Trial Outcomes & Findings for Study to Assess the Efficacy and Long-term Safety of Dupilumab (REGN668/SAR231893) in Adult Participants With Moderate-to-Severe Atopic Dermatitis (NCT NCT02260986)

Results Overview

IGA is an assessment scale used to determine severity of AD and clinical response to treatment on a 5-point scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe) based on erythema and papulation/infiltration. Therapeutic response is an IGA score of 0 (clear) or 1 (almost clear). Participants with IGA score "0" or "1" and a reduction from baseline of ≥2 points at Week 16 were reported.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

740 participants

Primary outcome timeframe

Baseline to Week 16

Results posted on

2017-10-17

Participant Flow

The study was conducted in 14 countries between 16 Sep 2014 and 19 Oct 2016. A total of 957 participants were screened in the study.

Out of 957 participants, 740 participants were randomized and treated in the study. Participants were randomized in 3:1:3 ratio to receive Dupilumab 300 mg once weekly (qw) or Dupilumab 300 mg every 2 weeks (q2w) or placebo (for Dupilumab) qw.

Participant milestones

Participant milestones
Measure	Placebo qw Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51.	Dupilumab 300 mg q2w Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.	Dupilumab 300 mg qw Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 51.
Overall Study STARTED	315	106	319
Overall Study Safety Population	315	110	315
Overall Study COMPLETED	225	93	278
Overall Study NOT COMPLETED	90	13	41

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo qw Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51.	Dupilumab 300 mg q2w Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.	Dupilumab 300 mg qw Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 51.
Overall Study Adverse Event	24	0	11
Overall Study Lack of Efficacy	27	3	0
Overall Study Protocol Violation	14	5	16
Overall Study Car accident	0	0	1
Overall Study Withdrawal by Subject	17	4	9
Overall Study Incorrect randomization	0	1	0
Overall Study Lack of investigation product supply	2	0	1
Overall Study Lost to Follow-up	4	0	3
Overall Study Pregnancy	2	0	0

Baseline Characteristics

Number of participants analyzed = participants with available data for this baseline parameter.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo qw n=315 Participants Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51.	Dupilumab 300 mg q2w n=106 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.	Dupilumab 300 mg qw n=319 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 51.	Total n=740 Participants Total of all reporting groups
Age, Continuous	36.6 years STANDARD_DEVIATION 13.01 • n=315 Participants	39.6 years STANDARD_DEVIATION 13.98 • n=106 Participants	36.9 years STANDARD_DEVIATION 13.67 • n=319 Participants	37.1 years STANDARD_DEVIATION 13.46 • n=740 Participants
Sex: Female, Male Female	122 Participants n=315 Participants	44 Participants n=106 Participants	128 Participants n=319 Participants	294 Participants n=740 Participants
Sex: Female, Male Male	193 Participants n=315 Participants	62 Participants n=106 Participants	191 Participants n=319 Participants	446 Participants n=740 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	10 Participants n=315 Participants	2 Participants n=106 Participants	5 Participants n=319 Participants	17 Participants n=740 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	299 Participants n=315 Participants	103 Participants n=106 Participants	309 Participants n=319 Participants	711 Participants n=740 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	6 Participants n=315 Participants	1 Participants n=106 Participants	5 Participants n=319 Participants	12 Participants n=740 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=315 Participants	0 Participants n=106 Participants	0 Participants n=319 Participants	0 Participants n=740 Participants
Race (NIH/OMB) Asian	83 Participants n=315 Participants	29 Participants n=106 Participants	89 Participants n=319 Participants	201 Participants n=740 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=315 Participants	0 Participants n=106 Participants	0 Participants n=319 Participants	0 Participants n=740 Participants
Race (NIH/OMB) Black or African American	19 Participants n=315 Participants	2 Participants n=106 Participants	13 Participants n=319 Participants	34 Participants n=740 Participants
Race (NIH/OMB) White	208 Participants n=315 Participants	74 Participants n=106 Participants	208 Participants n=319 Participants	490 Participants n=740 Participants
Race (NIH/OMB) More than one race	0 Participants n=315 Participants	0 Participants n=106 Participants	0 Participants n=319 Participants	0 Participants n=740 Participants
Race (NIH/OMB) Unknown or Not Reported	5 Participants n=315 Participants	1 Participants n=106 Participants	9 Participants n=319 Participants	15 Participants n=740 Participants
Region of Enrollment Romania	2 participants n=315 Participants	0 participants n=106 Participants	2 participants n=319 Participants	4 participants n=740 Participants
Region of Enrollment Hungary	11 participants n=315 Participants	5 participants n=106 Participants	11 participants n=319 Participants	27 participants n=740 Participants
Region of Enrollment United States	61 participants n=315 Participants	19 participants n=106 Participants	59 participants n=319 Participants	139 participants n=740 Participants
Region of Enrollment Japan	54 participants n=315 Participants	16 participants n=106 Participants	47 participants n=319 Participants	117 participants n=740 Participants
Region of Enrollment United Kingdom	17 participants n=315 Participants	4 participants n=106 Participants	15 participants n=319 Participants	36 participants n=740 Participants
Region of Enrollment Spain	4 participants n=315 Participants	2 participants n=106 Participants	4 participants n=319 Participants	10 participants n=740 Participants
Region of Enrollment New Zealand	1 participants n=315 Participants	1 participants n=106 Participants	3 participants n=319 Participants	5 participants n=740 Participants
Region of Enrollment Canada	47 participants n=315 Participants	17 participants n=106 Participants	51 participants n=319 Participants	115 participants n=740 Participants
Region of Enrollment Czech Republic	7 participants n=315 Participants	7 participants n=106 Participants	6 participants n=319 Participants	20 participants n=740 Participants
Region of Enrollment Netherlands	17 participants n=315 Participants	7 participants n=106 Participants	19 participants n=319 Participants	43 participants n=740 Participants
Region of Enrollment Korea, Republic of	8 participants n=315 Participants	4 participants n=106 Participants	14 participants n=319 Participants	26 participants n=740 Participants
Region of Enrollment Poland	63 participants n=315 Participants	17 participants n=106 Participants	64 participants n=319 Participants	144 participants n=740 Participants
Region of Enrollment Italy	5 participants n=315 Participants	1 participants n=106 Participants	7 participants n=319 Participants	13 participants n=740 Participants
Region of Enrollment Australia	18 participants n=315 Participants	6 participants n=106 Participants	17 participants n=319 Participants	41 participants n=740 Participants
Eczema Area and Severity Index (EASI) Score	32.6 units on a scale STANDARD_DEVIATION 12.93 • n=315 Participants	33.6 units on a scale STANDARD_DEVIATION 13.30 • n=106 Participants	32.1 units on a scale STANDARD_DEVIATION 12.76 • n=319 Participants	32.5 units on a scale STANDARD_DEVIATION 12.90 • n=740 Participants
Investigator Global Assessment (IGA) Score	3.5 units on a scale STANDARD_DEVIATION 0.50 • n=315 Participants	3.5 units on a scale STANDARD_DEVIATION 0.50 • n=106 Participants	3.5 units on a scale STANDARD_DEVIATION 0.50 • n=319 Participants	3.5 units on a scale STANDARD_DEVIATION 0.50 • n=740 Participants
Weekly Peak Averaged Pruritus Numeric Rating Scale (NRS)	7.3 units on a scale STANDARD_DEVIATION 1.84 • n=315 Participants	7.4 units on a scale STANDARD_DEVIATION 1.66 • n=106 Participants	7.1 units on a scale STANDARD_DEVIATION 1.90 • n=319 Participants	7.3 units on a scale STANDARD_DEVIATION 1.84 • n=740 Participants
Body Surface Area (BSA) Involvement with Atopic Dermatitis	56.9 Percentage of body surface area STANDARD_DEVIATION 21.69 • n=315 Participants	59.5 Percentage of body surface area STANDARD_DEVIATION 20.84 • n=106 Participants	54.1 Percentage of body surface area STANDARD_DEVIATION 21.76 • n=319 Participants	56.1 Percentage of body surface area STANDARD_DEVIATION 21.66 • n=740 Participants
SCORing Atopic Dermatitis (SCORAD) Score	66.0 units on a scale STANDARD_DEVIATION 13.53 • n=313 Participants • Number of participants analyzed = participants with available data for this baseline parameter.	69.3 units on a scale STANDARD_DEVIATION 15.24 • n=105 Participants • Number of participants analyzed = participants with available data for this baseline parameter.	65.9 units on a scale STANDARD_DEVIATION 13.63 • n=316 Participants • Number of participants analyzed = participants with available data for this baseline parameter.	66.4 units on a scale STANDARD_DEVIATION 13.86 • n=734 Participants • Number of participants analyzed = participants with available data for this baseline parameter.
Dermatology Life Quality Index (DLQI) Total Score	14.7 units on a scale STANDARD_DEVIATION 7.37 • n=315 Participants	14.5 units on a scale STANDARD_DEVIATION 7.31 • n=106 Participants	14.4 units on a scale STANDARD_DEVIATION 7.17 • n=319 Participants	14.5 units on a scale STANDARD_DEVIATION 7.27 • n=740 Participants
Patient Oriented Eczema Measure (POEM)	20.0 units on a scale STANDARD_DEVIATION 5.99 • n=314 Participants • Number of participants analyzed = participants with available data for this baseline parameter.	20.3 units on a scale STANDARD_DEVIATION 5.68 • n=106 Participants • Number of participants analyzed = participants with available data for this baseline parameter.	20.1 units on a scale STANDARD_DEVIATION 6.05 • n=319 Participants • Number of participants analyzed = participants with available data for this baseline parameter.	20.1 units on a scale STANDARD_DEVIATION 5.95 • n=739 Participants • Number of participants analyzed = participants with available data for this baseline parameter.
Global Individual Signs Score (GISS)	8.7 units on a scale STANDARD_DEVIATION 1.84 • n=315 Participants	8.9 units on a scale STANDARD_DEVIATION 2.04 • n=106 Participants	8.9 units on a scale STANDARD_DEVIATION 1.80 • n=319 Participants	8.8 units on a scale STANDARD_DEVIATION 1.85 • n=740 Participants
Total Hospital Anxiety Depression Scale (HADS)	12.6 units on a scale STANDARD_DEVIATION 8.06 • n=315 Participants	12.9 units on a scale STANDARD_DEVIATION 7.73 • n=106 Participants	12.8 units on a scale STANDARD_DEVIATION 8.01 • n=319 Participants	12.7 units on a scale STANDARD_DEVIATION 7.98 • n=740 Participants

PRIMARY outcome

Timeframe: Baseline to Week 16

Population: All efficacy analyses were performed on the Full Analysis Set (FAS), which included all randomized participants. Efficacy analyses were based on the treatment allocated by interactive voice response system/ interactive web response system (IVRS/IWRS) at randomization (as randomized).

IGA is an assessment scale used to determine severity of AD and clinical response to treatment on a 5-point scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe) based on erythema and papulation/infiltration. Therapeutic response is an IGA score of 0 (clear) or 1 (almost clear). Participants with IGA score "0" or "1" and a reduction from baseline of ≥2 points at Week 16 were reported.

Outcome measures

Outcome measures
Measure	Placebo qw n=315 Participants Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51	Dupilumab 300 mg q2w n=106 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.	Dupilumab 300 mg qw n=319 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 51.
Percentage of Participants With Investigator's Global Assessment (IGA) Score of "0" or "1" and Reduction From Baseline of ≥2 Points at Week 16	12.4 percentage of participants	38.7 percentage of participants	39.2 percentage of participants

SECONDARY outcome

Timeframe: Baseline to Week 16

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).

The EASI score was used to measure the severity and extent of atopic dermatitis (AD) and measures erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI-75 responders were the participants who achieved ≥75% overall improvement in EASI score from baseline to Week 16.

Outcome measures

Outcome measures
Measure	Placebo qw n=315 Participants Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51	Dupilumab 300 mg q2w n=106 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.	Dupilumab 300 mg qw n=319 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 51.
Percentage of Participants With Eczema Area and Severity Index-75 (EASI-75) (≥75% Improvement From Baseline) at Week 16	23.2 percentage of participants	68.9 percentage of participants	63.9 percentage of participants

SECONDARY outcome

Timeframe: Baseline to Week 16

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of participants analyzed = participants with baseline peak pruritus NRS score ≥4.

Pruritus NRS was an assessment tool that was used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 \[0 = no itch; 10 = worst itch imaginable\]). Participants achieving a reduction of ≥4 points from baseline in weekly average of peak daily pruritus NRS score at Week 16 were reported.

Outcome measures

Outcome measures
Measure	Placebo qw n=299 Participants Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51	Dupilumab 300 mg q2w n=102 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.	Dupilumab 300 mg qw n=295 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 51.
Percentage of Participants With Improvement (Reduction ≥4 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 16	19.7 percentage of participants	58.8 percentage of participants	50.8 percentage of participants

SECONDARY outcome

Timeframe: Baseline to Week 16

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of participants analyzed = participants with baseline peak pruritus NRS score ≥3.

Pruritus NRS was an assessment tool that was used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 \[0 = no itch; 10 = worst itch imaginable\]). Participants achieving a reduction of ≥3 points from baseline in weekly average of peak daily pruritus NRS score at Week 16 were reported.

Outcome measures

Outcome measures
Measure	Placebo qw n=306 Participants Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51	Dupilumab 300 mg q2w n=105 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.	Dupilumab 300 mg qw n=309 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 51.
Percentage of Participants With Improvement (Reduction ≥3 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 16	27.8 percentage of participants	65.7 percentage of participants	62.5 percentage of participants

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of participants analyzed = participants with available data for this endpoint.

IGA is an assessment scale used to determine severity of AD and clinical response to treatment on a 5-point scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe) based on erythema and papulation/infiltration. Therapeutic response is an IGA score of 0 (clear) or 1 (almost clear). Participants with IGA score of "0" or "1" and a reduction from baseline of ≥2 points at Week 52 were reported.

Outcome measures

Outcome measures
Measure	Placebo qw n=264 Participants Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51	Dupilumab 300 mg q2w n=89 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.	Dupilumab 300 mg qw n=270 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 51.
Percentage of Participants With Investigator's Global Assessment (IGA) Score of "0" or "1" and Reduction From Baseline of ≥2 Points at Week 52	12.5 percentage of participants	36.0 percentage of participants	40.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of participants analyzed = participants with available data for this endpoint.

The EASI score was used to measure the severity and extent of AD and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI-75 responders were the participants who achieved ≥75% overall improvement in EASI score from baseline to Week 52.

Outcome measures

Outcome measures
Measure	Placebo qw n=264 Participants Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51	Dupilumab 300 mg q2w n=89 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.	Dupilumab 300 mg qw n=270 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 51.
Percentage of Participants With Eczema Area and Severity Index-75 (EASI-75) (≥75% Improvement From Baseline) at Week 52	21.6 percentage of participants	65.2 percentage of participants	64.1 percentage of participants

SECONDARY outcome

Timeframe: Baseline to Week 16

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).

Pruritus NRS was an assessment tool that was used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 \[0 = no itch; 10 = worst itch imaginable\]).

Outcome measures

Outcome measures
Measure	Placebo qw n=315 Participants Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51	Dupilumab 300 mg q2w n=106 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.	Dupilumab 300 mg qw n=319 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 51.
Percent Change From Baseline in Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score to Week 16	-30.3 percent change Standard Error 2.36	-56.6 percent change Standard Error 3.95	-57.1 percent change Standard Error 2.11

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of participants analyzed = participants with baseline peak pruritus NRS score ≥4.

Pruritus NRS was an assessment tool that was used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 \[0 = no itch; 10 = worst itch imaginable\]). Participants achieving a reduction of ≥4 points from baseline in weekly average of peak daily pruritus NRS score at Week 52 were reported.

Outcome measures

Outcome measures
Measure	Placebo qw n=249 Participants Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51	Dupilumab 300 mg q2w n=86 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.	Dupilumab 300 mg qw n=249 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 51.
Percentage of Participants With Improvement (Reduction ≥4 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 52	12.9 percentage of participants	51.2 percentage of participants	39.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of participants analyzed = participants with baseline peak pruritus NRS score ≥3.

Pruritus NRS was an assessment tool that was used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 \[0 = no itch; 10 = worst itch imaginable\]). Participants achieving a reduction of ≥3 points from baseline in weekly average of peak daily pruritus NRS score at Week 52 were reported.

Outcome measures

Outcome measures
Measure	Placebo qw n=256 Participants Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51	Dupilumab 300 mg q2w n=88 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.	Dupilumab 300 mg qw n=261 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 51.
Percentage of Participants With Improvement (Reduction ≥3 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 52	15.6 percentage of participants	55.7 percentage of participants	42.9 percentage of participants

SECONDARY outcome

Timeframe: Baseline to Week 24

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of participants analyzed = participants with baseline peak pruritus NRS score ≥4.

Pruritus NRS was an assessment tool that was used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 \[0 = no itch; 10 = worst itch imaginable\]). Participants achieving a reduction of ≥4 points from baseline in weekly average of peak daily pruritus NRS score at Week 24 were reported.

Outcome measures

Outcome measures
Measure	Placebo qw n=299 Participants Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51	Dupilumab 300 mg q2w n=102 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.	Dupilumab 300 mg qw n=295 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 51.
Percentage of Participants With Improvement (Reduction ≥4 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 24	16.1 percentage of participants	53.9 percentage of participants	43.7 percentage of participants

SECONDARY outcome

Timeframe: Baseline to Week 4

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of participants analyzed = participants with baseline peak pruritus NRS score ≥4.

Pruritus NRS was an assessment tool that was used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 \[0 = no itch; 10 = worst itch imaginable\]). Participants achieving a reduction of ≥4 points from baseline in weekly average of peak daily pruritus NRS score at Week 4 were reported.

Outcome measures

Outcome measures
Measure	Placebo qw n=299 Participants Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51	Dupilumab 300 mg q2w n=102 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.	Dupilumab 300 mg qw n=295 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 51.
Percentage of Participants With Improvement (Reduction ≥4 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 4	16.4 percentage of participants	37.3 percentage of participants	27.1 percentage of participants

SECONDARY outcome

Timeframe: Baseline to Week 2

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of participants analyzed = participants with baseline peak pruritus NRS score ≥4.

Pruritus NRS was an assessment tool that was used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 \[0 = no itch; 10 = worst itch imaginable\]). Participants achieving a reduction of ≥4 points from baseline in weekly average of peak daily pruritus NRS score at Week 2 were reported.

Outcome measures

Outcome measures
Measure	Placebo qw n=299 Participants Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51	Dupilumab 300 mg q2w n=102 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.	Dupilumab 300 mg qw n=295 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 51.
Percentage of Participants With Improvement (Reduction ≥4 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 2	8.0 percentage of participants	17.6 percentage of participants	13.6 percentage of participants

SECONDARY outcome

Timeframe: Baseline to Week 16

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).

Pruritus NRS was an assessment tool that was used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 \[0 = no itch; 10 = worst itch imaginable\]).

Outcome measures

Outcome measures
Measure	Placebo qw n=315 Participants Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51	Dupilumab 300 mg q2w n=106 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.	Dupilumab 300 mg qw n=319 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 51.
Change From Baseline in Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score to Week 16	-2.36 units on a scale Standard Error 0.138	-4.17 units on a scale Standard Error 0.207	-4.27 units on a scale Standard Error 0.126

SECONDARY outcome

Timeframe: Baseline to Week 16

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).

The EASI score was used to measure the severity and extent of AD and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD.

Outcome measures

Outcome measures
Measure	Placebo qw n=188 Participants Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51	Dupilumab 300 mg q2w n=92 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.	Dupilumab 300 mg qw n=269 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 51.
Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score to Week 16	-48.4 percent change Standard Error 3.82	-80.5 percent change Standard Error 6.34	-81.5 percent change Standard Error 5.78

SECONDARY outcome

Timeframe: Baseline to Week 16

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).

BSA affected by AD was assessed for each section of the body (the possible highest score for each region was: head and neck \[9%\], anterior trunk \[18%\], back \[18%\], upper limbs \[18%\], lower limbs \[36%\], and genitals \[1%\]). It was reported as a percentage of all major body sections combined.

Outcome measures

Outcome measures
Measure	Placebo qw n=315 Participants Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51	Dupilumab 300 mg q2w n=106 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.	Dupilumab 300 mg qw n=319 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 51.
Change From Baseline in Percent Body Surface Area (BSA) Affected by Atopic Dermatitis to Week 16	-22.01 Percentage of BSA Standard Error 1.158	-40.39 Percentage of BSA Standard Error 1.844	-39.58 Percentage of BSA Standard Error 1.065

SECONDARY outcome

Timeframe: Baseline to Week 16

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).

SCORAD was a clinical tool for assessing the severity of AD developed by the European Task Force on Atopic Dermatitis (Severity scoring of atopic dermatitis: the SCORAD index). Consensus Report of the European Task Force on Atopic Dermatitis. Dermatology (Basel) 186 (1): 23-31. 1993. Extent and intensity of eczema as well as subjective signs (insomnia, etc.) were assessed and scored. Total score ranges from 0 (absent disease) to 103 (severe disease).

Outcome measures

Outcome measures
Measure	Placebo qw n=315 Participants Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51	Dupilumab 300 mg q2w n=106 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.	Dupilumab 300 mg qw n=319 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 51.
Percent Change From Baseline in the SCORing Atopic Dermatitis (SCORAD) Score to Week 16	-36.2 percent change Standard Error 1.66	-63.9 percent change Standard Error 2.52	-65.9 percent change Standard Error 1.49

SECONDARY outcome

Timeframe: Baseline to Week 16

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).

The DLQI was a 10-item, validated questionnaire used in clinical practice and clinical trials to assess the impact of AD disease symptoms and treatment on quality of life (QOL). The 10 questions assessed QOL over the past week, with an overall scoring of 0 (absent disease) to 30 (severe disease); a high score was indicative of a poor QOL.

Outcome measures

Outcome measures
Measure	Placebo qw n=315 Participants Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51	Dupilumab 300 mg q2w n=106 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.	Dupilumab 300 mg qw n=319 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 51.
Change From Baseline in Dermatology Life Quality Index (DLQI) to Week 16	-5.8 units on a scale Standard Error 0.34	-10.0 units on a scale Standard Error 0.5	-10.7 units on a scale Standard Error 0.31

SECONDARY outcome

Timeframe: Baseline to Week 16

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).

The POEM was a 7-item questionnaire that assessed disease symptoms (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) with a scoring system of 0 (absent disease) to 28 (severe disease) (high score indicative of poor quality of life \[QOL\]).

Outcome measures

Outcome measures
Measure	Placebo qw n=315 Participants Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51	Dupilumab 300 mg q2w n=106 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.	Dupilumab 300 mg qw n=319 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 51.
Change From Baseline in Patient Oriented Eczema Measure (POEM) to Week 16	-5.3 units on a scale Standard Error 0.41	-12.7 units on a scale Standard Error 0.64	-12.9 units on a scale Standard Error 0.37

SECONDARY outcome

Timeframe: Baseline to Week 16

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).

HADS is a fourteen item scale. Seven of the items relate to anxiety and seven items relate to depression. Each item on the questionnaire scored from 0 (minimum score) - 3 (maximum score) and this means that a person can score between 0 (no symptoms) and 21 (severe symptoms) for either anxiety or depression. Cut-offs for identifying psychiatric distress has been reported as 7 to 8 for possible presence, 10 to 11 for probable presence, and 14 to 15 for severe anxiety or depression.

Outcome measures

Outcome measures
Measure	Placebo qw n=315 Participants Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51	Dupilumab 300 mg q2w n=106 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.	Dupilumab 300 mg qw n=319 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 51.
Change From Baseline in Hospital Anxiety Depression Scale (HADS) to Week 16	-4.0 units on a scale Standard Error 0.37	-4.9 units on a scale Standard Error 0.58	-5.4 units on a scale Standard Error 0.35

SECONDARY outcome

Timeframe: Baseline to Week 16

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).

Individual components of the AD lesions (erythema, infiltration/ papulation, excoriations, and lichenification) were rated globally (each assessed for the whole body, not by anatomical region) on a 4-point scale (0= none, 1= mild, 2= moderate and 3= severe) using the EASI severity grading criteria. Total score ranges from 0 (absent disease) to 12 (severe disease).

Outcome measures

Outcome measures
Measure	Placebo qw n=315 Participants Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51	Dupilumab 300 mg q2w n=106 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.	Dupilumab 300 mg qw n=319 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 51.
Percent Change From Baseline in Total Global Individual Signs Score (GISS) to Week 16	-33.3 percent change Standard Error 1.89	-55.4 percent change Standard Error 2.69	-59.3 percent change Standard Error 1.64

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).

Proportion of topical AD medication-free days through Week 52 was calculated as the number of days that a participant used neither topical corticosteroid (TCS)/ topical calcineurin inhibitors (TCI) nor system rescue therapy divided by the study days of each period.

Outcome measures

Outcome measures
Measure	Placebo qw n=315 Participants Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51	Dupilumab 300 mg q2w n=106 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.	Dupilumab 300 mg qw n=319 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 51.
Proportion of Topical Atopic Dermatitis Medication-Free Days Through Week 52	10.5 days Standard Deviation 23.68	16.6 days Standard Deviation 30.08	22.5 days Standard Deviation 33.69

SECONDARY outcome

Timeframe: Baseline to Week 2

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).

Pruritus NRS was an assessment tool that was used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 \[0 = no itch; 10 = worst itch imaginable\]).

Outcome measures

Outcome measures
Measure	Placebo qw n=315 Participants Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51	Dupilumab 300 mg q2w n=106 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.	Dupilumab 300 mg qw n=319 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 51.
Percent Change From Baseline in Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score to Week 2	-19.7 percent change Standard Error 1.58	-27.3 percent change Standard Error 2.67	-25.7 percent change Standard Error 1.57

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of participants analyzed = participants with available data for this endpoint.

The EASI score was used to measure the severity and extent of AD and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD.

Outcome measures

Outcome measures
Measure	Placebo qw n=264 Participants Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51	Dupilumab 300 mg q2w n=89 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.	Dupilumab 300 mg qw n=270 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 51.
Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score to Week 52	-60.9 percent change Standard Error 4.29	-84.9 percent change Standard Error 6.73	-87.8 percent change Standard Error 6.19

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of participants analyzed = participants with available data for this endpoint.

BSA affected by AD was assessed for each section of the body (the possible highest score for each region was: head and neck \[9%\], anterior trunk \[18%\], back \[18%\], upper limbs \[18%\], lower limbs \[36%\], and genitals \[1%\]). It was reported as a percentage of all major body sections combined.

Outcome measures

Outcome measures
Measure	Placebo qw n=264 Participants Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51	Dupilumab 300 mg q2w n=89 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.	Dupilumab 300 mg qw n=270 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 51.
Change From Baseline in Percent Body Surface Area (BSA) Affected by Atopic Dermatitis to Week 52	-29.41 Percentage of BSA Standard Error 1.443	-43.75 Percentage of BSA Standard Error 1.874	-43.67 Percentage of BSA Standard Error 1.143

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of participants analyzed = participants with available data for this endpoint.

SCORAD was a clinical tool for assessing the severity of AD developed by the European Task Force on Atopic Dermatitis (Severity scoring of atopic dermatitis: the SCORAD index). Consensus Report of the European Task Force on Atopic Dermatitis. Dermatology (Basel) 186 (1): 23-31. 1993. Extent and intensity of eczema as well as subjective signs (insomnia, etc.) were assessed and scored. Total score ranges from 0 (absent disease) to 103 (severe disease).

Outcome measures

Outcome measures
Measure	Placebo qw n=264 Participants Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51	Dupilumab 300 mg q2w n=89 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.	Dupilumab 300 mg qw n=270 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 51.
Percent Change From Baseline in the SCORing Atopic Dermatitis (SCORAD) Score to Week 52	-47.3 percent change Standard Error 2.18	-69.7 percent change Standard Error 3.06	-70.4 percent change Standard Error 1.72

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of participants analyzed = participants with available data for this endpoint.

Individual components of the AD lesions (erythema, infiltration/ papulation, excoriations, and lichenification) were rated globally (each assessed for the whole body, not by anatomical region) on a 4-point scale (0= none, 1= mild, 2= moderate and 3= severe) using the EASI severity grading criteria. Total score ranges from 0 (absent disease) to 12 (severe disease).

Outcome measures

Outcome measures
Measure	Placebo qw n=264 Participants Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51	Dupilumab 300 mg q2w n=89 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.	Dupilumab 300 mg qw n=270 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 51.
Percent Change From Baseline in Global Individual Signs Score (GISS) to Week 52	-40.8 percent change Standard Error 2.72	-62.8 percent change Standard Error 3.35	-64.4 percent change Standard Error 2.13

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of participants analyzed = participants with available data for this endpoint.

The DLQI was a 10-item, validated questionnaire used in clinical practice and clinical trials to assess the impact of AD disease symptoms and treatment on quality of life (QOL). The 10 questions assessed QOL over the past week, with an overall scoring of 0 (absent disease) to 30 (severe disease); a high score was indicative of a poor QOL.

Outcome measures

Outcome measures
Measure	Placebo qw n=264 Participants Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51	Dupilumab 300 mg q2w n=89 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.	Dupilumab 300 mg qw n=270 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 51.
Change From Baseline in Dermatology Life Quality Index (DLQI) to Week 52	-7.2 units on a scale Standard Error 0.4	-11.4 units on a scale Standard Error 0.57	-11.1 units on a scale Standard Error 0.36

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of participants analyzed = participants with available data for this endpoint.

The POEM was 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 \[QOL\]).

Outcome measures

Outcome measures
Measure	Placebo qw n=264 Participants Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51	Dupilumab 300 mg q2w n=89 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.	Dupilumab 300 mg qw n=270 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 51.
Change From Baseline in Patient Oriented Eczema Measure (POEM) to Week 52	-7.0 units on a scale Standard Error 0.57	-14.2 units on a scale Standard Error 0.78	-13.2 units on a scale Standard Error 0.45

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of participants analyzed = participants with available data for this endpoint.

HADS is a fourteen item scale. Seven of the items relate to anxiety and seven items relate to depression. Each item on the questionnaire is scored from 0 (minimum score) - 3 (maximum score) and this means that a person can score between 0 (no symptoms) and 21 (severe symptoms) for either anxiety or depression. Cut-offs for identifying psychiatric distress has been reported as 7 to 8 for possible presence, 10 to 11 for probable presence, and 14 to 15 for severe anxiety or depression.

Outcome measures

Outcome measures
Measure	Placebo qw n=264 Participants Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51	Dupilumab 300 mg q2w n=89 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.	Dupilumab 300 mg qw n=270 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 51.
Change From Baseline in Hospital Anxiety Depression Scale (HADS) to Week 52	-3.8 units on a scale Standard Error 0.47	-5.5 units on a scale Standard Error 0.71	-5.9 units on a scale Standard Error 0.42

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: All safety analysis were performed on safety analysis set (SAF) that included all randomized participants who received any study drug, and were analyzed as-treated.

Atopic dermatitis (AD) flares were defined as worsening of the disease that required escalation/intensification of AD treatment. Number of flares occurred in the participants starting from first dose through Week 52 were reported.

Outcome measures

Outcome measures
Measure	Placebo qw n=315 Participants Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51	Dupilumab 300 mg q2w n=110 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.	Dupilumab 300 mg qw n=315 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 51.
Number of Flares Through Week 52	216 flares	20 flares	51 flares

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: All safety analysis were performed on SAF that included all randomized participants who received any study drug, and was analyzed as-treated.

Any untoward medical occurrence in a participant who received investigational medicinal product (IMP) was considered an AE without regard to possibility of causal relationship with this treatment. A Serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs.

Outcome measures

Outcome measures
Measure	Placebo qw n=315 Participants Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51	Dupilumab 300 mg q2w n=110 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.	Dupilumab 300 mg qw n=315 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 51.
Number of Serious Treatment Emergent Adverse Events (TEAEs) Leading to Study Drug Discontinuation Through Week 52	28 events	2 events	10 events

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: All safety analysis were performed on SAF that included all randomized participants who received any study drug, and was analyzed as-treated.

Any untoward medical occurrence in a participants who received IMP was considered an AE without regard to possibility of causal relationship with this treatment. TEAEs were defined as AEs that developed or worsened or became serious during on-treatment period (time from the first dose of study drug up to end of treatment at Week 52). Any TEAE included participants with both serious and non-serious AEs. Skin infection TEAEs were identified based on blinded adjudication of all reported TEAEs under the 2 primary System Organ Classes (SOC): SOC = "Infection and Infestations" or SOC = "Skin and Subcutaneous Tissue Disorders". Blinded adjudication was performed and finalized by the study medical monitor before database lock.

Outcome measures

Outcome measures
Measure	Placebo qw n=315 Participants Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51	Dupilumab 300 mg q2w n=110 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.	Dupilumab 300 mg qw n=315 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 51.
Percentage of Participants With Skin Infection Treatment Emergent Adverse Events (TEAEs) (Excluding Herpetic Infections) From Baseline Through Week 52	17.8 percentage of participants	10.9 percentage of participants	8.3 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: All safety analysis were performed on SAF that included all randomized participants who received any study drug, and was analyzed as-treated.

Any untoward medical occurrence in a participant who received IMP was considered an AE without regard to possibility of causal relationship with this treatment. TEAEs were defined as AEs that developed or worsened or became serious during on-treatment period (time from the first dose of study drug up to end of treatment at Week 52). Any TEAE included participants with both serious and non-serious AEs. Skin infection TEAEs were identified based on blinded adjudication of all reported TEAEs under the 2 primary System Organ Classes (SOC): SOC = "Infection and Infestations" or SOC = "Skin and Subcutaneous Tissue Disorders". Blinded adjudication was performed and finalized by the study medical monitor before database lock.

Outcome measures

Outcome measures
Measure	Placebo qw n=315 Participants Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51	Dupilumab 300 mg q2w n=110 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.	Dupilumab 300 mg qw n=315 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 51.
Number of Skin Infection TEAEs (Excluding Herpetic Infections) From Baseline Through Week 52	80 events	15 events	29 events

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: All safety analysis were performed on SAF that included all randomized participants who received any study drug, and was analyzed as-treated.

Any untoward medical occurrence in a participant who received IMP was considered an AE without regard to possibility of causal relationship with this treatment. TEAEs were defined as AEs that developed or worsened or became serious during on-treatment period (time from the first dose of study drug up to end of treatment at Week 52). Any TEAE included participants with both serious and non-serious AEs. Skin infection TEAEs were identified based on blinded adjudication of all reported TEAEs under the 2 primary System Organ Classes (SOC): SOC = "Infection and Infestations" or SOC = "Skin and Subcutaneous Tissue Disorders". Blinded adjudication was performed and finalized by the study medical monitor before database lock.

Outcome measures

Outcome measures
Measure	Placebo qw n=315 Participants Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51	Dupilumab 300 mg q2w n=110 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.	Dupilumab 300 mg qw n=315 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 51.
Percentage of Participants With Skin Infection Treatment Emergent Adverse Events (TEAEs) (Excluding Herpetic Infections) Requiring Systemic Treatment From Baseline Through Week 52	9.5 percentage of participants	5.5 percentage of participants	3.8 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: All safety analysis were performed on SAF that included all randomized participants who received any study drug, and was analyzed as-treated.

Any untoward medical occurrence in a participant who received IMP was considered an AE without regard to possibility of causal relationship with this treatment. TEAEs were defined as AEs that developed or worsened or became serious during on-treatment period (time from the first dose of study drug up to end of treatment at Week 52). Any TEAE included participants with both serious and non-serious AEs. Skin infection TEAEs were identified based on blinded adjudication of all reported TEAEs under the 2 primary System Organ Classes (SOC): SOC = "Infection and Infestations" or SOC = "Skin and Subcutaneous Tissue Disorders". Blinded adjudication was performed and finalized by the study medical monitor before database lock.

Outcome measures

Outcome measures
Measure	Placebo qw n=315 Participants Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51	Dupilumab 300 mg q2w n=110 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.	Dupilumab 300 mg qw n=315 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 51.
Number of Skin Infection Treatment Emergent Adverse Events (TEAEs) (Excluding Herpetic Infections) Requiring Systemic Treatment From Baseline Through Week 52	44 events	7 events	13 events

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Week 16

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of participants analyzed = participants with available data for this endpoint.

The SNOT 22 was a validated measure of health related quality of life in sinonasal disease. It was a 22 item questionnaire with each item assigned a score ranging from 0-5. The total score may range from 0 (no disease) -110 (worst disease) (lower scores represent better health related quality of life). The SNOT-22 was administered only to participants with chronic inflammatory conditions of the nasal mucosa and/or paranasal sinuses.

Outcome measures

Outcome measures
Measure	Placebo qw n=99 Participants Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51	Dupilumab 300 mg q2w n=45 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.	Dupilumab 300 mg qw n=99 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 51.
Change From Baseline in Sinonasal Outcome Test (SNOT-22) Score to Week 16	-4.77 units on a scale Standard Error 1.903	-6.38 units on a scale Standard Error 2.445	-10.39 units on a scale Standard Error 1.63

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Week 16

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of participants analyzed = participants with ACQ-5 value at baseline.

ACQ-5 questionnaire was a validated questionnaire comprising of 5 questions for asthma symptoms: woken at night by symptoms, wake in the mornings with symptoms, limitation of daily activities, shortness of breath, and wheeze. Participants were asked to rate their asthma symptoms during the previous week on a 7-point scale as 0=no impairment, 6=maximum impairment. ACQ-5 score was the mean of the 5 questions and range between 0 (totally controlled) and 6 (severely uncontrolled) (a higher score indicated lower asthma control). The ACQ-5 questionnaire was administered only to the participants with a medical history of asthma.

Outcome measures

Outcome measures
Measure	Placebo qw n=154 Participants Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51	Dupilumab 300 mg q2w n=48 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.	Dupilumab 300 mg qw n=145 Participants Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 51.
Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score to Week 16	-0.12 units on a scale Standard Error 0.082	-0.19 units on a scale Standard Error 0.113	-0.36 units on a scale Standard Error 0.068

Adverse Events

Placebo qw

Serious events: 20 serious events

Other events: 216 other events

Deaths: 0 deaths

Dupilumab 300 mg q2w

Serious events: 4 serious events

Other events: 74 other events

Deaths: 0 deaths

Dupilumab 300 mg qw

Serious events: 12 serious events

Other events: 228 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo qw n=315 participants at risk Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 51.	Dupilumab 300 mg q2w n=110 participants at risk Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo. Four participants received fewer injections of Dupilumab 300 mg in Dupilumab 300 qw arm, were analyzed in Dupilumab 300 mg q2w arm.	Dupilumab 300 mg qw n=315 participants at risk Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 51. Four participants received fewer injections of Dupilumab 300 mg in Dupilumab 300 qw arm, were analyzed in Dupilumab 300 mg q2w arm.
Eye disorders Blepharitis	0.95% 3/315 • Number of events 3 • Time-frame was 'On treatment (Week 52) period' defined time from administration of first dose of study drug to study completion date of Week 52 visit (365 days starting from first dose of study drug if the date of Week 52 visit was unavailable). All Adverse Events (AEs) were collected from signature of informed consent form up to study completion date of the Week 52 visit regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment-emergent that is AEs that developed/worsened and deaths that occurred during 'On treatment (Week 52) period'. Analysis was performed on SAF.	5.5% 6/110 • Number of events 7 • Time-frame was 'On treatment (Week 52) period' defined time from administration of first dose of study drug to study completion date of Week 52 visit (365 days starting from first dose of study drug if the date of Week 52 visit was unavailable). All Adverse Events (AEs) were collected from signature of informed consent form up to study completion date of the Week 52 visit regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment-emergent that is AEs that developed/worsened and deaths that occurred during 'On treatment (Week 52) period'. Analysis was performed on SAF.	3.5% 11/315 • Number of events 14 • Time-frame was 'On treatment (Week 52) period' defined time from administration of first dose of study drug to study completion date of Week 52 visit (365 days starting from first dose of study drug if the date of Week 52 visit was unavailable). All Adverse Events (AEs) were collected from signature of informed consent form up to study completion date of the Week 52 visit regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment-emergent that is AEs that developed/worsened and deaths that occurred during 'On treatment (Week 52) period'. Analysis was performed on SAF.
Eye disorders Conjunctivitis allergic	6.0% 19/315 • Number of events 22 • Time-frame was 'On treatment (Week 52) period' defined time from administration of first dose of study drug to study completion date of Week 52 visit (365 days starting from first dose of study drug if the date of Week 52 visit was unavailable). All Adverse Events (AEs) were collected from signature of informed consent form up to study completion date of the Week 52 visit regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment-emergent that is AEs that developed/worsened and deaths that occurred during 'On treatment (Week 52) period'. Analysis was performed on SAF.	11.8% 13/110 • Number of events 20 • Time-frame was 'On treatment (Week 52) period' defined time from administration of first dose of study drug to study completion date of Week 52 visit (365 days starting from first dose of study drug if the date of Week 52 visit was unavailable). All Adverse Events (AEs) were collected from signature of informed consent form up to study completion date of the Week 52 visit regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment-emergent that is AEs that developed/worsened and deaths that occurred during 'On treatment (Week 52) period'. Analysis was performed on SAF.	17.1% 54/315 • Number of events 74 • Time-frame was 'On treatment (Week 52) period' defined time from administration of first dose of study drug to study completion date of Week 52 visit (365 days starting from first dose of study drug if the date of Week 52 visit was unavailable). All Adverse Events (AEs) were collected from signature of informed consent form up to study completion date of the Week 52 visit regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment-emergent that is AEs that developed/worsened and deaths that occurred during 'On treatment (Week 52) period'. Analysis was performed on SAF.
General disorders Injection site reaction	7.6% 24/315 • Number of events 102 • Time-frame was 'On treatment (Week 52) period' defined time from administration of first dose of study drug to study completion date of Week 52 visit (365 days starting from first dose of study drug if the date of Week 52 visit was unavailable). All Adverse Events (AEs) were collected from signature of informed consent form up to study completion date of the Week 52 visit regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment-emergent that is AEs that developed/worsened and deaths that occurred during 'On treatment (Week 52) period'. Analysis was performed on SAF.	14.5% 16/110 • Number of events 34 • Time-frame was 'On treatment (Week 52) period' defined time from administration of first dose of study drug to study completion date of Week 52 visit (365 days starting from first dose of study drug if the date of Week 52 visit was unavailable). All Adverse Events (AEs) were collected from signature of informed consent form up to study completion date of the Week 52 visit regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment-emergent that is AEs that developed/worsened and deaths that occurred during 'On treatment (Week 52) period'. Analysis was performed on SAF.	19.0% 60/315 • Number of events 224 • Time-frame was 'On treatment (Week 52) period' defined time from administration of first dose of study drug to study completion date of Week 52 visit (365 days starting from first dose of study drug if the date of Week 52 visit was unavailable). All Adverse Events (AEs) were collected from signature of informed consent form up to study completion date of the Week 52 visit regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment-emergent that is AEs that developed/worsened and deaths that occurred during 'On treatment (Week 52) period'. Analysis was performed on SAF.
Infections and infestations Influenza	5.4% 17/315 • Number of events 25 • Time-frame was 'On treatment (Week 52) period' defined time from administration of first dose of study drug to study completion date of Week 52 visit (365 days starting from first dose of study drug if the date of Week 52 visit was unavailable). All Adverse Events (AEs) were collected from signature of informed consent form up to study completion date of the Week 52 visit regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment-emergent that is AEs that developed/worsened and deaths that occurred during 'On treatment (Week 52) period'. Analysis was performed on SAF.	3.6% 4/110 • Number of events 4 • Time-frame was 'On treatment (Week 52) period' defined time from administration of first dose of study drug to study completion date of Week 52 visit (365 days starting from first dose of study drug if the date of Week 52 visit was unavailable). All Adverse Events (AEs) were collected from signature of informed consent form up to study completion date of the Week 52 visit regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment-emergent that is AEs that developed/worsened and deaths that occurred during 'On treatment (Week 52) period'. Analysis was performed on SAF.	2.9% 9/315 • Number of events 13 • Time-frame was 'On treatment (Week 52) period' defined time from administration of first dose of study drug to study completion date of Week 52 visit (365 days starting from first dose of study drug if the date of Week 52 visit was unavailable). All Adverse Events (AEs) were collected from signature of informed consent form up to study completion date of the Week 52 visit regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment-emergent that is AEs that developed/worsened and deaths that occurred during 'On treatment (Week 52) period'. Analysis was performed on SAF.
Infections and infestations Nasopharyngitis	19.7% 62/315 • Number of events 89 • Time-frame was 'On treatment (Week 52) period' defined time from administration of first dose of study drug to study completion date of Week 52 visit (365 days starting from first dose of study drug if the date of Week 52 visit was unavailable). All Adverse Events (AEs) were collected from signature of informed consent form up to study completion date of the Week 52 visit regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment-emergent that is AEs that developed/worsened and deaths that occurred during 'On treatment (Week 52) period'. Analysis was performed on SAF.	23.6% 26/110 • Number of events 40 • Time-frame was 'On treatment (Week 52) period' defined time from administration of first dose of study drug to study completion date of Week 52 visit (365 days starting from first dose of study drug if the date of Week 52 visit was unavailable). All Adverse Events (AEs) were collected from signature of informed consent form up to study completion date of the Week 52 visit regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment-emergent that is AEs that developed/worsened and deaths that occurred during 'On treatment (Week 52) period'. Analysis was performed on SAF.	20.0% 63/315 • Number of events 88 • Time-frame was 'On treatment (Week 52) period' defined time from administration of first dose of study drug to study completion date of Week 52 visit (365 days starting from first dose of study drug if the date of Week 52 visit was unavailable). All Adverse Events (AEs) were collected from signature of informed consent form up to study completion date of the Week 52 visit regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment-emergent that is AEs that developed/worsened and deaths that occurred during 'On treatment (Week 52) period'. Analysis was performed on SAF.
Infections and infestations Oral herpes	3.2% 10/315 • Number of events 15 • Time-frame was 'On treatment (Week 52) period' defined time from administration of first dose of study drug to study completion date of Week 52 visit (365 days starting from first dose of study drug if the date of Week 52 visit was unavailable). All Adverse Events (AEs) were collected from signature of informed consent form up to study completion date of the Week 52 visit regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment-emergent that is AEs that developed/worsened and deaths that occurred during 'On treatment (Week 52) period'. Analysis was performed on SAF.	3.6% 4/110 • Number of events 9 • Time-frame was 'On treatment (Week 52) period' defined time from administration of first dose of study drug to study completion date of Week 52 visit (365 days starting from first dose of study drug if the date of Week 52 visit was unavailable). All Adverse Events (AEs) were collected from signature of informed consent form up to study completion date of the Week 52 visit regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment-emergent that is AEs that developed/worsened and deaths that occurred during 'On treatment (Week 52) period'. Analysis was performed on SAF.	5.4% 17/315 • Number of events 31 • Time-frame was 'On treatment (Week 52) period' defined time from administration of first dose of study drug to study completion date of Week 52 visit (365 days starting from first dose of study drug if the date of Week 52 visit was unavailable). All Adverse Events (AEs) were collected from signature of informed consent form up to study completion date of the Week 52 visit regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment-emergent that is AEs that developed/worsened and deaths that occurred during 'On treatment (Week 52) period'. Analysis was performed on SAF.
Infections and infestations Sinusitis	2.9% 9/315 • Number of events 11 • Time-frame was 'On treatment (Week 52) period' defined time from administration of first dose of study drug to study completion date of Week 52 visit (365 days starting from first dose of study drug if the date of Week 52 visit was unavailable). All Adverse Events (AEs) were collected from signature of informed consent form up to study completion date of the Week 52 visit regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment-emergent that is AEs that developed/worsened and deaths that occurred during 'On treatment (Week 52) period'. Analysis was performed on SAF.	1.8% 2/110 • Number of events 2 • Time-frame was 'On treatment (Week 52) period' defined time from administration of first dose of study drug to study completion date of Week 52 visit (365 days starting from first dose of study drug if the date of Week 52 visit was unavailable). All Adverse Events (AEs) were collected from signature of informed consent form up to study completion date of the Week 52 visit regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment-emergent that is AEs that developed/worsened and deaths that occurred during 'On treatment (Week 52) period'. Analysis was performed on SAF.	5.7% 18/315 • Number of events 20 • Time-frame was 'On treatment (Week 52) period' defined time from administration of first dose of study drug to study completion date of Week 52 visit (365 days starting from first dose of study drug if the date of Week 52 visit was unavailable). All Adverse Events (AEs) were collected from signature of informed consent form up to study completion date of the Week 52 visit regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment-emergent that is AEs that developed/worsened and deaths that occurred during 'On treatment (Week 52) period'. Analysis was performed on SAF.
Infections and infestations Upper respiratory tract infection	10.8% 34/315 • Number of events 52 • Time-frame was 'On treatment (Week 52) period' defined time from administration of first dose of study drug to study completion date of Week 52 visit (365 days starting from first dose of study drug if the date of Week 52 visit was unavailable). All Adverse Events (AEs) were collected from signature of informed consent form up to study completion date of the Week 52 visit regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment-emergent that is AEs that developed/worsened and deaths that occurred during 'On treatment (Week 52) period'. Analysis was performed on SAF.	10.0% 11/110 • Number of events 21 • Time-frame was 'On treatment (Week 52) period' defined time from administration of first dose of study drug to study completion date of Week 52 visit (365 days starting from first dose of study drug if the date of Week 52 visit was unavailable). All Adverse Events (AEs) were collected from signature of informed consent form up to study completion date of the Week 52 visit regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment-emergent that is AEs that developed/worsened and deaths that occurred during 'On treatment (Week 52) period'. Analysis was performed on SAF.	14.6% 46/315 • Number of events 78 • Time-frame was 'On treatment (Week 52) period' defined time from administration of first dose of study drug to study completion date of Week 52 visit (365 days starting from first dose of study drug if the date of Week 52 visit was unavailable). All Adverse Events (AEs) were collected from signature of informed consent form up to study completion date of the Week 52 visit regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment-emergent that is AEs that developed/worsened and deaths that occurred during 'On treatment (Week 52) period'. Analysis was performed on SAF.
Infections and infestations Urinary tract infection	4.4% 14/315 • Number of events 16 • Time-frame was 'On treatment (Week 52) period' defined time from administration of first dose of study drug to study completion date of Week 52 visit (365 days starting from first dose of study drug if the date of Week 52 visit was unavailable). All Adverse Events (AEs) were collected from signature of informed consent form up to study completion date of the Week 52 visit regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment-emergent that is AEs that developed/worsened and deaths that occurred during 'On treatment (Week 52) period'. Analysis was performed on SAF.	1.8% 2/110 • Number of events 3 • Time-frame was 'On treatment (Week 52) period' defined time from administration of first dose of study drug to study completion date of Week 52 visit (365 days starting from first dose of study drug if the date of Week 52 visit was unavailable). All Adverse Events (AEs) were collected from signature of informed consent form up to study completion date of the Week 52 visit regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment-emergent that is AEs that developed/worsened and deaths that occurred during 'On treatment (Week 52) period'. Analysis was performed on SAF.	5.1% 16/315 • Number of events 22 • Time-frame was 'On treatment (Week 52) period' defined time from administration of first dose of study drug to study completion date of Week 52 visit (365 days starting from first dose of study drug if the date of Week 52 visit was unavailable). All Adverse Events (AEs) were collected from signature of informed consent form up to study completion date of the Week 52 visit regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment-emergent that is AEs that developed/worsened and deaths that occurred during 'On treatment (Week 52) period'. Analysis was performed on SAF.
Nervous system disorders Headache	6.0% 19/315 • Number of events 30 • Time-frame was 'On treatment (Week 52) period' defined time from administration of first dose of study drug to study completion date of Week 52 visit (365 days starting from first dose of study drug if the date of Week 52 visit was unavailable). All Adverse Events (AEs) were collected from signature of informed consent form up to study completion date of the Week 52 visit regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment-emergent that is AEs that developed/worsened and deaths that occurred during 'On treatment (Week 52) period'. Analysis was performed on SAF.	4.5% 5/110 • Number of events 5 • Time-frame was 'On treatment (Week 52) period' defined time from administration of first dose of study drug to study completion date of Week 52 visit (365 days starting from first dose of study drug if the date of Week 52 visit was unavailable). All Adverse Events (AEs) were collected from signature of informed consent form up to study completion date of the Week 52 visit regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment-emergent that is AEs that developed/worsened and deaths that occurred during 'On treatment (Week 52) period'. Analysis was performed on SAF.	7.6% 24/315 • Number of events 48 • Time-frame was 'On treatment (Week 52) period' defined time from administration of first dose of study drug to study completion date of Week 52 visit (365 days starting from first dose of study drug if the date of Week 52 visit was unavailable). All Adverse Events (AEs) were collected from signature of informed consent form up to study completion date of the Week 52 visit regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment-emergent that is AEs that developed/worsened and deaths that occurred during 'On treatment (Week 52) period'. Analysis was performed on SAF.
Respiratory, thoracic and mediastinal disorders Asthma	6.0% 19/315 • Number of events 23 • Time-frame was 'On treatment (Week 52) period' defined time from administration of first dose of study drug to study completion date of Week 52 visit (365 days starting from first dose of study drug if the date of Week 52 visit was unavailable). All Adverse Events (AEs) were collected from signature of informed consent form up to study completion date of the Week 52 visit regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment-emergent that is AEs that developed/worsened and deaths that occurred during 'On treatment (Week 52) period'. Analysis was performed on SAF.	4.5% 5/110 • Number of events 5 • Time-frame was 'On treatment (Week 52) period' defined time from administration of first dose of study drug to study completion date of Week 52 visit (365 days starting from first dose of study drug if the date of Week 52 visit was unavailable). All Adverse Events (AEs) were collected from signature of informed consent form up to study completion date of the Week 52 visit regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment-emergent that is AEs that developed/worsened and deaths that occurred during 'On treatment (Week 52) period'. Analysis was performed on SAF.	2.2% 7/315 • Number of events 7 • Time-frame was 'On treatment (Week 52) period' defined time from administration of first dose of study drug to study completion date of Week 52 visit (365 days starting from first dose of study drug if the date of Week 52 visit was unavailable). All Adverse Events (AEs) were collected from signature of informed consent form up to study completion date of the Week 52 visit regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment-emergent that is AEs that developed/worsened and deaths that occurred during 'On treatment (Week 52) period'. Analysis was performed on SAF.
Skin and subcutaneous tissue disorders Dermatitis atopic	51.1% 161/315 • Number of events 278 • Time-frame was 'On treatment (Week 52) period' defined time from administration of first dose of study drug to study completion date of Week 52 visit (365 days starting from first dose of study drug if the date of Week 52 visit was unavailable). All Adverse Events (AEs) were collected from signature of informed consent form up to study completion date of the Week 52 visit regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment-emergent that is AEs that developed/worsened and deaths that occurred during 'On treatment (Week 52) period'. Analysis was performed on SAF.	36.4% 40/110 • Number of events 52 • Time-frame was 'On treatment (Week 52) period' defined time from administration of first dose of study drug to study completion date of Week 52 visit (365 days starting from first dose of study drug if the date of Week 52 visit was unavailable). All Adverse Events (AEs) were collected from signature of informed consent form up to study completion date of the Week 52 visit regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment-emergent that is AEs that developed/worsened and deaths that occurred during 'On treatment (Week 52) period'. Analysis was performed on SAF.	28.9% 91/315 • Number of events 133 • Time-frame was 'On treatment (Week 52) period' defined time from administration of first dose of study drug to study completion date of Week 52 visit (365 days starting from first dose of study drug if the date of Week 52 visit was unavailable). All Adverse Events (AEs) were collected from signature of informed consent form up to study completion date of the Week 52 visit regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment-emergent that is AEs that developed/worsened and deaths that occurred during 'On treatment (Week 52) period'. Analysis was performed on SAF.

Additional Information

Clinical Trial Management

Regeneron Pharmaceuticals, Inc.

Email: [email protected]

Results disclosure agreements

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