Trial Outcomes & Findings for Study to Determine the Safety and Effectiveness of Dupilumab for Treatment of Atopic Dermatitis (AD) (NCT NCT01979016)

Results Overview

The EASI score was used to measure the severity and extent of atopic dermatitis (AD) and measures erythema (E), infiltration (I), excoriation (Ex) and lichenification (L) on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. Values after first rescue medication use were set to missing and missing values imputed by last observation carried forward (LOCF).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

54 participants

Primary outcome timeframe

Baseline to Week 16

Results posted on

2020-03-18

Participant Flow

The study was conducted at 5 sites in USA and Canada between 05 December 2013 and 30 January 2015. A total of 66 participants were screened in the study.

Out of 66 participants, 54 participants were randomized and treated in the study. Participants were randomized in 1:1 ratio to receive Dupilumab 200 mg once weekly (qw) or placebo qw.

Participant milestones

Participant milestones
Measure	Placebo qw Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 15.	Dupilumab 200 mg qw Two subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1, followed by a single 200 mg injection qw from Week 1 to Week 15.
Overall Study STARTED	27	27
Overall Study COMPLETED	25	26
Overall Study NOT COMPLETED	2	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo qw Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 15.	Dupilumab 200 mg qw Two subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1, followed by a single 200 mg injection qw from Week 1 to Week 15.
Overall Study Withdrawal by Subject	2	0
Overall Study Adverse Event	0	1

Baseline Characteristics

Study to Determine the Safety and Effectiveness of Dupilumab for Treatment of Atopic Dermatitis (AD)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo qw n=27 Participants Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 15.	Dupilumab 200 mg qw n=27 Participants Two subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1, followed by a single 200 mg injection qw from Week 1 to Week 15.	Total n=54 Participants Total of all reporting groups
Age, Continuous	44.1 years STANDARD_DEVIATION 15.73 • n=5 Participants	38.5 years STANDARD_DEVIATION 13.55 • n=7 Participants	41.3 years STANDARD_DEVIATION 14.81 • n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants	11 Participants n=7 Participants	24 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	16 Participants n=7 Participants	30 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	25 Participants n=5 Participants	26 Participants n=7 Participants	51 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized White	20 Participants n=5 Participants	19 Participants n=7 Participants	39 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Race/Ethnicity, Customized Asian	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Eczema Area and Severity Index (EASI) Score	34.2 units on a scale STANDARD_DEVIATION 14.59 • n=5 Participants	33.4 units on a scale STANDARD_DEVIATION 15.41 • n=7 Participants	33.8 units on a scale STANDARD_DEVIATION 14.87 • n=5 Participants
Investigator Global Assessment (IGA) Score	3.5 units on a scale STANDARD_DEVIATION 0.51 • n=5 Participants	3.5 units on a scale STANDARD_DEVIATION 0.51 • n=7 Participants	3.5 units on a scale STANDARD_DEVIATION 0.50 • n=5 Participants
Weekly Peak Pruritus Numeric Rating Scale (NRS)	7.4 units on a scale STANDARD_DEVIATION 2.04 • n=5 Participants	7.1 units on a scale STANDARD_DEVIATION 2.42 • n=7 Participants	7.3 units on a scale STANDARD_DEVIATION 2.22 • n=5 Participants
Global Individual Signs Score (GISS) Total Score	8.9 units on a scale STANDARD_DEVIATION 1.69 • n=5 Participants	8.4 units on a scale STANDARD_DEVIATION 1.82 • n=7 Participants	8.6 units on a scale STANDARD_DEVIATION 1.76 • n=5 Participants
Patient Oriented Eczema Measure (POEM) Score	21.4 units on a scale STANDARD_DEVIATION 5.60 • n=5 Participants	21.7 units on a scale STANDARD_DEVIATION 5.55 • n=7 Participants	21.6 units on a scale STANDARD_DEVIATION 5.52 • n=5 Participants
Body Surface Area (BSA) Involvement with Atopic Dermatitis	54.5 Percentage of BSA STANDARD_DEVIATION 26.91 • n=5 Participants	53.8 Percentage of BSA STANDARD_DEVIATION 29.72 • n=7 Participants	54.2 Percentage of BSA STANDARD_DEVIATION 28.08 • n=5 Participants
SCORing Atopic Dermatitis (SCORAD) Score	65.1 Units on a scale STANDARD_DEVIATION 13.36 • n=5 Participants	64.2 Units on a scale STANDARD_DEVIATION 17.67 • n=7 Participants	64.6 Units on a scale STANDARD_DEVIATION 15.52 • n=5 Participants
Dermatology Life Quality Index (DLQI) Score	14.9 Units on a scale STANDARD_DEVIATION 7.05 • n=5 Participants	17.0 Units on a scale STANDARD_DEVIATION 7.67 • n=7 Participants	16.0 Units on a scale STANDARD_DEVIATION 7.38 • n=5 Participants
Total Hospital Anxiety Depression Scale (HADS)	12.7 Units on a scale STANDARD_DEVIATION 6.70 • n=5 Participants	13.3 Units on a scale STANDARD_DEVIATION 7.66 • n=7 Participants	13.0 Units on a scale STANDARD_DEVIATION 7.13 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline to Week 16

Population: Full analysis set (FAS) population that included all participants who were randomized into this study and received at least 1 dose of study drug.

The EASI score was used to measure the severity and extent of atopic dermatitis (AD) and measures erythema (E), infiltration (I), excoriation (Ex) and lichenification (L) on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. Values after first rescue medication use were set to missing and missing values imputed by last observation carried forward (LOCF).

Outcome measures

Outcome measures
Measure	Placebo qw n=27 Participants Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 15.	Dupilumab 200 mg qw n=27 Participants Two subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1, followed by a single 200 mg injection qw from Week 1 to Week 15.
Percent Change From Baseline in the Eczema Area Severity Index Score (EASI) to Week 16	-5.8 percent change Standard Error 8.16	-75.2 percent change Standard Error 8.15

SECONDARY outcome

Timeframe: Week 16

Population: FAS population was used.

IGA was 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 was an IGA score of 0 (clear) or 1 (almost clear). Values after first rescue medication were set to missing and participants with missing IGA score at Week 16 were considered as non-responders.

Outcome measures

Outcome measures
Measure	Placebo qw n=27 Participants Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 15.	Dupilumab 200 mg qw n=27 Participants Two subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1, followed by a single 200 mg injection qw from Week 1 to Week 15.
Percentage of Participants With Investigator's Global Assessment (IGA) Score of "0" or "1" at Week 16	0 percentage of participants	37.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline to Week 16

Population: FAS population was used.

IGA was 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. Participants with reduction in IGA score from baseline of ≥2 points at Week 16 were reported. Values after first rescue medication were set to missing and participants with missing IGA score at Week 16 were treated as non-responders.

Outcome measures

Outcome measures
Measure	Placebo qw n=27 Participants Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 15.	Dupilumab 200 mg qw n=27 Participants Two subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1, followed by a single 200 mg injection qw from Week 1 to Week 15.
Percentage of Participants Who Achieved IGA Score Reduction From Baseline of ≥2 Points at Week 16	3.7 percentage of participants	51.9 percentage of participants

SECONDARY outcome

Timeframe: Baseline to Week 16

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

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

Outcome measures

Outcome measures
Measure	Placebo qw n=27 Participants Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 15.	Dupilumab 200 mg qw n=26 Participants Two subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1, followed by a single 200 mg injection qw from Week 1 to Week 15.
Absolute Change From Baseline in Pruritus Numeric Rating Scale (NRS) at Week 16	-0.98 units on a scale Standard Error 0.398	-3.64 units on a scale Standard Error 0.405

SECONDARY outcome

Timeframe: Baseline to Week 16

Population: FAS population. Here, number of participants analyzed = participants with available data for this endpoint.

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

Outcome measures

Outcome measures
Measure	Placebo qw n=27 Participants Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 15.	Dupilumab 200 mg qw n=26 Participants Two subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1, followed by a single 200 mg injection qw from Week 1 to Week 15.
Percent Change From Baseline in Pruritus Numeric Rating Scale (NRS) at Week 16	-8.36 percent change Standard Error 8.098	-56.44 percent change Standard Error 8.248

SECONDARY outcome

Timeframe: Baseline to Week 16

Population: FAS population was used.

The EASI score was used to measure the severity and extent of AD and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. Values after first rescue medication use were set to missing and missing values were imputed by LOCF.

Outcome measures

Outcome measures
Measure	Placebo qw n=27 Participants Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 15.	Dupilumab 200 mg qw n=27 Participants Two subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1, followed by a single 200 mg injection qw from Week 1 to Week 15.
Absolute Change From Baseline in EASI Score to Week 16	-3.7 units on a scale Standard Error 2.65	-25.2 units on a scale Standard Error 2.65

SECONDARY outcome

Timeframe: Baseline to Week 16

Population: FAS population was used.

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

Outcome measures

Outcome measures
Measure	Placebo qw n=27 Participants Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 15.	Dupilumab 200 mg qw n=27 Participants Two subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1, followed by a single 200 mg injection qw from Week 1 to Week 15.
Absolute Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score to Week 16	-5.1 units on a scale Standard Error 3.60	-36.4 units on a scale Standard Error 3.60

SECONDARY outcome

Timeframe: Baseline to Week 16

Population: FAS Population was used.

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

Outcome measures

Outcome measures
Measure	Placebo qw n=27 Participants Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 15.	Dupilumab 200 mg qw n=27 Participants Two subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1, followed by a single 200 mg injection qw from Week 1 to Week 15.
Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score to Week 16	-8.2 percent change Standard Error 5.41	-54.8 percent change Standard Error 5.40

SECONDARY outcome

Timeframe: Baseline to Week 16

Population: FAS population was used.

EASI score was used to measure the severity and extent of AD and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranged from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI-50, EASI-75 and EASI-90 responders were the participants who achieved ≥50%, ≥75% and ≥90% respectively, overall improvement in EASI score from baseline to Week 16. Values after first rescue treatment were set to missing and participants with missing EASI score at Week 16 were counted as non-responders.

Outcome measures

Outcome measures
Measure	Placebo qw n=27 Participants Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 15.	Dupilumab 200 mg qw n=27 Participants Two subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1, followed by a single 200 mg injection qw from Week 1 to Week 15.
Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in EASI Score ( EASI-50, EASI-75, and EASI-90 Respectively) at Week 16 Participants with EASI-50	22.2 percentage of participants	77.8 percentage of participants
Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in EASI Score ( EASI-50, EASI-75, and EASI-90 Respectively) at Week 16 Participants with EASI-75	14.8 percentage of participants	66.7 percentage of participants
Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in EASI Score ( EASI-50, EASI-75, and EASI-90 Respectively) at Week 16 Participants with EASI-90	0 percentage of participants	33.3 percentage of participants

SECONDARY outcome

Timeframe: Baseline to Week 16

Population: FAS population was used.

SCORAD was a clinical tool for assessing the severity of atopic dermatitis developed by the European Task Force on Atopic Dermatitis (Severity scoring of atopic dermatitis: the SCORAD index). Consensus Report of the European Task Force on Atopic Dermatitis. Dermatology (Basel) 186 (1): 23-31. 1993. Extent and intensity of eczema as well as subjective signs (insomnia, etc.) were assessed and scored. Total score ranges from 0 (absent disease) to 103 (severe disease). SCORAD-50, SCORAD-75 and SCORAD-90 responders were the participants who achieved ≥50%, ≥75% and ≥90% respectively, overall improvement in SCORAD score from baseline to Week 16. Values after first rescue treatment were set to missing and participants with missing SCORAD score at Week 16 were counted as non-responders.

Outcome measures

Outcome measures
Measure	Placebo qw n=27 Participants Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 15.	Dupilumab 200 mg qw n=27 Participants Two subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1, followed by a single 200 mg injection qw from Week 1 to Week 15.
Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in SCORAD Score (SCORAD-50, SCORAD-75 and SCORAD-90 Respectively) at Week 16 Participants with SCORAD-50	7.4 percentage of participants	55.6 percentage of participants
Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in SCORAD Score (SCORAD-50, SCORAD-75 and SCORAD-90 Respectively) at Week 16 Participants with SCORAD-75	0 percentage of participants	11.1 percentage of participants
Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in SCORAD Score (SCORAD-50, SCORAD-75 and SCORAD-90 Respectively) at Week 16 Participants with SCORAD-90	0 percentage of participants	7.4 percentage of participants

SECONDARY outcome

Timeframe: Baseline to Week 16

Population: FAS population was used.

POEM was a 7-item questionnaire that assessed disease symptoms (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) with a scoring system of 0 (absent disease) to 28 (severe disease) (high score indicative of poor quality of life \[QOL\]). Values after first rescue medication use were set to missing and missing values were imputed by LOCF.

Outcome measures

Outcome measures
Measure	Placebo qw n=27 Participants Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 15.	Dupilumab 200 mg qw n=27 Participants Two subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1, followed by a single 200 mg injection qw from Week 1 to Week 15.
Absolute Change From Baseline in Participant's Oriented Eczema Measure (POEM) Score to Week 16	-2.6 units on a scale Standard Error 1.34	-13.1 units on a scale Standard Error 1.37

SECONDARY outcome

Timeframe: Baseline to Week 16

Population: FAS population was used.

POEM was a 7-item questionnaire that assesses disease symptoms (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) with a scoring system of 0 (absent disease) to 28 (severe disease) (high score indicative of poor quality of life \[QOL\]). Values after first rescue medication use were set to missing and missing values were imputed by LOCF.

Outcome measures

Outcome measures
Measure	Placebo qw n=27 Participants Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 15.	Dupilumab 200 mg qw n=27 Participants Two subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1, followed by a single 200 mg injection qw from Week 1 to Week 15.
Percent Change From Baseline in Participant's Oriented Eczema Measure (POEM) Score to Week 16	-12.1 percent change Standard Error 6.18	-58.3 percent change Standard Error 6.31

SECONDARY outcome

Timeframe: Baseline to Week 16

Population: FAS population was used.

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).Values after first rescue medication use were set to missing and missing values were imputed by LOCF.

Outcome measures

Outcome measures
Measure	Placebo qw n=27 Participants Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 15.	Dupilumab 200 mg qw n=27 Participants Two subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1, followed by a single 200 mg injection qw from Week 1 to Week 15.
Change From Baseline in Global Individual Signs Score (GISS) Components (Erythema, Infiltration/Papulation, Excoriations, and Lichenification) to Week 16 Change in Erythema GISS	0.0 units on a scale Standard Error 0.14	-0.7 units on a scale Standard Error 0.14
Change From Baseline in Global Individual Signs Score (GISS) Components (Erythema, Infiltration/Papulation, Excoriations, and Lichenification) to Week 16 Change in Infiltration/Papulation GISS	-0.1 units on a scale Standard Error 0.13	-1.0 units on a scale Standard Error 0.13
Change From Baseline in Global Individual Signs Score (GISS) Components (Erythema, Infiltration/Papulation, Excoriations, and Lichenification) to Week 16 Change in Excoriation GISS	-0.3 units on a scale Standard Error 0.14	-1.3 units on a scale Standard Error 0.14
Change From Baseline in Global Individual Signs Score (GISS) Components (Erythema, Infiltration/Papulation, Excoriations, and Lichenification) to Week 16 Change in Lichenification GISS	-0.1 units on a scale Standard Error 0.14	-1.2 units on a scale Standard Error 0.14

SECONDARY outcome

Timeframe: Baseline to Week 16

Population: FAS population was used.

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).Values after first rescue medication use were set to missing and missing values were imputed by LOCF.

Outcome measures

Outcome measures
Measure	Placebo qw n=27 Participants Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 15.	Dupilumab 200 mg qw n=27 Participants Two subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1, followed by a single 200 mg injection qw from Week 1 to Week 15.
Changes From Baseline in GISS Cumulative Score to Week 16	-0.5 units on a scale Standard Error 0.46	-4.2 units on a scale Standard Error 0.46

Adverse Events

Placebo qw

Serious events: 3 serious events

Other events: 17 other events

Deaths: 0 deaths

Dupilumab 200 mg qw

Serious events: 0 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo qw n=27 participants at risk Participants exposed to Placebo (for Dupilumab) (mean exposure of 10 weeks).	Dupilumab 200 mg qw n=27 participants at risk Participants exposed to Dupilumab 200 mg qw (mean exposure of 14 weeks).
Cardiac disorders Coronary artery stenosis	3.7% 1/27 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events: AEs that developed/worsened during the on treatment period (time period from the administration of first dose of study drug to the final visit \[Week 32\]).	0.00% 0/27 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events: AEs that developed/worsened during the on treatment period (time period from the administration of first dose of study drug to the final visit \[Week 32\]).
Hepatobiliary disorders Cholecystitis	3.7% 1/27 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events: AEs that developed/worsened during the on treatment period (time period from the administration of first dose of study drug to the final visit \[Week 32\]).	0.00% 0/27 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events: AEs that developed/worsened during the on treatment period (time period from the administration of first dose of study drug to the final visit \[Week 32\]).
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	3.7% 1/27 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events: AEs that developed/worsened during the on treatment period (time period from the administration of first dose of study drug to the final visit \[Week 32\]).	0.00% 0/27 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events: AEs that developed/worsened during the on treatment period (time period from the administration of first dose of study drug to the final visit \[Week 32\]).

Other adverse events

Additional Information

Clinical Trial Management

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

Measure	Placebo qw n=27 participants at risk Participants exposed to Placebo (for Dupilumab) (mean exposure of 10 weeks).	Dupilumab 200 mg qw n=27 participants at risk Participants exposed to Dupilumab 200 mg qw (mean exposure of 14 weeks).
Eye disorders Conjunctivitis allergic	0.00% 0/27 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events: AEs that developed/worsened during the on treatment period (time period from the administration of first dose of study drug to the final visit \[Week 32\]).	7.4% 2/27 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events: AEs that developed/worsened during the on treatment period (time period from the administration of first dose of study drug to the final visit \[Week 32\]).
General disorders Fatigue	3.7% 1/27 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events: AEs that developed/worsened during the on treatment period (time period from the administration of first dose of study drug to the final visit \[Week 32\]).	7.4% 2/27 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events: AEs that developed/worsened during the on treatment period (time period from the administration of first dose of study drug to the final visit \[Week 32\]).
General disorders Injection site erythema	3.7% 1/27 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events: AEs that developed/worsened during the on treatment period (time period from the administration of first dose of study drug to the final visit \[Week 32\]).	7.4% 2/27 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events: AEs that developed/worsened during the on treatment period (time period from the administration of first dose of study drug to the final visit \[Week 32\]).
General disorders Injection site reaction	0.00% 0/27 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events: AEs that developed/worsened during the on treatment period (time period from the administration of first dose of study drug to the final visit \[Week 32\]).	7.4% 2/27 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events: AEs that developed/worsened during the on treatment period (time period from the administration of first dose of study drug to the final visit \[Week 32\]).
Infections and infestations Folliculitis	0.00% 0/27 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events: AEs that developed/worsened during the on treatment period (time period from the administration of first dose of study drug to the final visit \[Week 32\]).	7.4% 2/27 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events: AEs that developed/worsened during the on treatment period (time period from the administration of first dose of study drug to the final visit \[Week 32\]).
Infections and infestations Gastroenteritis	0.00% 0/27 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events: AEs that developed/worsened during the on treatment period (time period from the administration of first dose of study drug to the final visit \[Week 32\]).	7.4% 2/27 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events: AEs that developed/worsened during the on treatment period (time period from the administration of first dose of study drug to the final visit \[Week 32\]).
Infections and infestations Nasopharyngitis	18.5% 5/27 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events: AEs that developed/worsened during the on treatment period (time period from the administration of first dose of study drug to the final visit \[Week 32\]).	11.1% 3/27 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events: AEs that developed/worsened during the on treatment period (time period from the administration of first dose of study drug to the final visit \[Week 32\]).
Infections and infestations Post procedural infection	0.00% 0/27 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events: AEs that developed/worsened during the on treatment period (time period from the administration of first dose of study drug to the final visit \[Week 32\]).	7.4% 2/27 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events: AEs that developed/worsened during the on treatment period (time period from the administration of first dose of study drug to the final visit \[Week 32\]).
Infections and infestations Upper respiratory tract infection	14.8% 4/27 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events: AEs that developed/worsened during the on treatment period (time period from the administration of first dose of study drug to the final visit \[Week 32\]).	14.8% 4/27 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events: AEs that developed/worsened during the on treatment period (time period from the administration of first dose of study drug to the final visit \[Week 32\]).
Infections and infestations Viral upper respiratory tract infection	7.4% 2/27 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events: AEs that developed/worsened during the on treatment period (time period from the administration of first dose of study drug to the final visit \[Week 32\]).	11.1% 3/27 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events: AEs that developed/worsened during the on treatment period (time period from the administration of first dose of study drug to the final visit \[Week 32\]).
Musculoskeletal and connective tissue disorders Back pain	7.4% 2/27 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events: AEs that developed/worsened during the on treatment period (time period from the administration of first dose of study drug to the final visit \[Week 32\]).	3.7% 1/27 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events: AEs that developed/worsened during the on treatment period (time period from the administration of first dose of study drug to the final visit \[Week 32\]).
Nervous system disorders Headache	3.7% 1/27 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events: AEs that developed/worsened during the on treatment period (time period from the administration of first dose of study drug to the final visit \[Week 32\]).	7.4% 2/27 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events: AEs that developed/worsened during the on treatment period (time period from the administration of first dose of study drug to the final visit \[Week 32\]).
Nervous system disorders Presyncope	0.00% 0/27 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events: AEs that developed/worsened during the on treatment period (time period from the administration of first dose of study drug to the final visit \[Week 32\]).	7.4% 2/27 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events: AEs that developed/worsened during the on treatment period (time period from the administration of first dose of study drug to the final visit \[Week 32\]).
Skin and subcutaneous tissue disorders Dermatitis atopic	14.8% 4/27 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events: AEs that developed/worsened during the on treatment period (time period from the administration of first dose of study drug to the final visit \[Week 32\]).	14.8% 4/27 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events: AEs that developed/worsened during the on treatment period (time period from the administration of first dose of study drug to the final visit \[Week 32\]).
Infections and infestations Dermatitis Infected	7.4% 2/27 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events: AEs that developed/worsened during the on treatment period (time period from the administration of first dose of study drug to the final visit \[Week 32\]).	0.00% 0/27 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events: AEs that developed/worsened during the on treatment period (time period from the administration of first dose of study drug to the final visit \[Week 32\]).
Injury, poisoning and procedural complications Contusion	0.00% 0/27 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events: AEs that developed/worsened during the on treatment period (time period from the administration of first dose of study drug to the final visit \[Week 32\]).	7.4% 2/27 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events: AEs that developed/worsened during the on treatment period (time period from the administration of first dose of study drug to the final visit \[Week 32\]).