 Participants	10 Participants n=4 Participants	5 Participants n=21 Participants	6 Participants n=8 Participants	31 Participants n=8 Participants
Age, Customized ≥2 years and <6 years	10 Participants n=5 Participants	10 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	74 Participants n=21 Participants	77 Participants n=8 Participants	171 Participants n=8 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants	24 Participants n=21 Participants	39 Participants n=8 Participants	73 Participants n=8 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	7 Participants n=7 Participants	9 Participants n=5 Participants	8 Participants n=4 Participants	55 Participants n=21 Participants	44 Participants n=8 Participants	129 Participants n=8 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants	9 Participants n=21 Participants	11 Participants n=8 Participants	29 Participants n=8 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants n=5 Participants	8 Participants n=7 Participants	8 Participants n=5 Participants	8 Participants n=4 Participants	70 Participants n=21 Participants	72 Participants n=8 Participants	173 Participants n=8 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants
Investigator Global Assessment (IGA) IGA=3 (moderate)	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	17 Participants n=21 Participants	20 Participants n=8 Participants	37 Participants n=8 Participants
Investigator Global Assessment (IGA) IGA=4 (severe)	10 Participants n=5 Participants	10 Participants n=7 Participants	10 Participants n=5 Participants	10 Participants n=4 Participants	62 Participants n=21 Participants	63 Participants n=8 Participants	165 Participants n=8 Participants

PRIMARY outcome

Timeframe: Post-dose on Days 1, 3, 8, 18, and 29

Population: 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.

Serum concentration of functional dupilumab was reported.

Outcome measures

Measure	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg n=9 Participants 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.	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg n=10 Participants 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg n=10 Participants 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg n=10 Participants 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.
Part A: Maximum Observed Serum Concentration (Cmax) of Functional Dupilumab	25.2 Milligrams per Liter (mg/L) Standard Deviation 7.44 • Interval 7.44 to	49.8 Milligrams per Liter (mg/L) Standard Deviation 11.3 • Interval 11.3 to	20.1 Milligrams per Liter (mg/L) Standard Deviation 6.81 • Interval 6.81 to	46.1 Milligrams per Liter (mg/L) Standard Deviation 11.1 • Interval 11.1 to

PRIMARY outcome

Timeframe: Post-dose on Days 1, 3, 8, 18, and 29

Population: 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.

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]).

Outcome measures

Measure	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg n=9 Participants 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.	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg n=10 Participants 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg n=10 Participants 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg n=10 Participants 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.
Part A: Dose Normalized Maximum Observed Serum Concentration (Cmax/Dose) of Dupilumab	8.39 [mg/L]/[mg/kg] Standard Deviation 2.48 • Interval 2.48 to	8.30 [mg/L]/[mg/kg] Standard Deviation 1.89 • Interval 1.89 to	6.70 [mg/L]/[mg/kg] Standard Deviation 2.27 • Interval 2.27 to	7.68 [mg/L]/[mg/kg] Standard Deviation 1.86 • Interval 1.86 to

PRIMARY outcome

Timeframe: Post-dose on Days 1, 3, 8, 18, and 29

Population: 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.

Tmax was obtained directly from the concentration versus time curve.

Outcome measures

Measure	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg n=10 Participants 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.	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg n=10 Participants 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg n=10 Participants 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg n=9 Participants 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.
Part A: Time to Reach the Maximum Serum Concentration (Tmax) of Dupilumab	1.97 Days Full Range 1.87 • Interval 1.87 to 7.82	1.95 Days Full Range 1.75 • Interval 1.75 to 3.08	2.10 Days Full Range 1.80 • Interval 1.8 to 7.99	1.92 Days Full Range 1.72 • Interval 1.72 to 3.02

PRIMARY outcome

Timeframe: Post-dose on Days 1, 3, 8, 18, and 29

Population: 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.

Clast is the last measurable serum concentration of dupilumab.

Outcome measures

Measure	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg n=9 Participants 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.	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg n=10 Participants 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg n=10 Participants 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg n=10 Participants 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.
Part A: Last Quantifiable Serum Concentration (Clast) of Dupilumab	6.64 mg/L Standard Deviation 6.16 • Interval 6.16 to	6.14 mg/L Standard Deviation 4.69 • Interval 4.69 to	5.64 mg/L Standard Deviation 4.52 • Interval 4.52 to	15.1 mg/L Standard Deviation 9.48 • Interval 9.48 to

PRIMARY outcome

Timeframe: Post-dose on Days 1, 3, 8, 18, and 29

Population: 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.

Tlast was defined as the last time point with a measurable serum concentration of dupilumab.

Outcome measures

Measure	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg n=9 Participants 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.	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg n=10 Participants 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg n=10 Participants 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg n=10 Participants 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.
Part A: Time of the Last Quantifiable Serum Concentration (Tlast) of Dupilumab	14.8 Days Full Range 6.79 • Interval 6.79 to 28.0	26.5 Days Full Range 15.0 • Interval 15.0 to 32.0	8.56 Days Full Range 6.88 • Interval 6.88 to 16.9	16.0 Days Full Range 6.95 • Interval 6.95 to 28.0

PRIMARY outcome

Timeframe: Post-dose on Days 1, 3, 8, 18, and 29

Population: 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.

AUClast was defined as area under the serum concentration time-curve from zero to the last measured concentration.

Outcome measures

Measure	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg n=9 Participants 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.	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg n=10 Participants 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg n=10 Participants 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg n=10 Participants 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.
Part A: Area Under the Serum Concentration-Time Curve From Time Zero to the Time of the Last Measurable Concentration (AUClast) of Dupilumab	198 Days*Milligrams per Liter (day*mg/L) Standard Deviation 125 • Interval 125.0 to	622 Days*Milligrams per Liter (day*mg/L) Standard Deviation 184 • Interval 184.0 to	123 Days*Milligrams per Liter (day*mg/L) Standard Deviation 86.0 • Interval 86.0 to	493 Days*Milligrams per Liter (day*mg/L) Standard Deviation 294 • Interval 294.0 to

PRIMARY outcome

Timeframe: Post-dose on Days 1, 3, 8, 18, and 29

Population: 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.

Dose normalized AUClast was calculated by AUClast/dose.

Outcome measures

Measure	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg n=9 Participants 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.	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg n=10 Participants 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg n=10 Participants 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg n=10 Participants 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.
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	66.0 [day*mg/L]/[mg/kg] Standard Deviation 41.6 • Interval 41.6 to	104 [day*mg/L]/[mg/kg] Standard Deviation 30.6 • Interval 30.6 to	41.0 [day*mg/L]/[mg/kg] Standard Deviation 28.7 • Interval 28.7 to	82.1 [day*mg/L]/[mg/kg] Standard Deviation 48.9 • Interval 48.9 to

PRIMARY outcome

Timeframe: Baseline up to Week 4

Population: The safety analysis set (SAF) included all participants who received any study drug and were analyzed based on the actual treatment received.

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.

Outcome measures

Measure	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg n=10 Participants 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.	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg n=10 Participants 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg n=10 Participants 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg n=10 Participants 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.
Part A: Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE)	3 Participants	2 Participants	7 Participants	7 Participants

PRIMARY outcome

Timeframe: Baseline up to Week 4

Population: The SAF included all participants who received any study drug and were analyzed based on the actual treatment received.

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.

Outcome measures

Measure	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg n=10 Participants 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.	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg n=10 Participants 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg n=10 Participants 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg n=10 Participants 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.
Part A: Number of Participants With TEAEs by Severity According to Qualitative Toxicity Scale Mild	1 Participants	2 Participants	4 Participants	5 Participants
Part A: Number of Participants With TEAEs by Severity According to Qualitative Toxicity Scale Moderate	2 Participants	0 Participants	2 Participants	2 Participants
Part A: Number of Participants With TEAEs by Severity According to Qualitative Toxicity Scale Severe	0 Participants	0 Participants	1 Participants	0 Participants

PRIMARY outcome

Timeframe: Week 16

Population: 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.

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.

Outcome measures

Measure	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg n=79 Participants 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.	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg n=83 Participants 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg 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.
Part B: Percentage of Participants With Investigator's Global Assessment (IGA) Score 0 or 1 at Week 16	3.9 Percentage of Participants 95% Confidence Interval -0.42 • Interval -0.42 to 8.21	27.7 Percentage of Participants 95% Confidence Interval 18.45 • Interval 18.45 to 38.62	—	—

PRIMARY outcome

Timeframe: Week 16

Population: 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.

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.

Outcome measures

Measure	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg n=79 Participants 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.	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg n=83 Participants 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg 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.
Part B: Percentage of Participants With Eczema Area and Severity Index (EASI) -75 (EASI-75) (≥75% Improvement From Baseline) at Week 16	10.7 Percentage of Participants 95% Confidence Interval 3.65 • Interval 3.65 to 17.74	53.0 Percentage of Participants 95% Confidence Interval 41.74 • Interval 41.74 to 64.07	—	—

SECONDARY outcome

Timeframe: Baseline up to Week 4

Population: The SAF included all participants who received any study drug and was analyzed based on the actual treatment received.

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.

Outcome measures

Measure	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg n=10 Participants 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.	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg n=10 Participants 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg n=10 Participants 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg n=10 Participants 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.
Part A: Number of Participants With Serious TEAEs and Severe TEAEs Participants with serious TEAEs	1 Participants	0 Participants	1 Participants	0 Participants
Part A: Number of Participants With Serious TEAEs and Severe TEAEs Participants with severe TEAEs	0 Participants	0 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Week 4

Population: The SAF included all participants who received any study drug and was analyzed based on the actual treatment received.

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.

Outcome measures

Measure	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg n=10 Participants 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.	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg n=10 Participants 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg n=10 Participants 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg n=10 Participants 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.
Part A: Percent Change From Baseline in EASI Score at Week 4	-26.6 Percent Change Standard Deviation 47.37 • Interval 47.37 to	-48.7 Percent Change Standard Deviation 28.89 • Interval 28.89 to	-22.4 Percent Change Standard Deviation 42.52 • Interval 42.52 to	-43.2 Percent Change Standard Deviation 35.55 • Interval 35.55 to

SECONDARY outcome

Timeframe: Week 4

Population: SAF included all participants who received any study drug and was analyzed based on the actual treatment received.

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.

Outcome measures

Measure	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg n=10 Participants 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.	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg n=10 Participants 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg n=10 Participants 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg n=10 Participants 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.
Part A: Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score at Week 4	-18.6 Percent Change Standard Deviation 26.18 • Interval 26.18 to	-31.9 Percent Change Standard Deviation 17.45 • Interval 17.45 to	-22.4 Percent Change Standard Deviation 26.44 • Interval 26.44 to	-28.1 Percent Change Standard Deviation 27.84 • Interval 27.84 to

SECONDARY outcome

Timeframe: Week 4

Population: SAF included all participants who received any study drug and was analyzed based on the actual treatment received.

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.

Outcome measures

Measure	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg n=10 Participants 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.	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg n=10 Participants 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg n=10 Participants 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg n=10 Participants 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.
Part A: Percentage of Participants With IGA Score 0 or 1 at Week 4	10.0 Percentage of Participants 95% Confidence Interval 0.25 • Interval 0.25 to 44.5	0.0 Percentage of Participants 95% Confidence Interval 0.00 • Interval 0.0 to 30.85	10.0 Percentage of Participants 95% Confidence Interval 0.25 • Interval 0.25 to 44.5	10.0 Percentage of Participants 95% Confidence Interval 0.25 • Interval 0.25 to 44.5

SECONDARY outcome

Timeframe: Baseline up to Day 57

Population: 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.

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.

Outcome measures

Measure	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg n=10 Participants 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.	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg n=10 Participants 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg n=10 Participants 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg n=10 Participants 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.
Part A: Number of Participants With at Least One Positive Treatment-Emergent Anti-Drug Antibodies (ADA) TB Response	0 Participants	0 Participants	1 Participants	0 Participants
Part A: Number of Participants With at Least One Positive Treatment-Emergent Anti-Drug Antibodies (ADA) TE Response	5 Participants	4 Participants	5 Participants	5 Participants

SECONDARY outcome

Timeframe: Baseline through Week 16

Population: SAF included all randomized participants who received at least one dose of study drug and was analysed as treated.

Outcome measures

Measure	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg n=78 Participants 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.	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg n=83 Participants 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg 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.
Part B: Number of Participants With at Least One Serious Adverse Event (SAE) Through Week 16	4 Participants	0 Participants	—	—

SECONDARY outcome

Timeframe: Baseline through Week 16

Population: SAF included all randomized participants who received at least one dose of study drug and was analysed as treated.

Outcome measures

Measure	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg n=78 Participants 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.	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg n=83 Participants 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg 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.
Part B: Number of Participants With at Least One Skin Infection Treatment Emergent Adverse Event (TEAE) (Excluding Herpetic Infection) Through Week 16	19 Participants	10 Participants	—	—

SECONDARY outcome

Timeframe: Baseline up to Day 197

Population: 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.

Treatment emergent (TE): Post-dose positive result when baseline results were negative.

Outcome measures

Measure	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg n=69 Participants 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.	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg n=74 Participants 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg 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.
Part B: Number of Participants With at Least One Positive Treatment-Emergent ADA	0 Participants	1 Participants	—	—

SECONDARY outcome

Timeframe: Week 16

Population: 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.

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.

Outcome measures

Measure	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg n=79 Participants 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.	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg n=83 Participants 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg 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.
Part B: Percent Change From Baseline in EASI Score at Week 16	-19.6 Percent Change Standard Error 5.13 • Interval 5.13 to	-70.0 Percent Change Standard Error 4.85 • Interval 4.85 to	—	—

SECONDARY outcome

Timeframe: Week 16

Population: 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.

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.

Outcome measures

Measure	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg n=79 Participants 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.	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg n=83 Participants 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg 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.
Part B: Percent Change From Baseline in Weekly Average of Daily Worst Scratch/Itch/Numerical Rating Scale (NRS) at Week 16	-2.2 Percent Change Standard Error 5.22 • Interval 5.22 to	-49.4 Percent Change Standard Error 5.03 • Interval 5.03 to	—	—

SECONDARY outcome

Timeframe: Week 16

Population: 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.

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.

Outcome measures

Measure	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg n=78 Participants 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.	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg n=83 Participants 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg 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.
Part B: Percentage of Participants With Improvement (Reduction From Baseline) of Weekly Average of Daily Worst Scratch/Itch/NRS ≥4 Points at Week 16	8.9 Percentage of Participants 95% Confidence Interval 2.25 • Interval 2.25 to 15.51	48.1 Percentage of Participants 95% Confidence Interval 37.05 • Interval 37.05 to 59.15	—	—

SECONDARY outcome

Timeframe: Week 16

Population: 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.

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.

Outcome measures

Measure	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg n=78 Participants 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.	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg n=83 Participants 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg 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.
Part B: Percentage of Participants With Improvement (Reduction From Baseline) of Weekly Average of Daily Worst Scratch/Itch/NRS ≥3 Points at Week 16	9.9 Percentage of Participants 95% Confidence Interval 2.59 • Interval 2.59 to 17.22	53.3 Percentage of Participants 95% Confidence Interval 42.29 • Interval 42.29 to 64.22	—	—

SECONDARY outcome

Timeframe: Week 16

Population: 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.

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.

Outcome measures

Measure	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg n=79 Participants 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.	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg n=83 Participants 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg 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.
Part B: Percentage of Participants Who Achieved EASI-50 (≥50% Improvement From Baseline) at Week 16	20.2 Percentage of Participants 95% Confidence Interval 11.09 • Interval 11.09 to 29.23	68.7 Percentage of Participants 95% Confidence Interval 57.56 • Interval 57.56 to 78.41	—	—

SECONDARY outcome

Timeframe: Week 16

Population: 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.

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.

Outcome measures

Measure	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg n=79 Participants 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.	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg n=83 Participants 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg 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.
Part B: Percentage of Participants Who Achieved EASI-90 (≥90% Improvement From Baseline) at Week 16	2.8 Percentage of Participants 95% Confidence Interval -1.02 • Interval -1.02 to 6.66	25.3 Percentage of Participants 95% Confidence Interval 16.39 • Interval 16.39 to 36.04	—	—

SECONDARY outcome

Timeframe: Week 16

Population: 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.

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.

Outcome measures

Measure	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg n=79 Participants 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.	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg n=83 Participants 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg 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.
Part B: Change From Baseline in Percent Body Surface Area (BSA) Affected by Atopic Dermatitis (AD) at Week 16	-10.74 Percentage of Body Surface Area (BSA) Standard Error 2.926 • Interval 2.926 to	-35.00 Percentage of Body Surface Area (BSA) Standard Error 2.815 • Interval 2.815 to	—	—

SECONDARY outcome

Timeframe: Week 16

Population: 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.

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.

Outcome measures

Measure	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg n=79 Participants 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.	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg n=83 Participants 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg 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.
Part B: Change From Baseline in Patient Oriented Eczema Measure (POEM) at Week 16	-3.8 Score on a Scale Standard Error 0.92 • Interval 0.92 to	-12.9 Score on a Scale Standard Error 0.89 • Interval 0.89 to	—	—

SECONDARY outcome

Timeframe: Week 16

Population: 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.

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.

Outcome measures

Measure	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg n=79 Participants 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.	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg n=83 Participants 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg 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.
Part B: Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) at Week 16	-16.2 Percent Change Standard Error 3.54 • Interval 3.54 to	-54.7 Percent Change Standard Error 3.39 • Interval 3.39 to	—	—

SECONDARY outcome

Timeframe: Week 16

Population: 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.

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.

Outcome measures

Measure	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg n=79 Participants 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.	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg n=83 Participants 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg 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.
Part B: Change From Baseline in Participant's Sleep Quality NRS at Week 16	0.34 Score on a Scale Standard Error 0.256 • Interval 0.256 to	2.04 Score on a Scale Standard Error 0.251 • Interval 0.251 to	—	—

SECONDARY outcome

Timeframe: Week 16

Population: 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.

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.

Outcome measures

Measure	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg n=79 Participants 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.	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg n=83 Participants 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg 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.
Part B: Change From Baseline in Participant's Skin Pain NRS at Week 16	-0.62 Score on a Scale Standard Error 0.302 • Interval 0.302 to	-3.93 Score on a Scale Standard Error 0.295 • Interval 0.295 to	—	—

SECONDARY outcome

Timeframe: Week 16

Population: 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.

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.

Outcome measures

Measure	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg n=79 Participants 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.	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg n=83 Participants 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg 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.
Part B: Change From Baseline in Dermatitis Family Index (DFI) at Week 16	-2.68 Score on a Scale Standard Error 0.839 • Interval 0.839 to	-10.48 Score on a Scale Standard Error 0.806 • Interval 0.806 to	—	—

SECONDARY outcome

Timeframe: Week 16

Population: 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.

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.

Outcome measures

Measure	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg n=38 Participants 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.	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg n=47 Participants 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg 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.
Part B: Change From Baseline in Children's Dermatology Life Quality Index (CDLQI) at Week 16	-2.5 Score on a Scale Standard Error 1.66 • Interval 1.66 to	-10.0 Score on a Scale Standard Error 1.56 • Interval 1.56 to	—	—

SECONDARY outcome

Timeframe: Week 16

Population: 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.

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.

Outcome measures

Measure	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg n=41 Participants 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.	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg n=36 Participants 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg 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.
Part B: Change From Baseline in Infants' Dermatology Quality of Life Index (IDQOL) at Week 16	-1.95 Score on a Scale Standard Error 1.078 • Interval 1.078 to	-10.91 Score on a Scale Standard Error 1.159 • Interval 1.159 to	—	—

SECONDARY outcome

Timeframe: Baseline up to Week 16

Population: The FAS included all randomized participants. Efficacy analyses were based on the treatment allocated at randomization (as randomized).

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.

Outcome measures

Measure	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg n=77 Participants 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.	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg n=82 Participants 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg 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.
Part B: Percentage of Topical Corticosteroid (TCS) Medication-free Days From Baseline to Week 16	0.04 Percentage of Days Full Range 0.0 • Interval 0.0 to 0.9	0.21 Percentage of Days Full Range 0.0 • Interval 0.0 to 1.0	—	—

SECONDARY outcome

Timeframe: Baseline up to Week 16

Population: The FAS included all randomized participants. Efficacy analyses were based on the treatment allocated at randomization (as randomized).

Mean weekly dose of TCS in grams/week for low potency TCS from baseline to Week 16 is reported.

Outcome measures

Measure	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg n=78 Participants 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.	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg n=81 Participants 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg 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.
Part B: Mean Weekly Dose of Low Potency TCS in Grams From Baseline to Week 16	13.4 Grams per Week Standard Error 1.44 • Interval 1.44 to	10.5 Grams per Week Standard Error 1.39 • Interval 1.39 to	—	—

SECONDARY outcome

Timeframe: Baseline up to Week 16

Population: The FAS included all randomized participants. Efficacy analyses were based on the treatment allocated at randomization (as randomized).

Mean weekly dose of TCS in grams/week for medium or high potency TCS from baseline to Week 16 is reported.

Outcome measures

Measure	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg n=43 Participants 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.	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg n=24 Participants 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg 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.
Part B: Mean Weekly Dose of TCS in Grams for Medium or High Potency TCS From Baseline to Week 16	6.1 Grams per Week Standard Error 1.70 • Interval 1.7 to	3.0 Grams per Week Standard Error 1.54 • Interval 1.54 to	—	—

SECONDARY outcome

Timeframe: Baseline through Week 16

Population: The FAS included all randomized participants. Efficacy analyses were based on the treatment allocated at randomization (as randomized).

Mean of number of caregiver missed work days through Week 16 is reported.

Outcome measures

Measure	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg n=57 Participants 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.	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg n=57 Participants 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg 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.
Part B: Mean Number of Caregiver Missed Work Days Through Week 16	5.05 Days Standard Deviation 8.975 • Interval 8.975 to	2.49 Days Standard Deviation 5.524 • Interval 5.524 to	—	—

Adverse Events

Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Part B: Placebo + TCS

Serious events: 4 serious events

Other events: 45 other events

Deaths: 0 deaths

Part B: Dupilumab 200 mg or 300 mg Q4W + TCS

Serious events: 0 serious events

Other events: 29 other events

Deaths: 0 deaths

Serious adverse events

Measure	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg n=10 participants at risk 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.	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg n=10 participants at risk 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg n=10 participants at risk 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg n=10 participants at risk 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.	Part B: Placebo + TCS n=78 participants at risk 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).	Part B: Dupilumab 200 mg or 300 mg Q4W + TCS n=83 participants at risk 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).
Immune system disorders Anaphylactic reaction	10.0% 1/10 • Number of events 1 • From day of first treatment up to Week 28 (end of study)	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	10.0% 1/10 • Number of events 1 • From day of first treatment up to Week 28 (end of study)	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	0.00% 0/78 • From day of first treatment up to Week 28 (end of study)	0.00% 0/83 • From day of first treatment up to Week 28 (end of study)
Immune system disorders Hypersensitivity	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	1.3% 1/78 • Number of events 1 • From day of first treatment up to Week 28 (end of study)	0.00% 0/83 • From day of first treatment up to Week 28 (end of study)
Infections and infestations Cellulitis staphylococcal	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	1.3% 1/78 • Number of events 1 • From day of first treatment up to Week 28 (end of study)	0.00% 0/83 • From day of first treatment up to Week 28 (end of study)
Infections and infestations Dermatitis infected	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	1.3% 1/78 • Number of events 1 • From day of first treatment up to Week 28 (end of study)	0.00% 0/83 • From day of first treatment up to Week 28 (end of study)
Infections and infestations Staphylococcal bacteraemia	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	1.3% 1/78 • Number of events 1 • From day of first treatment up to Week 28 (end of study)	0.00% 0/83 • From day of first treatment up to Week 28 (end of study)
Skin and subcutaneous tissue disorders Dermatitis atopic	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	1.3% 1/78 • Number of events 1 • From day of first treatment up to Week 28 (end of study)	0.00% 0/83 • From day of first treatment up to Week 28 (end of study)

Other adverse events

Measure	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 3 mg/kg n=10 participants at risk 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.	Part A: Cohort 1 (≥2 to <6 Years Old): Dupilumab 6 mg/kg n=10 participants at risk 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 3 mg/kg n=10 participants at risk 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.	Part A: Cohort 2 (≥6 Months to <2 Years): Dupilumab 6 mg/kg n=10 participants at risk 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.	Part B: Placebo + TCS n=78 participants at risk 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).	Part B: Dupilumab 200 mg or 300 mg Q4W + TCS n=83 participants at risk 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).
Infections and infestations Nasopharyngitis	10.0% 1/10 • Number of events 1 • From day of first treatment up to Week 28 (end of study)	20.0% 2/10 • Number of events 2 • From day of first treatment up to Week 28 (end of study)	10.0% 1/10 • Number of events 1 • From day of first treatment up to Week 28 (end of study)	10.0% 1/10 • Number of events 1 • From day of first treatment up to Week 28 (end of study)	9.0% 7/78 • Number of events 8 • From day of first treatment up to Week 28 (end of study)	8.4% 7/83 • Number of events 8 • From day of first treatment up to Week 28 (end of study)
Infections and infestations Upper respiratory tract infection	10.0% 1/10 • Number of events 1 • From day of first treatment up to Week 28 (end of study)	10.0% 1/10 • Number of events 1 • From day of first treatment up to Week 28 (end of study)	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	9.0% 7/78 • Number of events 9 • From day of first treatment up to Week 28 (end of study)	6.0% 5/83 • Number of events 5 • From day of first treatment up to Week 28 (end of study)
Infections and infestations Impetigo	10.0% 1/10 • Number of events 1 • From day of first treatment up to Week 28 (end of study)	10.0% 1/10 • Number of events 1 • From day of first treatment up to Week 28 (end of study)	10.0% 1/10 • Number of events 1 • From day of first treatment up to Week 28 (end of study)	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	7.7% 6/78 • Number of events 7 • From day of first treatment up to Week 28 (end of study)	3.6% 3/83 • Number of events 3 • From day of first treatment up to Week 28 (end of study)
Infections and infestations Folliculitis	10.0% 1/10 • Number of events 1 • From day of first treatment up to Week 28 (end of study)	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	0.00% 0/78 • From day of first treatment up to Week 28 (end of study)	0.00% 0/83 • From day of first treatment up to Week 28 (end of study)
Skin and subcutaneous tissue disorders Dermatitis atopic	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	10.0% 1/10 • Number of events 1 • From day of first treatment up to Week 28 (end of study)	10.0% 1/10 • Number of events 1 • From day of first treatment up to Week 28 (end of study)	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	30.8% 24/78 • Number of events 46 • From day of first treatment up to Week 28 (end of study)	14.5% 12/83 • Number of events 17 • From day of first treatment up to Week 28 (end of study)
Skin and subcutaneous tissue disorders Urticaria	10.0% 1/10 • Number of events 1 • From day of first treatment up to Week 28 (end of study)	10.0% 1/10 • Number of events 1 • From day of first treatment up to Week 28 (end of study)	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	5.1% 4/78 • Number of events 4 • From day of first treatment up to Week 28 (end of study)	1.2% 1/83 • Number of events 1 • From day of first treatment up to Week 28 (end of study)
Blood and lymphatic system disorders Lymphadenopathy	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	7.7% 6/78 • Number of events 9 • From day of first treatment up to Week 28 (end of study)	3.6% 3/83 • Number of events 3 • From day of first treatment up to Week 28 (end of study)
Blood and lymphatic system disorders Thrombocytosis	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	10.0% 1/10 • Number of events 1 • From day of first treatment up to Week 28 (end of study)	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	0.00% 0/78 • From day of first treatment up to Week 28 (end of study)	0.00% 0/83 • From day of first treatment up to Week 28 (end of study)
Gastrointestinal disorders Constipation	10.0% 1/10 • Number of events 1 • From day of first treatment up to Week 28 (end of study)	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	0.00% 0/78 • From day of first treatment up to Week 28 (end of study)	2.4% 2/83 • Number of events 3 • From day of first treatment up to Week 28 (end of study)
Gastrointestinal disorders Diarrhoea	10.0% 1/10 • Number of events 1 • From day of first treatment up to Week 28 (end of study)	10.0% 1/10 • Number of events 1 • From day of first treatment up to Week 28 (end of study)	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	2.6% 2/78 • Number of events 2 • From day of first treatment up to Week 28 (end of study)	1.2% 1/83 • Number of events 1 • From day of first treatment up to Week 28 (end of study)
Gastrointestinal disorders Teething	10.0% 1/10 • Number of events 1 • From day of first treatment up to Week 28 (end of study)	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	0.00% 0/78 • From day of first treatment up to Week 28 (end of study)	0.00% 0/83 • From day of first treatment up to Week 28 (end of study)
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	6.4% 5/78 • Number of events 8 • From day of first treatment up to Week 28 (end of study)	3.6% 3/83 • Number of events 3 • From day of first treatment up to Week 28 (end of study)
Respiratory, thoracic and mediastinal disorders Cough	10.0% 1/10 • Number of events 1 • From day of first treatment up to Week 28 (end of study)	10.0% 1/10 • Number of events 1 • From day of first treatment up to Week 28 (end of study)	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	10.0% 1/10 • Number of events 1 • From day of first treatment up to Week 28 (end of study)	6.4% 5/78 • Number of events 6 • From day of first treatment up to Week 28 (end of study)	0.00% 0/83 • From day of first treatment up to Week 28 (end of study)
General disorders Injection site erythema	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	10.0% 1/10 • Number of events 1 • From day of first treatment up to Week 28 (end of study)	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	0.00% 0/78 • From day of first treatment up to Week 28 (end of study)	1.2% 1/83 • Number of events 1 • From day of first treatment up to Week 28 (end of study)
General disorders Pyrexia	20.0% 2/10 • Number of events 2 • From day of first treatment up to Week 28 (end of study)	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	10.0% 1/10 • Number of events 1 • From day of first treatment up to Week 28 (end of study)	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	9.0% 7/78 • Number of events 9 • From day of first treatment up to Week 28 (end of study)	1.2% 1/83 • Number of events 1 • From day of first treatment up to Week 28 (end of study)
Eye disorders Lacrimation increased	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	10.0% 1/10 • Number of events 1 • From day of first treatment up to Week 28 (end of study)	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	0.00% 0/78 • From day of first treatment up to Week 28 (end of study)	0.00% 0/83 • From day of first treatment up to Week 28 (end of study)
Injury, poisoning and procedural complications Skin abrasion	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	10.0% 1/10 • Number of events 1 • From day of first treatment up to Week 28 (end of study)	0.00% 0/78 • From day of first treatment up to Week 28 (end of study)	0.00% 0/83 • From day of first treatment up to Week 28 (end of study)
Musculoskeletal and connective tissue disorders Joint swelling	10.0% 1/10 • Number of events 1 • From day of first treatment up to Week 28 (end of study)	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	0.00% 0/10 • From day of first treatment up to Week 28 (end of study)	0.00% 0/78 • From day of first treatment up to Week 28 (end of study)	0.00% 0/83 • From day of first treatment up to Week 28 (end of study)

Additional Information

Clinical Trials Administrator

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