Trial Outcomes & Findings for A Study to Assess the Efficacy and Safety of Dupilumab in Participants With Severe Atopic Dermatitis (AD) That Are Not Controlled With Oral Cyclosporine A (CSA) or for Those Who Cannot Take Oral CSA Because it is Not Medically Advisable (NCT NCT02755649)

Results Overview

The EASI score is used to measure the severity and extent of atopic dermatitis (AD) and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score 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. The analysis population for efficacy analyses is the Full Analysis Set (FAS) which included all randomized participants. Efficacy analyses were based on the treatment allocated (as randomized).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

325 participants

Primary outcome timeframe

Baseline, Week 16

Results posted on

2020-08-20

Participant Flow

The study was conducted at 73 sites in Europe. A total of 390 participants were screened between 28 Jan 2016 and 14 Sep 2016. Of those, 325 participants were enrolled into the study and randomized. Sixty participants were considered screen failures, mostly due to unmet eligibility criteria.

After providing informed consent, participants were assessed for study eligibility. Screening assessments were performed between day -28 \& day -15, prior to randomization. Participants who met eligibility criteria at baseline (day 1) were randomized in a 1:1:1 ratio to receive dupilumab (weekly \[QW\] or every 2 weeks \[Q2W\]) or placebo.

Participant milestones

Participant milestones
Measure	Placebo QW + TCS Participants received one subcutaneous (SC) injection of matching placebo once per week (QW) (following two SC injections on day 1) from Week 1 to Week 15. All participants required to undergo treatment with topical corticosteroids (TCS) using standardized regimen that continued through the end of treatment period (Week 16). At week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).	Dupilumab 300 mg Q2W + TCS Participants received one subcutaneous (SC) injection of dupilumab 300 mg every 2 weeks (Q2W) from Week 1 to Week 15 (following a SC loading dose of 600 mg on day 1). During weeks in which dupilumab was not administered, participants received matching placebo. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).	Dupilumab 300 mg QW + TCS Participants received one subcutaneous (SC) injection of dupilumab 300 mg once per week (QW) (following an SC loading dose of 600 mg on day 1) from Week 1 to Week 15. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).
Overall Study STARTED	108	107	110
Overall Study Completed Treatment (Week 16)	107	106	109
Overall Study Completed Study (Week 28)	7	8	8
Overall Study COMPLETED	7	8	8
Overall Study NOT COMPLETED	101	99	102

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo QW + TCS Participants received one subcutaneous (SC) injection of matching placebo once per week (QW) (following two SC injections on day 1) from Week 1 to Week 15. All participants required to undergo treatment with topical corticosteroids (TCS) using standardized regimen that continued through the end of treatment period (Week 16). At week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).	Dupilumab 300 mg Q2W + TCS Participants received one subcutaneous (SC) injection of dupilumab 300 mg every 2 weeks (Q2W) from Week 1 to Week 15 (following a SC loading dose of 600 mg on day 1). During weeks in which dupilumab was not administered, participants received matching placebo. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).	Dupilumab 300 mg QW + TCS Participants received one subcutaneous (SC) injection of dupilumab 300 mg once per week (QW) (following an SC loading dose of 600 mg on day 1) from Week 1 to Week 15. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).
Overall Study Transitioned into OLE study	99	98	100
Overall Study Did Not Complete Follow-up Visits	1	0	0
Overall Study Physician Decision	0	0	2
Overall Study Withdrawal by Subject	0	1	0
Overall Study Undecided	1	0	0

Baseline Characteristics

Here "Number of Participants Analyzed" = Participants who were evaluable for this baseline characteristic

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo QW + TCS n=108 Participants Participants received one subcutaneous (SC) injection of matching placebo once per week (QW) (following two SC injections on day 1) from Week 1 to Week 15. All participants required to undergo treatment with topical corticosteroids (TCS) using standardized regimen that continued through the end of treatment period (Week 16). At week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).	Dupilumab 300 mg Q2W + TCS n=107 Participants Participants received one subcutaneous (SC) injection of dupilumab 300 mg every 2 weeks (Q2W) from Week 1 to Week 15 (following a SC loading dose of 600 mg on day 1). During weeks in which dupilumab was not administered, participants received matching placebo. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).	Dupilumab 300 mg QW + TCS n=110 Participants Participants received one subcutaneous (SC) injection of dupilumab 300 mg once per week (QW) (following an SC loading dose of 600 mg on day 1) from Week 1 to Week 15. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).	Total n=325 Participants Total of all reporting groups
Age, Continuous	38.9 years STANDARD_DEVIATION 13.35 • n=108 Participants	37.5 years STANDARD_DEVIATION 12.89 • n=107 Participants	38.7 years STANDARD_DEVIATION 13.21 • n=110 Participants	38.4 years STANDARD_DEVIATION 13.13 • n=325 Participants
Sex: Female, Male Female	40 Participants n=108 Participants	42 Participants n=107 Participants	44 Participants n=110 Participants	126 Participants n=325 Participants
Sex: Female, Male Male	68 Participants n=108 Participants	65 Participants n=107 Participants	66 Participants n=110 Participants	199 Participants n=325 Participants
Eczema Area and Severity Index (EASI) Score	32.9 Score on a Scale STANDARD_DEVIATION 10.80 • n=108 Participants	33.3 Score on a Scale STANDARD_DEVIATION 9.93 • n=107 Participants	33.1 Score on a Scale STANDARD_DEVIATION 11.02 • n=110 Participants	33.1 Score on a Scale STANDARD_DEVIATION 10.56 • n=325 Participants
Peak Weekly Averaged Pruritus Numerical Rating Scale (NRS) score	6.4 Score on a Scale STANDARD_DEVIATION 2.23 • n=107 Participants • Here "Number of Participants Analyzed" = Participants who were evaluable for this baseline characteristic	6.6 Score on a Scale STANDARD_DEVIATION 2.10 • n=107 Participants • Here "Number of Participants Analyzed" = Participants who were evaluable for this baseline characteristic	6.2 Score on a Scale STANDARD_DEVIATION 2.01 • n=110 Participants • Here "Number of Participants Analyzed" = Participants who were evaluable for this baseline characteristic	6.4 Score on a Scale STANDARD_DEVIATION 2.11 • n=324 Participants • Here "Number of Participants Analyzed" = Participants who were evaluable for this baseline characteristic
Body Surface Area (BSA) Involvement of Atopic Dermatitis	55.0 Score on a Scale STANDARD_DEVIATION 20.51 • n=108 Participants	56.1 Score on a Scale STANDARD_DEVIATION 17.83 • n=107 Participants	56.0 Score on a Scale STANDARD_DEVIATION 19.26 • n=110 Participants	55.7 Score on a Scale STANDARD_DEVIATION 19.18 • n=325 Participants
Global Individual Signs Score (GISS)	9.4 Score on a Scale STANDARD_DEVIATION 1.63 • n=108 Participants	9.3 Score on a Scale STANDARD_DEVIATION 1.64 • n=107 Participants	9.1 Score on a Scale STANDARD_DEVIATION 1.63 • n=110 Participants	9.3 Score on a Scale STANDARD_DEVIATION 1.64 • n=325 Participants
Dermatology Life Quality Index (DLQI) Total Score	13.2 Score on a Scale STANDARD_DEVIATION 7.60 • n=108 Participants	14.5 Score on a Scale STANDARD_DEVIATION 7.63 • n=107 Participants	13.8 Score on a Scale STANDARD_DEVIATION 8.03 • n=110 Participants	13.8 Score on a Scale STANDARD_DEVIATION 7.75 • n=325 Participants
Patient Oriented Eczema Measure (POEM)	19.1 Score on a Scale STANDARD_DEVIATION 5.99 • n=107 Participants • Here "Number of Participants Analyzed" = Participants who were evaluable for this baseline characteristic	19.3 Score on a Scale STANDARD_DEVIATION 6.21 • n=107 Participants • Here "Number of Participants Analyzed" = Participants who were evaluable for this baseline characteristic	18.6 Score on a Scale STANDARD_DEVIATION 6.97 • n=110 Participants • Here "Number of Participants Analyzed" = Participants who were evaluable for this baseline characteristic	19.0 Score on a Scale STANDARD_DEVIATION 6.40 • n=324 Participants • Here "Number of Participants Analyzed" = Participants who were evaluable for this baseline characteristic
Total Hospital Anxiety and Depression Scale (HADS)	13.0 Score on a Scale STANDARD_DEVIATION 7.85 • n=108 Participants	12.8 Score on a Scale STANDARD_DEVIATION 8.01 • n=107 Participants	13.3 Score on a Scale STANDARD_DEVIATION 8.15 • n=110 Participants	13.0 Score on a Scale STANDARD_DEVIATION 7.98 • n=325 Participants
SCORing Atopic Dermatitis (SCORAD) score	67.0 Score on a Scale STANDARD_DEVIATION 12.20 • n=108 Participants	68.6 Score on a Scale STANDARD_DEVIATION 11.91 • n=107 Participants	66.0 Score on a Scale STANDARD_DEVIATION 12.70 • n=110 Participants	67.2 Score on a Scale STANDARD_DEVIATION 12.29 • n=325 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=108 Participants	1 Participants n=107 Participants	5 Participants n=110 Participants	9 Participants n=325 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	101 Participants n=108 Participants	99 Participants n=107 Participants	101 Participants n=110 Participants	301 Participants n=325 Participants
Ethnicity (NIH/OMB) Not Reported/Missing	4 Participants n=108 Participants	7 Participants n=107 Participants	4 Participants n=110 Participants	15 Participants n=325 Participants
Race (NIH/OMB) White	104 Participants n=108 Participants	104 Participants n=107 Participants	105 Participants n=110 Participants	313 Participants n=325 Participants
Race (NIH/OMB) Black or African American	0 Participants n=108 Participants	0 Participants n=107 Participants	2 Participants n=110 Participants	2 Participants n=325 Participants
Race (NIH/OMB) Asian	2 Participants n=108 Participants	2 Participants n=107 Participants	2 Participants n=110 Participants	6 Participants n=325 Participants
Race (NIH/OMB) Other	2 Participants n=108 Participants	0 Participants n=107 Participants	1 Participants n=110 Participants	3 Participants n=325 Participants
Race (NIH/OMB) Not Reported / Missing	0 Participants n=108 Participants	1 Participants n=107 Participants	0 Participants n=110 Participants	1 Participants n=325 Participants
Investigator's Global Assessment (IGA) score IGA score = 3	56 Participants n=108 Participants	57 Participants n=107 Participants	58 Participants n=110 Participants	171 Participants n=325 Participants
Investigator's Global Assessment (IGA) score IGA score = 4	52 Participants n=108 Participants	50 Participants n=107 Participants	52 Participants n=110 Participants	154 Participants n=325 Participants

PRIMARY outcome

Timeframe: Baseline, Week 16

The EASI score is used to measure the severity and extent of atopic dermatitis (AD) and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score 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. The analysis population for efficacy analyses is the Full Analysis Set (FAS) which included all randomized participants. Efficacy analyses were based on the treatment allocated (as randomized).

Outcome measures

Outcome measures
Measure	Placebo QW + TCS n=108 Participants Participants received one subcutaneous (SC) injection of matching placebo once per week (QW) (following two SC injections on day 1) from Week 1 to Week 15. All participants required to undergo treatment with topical corticosteroids (TCS) using standardized regimen that continued through the end of treatment period (Week 16). At week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).	Dupilumab 300 mg Q2W + TCS n=107 Participants Participants received one subcutaneous (SC) injection of dupilumab 300 mg every 2 weeks (Q2W) from Week 1 to Week 15 (following a SC loading dose of 600 mg on day 1). During weeks in which dupilumab was not administered, participants received matching placebo. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).	Dupilumab 300 mg QW + TCS n=110 Participants Participants received one subcutaneous (SC) injection of dupilumab 300 mg once per week (QW) (following an SC loading dose of 600 mg on day 1) from Week 1 to Week 15. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).
Percentage of Participants With Eczema Area and Severity Index (EASI) 75 (≥75% Improvement From Baseline) at Week 16	29.6 Percentage of Participants	62.6 Percentage of Participants	59.1 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline, Week 16

The EASI score is used to measure the severity and extent of atopic dermatitis (AD) and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. The analysis population for efficacy analyses is the FAS which included all randomized participants. Efficacy analyses were based on the treatment allocated (as randomized). Here "number of participants analyzed" = participants who were evaluable for this endpoint.

Outcome measures

Outcome measures
Measure	Placebo QW + TCS n=89 Participants Participants received one subcutaneous (SC) injection of matching placebo once per week (QW) (following two SC injections on day 1) from Week 1 to Week 15. All participants required to undergo treatment with topical corticosteroids (TCS) using standardized regimen that continued through the end of treatment period (Week 16). At week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).	Dupilumab 300 mg Q2W + TCS n=103 Participants Participants received one subcutaneous (SC) injection of dupilumab 300 mg every 2 weeks (Q2W) from Week 1 to Week 15 (following a SC loading dose of 600 mg on day 1). During weeks in which dupilumab was not administered, participants received matching placebo. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).	Dupilumab 300 mg QW + TCS n=105 Participants Participants received one subcutaneous (SC) injection of dupilumab 300 mg once per week (QW) (following an SC loading dose of 600 mg on day 1) from Week 1 to Week 15. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).
Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score at Week 16	-46.6 Percent Change Standard Error 2.76 • Interval 2.76 to	-79.8 Percent Change Standard Error 2.59 • Interval 2.59 to	-78.2 Percent Change Standard Error 2.55 • Interval 2.55 to

SECONDARY outcome

Timeframe: Baseline, Week 16

The Pruritus NRS is an assessment tool 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 you rate your itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 \[0 = no itch; 10 = worst itch imaginable\]). The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). Here "Number of Participants Analyzed" = Participants who were evaluable for this endpoint.

Outcome measures

Outcome measures
Measure	Placebo QW + TCS n=89 Participants Participants received one subcutaneous (SC) injection of matching placebo once per week (QW) (following two SC injections on day 1) from Week 1 to Week 15. All participants required to undergo treatment with topical corticosteroids (TCS) using standardized regimen that continued through the end of treatment period (Week 16). At week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).	Dupilumab 300 mg Q2W + TCS n=102 Participants Participants received one subcutaneous (SC) injection of dupilumab 300 mg every 2 weeks (Q2W) from Week 1 to Week 15 (following a SC loading dose of 600 mg on day 1). During weeks in which dupilumab was not administered, participants received matching placebo. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).	Dupilumab 300 mg QW + TCS n=103 Participants Participants received one subcutaneous (SC) injection of dupilumab 300 mg once per week (QW) (following an SC loading dose of 600 mg on day 1) from Week 1 to Week 15. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).
Percent Change From Baseline in Weekly Average of Peak Pruritus Numerical Rating Scale (NRS) at Week 16	-25.4 Percent Change Standard Error 3.39	-53.9 Percent Change Standard Error 3.14	-51.7 Percent Change Standard Error 3.09

SECONDARY outcome

Timeframe: Baseline, Week 16

The SCORAD is a clinical tool for assessing the severity of AD. Extent and intensity of eczema as well as subjective signs (insomnia, etc.) are assessed and scored. Total score ranges from 0 (absent disease) to 103 (severe disease). The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). Here "Number of Participants analyzed" = Participants who were evaluable for this endpoint.

Outcome measures

Outcome measures
Measure	Placebo QW + TCS n=89 Participants Participants received one subcutaneous (SC) injection of matching placebo once per week (QW) (following two SC injections on day 1) from Week 1 to Week 15. All participants required to undergo treatment with topical corticosteroids (TCS) using standardized regimen that continued through the end of treatment period (Week 16). At week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).	Dupilumab 300 mg Q2W + TCS n=103 Participants Participants received one subcutaneous (SC) injection of dupilumab 300 mg every 2 weeks (Q2W) from Week 1 to Week 15 (following a SC loading dose of 600 mg on day 1). During weeks in which dupilumab was not administered, participants received matching placebo. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).	Dupilumab 300 mg QW + TCS n=104 Participants Participants received one subcutaneous (SC) injection of dupilumab 300 mg once per week (QW) (following an SC loading dose of 600 mg on day 1) from Week 1 to Week 15. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).
Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score at Week 16	-29.5 Percent Change Standard Error 2.55 • Interval 2.55 to	-62.4 Percent Change Standard Error 2.48 • Interval 2.48 to	-58.3 Percent Change Standard Error 2.45 • Interval 2.45 to

SECONDARY outcome

Timeframe: Baseline to Week 16

Pruritus NRS is an assessment tool 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. The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). Here "Number of participants analyzed" = participants who were evaluable for this endpoint.

Outcome measures

Outcome measures
Measure	Placebo QW + TCS n=91 Participants Participants received one subcutaneous (SC) injection of matching placebo once per week (QW) (following two SC injections on day 1) from Week 1 to Week 15. All participants required to undergo treatment with topical corticosteroids (TCS) using standardized regimen that continued through the end of treatment period (Week 16). At week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).	Dupilumab 300 mg Q2W + TCS n=94 Participants Participants received one subcutaneous (SC) injection of dupilumab 300 mg every 2 weeks (Q2W) from Week 1 to Week 15 (following a SC loading dose of 600 mg on day 1). During weeks in which dupilumab was not administered, participants received matching placebo. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).	Dupilumab 300 mg QW + TCS n=94 Participants Participants received one subcutaneous (SC) injection of dupilumab 300 mg once per week (QW) (following an SC loading dose of 600 mg on day 1) from Week 1 to Week 15. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).
Percentage of Participants With Improvement (Reduction ≥4 Points) of Weekly Average of Peak Daily Pruritus NRS From Baseline to Week 16	14.3 Percentage of participants	45.7 Percentage of participants	40.4 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 16

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. The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). Here "number of participants analyzed" = participants who were evaluable for this endpoint.

Outcome measures

Outcome measures
Measure	Placebo QW + TCS n=89 Participants Participants received one subcutaneous (SC) injection of matching placebo once per week (QW) (following two SC injections on day 1) from Week 1 to Week 15. All participants required to undergo treatment with topical corticosteroids (TCS) using standardized regimen that continued through the end of treatment period (Week 16). At week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).	Dupilumab 300 mg Q2W + TCS n=103 Participants Participants received one subcutaneous (SC) injection of dupilumab 300 mg every 2 weeks (Q2W) from Week 1 to Week 15 (following a SC loading dose of 600 mg on day 1). During weeks in which dupilumab was not administered, participants received matching placebo. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).	Dupilumab 300 mg QW + TCS n=104 Participants Participants received one subcutaneous (SC) injection of dupilumab 300 mg once per week (QW) (following an SC loading dose of 600 mg on day 1) from Week 1 to Week 15. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).
Change From Baseline in Percent Body Surface Area (BSA) Involvement With Atopic Dermatitis (AD) at Week 16	-19.57 Percent BSA Standard Error 1.798 • Interval 1.798 to	-39.23 Percent BSA Standard Error 1.715 • Interval 1.715 to	-37.52 Percent BSA Standard Error 1.690 • Interval 1.69 to

SECONDARY outcome

Timeframe: Baseline, Week 16

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 16 were reported. The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized).

Outcome measures

Outcome measures
Measure	Placebo QW + TCS n=108 Participants Participants received one subcutaneous (SC) injection of matching placebo once per week (QW) (following two SC injections on day 1) from Week 1 to Week 15. All participants required to undergo treatment with topical corticosteroids (TCS) using standardized regimen that continued through the end of treatment period (Week 16). At week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).	Dupilumab 300 mg Q2W + TCS n=107 Participants Participants received one subcutaneous (SC) injection of dupilumab 300 mg every 2 weeks (Q2W) from Week 1 to Week 15 (following a SC loading dose of 600 mg on day 1). During weeks in which dupilumab was not administered, participants received matching placebo. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).	Dupilumab 300 mg QW + TCS n=110 Participants Participants received one subcutaneous (SC) injection of dupilumab 300 mg once per week (QW) (following an SC loading dose of 600 mg on day 1) from Week 1 to Week 15. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).
Percentage of Participants With Investigator Global Assessment (IGA) 0 or 1 (on the 0 to 4 IGA Scale) and a Reduction From Baseline of ≥2 Points at Week 16	13.9 Percentage of Participants	40.2 Percentage of Participants	39.1 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline, Week 16

The DLQI is a 10-item, validated questionnaire used in clinical practice and clinical trials to assess the impact of AD disease symptoms and treatment on quality of life (QOL). The 10 questions assessed QOL over the past week, with an overall scoring of 0 (absent disease) to 30 (severe disease); a high score is indicative of a poor QOL. The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). Here "Number of Participants Analyzed" = Participants who were evaluable for this endpoint.

Outcome measures

Outcome measures
Measure	Placebo QW + TCS n=89 Participants Participants received one subcutaneous (SC) injection of matching placebo once per week (QW) (following two SC injections on day 1) from Week 1 to Week 15. All participants required to undergo treatment with topical corticosteroids (TCS) using standardized regimen that continued through the end of treatment period (Week 16). At week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).	Dupilumab 300 mg Q2W + TCS n=103 Participants Participants received one subcutaneous (SC) injection of dupilumab 300 mg every 2 weeks (Q2W) from Week 1 to Week 15 (following a SC loading dose of 600 mg on day 1). During weeks in which dupilumab was not administered, participants received matching placebo. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).	Dupilumab 300 mg QW + TCS n=104 Participants Participants received one subcutaneous (SC) injection of dupilumab 300 mg once per week (QW) (following an SC loading dose of 600 mg on day 1) from Week 1 to Week 15. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).
Change From Baseline in the Dermatology Life Quality Index (DLQI) at Week 16	-4.5 Score on a Scale Standard Error 0.49 • Interval 0.49 to	-9.5 Score on a Scale Standard Error 0.46 • Interval 0.46 to	-8.8 Score on a Scale Standard Error 0.45 • Interval 0.45 to

SECONDARY outcome

Timeframe: Baseline, Week 16

The POEM is a 7-item questionnaire that assesses disease symptoms (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) with a scoring system of 0 (absent disease) to 28 (severe disease) (high score indicative of poor quality of life \[QOL\]). The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). Here "Number of Participants Analyzed" = participants who were evaluable for this endpoint.

Outcome measures

Outcome measures
Measure	Placebo QW + TCS n=88 Participants Participants received one subcutaneous (SC) injection of matching placebo once per week (QW) (following two SC injections on day 1) from Week 1 to Week 15. All participants required to undergo treatment with topical corticosteroids (TCS) using standardized regimen that continued through the end of treatment period (Week 16). At week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).	Dupilumab 300 mg Q2W + TCS n=103 Participants Participants received one subcutaneous (SC) injection of dupilumab 300 mg every 2 weeks (Q2W) from Week 1 to Week 15 (following a SC loading dose of 600 mg on day 1). During weeks in which dupilumab was not administered, participants received matching placebo. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).	Dupilumab 300 mg QW + TCS n=104 Participants Participants received one subcutaneous (SC) injection of dupilumab 300 mg once per week (QW) (following an SC loading dose of 600 mg on day 1) from Week 1 to Week 15. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).
Change From Baseline in the Patient Oriented Eczema Measure (POEM) at Week 16	-4.3 Score on a Scale Standard Error 0.62 • Interval 0.62 to	-11.9 Score on a Scale Standard Error 0.60 • Interval 0.6 to	-11.4 Score on a Scale Standard Error 0.59 • Interval 0.59 to

SECONDARY outcome

Timeframe: Baseline, Week 16

The EASI score is used to measure the severity and extent of atopic dermatitis (AD) and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score 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. The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). Here "Number of Participants Analyzed" = Participants who were evaluable for this endpoint.

Outcome measures

Outcome measures
Measure	Placebo QW + TCS n=72 Participants Participants received one subcutaneous (SC) injection of matching placebo once per week (QW) (following two SC injections on day 1) from Week 1 to Week 15. All participants required to undergo treatment with topical corticosteroids (TCS) using standardized regimen that continued through the end of treatment period (Week 16). At week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).	Dupilumab 300 mg Q2W + TCS n=69 Participants Participants received one subcutaneous (SC) injection of dupilumab 300 mg every 2 weeks (Q2W) from Week 1 to Week 15 (following a SC loading dose of 600 mg on day 1). During weeks in which dupilumab was not administered, participants received matching placebo. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).	Dupilumab 300 mg QW + TCS n=69 Participants Participants received one subcutaneous (SC) injection of dupilumab 300 mg once per week (QW) (following an SC loading dose of 600 mg on day 1) from Week 1 to Week 15. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).
Percentage of Participants With Eczema Area and Severity Index (EASI) Score (≥75% Improvement From Baseline) at Week 16 for Participants With Prior CSA Use	26.4 Percentage of Participants	58.0 Percentage of Participants	56.5 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline to week 16

The type, amount, frequency, and potency of topical products used during the study were recorded at home by participants in a medication diary. Participants returned TCS tubes at each clinic visit up until week 16, and these tubes were weighed by the site staff to determine the actual amount of TCS used. During the 16-week placebo-controlled study treatment period, medium-potency TCS dosing frequency was symptom-based (IGA score) adjusted every 4 weeks per the protocol-specified tapering algorithm. The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). Here "Number Analyzed" = Participants who were evaluable for this endpoint.

Outcome measures

Outcome measures
Measure	Placebo QW + TCS n=108 Participants Participants received one subcutaneous (SC) injection of matching placebo once per week (QW) (following two SC injections on day 1) from Week 1 to Week 15. All participants required to undergo treatment with topical corticosteroids (TCS) using standardized regimen that continued through the end of treatment period (Week 16). At week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).	Dupilumab 300 mg Q2W + TCS n=107 Participants Participants received one subcutaneous (SC) injection of dupilumab 300 mg every 2 weeks (Q2W) from Week 1 to Week 15 (following a SC loading dose of 600 mg on day 1). During weeks in which dupilumab was not administered, participants received matching placebo. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).	Dupilumab 300 mg QW + TCS n=110 Participants Participants received one subcutaneous (SC) injection of dupilumab 300 mg once per week (QW) (following an SC loading dose of 600 mg on day 1) from Week 1 to Week 15. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).
Change From Baseline in Mean Weekly Dose of Topical Corticosteroid (TCS) Use During Treatment Period	25.1 Grams Standard Error 1.48 • Interval 1.48 to	15.0 Grams Standard Error 1.51 • Interval 1.51 to	17.5 Grams Standard Error 1.49 • Interval 1.49 to

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: Analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). Here "Number of Participants Analyzed" = Participants who were evaluable for this endpoint.

The HADS is a 14-item scale, with 7 items relating to anxiety and 7 relating to depression. Each item on the questionnaire is scored from 0-3, for possible scores ranging from 0 (no symptoms) to 21 (severe symptoms) for each of the anxiety and depression subscales. Recommended cut-off scores for both subscales to identify psychiatric distress are: 7 to 8 for possible presence, 10 to 11 for probable presence, and 14 to 15 for severe anxiety or depression. Scores less than 7 do not indicate psychiatric distress. Total score is the sum of the two sub-scores.

Outcome measures

Outcome measures
Measure	Placebo QW + TCS n=89 Participants Participants received one subcutaneous (SC) injection of matching placebo once per week (QW) (following two SC injections on day 1) from Week 1 to Week 15. All participants required to undergo treatment with topical corticosteroids (TCS) using standardized regimen that continued through the end of treatment period (Week 16). At week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).	Dupilumab 300 mg Q2W + TCS n=103 Participants Participants received one subcutaneous (SC) injection of dupilumab 300 mg every 2 weeks (Q2W) from Week 1 to Week 15 (following a SC loading dose of 600 mg on day 1). During weeks in which dupilumab was not administered, participants received matching placebo. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).	Dupilumab 300 mg QW + TCS n=104 Participants Participants received one subcutaneous (SC) injection of dupilumab 300 mg once per week (QW) (following an SC loading dose of 600 mg on day 1) from Week 1 to Week 15. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).
Change From Baseline in Total Hospital Anxiety and Depression Scale (HADS) Score at Week 16	-2.3 Score on a Scale Standard Error 0.56 • Interval 0.56 to	-6.1 Score on a Scale Standard Error 0.54 • Interval 0.54 to	-5.2 Score on a Scale Standard Error 0.53 • Interval 0.53 to

SECONDARY outcome

Timeframe: Baseline, Week 16

The SCORAD is a clinical tool for assessing the severity of AD. Extent and intensity of eczema as well as subjective signs (insomnia, etc.) are assessed and scored. Total score ranges from 0 (absent disease) to 103 (severe disease). The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized).

Outcome measures

Outcome measures
Measure	Placebo QW + TCS n=108 Participants Participants received one subcutaneous (SC) injection of matching placebo once per week (QW) (following two SC injections on day 1) from Week 1 to Week 15. All participants required to undergo treatment with topical corticosteroids (TCS) using standardized regimen that continued through the end of treatment period (Week 16). At week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).	Dupilumab 300 mg Q2W + TCS n=107 Participants Participants received one subcutaneous (SC) injection of dupilumab 300 mg every 2 weeks (Q2W) from Week 1 to Week 15 (following a SC loading dose of 600 mg on day 1). During weeks in which dupilumab was not administered, participants received matching placebo. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).	Dupilumab 300 mg QW + TCS n=110 Participants Participants received one subcutaneous (SC) injection of dupilumab 300 mg once per week (QW) (following an SC loading dose of 600 mg on day 1) from Week 1 to Week 15. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).
Percentage of Participants Achieving SCORAD 50 (≥50% Improvement From Baseline) at Week 16	25.9 Percentage of Participants	66.4 Percentage of Participants	55.5 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline, Week 16

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). The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). Full Analysis Set (FAS) included all randomized. Here "Number of Participants Analyzed" = Participants who were evaluable for this endpoint.

Outcome measures

Outcome measures
Measure	Placebo QW + TCS n=89 Participants Participants received one subcutaneous (SC) injection of matching placebo once per week (QW) (following two SC injections on day 1) from Week 1 to Week 15. All participants required to undergo treatment with topical corticosteroids (TCS) using standardized regimen that continued through the end of treatment period (Week 16). At week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).	Dupilumab 300 mg Q2W + TCS n=103 Participants Participants received one subcutaneous (SC) injection of dupilumab 300 mg every 2 weeks (Q2W) from Week 1 to Week 15 (following a SC loading dose of 600 mg on day 1). During weeks in which dupilumab was not administered, participants received matching placebo. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).	Dupilumab 300 mg QW + TCS n=104 Participants Participants received one subcutaneous (SC) injection of dupilumab 300 mg once per week (QW) (following an SC loading dose of 600 mg on day 1) from Week 1 to Week 15. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).
Percent Change From Baseline in the Total Global Individual Signs Score (GISS) at Week 16 (Erythema, Infiltration/ Papulation, Excoriations, Lichenification)	-29.0 Percent Change Standard Error 2.75 • Interval 2.75 to	-55.2 Percent Change Standard Error 2.66 • Interval 2.66 to	-53.3 Percent Change Standard Error 2.65 • Interval 2.65 to

SECONDARY outcome

Timeframe: Baseline, Week 2

Pruritus NRS is an assessment tool 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 you rate your itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 \[0 = no itch; 10 = worst itch imaginable\]). The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). Here "Number of Participants analyzed" = Participants who were evaluable for this endpoint.

Outcome measures

Outcome measures
Measure	Placebo QW + TCS n=105 Participants Participants received one subcutaneous (SC) injection of matching placebo once per week (QW) (following two SC injections on day 1) from Week 1 to Week 15. All participants required to undergo treatment with topical corticosteroids (TCS) using standardized regimen that continued through the end of treatment period (Week 16). At week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).	Dupilumab 300 mg Q2W + TCS n=105 Participants Participants received one subcutaneous (SC) injection of dupilumab 300 mg every 2 weeks (Q2W) from Week 1 to Week 15 (following a SC loading dose of 600 mg on day 1). During weeks in which dupilumab was not administered, participants received matching placebo. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).	Dupilumab 300 mg QW + TCS n=110 Participants Participants received one subcutaneous (SC) injection of dupilumab 300 mg once per week (QW) (following an SC loading dose of 600 mg on day 1) from Week 1 to Week 15. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).
Percent Change From Baseline in Weekly Average of Peak Pruritus Numerical Rating Scale (NRS) Score at Week 2	-10.0 Percent Change Standard Error 2.24 • Interval 2.24 to	-17.2 Percent Change Standard Error 2.25 • Interval 2.25 to	-19.7 Percent Change Standard Error 2.21 • Interval 2.21 to

SECONDARY outcome

Timeframe: Baseline to Week 16

Treatment-emergent adverse events (TEAEs) were defined as AEs that developed or worsened or became serious during on-treatment period (time from the first dose of study drug to the last study dose (Week 16). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs. Safety analysis set (SAF) included all randomized participants who received any study drug; it was based on the treatment received (as treated).

Outcome measures

Outcome measures
Measure	Placebo QW + TCS n=108 Participants Participants received one subcutaneous (SC) injection of matching placebo once per week (QW) (following two SC injections on day 1) from Week 1 to Week 15. All participants required to undergo treatment with topical corticosteroids (TCS) using standardized regimen that continued through the end of treatment period (Week 16). At week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).	Dupilumab 300 mg Q2W + TCS n=107 Participants Participants received one subcutaneous (SC) injection of dupilumab 300 mg every 2 weeks (Q2W) from Week 1 to Week 15 (following a SC loading dose of 600 mg on day 1). During weeks in which dupilumab was not administered, participants received matching placebo. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).	Dupilumab 300 mg QW + TCS n=110 Participants Participants received one subcutaneous (SC) injection of dupilumab 300 mg once per week (QW) (following an SC loading dose of 600 mg on day 1) from Week 1 to Week 15. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).
Percentage of Participants With Skin Infection Treatment Emergent Adverse Events (TEAEs) (Excluding Herpetic Infections) From Baseline Through Treatment Period	8.3 Percentage of Participants	1.9 Percentage of Participants	3.6 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline to Week 16

Treatment-emergent adverse events (TEAEs) were defined as AEs that developed or worsened or became serious during on-treatment period (time from the first dose of study drug to the last study dose (Week 16). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs. SAF included all randomized participants who received any study drug; it was based on the treatment received (as treated).

Outcome measures

Outcome measures
Measure	Placebo QW + TCS n=108 Participants Participants received one subcutaneous (SC) injection of matching placebo once per week (QW) (following two SC injections on day 1) from Week 1 to Week 15. All participants required to undergo treatment with topical corticosteroids (TCS) using standardized regimen that continued through the end of treatment period (Week 16). At week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).	Dupilumab 300 mg Q2W + TCS n=107 Participants Participants received one subcutaneous (SC) injection of dupilumab 300 mg every 2 weeks (Q2W) from Week 1 to Week 15 (following a SC loading dose of 600 mg on day 1). During weeks in which dupilumab was not administered, participants received matching placebo. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).	Dupilumab 300 mg QW + TCS n=110 Participants Participants received one subcutaneous (SC) injection of dupilumab 300 mg once per week (QW) (following an SC loading dose of 600 mg on day 1) from Week 1 to Week 15. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).
Percentage of Participants Having at Least One Serious Treatment Emergent Adverse Event (TEAE) Through Treatment Period	1.9 Percentage of Participants	1.9 Percentage of Participants	1.8 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline to Week 16

Treatment-emergent adverse events (TEAEs) were defined as AEs that developed or worsened or became serious during on-treatment period (time from the first dose of study drug to the last study dose (Week 16). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs. SAF included all randomized participants who received any study drug; it was based on the treatment received (as treated).

Outcome measures

Outcome measures
Measure	Placebo QW + TCS n=108 Participants Participants received one subcutaneous (SC) injection of matching placebo once per week (QW) (following two SC injections on day 1) from Week 1 to Week 15. All participants required to undergo treatment with topical corticosteroids (TCS) using standardized regimen that continued through the end of treatment period (Week 16). At week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).	Dupilumab 300 mg Q2W + TCS n=107 Participants Participants received one subcutaneous (SC) injection of dupilumab 300 mg every 2 weeks (Q2W) from Week 1 to Week 15 (following a SC loading dose of 600 mg on day 1). During weeks in which dupilumab was not administered, participants received matching placebo. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).	Dupilumab 300 mg QW + TCS n=110 Participants Participants received one subcutaneous (SC) injection of dupilumab 300 mg once per week (QW) (following an SC loading dose of 600 mg on day 1) from Week 1 to Week 15. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).
Percentage of Participants Having at Least One Treatment-Emergent Adverse Event (TEAE) Leading to Treatment Discontinuation Through Treatment Period	0.9 Percentage of participants	0 Percentage of participants	1.8 Percentage of participants

SECONDARY outcome

Timeframe: Baseline to Week 16

Treatment-emergent adverse events (TEAEs) were defined as AEs that developed or worsened or became serious during on-treatment period (time from the first dose of study drug to the last study dose (Week 16). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs. SAF included all randomized participants who received any study drug; it was based on the treatment received (as treated).

Outcome measures

Outcome measures
Measure	Placebo QW + TCS n=108 Participants Participants received one subcutaneous (SC) injection of matching placebo once per week (QW) (following two SC injections on day 1) from Week 1 to Week 15. All participants required to undergo treatment with topical corticosteroids (TCS) using standardized regimen that continued through the end of treatment period (Week 16). At week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).	Dupilumab 300 mg Q2W + TCS n=107 Participants Participants received one subcutaneous (SC) injection of dupilumab 300 mg every 2 weeks (Q2W) from Week 1 to Week 15 (following a SC loading dose of 600 mg on day 1). During weeks in which dupilumab was not administered, participants received matching placebo. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).	Dupilumab 300 mg QW + TCS n=110 Participants Participants received one subcutaneous (SC) injection of dupilumab 300 mg once per week (QW) (following an SC loading dose of 600 mg on day 1) from Week 1 to Week 15. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).
Percentage of Participants With Treatment-Emergent Adverse Events Through Treatment Period	69.4 Percentage of participants	72.0 Percentage of participants	69.1 Percentage of participants

Adverse Events

Placebo QW + TCS

Serious events: 2 serious events

Other events: 45 other events

Deaths: 0 deaths

Dupilumab 300 mg Q2W + TCS

Serious events: 2 serious events

Other events: 54 other events

Deaths: 0 deaths

Dupilumab 300 mg QW + TCS

Serious events: 3 serious events

Other events: 51 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo QW + TCS n=108 participants at risk Participants received one subcutaneous (SC) injection of matching placebo once per week (QW) (following two SC injections on day 1) from Week 1 to Week 15. All participants required to undergo treatment with topical corticosteroids (TCS) using standardized regimen that continued through the end of treatment period (Week 16). At week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).	Dupilumab 300 mg Q2W + TCS n=107 participants at risk Participants received one subcutaneous (SC) injection of dupilumab 300 mg every 2 weeks (Q2W) from Week 1 to Week 15 (following a SC loading dose of 600 mg on day 1). During weeks in which dupilumab was not administered, participants received matching placebo. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).	Dupilumab 300 mg QW + TCS n=110 participants at risk Participants received one subcutaneous (SC) injection of dupilumab 300 mg once per week (QW) (following an SC loading dose of 600 mg on day 1) from Week 1 to Week 15. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).
Gastrointestinal disorders Pancreatitis acute	0.00% 0/108 • All Adverse Events (AEs) were collected from signature of informed consent form up to end of study (EOS), Week 28, regardless of seriousness or relationship to investigational product. Pre-treatment AEs were AEs that developed/worsened in severity during pre-treatment period (from informed consent to first dose of study drug); All AEs collected during treatment and follow-up period were considered treatment emergent AEs (TEAEs). TEAEs were AEs that developed or worsened in severity compared to baseline during treatment and follow-up period.	0.93% 1/107 • Number of events 1 • All Adverse Events (AEs) were collected from signature of informed consent form up to end of study (EOS), Week 28, regardless of seriousness or relationship to investigational product. Pre-treatment AEs were AEs that developed/worsened in severity during pre-treatment period (from informed consent to first dose of study drug); All AEs collected during treatment and follow-up period were considered treatment emergent AEs (TEAEs). TEAEs were AEs that developed or worsened in severity compared to baseline during treatment and follow-up period.	0.00% 0/110 • All Adverse Events (AEs) were collected from signature of informed consent form up to end of study (EOS), Week 28, regardless of seriousness or relationship to investigational product. Pre-treatment AEs were AEs that developed/worsened in severity during pre-treatment period (from informed consent to first dose of study drug); All AEs collected during treatment and follow-up period were considered treatment emergent AEs (TEAEs). TEAEs were AEs that developed or worsened in severity compared to baseline during treatment and follow-up period.
Hepatobiliary disorders Hepatotoxicity	0.00% 0/108 • All Adverse Events (AEs) were collected from signature of informed consent form up to end of study (EOS), Week 28, regardless of seriousness or relationship to investigational product. Pre-treatment AEs were AEs that developed/worsened in severity during pre-treatment period (from informed consent to first dose of study drug); All AEs collected during treatment and follow-up period were considered treatment emergent AEs (TEAEs). TEAEs were AEs that developed or worsened in severity compared to baseline during treatment and follow-up period.	0.93% 1/107 • Number of events 1 • All Adverse Events (AEs) were collected from signature of informed consent form up to end of study (EOS), Week 28, regardless of seriousness or relationship to investigational product. Pre-treatment AEs were AEs that developed/worsened in severity during pre-treatment period (from informed consent to first dose of study drug); All AEs collected during treatment and follow-up period were considered treatment emergent AEs (TEAEs). TEAEs were AEs that developed or worsened in severity compared to baseline during treatment and follow-up period.	0.00% 0/110 • All Adverse Events (AEs) were collected from signature of informed consent form up to end of study (EOS), Week 28, regardless of seriousness or relationship to investigational product. Pre-treatment AEs were AEs that developed/worsened in severity during pre-treatment period (from informed consent to first dose of study drug); All AEs collected during treatment and follow-up period were considered treatment emergent AEs (TEAEs). TEAEs were AEs that developed or worsened in severity compared to baseline during treatment and follow-up period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.00% 0/108 • All Adverse Events (AEs) were collected from signature of informed consent form up to end of study (EOS), Week 28, regardless of seriousness or relationship to investigational product. Pre-treatment AEs were AEs that developed/worsened in severity during pre-treatment period (from informed consent to first dose of study drug); All AEs collected during treatment and follow-up period were considered treatment emergent AEs (TEAEs). TEAEs were AEs that developed or worsened in severity compared to baseline during treatment and follow-up period.	0.00% 0/107 • All Adverse Events (AEs) were collected from signature of informed consent form up to end of study (EOS), Week 28, regardless of seriousness or relationship to investigational product. Pre-treatment AEs were AEs that developed/worsened in severity during pre-treatment period (from informed consent to first dose of study drug); All AEs collected during treatment and follow-up period were considered treatment emergent AEs (TEAEs). TEAEs were AEs that developed or worsened in severity compared to baseline during treatment and follow-up period.	0.91% 1/110 • Number of events 1 • All Adverse Events (AEs) were collected from signature of informed consent form up to end of study (EOS), Week 28, regardless of seriousness or relationship to investigational product. Pre-treatment AEs were AEs that developed/worsened in severity during pre-treatment period (from informed consent to first dose of study drug); All AEs collected during treatment and follow-up period were considered treatment emergent AEs (TEAEs). TEAEs were AEs that developed or worsened in severity compared to baseline during treatment and follow-up period.
Nervous system disorders Hemiparesis	0.93% 1/108 • Number of events 1 • All Adverse Events (AEs) were collected from signature of informed consent form up to end of study (EOS), Week 28, regardless of seriousness or relationship to investigational product. Pre-treatment AEs were AEs that developed/worsened in severity during pre-treatment period (from informed consent to first dose of study drug); All AEs collected during treatment and follow-up period were considered treatment emergent AEs (TEAEs). TEAEs were AEs that developed or worsened in severity compared to baseline during treatment and follow-up period.	0.00% 0/107 • All Adverse Events (AEs) were collected from signature of informed consent form up to end of study (EOS), Week 28, regardless of seriousness or relationship to investigational product. Pre-treatment AEs were AEs that developed/worsened in severity during pre-treatment period (from informed consent to first dose of study drug); All AEs collected during treatment and follow-up period were considered treatment emergent AEs (TEAEs). TEAEs were AEs that developed or worsened in severity compared to baseline during treatment and follow-up period.	0.00% 0/110 • All Adverse Events (AEs) were collected from signature of informed consent form up to end of study (EOS), Week 28, regardless of seriousness or relationship to investigational product. Pre-treatment AEs were AEs that developed/worsened in severity during pre-treatment period (from informed consent to first dose of study drug); All AEs collected during treatment and follow-up period were considered treatment emergent AEs (TEAEs). TEAEs were AEs that developed or worsened in severity compared to baseline during treatment and follow-up period.
Renal and urinary disorders Ureterolithiasis	0.00% 0/108 • All Adverse Events (AEs) were collected from signature of informed consent form up to end of study (EOS), Week 28, regardless of seriousness or relationship to investigational product. Pre-treatment AEs were AEs that developed/worsened in severity during pre-treatment period (from informed consent to first dose of study drug); All AEs collected during treatment and follow-up period were considered treatment emergent AEs (TEAEs). TEAEs were AEs that developed or worsened in severity compared to baseline during treatment and follow-up period.	0.00% 0/107 • All Adverse Events (AEs) were collected from signature of informed consent form up to end of study (EOS), Week 28, regardless of seriousness or relationship to investigational product. Pre-treatment AEs were AEs that developed/worsened in severity during pre-treatment period (from informed consent to first dose of study drug); All AEs collected during treatment and follow-up period were considered treatment emergent AEs (TEAEs). TEAEs were AEs that developed or worsened in severity compared to baseline during treatment and follow-up period.	0.91% 1/110 • Number of events 1 • All Adverse Events (AEs) were collected from signature of informed consent form up to end of study (EOS), Week 28, regardless of seriousness or relationship to investigational product. Pre-treatment AEs were AEs that developed/worsened in severity during pre-treatment period (from informed consent to first dose of study drug); All AEs collected during treatment and follow-up period were considered treatment emergent AEs (TEAEs). TEAEs were AEs that developed or worsened in severity compared to baseline during treatment and follow-up period.
Respiratory, thoracic and mediastinal disorders Emphysema	0.93% 1/108 • Number of events 1 • All Adverse Events (AEs) were collected from signature of informed consent form up to end of study (EOS), Week 28, regardless of seriousness or relationship to investigational product. Pre-treatment AEs were AEs that developed/worsened in severity during pre-treatment period (from informed consent to first dose of study drug); All AEs collected during treatment and follow-up period were considered treatment emergent AEs (TEAEs). TEAEs were AEs that developed or worsened in severity compared to baseline during treatment and follow-up period.	0.00% 0/107 • All Adverse Events (AEs) were collected from signature of informed consent form up to end of study (EOS), Week 28, regardless of seriousness or relationship to investigational product. Pre-treatment AEs were AEs that developed/worsened in severity during pre-treatment period (from informed consent to first dose of study drug); All AEs collected during treatment and follow-up period were considered treatment emergent AEs (TEAEs). TEAEs were AEs that developed or worsened in severity compared to baseline during treatment and follow-up period.	0.00% 0/110 • All Adverse Events (AEs) were collected from signature of informed consent form up to end of study (EOS), Week 28, regardless of seriousness or relationship to investigational product. Pre-treatment AEs were AEs that developed/worsened in severity during pre-treatment period (from informed consent to first dose of study drug); All AEs collected during treatment and follow-up period were considered treatment emergent AEs (TEAEs). TEAEs were AEs that developed or worsened in severity compared to baseline during treatment and follow-up period.
Skin and subcutaneous tissue disorders Dermatitis atopic	0.00% 0/108 • All Adverse Events (AEs) were collected from signature of informed consent form up to end of study (EOS), Week 28, regardless of seriousness or relationship to investigational product. Pre-treatment AEs were AEs that developed/worsened in severity during pre-treatment period (from informed consent to first dose of study drug); All AEs collected during treatment and follow-up period were considered treatment emergent AEs (TEAEs). TEAEs were AEs that developed or worsened in severity compared to baseline during treatment and follow-up period.	0.00% 0/107 • All Adverse Events (AEs) were collected from signature of informed consent form up to end of study (EOS), Week 28, regardless of seriousness or relationship to investigational product. Pre-treatment AEs were AEs that developed/worsened in severity during pre-treatment period (from informed consent to first dose of study drug); All AEs collected during treatment and follow-up period were considered treatment emergent AEs (TEAEs). TEAEs were AEs that developed or worsened in severity compared to baseline during treatment and follow-up period.	0.91% 1/110 • Number of events 1 • All Adverse Events (AEs) were collected from signature of informed consent form up to end of study (EOS), Week 28, regardless of seriousness or relationship to investigational product. Pre-treatment AEs were AEs that developed/worsened in severity during pre-treatment period (from informed consent to first dose of study drug); All AEs collected during treatment and follow-up period were considered treatment emergent AEs (TEAEs). TEAEs were AEs that developed or worsened in severity compared to baseline during treatment and follow-up period.

Other adverse events

Other adverse events
Measure	Placebo QW + TCS n=108 participants at risk Participants received one subcutaneous (SC) injection of matching placebo once per week (QW) (following two SC injections on day 1) from Week 1 to Week 15. All participants required to undergo treatment with topical corticosteroids (TCS) using standardized regimen that continued through the end of treatment period (Week 16). At week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).	Dupilumab 300 mg Q2W + TCS n=107 participants at risk Participants received one subcutaneous (SC) injection of dupilumab 300 mg every 2 weeks (Q2W) from Week 1 to Week 15 (following a SC loading dose of 600 mg on day 1). During weeks in which dupilumab was not administered, participants received matching placebo. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).	Dupilumab 300 mg QW + TCS n=110 participants at risk Participants received one subcutaneous (SC) injection of dupilumab 300 mg once per week (QW) (following an SC loading dose of 600 mg on day 1) from Week 1 to Week 15. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).
Eye disorders Conjunctivitis allergic	6.5% 7/108 • Number of events 9 • All Adverse Events (AEs) were collected from signature of informed consent form up to end of study (EOS), Week 28, regardless of seriousness or relationship to investigational product. Pre-treatment AEs were AEs that developed/worsened in severity during pre-treatment period (from informed consent to first dose of study drug); All AEs collected during treatment and follow-up period were considered treatment emergent AEs (TEAEs). TEAEs were AEs that developed or worsened in severity compared to baseline during treatment and follow-up period.	15.0% 16/107 • Number of events 18 • All Adverse Events (AEs) were collected from signature of informed consent form up to end of study (EOS), Week 28, regardless of seriousness or relationship to investigational product. Pre-treatment AEs were AEs that developed/worsened in severity during pre-treatment period (from informed consent to first dose of study drug); All AEs collected during treatment and follow-up period were considered treatment emergent AEs (TEAEs). TEAEs were AEs that developed or worsened in severity compared to baseline during treatment and follow-up period.	9.1% 10/110 • Number of events 11 • All Adverse Events (AEs) were collected from signature of informed consent form up to end of study (EOS), Week 28, regardless of seriousness or relationship to investigational product. Pre-treatment AEs were AEs that developed/worsened in severity during pre-treatment period (from informed consent to first dose of study drug); All AEs collected during treatment and follow-up period were considered treatment emergent AEs (TEAEs). TEAEs were AEs that developed or worsened in severity compared to baseline during treatment and follow-up period.
Infections and infestations Conjunctivitis	3.7% 4/108 • Number of events 4 • All Adverse Events (AEs) were collected from signature of informed consent form up to end of study (EOS), Week 28, regardless of seriousness or relationship to investigational product. Pre-treatment AEs were AEs that developed/worsened in severity during pre-treatment period (from informed consent to first dose of study drug); All AEs collected during treatment and follow-up period were considered treatment emergent AEs (TEAEs). TEAEs were AEs that developed or worsened in severity compared to baseline during treatment and follow-up period.	11.2% 12/107 • Number of events 14 • All Adverse Events (AEs) were collected from signature of informed consent form up to end of study (EOS), Week 28, regardless of seriousness or relationship to investigational product. Pre-treatment AEs were AEs that developed/worsened in severity during pre-treatment period (from informed consent to first dose of study drug); All AEs collected during treatment and follow-up period were considered treatment emergent AEs (TEAEs). TEAEs were AEs that developed or worsened in severity compared to baseline during treatment and follow-up period.	7.3% 8/110 • Number of events 8 • All Adverse Events (AEs) were collected from signature of informed consent form up to end of study (EOS), Week 28, regardless of seriousness or relationship to investigational product. Pre-treatment AEs were AEs that developed/worsened in severity during pre-treatment period (from informed consent to first dose of study drug); All AEs collected during treatment and follow-up period were considered treatment emergent AEs (TEAEs). TEAEs were AEs that developed or worsened in severity compared to baseline during treatment and follow-up period.
Infections and infestations Nasopharyngitis	16.7% 18/108 • Number of events 26 • All Adverse Events (AEs) were collected from signature of informed consent form up to end of study (EOS), Week 28, regardless of seriousness or relationship to investigational product. Pre-treatment AEs were AEs that developed/worsened in severity during pre-treatment period (from informed consent to first dose of study drug); All AEs collected during treatment and follow-up period were considered treatment emergent AEs (TEAEs). TEAEs were AEs that developed or worsened in severity compared to baseline during treatment and follow-up period.	20.6% 22/107 • Number of events 29 • All Adverse Events (AEs) were collected from signature of informed consent form up to end of study (EOS), Week 28, regardless of seriousness or relationship to investigational product. Pre-treatment AEs were AEs that developed/worsened in severity during pre-treatment period (from informed consent to first dose of study drug); All AEs collected during treatment and follow-up period were considered treatment emergent AEs (TEAEs). TEAEs were AEs that developed or worsened in severity compared to baseline during treatment and follow-up period.	16.4% 18/110 • Number of events 24 • All Adverse Events (AEs) were collected from signature of informed consent form up to end of study (EOS), Week 28, regardless of seriousness or relationship to investigational product. Pre-treatment AEs were AEs that developed/worsened in severity during pre-treatment period (from informed consent to first dose of study drug); All AEs collected during treatment and follow-up period were considered treatment emergent AEs (TEAEs). TEAEs were AEs that developed or worsened in severity compared to baseline during treatment and follow-up period.
Nervous system disorders Headache	9.3% 10/108 • Number of events 17 • All Adverse Events (AEs) were collected from signature of informed consent form up to end of study (EOS), Week 28, regardless of seriousness or relationship to investigational product. Pre-treatment AEs were AEs that developed/worsened in severity during pre-treatment period (from informed consent to first dose of study drug); All AEs collected during treatment and follow-up period were considered treatment emergent AEs (TEAEs). TEAEs were AEs that developed or worsened in severity compared to baseline during treatment and follow-up period.	9.3% 10/107 • Number of events 20 • All Adverse Events (AEs) were collected from signature of informed consent form up to end of study (EOS), Week 28, regardless of seriousness or relationship to investigational product. Pre-treatment AEs were AEs that developed/worsened in severity during pre-treatment period (from informed consent to first dose of study drug); All AEs collected during treatment and follow-up period were considered treatment emergent AEs (TEAEs). TEAEs were AEs that developed or worsened in severity compared to baseline during treatment and follow-up period.	10.0% 11/110 • Number of events 13 • All Adverse Events (AEs) were collected from signature of informed consent form up to end of study (EOS), Week 28, regardless of seriousness or relationship to investigational product. Pre-treatment AEs were AEs that developed/worsened in severity during pre-treatment period (from informed consent to first dose of study drug); All AEs collected during treatment and follow-up period were considered treatment emergent AEs (TEAEs). TEAEs were AEs that developed or worsened in severity compared to baseline during treatment and follow-up period.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	0.93% 1/108 • Number of events 2 • All Adverse Events (AEs) were collected from signature of informed consent form up to end of study (EOS), Week 28, regardless of seriousness or relationship to investigational product. Pre-treatment AEs were AEs that developed/worsened in severity during pre-treatment period (from informed consent to first dose of study drug); All AEs collected during treatment and follow-up period were considered treatment emergent AEs (TEAEs). TEAEs were AEs that developed or worsened in severity compared to baseline during treatment and follow-up period.	6.5% 7/107 • Number of events 8 • All Adverse Events (AEs) were collected from signature of informed consent form up to end of study (EOS), Week 28, regardless of seriousness or relationship to investigational product. Pre-treatment AEs were AEs that developed/worsened in severity during pre-treatment period (from informed consent to first dose of study drug); All AEs collected during treatment and follow-up period were considered treatment emergent AEs (TEAEs). TEAEs were AEs that developed or worsened in severity compared to baseline during treatment and follow-up period.	3.6% 4/110 • Number of events 7 • All Adverse Events (AEs) were collected from signature of informed consent form up to end of study (EOS), Week 28, regardless of seriousness or relationship to investigational product. Pre-treatment AEs were AEs that developed/worsened in severity during pre-treatment period (from informed consent to first dose of study drug); All AEs collected during treatment and follow-up period were considered treatment emergent AEs (TEAEs). TEAEs were AEs that developed or worsened in severity compared to baseline during treatment and follow-up period.
Skin and subcutaneous tissue disorders Dermatitis atopic	16.7% 18/108 • Number of events 26 • All Adverse Events (AEs) were collected from signature of informed consent form up to end of study (EOS), Week 28, regardless of seriousness or relationship to investigational product. Pre-treatment AEs were AEs that developed/worsened in severity during pre-treatment period (from informed consent to first dose of study drug); All AEs collected during treatment and follow-up period were considered treatment emergent AEs (TEAEs). TEAEs were AEs that developed or worsened in severity compared to baseline during treatment and follow-up period.	7.5% 8/107 • Number of events 10 • All Adverse Events (AEs) were collected from signature of informed consent form up to end of study (EOS), Week 28, regardless of seriousness or relationship to investigational product. Pre-treatment AEs were AEs that developed/worsened in severity during pre-treatment period (from informed consent to first dose of study drug); All AEs collected during treatment and follow-up period were considered treatment emergent AEs (TEAEs). TEAEs were AEs that developed or worsened in severity compared to baseline during treatment and follow-up period.	9.1% 10/110 • Number of events 15 • All Adverse Events (AEs) were collected from signature of informed consent form up to end of study (EOS), Week 28, regardless of seriousness or relationship to investigational product. Pre-treatment AEs were AEs that developed/worsened in severity during pre-treatment period (from informed consent to first dose of study drug); All AEs collected during treatment and follow-up period were considered treatment emergent AEs (TEAEs). TEAEs were AEs that developed or worsened in severity compared to baseline during treatment and follow-up period.

Additional Information

Clinical Trial Administrator

Regeneron Pharmaceuticals, Inc.

Phone: 844-734-6643

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The investigator has the right to independently publish study results from the investigator's site after a multi-center publication, or a defined period after the completion of the study by all sites. The investigator must provide the sponsor a copy of any such publication derived from the study for review and comment in advance of any submission, and delay publication, if requested, to allow the Sponsor to preserve its proprietary rights.
Publication restrictions are in place

Restriction type: OTHER