SOLO 1: Study of Dupilumab Monotherapy Administered to Adult Patients With Moderate-to-Severe Atopic Dermatitis

• Sponsor: Regeneron Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02277743
• Collaborator: Sanofi (Industry)
• Enrollment: 671
• Locations: 101
• Arms: 3
• Duration (Months): 16
• Patients Per Site: 6.6
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This is a randomized, double-blind, placebo-controlled, parallel group study to confirm the efficacy and safety of Dupilumab monotherapy in adults with moderate-to-severe atopic dermatitis (AD).

Condition or Disease	Intervention/Treatment	Phase
Dermatitis, Atopic	Drug: Dupilumab; Drug: Placebo (for Dupilumab)	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 671 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3 Confirmatory Study Investigating the Efficacy and Safety of Dupilumab Monotherapy Administered to Adult Patients With Moderate-to-Severe Atopic Dermatitis
• Study Start Date: Oct 1, 2014
• Actual Primary Completion Date: Nov 1, 2015
• Actual Study Completion Date: Feb 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Placebo Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection once weekly (qw) from Week 1 to Week 15.	Drug: Placebo (for Dupilumab); Subcutaneous injection alternated among the different quadrants of the abdomen, upper thighs and upper arms
Experimental: Dupilumab 300 mg once weekly (qw) Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 15.	Drug: Dupilumab; Subcutaneous injection alternated among the different quadrants of the abdomen, upper thighs and upper arms; Other Names: REGN668 SAR231893 DUPIXENT®
Experimental: Dupilumab 300 mg every 2 weeks (q2w) Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a placebo alternating with single 300 mg injection of Dupilumab qw from Week 1 to Week 15.	Drug: Dupilumab; Subcutaneous injection alternated among the different quadrants of the abdomen, upper thighs and upper arms; Other Names: REGN668 SAR231893 DUPIXENT® ; Drug: Placebo (for Dupilumab); Subcutaneous injection alternated among the different quadrants of the abdomen, upper thighs and upper arms

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Investigator's Global Assessment (IGA) Score of "0" or "1" and Reduction From Baseline of ≥2 Points at Week 16 [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. Values after first rescue treatment were set to missing and participants with missing IGA scores at Week 16 were considered as non-responders.

Secondary Outcome Measures

1. Percentage of Participants With Eczema Area and Severity Index-75 (EASI-75) (≥75% Improvement From Baseline) at Week 16 [Week 16]

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

2. Percentage of Participants With Improvement (Reduction ≥4 Points) of Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 16 [Baseline to Week 16]

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

3. Percentage of Participants With Improvement (Reduction ≥3 Points) of Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 16 [Baseline to Week 16]

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

4. Percent Change From Baseline in Peak Daily Pruritus Numerical Rating Scale (NRS) Score to Week 16 [Baseline to Week 16]

   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]).

5. Percentage of Participants With Improvement (Reduction ≥4 Points) of Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 4 [Baseline to Week 4]

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

6. Percentage of Participants With Improvement (Reduction ≥4 Points) of Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 2 [Baseline to Week 2]

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

7. Change From Baseline in Peak Daily Pruritus Numerical Rating Scale (NRS) Score to Week 16 [Baseline to Week 16]

   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]).

8. Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score to Week 16 [Baseline to Week 16]

   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.

9. Percentage of Participants With Eczema Area and Severity Index-50 (EASI-50) (≥50% Improvement From Baseline) at Week 16 [Week 16]

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

10. Percentage of Participants With Eczema Area and Severity Index-90 (EASI-90) (≥90% Improvement From Baseline) at Week 16 [Week 16]

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

11. Change From Baseline in Percent Body Surface Area (BSA) to Week 16 [Baseline to 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.

12. Percent Change From Baseline in the SCORing Atopic Dermatitis (SCORAD) Score to Week 16 [Baseline to Week 16]

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

13. Change From Baseline in Dermatology Life Quality Index (DLQI) to Week 16 [Baseline to 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 was indicative of a poor QOL.

14. Change From Baseline in Patient Oriented Eczema Measure (POEM) to Week 16 [Baseline to 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]).

15. Change From Baseline in Hospital Anxiety Depression Scale (HADS) to Week 16 [Baseline to Week 16]

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

16. Percent Change From Baseline in Global Individual Signs Score (GISS) to Week 16 [Baseline to 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).

17. Percent Change From Baseline in Peak Daily Pruritus NRS Score to Week 2 [Baseline to Week 2]

    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]).

18. Percentage of Participants With Skin Infection Treatment Emergent Adverse Events (TEAEs) Requiring Systemic Treatment [Baseline up 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 up to the end of study [Week 28]). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs. Statistical significance in the hierarchical testing of secondary hypotheses was broken at this endpoint. Therefore, subsequent secondary efficacy endpoints were not tested for statistical significance.

19. Percentage of Participants With Treatment Emergent Serious Adverse Events (TESAEs) From Baseline Through Week 16 [Baseline up to Week 16]

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

20. Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) Leading to Treatment Discontinuation From Baseline Through Week 16 [Baseline up to Week 16]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Male or female, 18 years or older

2. Chronic AD (according to American Academy of Dermatology Consensus Criteria Eichenfield 2014) that has been present for at least 3 years before the screening visit;

3. Eczema Area and Severity Index (EASI) Score ≥16 at the screening and baseline visits;

4. Investigator's Global Assessment (IGA) Score ≥3 (on the 0 to 4 IGA scale, in which 3 is moderate and 4 is severe) at the screening and baseline visits;

5. ≥10% body surface area (BSA) of AD involvement at the screening and baseline visits;

6. Documented recent history (within 6 months before the screening visit) of inadequate response to treatment with topical medications or for whom topical treatments are otherwise medically inadvisable (e.g, because of important side effects or safety risks).

Exclusion Criteria:

1. Participation in a prior Dupilumab clinical study;

2. Treatment with an investigational drug within 8 weeks or within 5 half-lives (if known), whichever was longer, before the baseline visit;

3. Having used any of the following treatments within 4 weeks before the baseline visit, or any condition that, in the opinion of the investigator, was likely to require such treatment(s) during the first 4 weeks of study treatment:

• Immunosuppressive/ immunomodulating drugs (e.g, systemic corticosteroids, cyclosporine, mycophenolate-mofetil, IFN-γ, Janus kinase inhibitors, azathioprine, methotrexate, etc.);

• Phototherapy for AD

1. Treatment with topical corticosteroids (TCS) or topical calcineurin inhibitors (TCI) within 1 week before the baseline visit;

2. Treatment with biologics as follows:

• Any cell-depleting agents including but not limited to rituximab: within 6 months before the baseline visit, or until lymphocyte count returns to normal, whichever was longer

• Other biologics: within 5 half-lives (if known) or 16 weeks prior to baseline visit, whichever was longer

1. Regular use (more than 2 visits per week) of a tanning booth/ parlor within 4 weeks of the screening visit;

2. Planned or anticipated use of any prohibited medications and procedures during study treatment;

3. Treatment with a live (attenuated) vaccine within 12 weeks before the baseline visit;

4. Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 2 weeks before the baseline visit, or superficial skin infections within 1 week before the baseline visit. NOTE: Participants might be rescreened after infection resolves;

5. Known or suspected history of immunosuppression, including history of invasive opportunistic infections (e.g, tuberculosis [TB], histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, aspergillosis) despite infection resolution: or unusually frequent, recurrent, or prolonged infections, per investigator judgment;

6. History of human immunodeficiency virus (HIV) infection or positive HIV serology at screening;

7. Positive with hepatitis B surface antigen (HBsAg) or hepatitis C antibody at the screening visit;

8. Participant was a member of the investigational team or his/her immediate family;

9. Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study;

10. Women unwilling to use adequate birth control, if of reproductive potential and sexually active.

Note: The information listed above is not intended to contain all considerations relevant to a participant's potential participation in this clinical trial therefore not all inclusion/ exclusion criteria are listed.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Birmingham	Alabama	United States
2		Fort Smith	Arkansas	United States
3		Rogers	Arkansas	United States
4		Clovis	California	United States
5		Lomita	California	United States
6		Los Angeles	California	United States
7		Oceanside	California	United States
8		Palmdale	California	United States
9		Rolling Hills Estates	California	United States
10		San Diego	California	United States
11		Santa Monica	California	United States
12		Stockton	California	United States
13		Boca Raton	Florida	United States
14		Clearwater	Florida	United States
15		Fort Lauderdale	Florida	United States
16		Miami Lakes	Florida	United States
17		Miami	Florida	United States
18		Pensacola	Florida	United States
19		Tampa	Florida	United States
20		Newnan	Georgia	United States
21		Chicago	Illinois	United States
22		Normal	Illinois	United States
23		Evansville	Indiana	United States
24		Indianapolis	Indiana	United States
25		Louisville	Kentucky	United States
26		Boston	Massachusetts	United States
27		Troy	Michigan	United States
28		Saint Louis	Missouri	United States
29		Newington	New Hampshire	United States
30		East Windsor	New Jersey	United States
31		Buffalo	New York	United States
32		Corning	New York	United States
33		New Hyde Park	New York	United States
34		Rochester	New York	United States
35		High Point	North Carolina	United States
36		Bethlehem	Pennsylvania	United States
37		Upland	Pennsylvania	United States
38		Chattanooga	Tennessee	United States
39		Knoxville	Tennessee	United States
40		San Antonio	Texas	United States
41		Waco	Texas	United States
42		Ogden	Utah	United States
43		Newport News	Virginia	United States
44		Norfolk	Virginia	United States
45		Spokane	Washington	United States
46		Dupnitsa		Bulgaria
47		Plovdiv		Bulgaria
48		Sofia		Bulgaria
49		Winnepeg	Manitoba	Canada
50		Bathurst	New Brunswick	Canada
51		Hamilton	Ontario	Canada
52		Mississauga	Ontario	Canada
53		Newmarket	Ontario	Canada
54		Ottawa	Ontario	Canada
55		Richmond Hill	Ontario	Canada
56		Toronto	Ontario	Canada
57		Copenhagen		Denmark
58		Hellerup		Denmark
59		Tallinn		Estonia
60		Tartu		Estonia
61		Helsinki		Finland
62		Tampere		Finland
63		Turku		Finland
64		Berlin		Germany
65		Bielefed		Germany
66		Blaubeuren		Germany
67		Erlangen		Germany
68		Halle		Germany
69		Hamburg		Germany
70		Hannover		Germany
71		Muenster		Germany
72		Munchen		Germany
73		Osnabruck		Germany
74		Schwerin		Germany
75		Stuttgart		Germany
76		Kurume	Fukuoka	Japan
77		Fukuyama	Hiroshima	Japan
78		Inashiki	Ibaraki	Japan
79		Yokohama	Kanagawa	Japan
80		Habikino	Osaka	Japan
81		Neyagawa	Osaka	Japan
82		Sakai	Osaka	Japan
83		Takatsuki	Osaka	Japan
84		Hamamatsu	Shizuoka	Japan
85		Bunkyo-ku	Tokyo	Japan
86		Chuo-ku	Tokyo	Japan
87		Nerima-ku	Tokyo	Japan
88		Shinagawa	Tokyo	Japan
89		Shinjuku	Tokyo	Japan
90		Kofu	Yamanashi	Japan
91		Gifu		Japan
92		Hiroshima		Japan
93		Kyoto		Japan
94		Osaka		Japan
95		Singapore		Singapore
96		Alcaniz		Spain
97		Alicante		Spain
98		Barcelona		Spain
99		Madrid		Spain
100		Sevilla		Spain
101		Valencia		Spain

Sponsors and Collaborators

• Regeneron Pharmaceuticals
• Sanofi

Investigators

• Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Regeneron Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02277743
• Other Study ID Numbers: R668-AD-1334
• First Posted: Oct 29, 2014
• Last Update Posted: Nov 21, 2017
• Last Verified: Nov 1, 2017

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Dermatitis, Atopic; Dermatitis; Antibodies, Monoclonal

Study Results

Participant Flow

Recruitment Details	The study was conducted in 10 countries between 28 Oct 2014 and 12 Feb 2016. A total of 917 participants were screened in the study.
Pre-assignment Detail	Out of 917 participants, 671 were randomized and 669 were treated in the study. Participants were randomized in 1:1:1 ratio to receive Dupilumab 300 mg once weekly (qw), Dupilumab 300 mg every 2 weeks (q2w) or Placebo qw.

Arm/Group Title	Placebo	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Arm/Group Description	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.	Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a placebo alternating with single 300 mg injection of Dupilumab qw from Week 1 to Week 15.	Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 15.
Period Title: Overall Study
STARTED	224	224	223
Treated	223	223	223
Safety Population	222	229	218
COMPLETED	184	208	197
NOT COMPLETED	40	16	26

Baseline Characteristics

Arm/Group Title	Placebo	Dupilumab 300 mg q2w	Dupilumab 300 mg qw	Total
Arm/Group Description	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.	Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a placebo alternating with single 300 mg injection of Dupilumab qw from Week 1 to Week 15.	Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 15.	Total of all reporting groups
Overall Participants	224	224	223	671
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	39.5 (13.91)	39.8 (14.68)	39.3 (14.39)	39.5 (14.31)
Sex: Female, Male (Count of Participants)
Female	106 47.3%	94 42%	81 36.3%	281 41.9%
Male	118 52.7%	130 58%	142 63.7%	390 58.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	11 4.9%	6 2.7%	8 3.6%	25 3.7%
Not Hispanic or Latino	212 94.6%	215 96%	212 95.1%	639 95.2%
Unknown or Not Reported	1 0.4%	3 1.3%	3 1.3%	7 1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	56 25%	54 24.1%	51 22.9%	161 24%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	16 7.1%	10 4.5%	20 9%	46 6.9%
White	146 65.2%	155 69.2%	149 66.8%	450 67.1%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	6 2.7%	5 2.2%	3 1.3%	14 2.1%
Region of Enrollment (Count of Participants)
North and South America	95 42.4%	95 42.4%	96 43%	286 42.6%
Asia Pacific	40 17.9%	42 18.8%	38 17%	120 17.9%
Eastern Europe	23 10.3%	22 9.8%	24 10.8%	69 10.3%
Western Europe	66 29.5%	65 29%	65 29.1%	196 29.2%
Eczema Area and Severity Index (EASI) Score (units on scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on scale]	34.5 (14.47)	33 (13.57)	33.2 (13.98)	33.6 (14.00)
Investigator's Global Assessment (IGA) Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	3.5 (0.5)	3.5 (0.5)	3.5 (0.5)	3.5 (0.5)
Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	7.4 (1.77)	7.2 (1.89)	7.2 (2.06)	7.3 (1.91)
Body Surface Area (BSA) Involvement with AD (percentage of body surface area) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage of body surface area]	57.5 (23.38)	54.7 (23.19)	56.1 (22.96)	56.1 (23.17)
SCORing Atopic Dermatitis (SCORAD) Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	68.3 (13.96)	66.9 (13.97)	67.5 (13.61)	67.6 (13.84)
Dermatology Life Quality Index (DLQI) Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	14.8 (7.23)	13.9 (7.37)	14.1 (7.51)	14.2 (7.37)
Patient Oriented Eczema Measure (POEM) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	20.3 (5.90)	19.8 (6.37)	20.4 (6.25)	20.1 (6.17)
Global Individual Signs Score (GISS) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	9.0 (1.85)	8.9 (1.81)	8.9 (1.74)	9.0 (1.80)
Total Hospital Anxiety Depression Scale (HADS) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	12.6 (8.33)	12.2 (7.26)	12.6 (7.95)	12.5 (7.85)

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Investigator's Global Assessment (IGA) Score of "0" or "1" and Reduction From Baseline of ≥2 Points at Week 16
Description	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. Values after first rescue treatment were set to missing and participants with missing IGA scores at Week 16 were considered as non-responders.
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomized participants.

Arm/Group Title	Placebo	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Arm/Group Description	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.	Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a placebo alternating with single 300 mg injection of Dupilumab qw from Week 1 to Week 15.	Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 15.
Measure Participants	224	224	223
Number [percentage of participants]	10.3 4.6%	37.9 16.9%	37.2 16.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dupilumab 300 mg q2w
	Comments	Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Threshold for significance at 0.025 level.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	difference in percentages
	Estimated Value	27.7
	Confidence Interval	(2-Sided) 95%; 20.18 to 35.17
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dupilumab 300 mg q2w vs Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dupilumab 300 mg qw
	Comments	Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Threshold for significance at 0.025 level.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	difference in percentages
	Estimated Value	27.0
	Confidence Interval	(2-Sided) 95%; 19.47 to 34.44
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dupilumab 300 mg qw vs Placebo

2. Secondary Outcome

Title	Percentage of Participants With Eczema Area and Severity Index-75 (EASI-75) (≥75% Improvement From Baseline) at Week 16
Description	The EASI score was used to measure the severity and extent of AD and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI-75 responders were the participants who achieved ≥75% overall improvement in EASI score from baseline to Week 16. Values after first rescue treatment use were set to missing and participants with missing EASI score at Week 16 were considered as non-responders.
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) included all randomized participants.

Arm/Group Title	Placebo	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Arm/Group Description	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.	Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a placebo alternating with single 300 mg injection of Dupilumab qw from Week 1 to Week 15.	Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 15.
Measure Participants	224	224	223
Number [percentage of participants]	14.7 6.6%	51.3 22.9%	52.5 23.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dupilumab 300 mg q2w
	Comments	A hierarchical testing procedure was used to control type I error and handle multiple secondary endpoint analyses. Testing was then performed sequentially in the order the endpoints are reported. The hierarchical testing sequence continued only when the previous endpoint was statistically significant at 0.025 level. Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Threshold for significance at 0.025 level.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	difference in percentages
	Estimated Value	36.6
	Confidence Interval	(2-Sided) 95%; 28.58 to 44.63
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dupilumab 300 mg q2w vs Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dupilumab 300 mg qw
	Comments	A hierarchical testing procedure was used to control type I error and handle multiple secondary endpoint analyses. Testing was then performed sequentially in the order the endpoints are reported. The hierarchical testing sequence continued only when the previous endpoint was statistically significant at 0.025 level. Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Threshold for significance at 0.025 level.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	difference in percentages
	Estimated Value	37.7
	Confidence Interval	(2-Sided) 95%; 29.70 to 45.77
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dupilumab 300 mg qw vs Placebo

3. Secondary Outcome

Title	Percentage of Participants With Improvement (Reduction ≥4 Points) of Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 16
Description	Pruritus NRS was an assessment tool that was used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 [0 = no itch; 10 = worst itch imaginable]). Participants achieving a reduction of ≥4 points from baseline in weekly average of peak daily pruritus NRS score at Week 16 were reported. Values after first rescue treatment were set to missing and participants with missing peak NRS at Week 16 were considered as non-responders.
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) included all randomized participants. Here, number of participants analyzed = participants with baseline peak pruritus NRS ≥4.

Arm/Group Title	Placebo	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Arm/Group Description	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.	Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a placebo alternating with single 300 mg injection of Dupilumab qw from Week 1 to Week 15.	Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 15.
Measure Participants	212	213	201
Number [percentage of participants]	12.3 5.5%	40.8 18.2%	40.3 18.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dupilumab 300 mg q2w
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Threshold for significance at 0.025 level.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	difference in percentages
	Estimated Value	28.6
	Confidence Interval	(2-Sided) 95%; 20.64 to 36.52
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dupilumab 300 mg q2w vs Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dupilumab 300 mg qw
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Threshold for significance at 0.025 level.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	difference in percentages
	Estimated Value	28.0
	Confidence Interval	(2-Sided) 95%; 19.94 to 36.13
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dupilumab 300 mg qw vs Placebo

4. Secondary Outcome

Title	Percentage of Participants With Improvement (Reduction ≥3 Points) of Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 16
Description	Pruritus NRS was an assessment tool that was used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 [0 = no itch; 10 = worst itch imaginable]). Participants achieving a reduction of ≥3 points from baseline in weekly average of peak daily pruritus NRS score at Week 16 were reported. Values after first rescue treatment were set to missing and participants with missing peak NRS at Week 16 were considered as non-responders.
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) included all randomized participants. Here, number of participants analyzed = participants with baseline peak pruritus NRS ≥3.

Arm/Group Title	Placebo	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Arm/Group Description	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.	Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a placebo alternating with single 300 mg injection of Dupilumab qw from Week 1 to Week 15.	Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 15.
Measure Participants	221	220	211
Number [percentage of participants]	17.2 7.7%	46.8 20.9%	51.7 23.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dupilumab 300 mg q2w
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Threshold for significance at 0.025 level.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	difference in percentages
	Estimated Value	29.6
	Confidence Interval	(2-Sided) 95%; 21.36 to 37.88
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dupilumab 300 mg q2w vs Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dupilumab 300 mg qw
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Threshold for significance at 0.025 level.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	difference in percentages
	Estimated Value	34.5
	Confidence Interval	(2-Sided) 95%; 26.08 to 42.84
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dupilumab 300 mg qw vs Placebo

5. Secondary Outcome

Title	Percent Change From Baseline in Peak Daily Pruritus Numerical Rating Scale (NRS) Score to Week 16
Description	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]).
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) included all randomized participants. Here, number of participants analyzed = participants with available data for this endpoint.

Arm/Group Title	Placebo	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Arm/Group Description	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.	Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a placebo alternating with single 300 mg injection of Dupilumab qw from Week 1 to Week 15.	Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 15.
Measure Participants	96	169	162
Mean (Standard Deviation) [percent change]	-26.8 (28.38)	-51.1 (28.81)	-49.0 (33.45)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dupilumab 300 mg q2w
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Threshold for significance at 0.025 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least square (LS) mean difference
	Estimated Value	-24.9
	Confidence Interval	(2-Sided) 95%; -32.26 to -17.52
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dupilumab 300 mg q2w vs Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dupilumab 300 mg qw
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Threshold for significance at 0.025 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-22.8
	Confidence Interval	(2-Sided) 95%; -30.33 to -15.33
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dupilumab 300 mg qw vs Placebo

6. Secondary Outcome

Title	Percentage of Participants With Improvement (Reduction ≥4 Points) of Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 4
Description	Pruritus NRS was an assessment tool that was used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 [0 = no itch; 10 = worst itch imaginable]). Participants achieving a reduction of ≥4 points from baseline in weekly average of peak daily pruritus NRS score at Week 4 were reported. Values after first rescue treatment were set to missing and subjects with missing peak NRS at Week 4 were considered as non-responders.
Time Frame	Baseline to Week 4

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) included all randomized participants. Here, number of participants analyzed = participants with baseline peak pruritus NRS ≥4.

Arm/Group Title	Placebo	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Arm/Group Description	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.	Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a placebo alternating with single 300 mg injection of Dupilumab qw from Week 1 to Week 15.	Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 15.
Measure Participants	212	213	201
Number [percentage of participants]	6.1 2.7%	16.0 7.1%	23.4 10.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dupilumab 300 mg q2w
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0012
	Comments	Threshold for significance at 0.025 level.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	difference in percentages
	Estimated Value	9.8
	Confidence Interval	(2-Sided) 95%; 3.95 to 15.71
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dupilumab 300 mg q2w vs Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dupilumab 300 mg qw
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Threshold for significance at 0.025 level.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	difference in percentages
	Estimated Value	17.3
	Confidence Interval	(2-Sided) 95%; 10.57 to 23.93
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dupilumab 300 mg qw vs Placebo

7. Secondary Outcome

Title	Percentage of Participants With Improvement (Reduction ≥4 Points) of Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 2
Description	Pruritus NRS was an assessment tool that was used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 [0 = no itch; 10 = worst itch imaginable]). Participants achieving a reduction of ≥4 points from baseline in weekly average of peak daily pruritus NRS score at Week 2 were reported. Values after first rescue treatment were set to missing and participants with missing peak NRS at Week 2 were considered as non-responders.
Time Frame	Baseline to Week 2

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) included all randomized participants. Here, number of participants analyzed = participants with baseline peak pruritus NRS ≥4.

Arm/Group Title	Placebo	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Arm/Group Description	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.	Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a placebo alternating with single 300 mg injection of Dupilumab qw from Week 1 to Week 15.	Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 15.
Measure Participants	212	213	201
Number [percentage of participants]	3.3 1.5%	9.4 4.2%	9.5 4.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dupilumab 300 mg q2w
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0097
	Comments	Threshold for significance at 0.025 level.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	difference in percentages
	Estimated Value	6.1
	Confidence Interval	(2-Sided) 95%; 1.49 to 10.68
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dupilumab 300 mg q2w vs Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dupilumab 300 mg qw
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0094
	Comments	Threshold for significance at 0.025 level.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	difference in percentages
	Estimated Value	6.2
	Confidence Interval	(2-Sided) 95%; 1.45 to 10.86
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dupilumab 300 mg qw vs Placebo

8. Secondary Outcome

Title	Change From Baseline in Peak Daily Pruritus Numerical Rating Scale (NRS) Score to Week 16
Description	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]).
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) included all randomized participants. Here, number of participants analyzed = participants with available data for this endpoint.

Arm/Group Title	Placebo	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Arm/Group Description	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.	Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a placebo alternating with single 300 mg injection of Dupilumab qw from Week 1 to Week 15.	Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 15.
Measure Participants	96	169	162
Mean (Standard Deviation) [units on a scale]	-2.13 (2.044)	-3.78 (2.325)	-3.72 (2.186)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dupilumab 300 mg q2w
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Threshold for significance at 0.025 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-1.75
	Confidence Interval	(2-Sided) 95%; -2.236 to -1.260
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dupilumab 300 mg q2w vs Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dupilumab 300 mg qw
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Threshold for significance at 0.025 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-1.69
	Confidence Interval	(2-Sided) 95%; -2.189 to -1.186
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dupilumab 300 mg qw vs Placebo

9. Secondary Outcome

Title	Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score to Week 16
Description	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.
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) included all randomized participants. Here, number of participants analyzed = participants with available data for this endpoint.

Arm/Group Title	Placebo	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Arm/Group Description	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.	Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a placebo alternating with single 300 mg injection of Dupilumab qw from Week 1 to Week 15.	Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 15.
Measure Participants	97	173	162
Mean (Standard Deviation) [percent change]	-39.5 (33.66)	-73.9 (26.28)	-73.8 (26.41)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dupilumab 300 mg q2w
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Threshold for significance at 0.025 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-34.6
	Confidence Interval	(2-Sided) 95%; -42.35 to -26.88
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dupilumab 300 mg q2w vs Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dupilumab 300 mg qw
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Threshold for significance at 0.025 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-34.4
	Confidence Interval	(2-Sided) 95%; -42.17 to -26.56
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dupilumab 300 mg qw vs Placebo

10. Secondary Outcome

Title	Percentage of Participants With Eczema Area and Severity Index-50 (EASI-50) (≥50% Improvement From Baseline) at Week 16
Description	The EASI score was used to measure the severity and extent of AD and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI-50 responders were the participants who achieved ≥50% overall improvement in EASI score from baseline to Week 16. Values after first rescue treatment were set to missing and participants with missing EASI-50 scores at Week 16 were considered as non-responders.
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) included all randomized participants.

Arm/Group Title	Placebo	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Arm/Group Description	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.	Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a placebo alternating with single 300 mg injection of Dupilumab qw from Week 1 to Week 15.	Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 15.
Measure Participants	224	224	223
Number [percentage of participants]	24.6 11%	68.8 30.7%	61.0 27.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dupilumab 300 mg q2w
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Threshold for significance at 0.025 level.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	difference in percentages
	Estimated Value	44.2
	Confidence Interval	(2-Sided) 95%; 35.91 to 52.48
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dupilumab 300 mg q2w vs Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dupilumab 300 mg qw
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Threshold for significance at 0.025 level.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	difference in percentages
	Estimated Value	36.4
	Confidence Interval	(2-Sided) 95%; 27.90 to 44.96
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dupilumab 300 mg qw vs Placebo

11. Secondary Outcome

Title	Percentage of Participants With Eczema Area and Severity Index-90 (EASI-90) (≥90% Improvement From Baseline) at Week 16
Description	The EASI score was used to measure the severity and extent of AD and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI-90 responders were the participants who achieved ≥90% overall improvement in EASI score from baseline to Week 16. Values after first rescue treatment were set to missing and participants with missing EASI-90 scores at Week 16 were considered as non-responders.
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) included all randomized participants.

Arm/Group Title	Placebo	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Arm/Group Description	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.	Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a placebo alternating with single 300 mg injection of Dupilumab qw from Week 1 to Week 15.	Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 15.
Measure Participants	224	224	223
Number [percentage of participants]	7.6 3.4%	35.7 15.9%	33.2 14.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dupilumab 300 mg q2w
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Threshold for significance at 0.025 level.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	difference in percentages
	Estimated Value	28.1
	Confidence Interval	(2-Sided) 95%; 20.96 to 35.29
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dupilumab 300 mg q2w vs Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dupilumab 300 mg qw
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Threshold for significance at 0.025 level.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	difference in percentages
	Estimated Value	25.6
	Confidence Interval	(2-Sided) 95%; 18.51 to 32.68
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dupilumab 300 mg qw vs Placebo

12. Secondary Outcome

Title	Change From Baseline in Percent Body Surface Area (BSA) to Week 16
Description	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.
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) included all randomized participants. Here, number of participants analyzed = participants with available data for this endpoint.

Arm/Group Title	Placebo	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Arm/Group Description	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.	Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a placebo alternating with single 300 mg injection of Dupilumab qw from Week 1 to Week 15.	Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 15.
Measure Participants	97	173	162
Mean (Standard Deviation) [percentage of body surface area]	-17.2 (17.381)	-33.72 (19.619)	-35.42 (19.926)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dupilumab 300 mg q2w
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Threshold for significance at 0.025 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-17.92
	Confidence Interval	(2-Sided) 95%; -22.487 to -13.353
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dupilumab 300 mg q2w vs Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dupilumab 300 mg qw
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Threshold for significance at 0.025 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-18.89
	Confidence Interval	(2-Sided) 95%; -23.125 to -14.650
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dupilumab 300 mg qw vs Placebo

13. Secondary Outcome

Title	Percent Change From Baseline in the SCORing Atopic Dermatitis (SCORAD) Score to Week 16
Description	SCORAD is a clinical tool for assessing the severity of AD developed by the European Task Force on Atopic Dermatitis (Severity scoring of atopic dermatitis: the SCORAD index). Consensus Report of the European Task Force on Atopic Dermatitis. Dermatology (Basel) 186 (1): 23-31. 1993. Extent and intensity of eczema as well as subjective signs (insomnia, etc.) are assessed and scored. Total score ranges from 0 (absent disease) to 103 (severe disease).
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) included all randomized participants. Here, number of participants analyzed = participants with available data for this endpoint.

Arm/Group Title	Placebo	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Arm/Group Description	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.	Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a placebo alternating with single 300 mg injection of Dupilumab qw from Week 1 to Week 15.	Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 15.
Measure Participants	97	172	161
Mean (Standard Deviation) [percent change]	-28.9 (24.25)	-57.2 (24.03)	-56.7 (24.27)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dupilumab 300 mg q2w
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Threshold for significance at 0.025 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-28.7
	Confidence Interval	(2-Sided) 95%; -35.79 to -21.54
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dupilumab 300 mg q2w vs Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dupilumab 300 mg qw
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Threshold for significance at 0.025 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-28.0
	Confidence Interval	(2-Sided) 95%; -35.09 to -20.87
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dupilumab 300 mg qw vs Placebo

14. Secondary Outcome

Title	Change From Baseline in Dermatology Life Quality Index (DLQI) to Week 16
Description	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 was indicative of a poor QOL.
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) included all randomized participants. Here, number of participants analyzed = participants with available data for this endpoint.

Arm/Group Title	Placebo	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Arm/Group Description	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.	Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a placebo alternating with single 300 mg injection of Dupilumab qw from Week 1 to Week 15.	Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 15.
Measure Participants	97	173	162
Mean (Standard Deviation) [units on a scale]	-5.6 (5.86)	-9.0 (6.61)	-8.8 (6.79)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dupilumab 300 mg q2w
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Threshold for significance at 0.025 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-4.0
	Confidence Interval	(2-Sided) 95%; -5.16 to -2.80
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dupilumab 300 mg q2w vs Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dupilumab 300 mg qw
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Threshold for significance at 0.025 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-3.7
	Confidence Interval	(2-Sided) 95%; -4.87 to -2.49
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dupilumab 300 mg qw vs Placebo

15. Secondary Outcome

Title	Change From Baseline in Patient Oriented Eczema Measure (POEM) to Week 16
Description	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]).
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) included all randomized participants. Here, number of participants analyzed = participants with available data for this endpoint.

Arm/Group Title	Placebo	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Arm/Group Description	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.	Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a placebo alternating with single 300 mg injection of Dupilumab qw from Week 1 to Week 15.	Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 15.
Measure Participants	96	173	162
Mean (Standard Deviation) [units on a scale]	-5.3 (6.24)	-11.5 (7.07)	-11.3 (6.36)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dupilumab 300 mg q2w
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Threshold for significance at 0.025 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-6.5
	Confidence Interval	(2-Sided) 95%; -8.02 to -5.01
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dupilumab 300 mg q2w vs Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dupilumab 300 mg qw
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Threshold for significance at 0.025 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-5.9
	Confidence Interval	(2-Sided) 95%; -7.44 to -4.32
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dupilumab 300 mg qw vs Placebo

16. Secondary Outcome

Title	Change From Baseline in Hospital Anxiety Depression Scale (HADS) to Week 16
Description	HADS is a fourteen item scale. Seven of the items relate to anxiety and seven items relate to depression. Each item on the questionnaire is scored from 0 (minimum score) - 3 (maximum score) and this means that a person can score between 0 (no symptoms) and 21 (severe symptoms) for either anxiety or depression. Cut-offs for identifying psychiatric distress has been reported as 7 to 8 for possible presence, 10 to 11 for probable presence, and 14 to 15 for severe anxiety or depression.
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) included all randomized participants. Here, number of participants analyzed = participants with available data for this endpoint.

Arm/Group Title	Placebo	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Arm/Group Description	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.	Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a placebo alternating with single 300 mg injection of Dupilumab qw from Week 1 to Week 15.	Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 15.
Measure Participants	82	159	146
Mean (Standard Deviation) [units on a scale]	-2.7 (4.40)	-4.8 (5.50)	-4.9 (5.36)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dupilumab 300 mg q2w
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0006
	Comments	Threshold for significance at 0.025 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-2.2
	Confidence Interval	(2-Sided) 95%; -3.44 to -0.95
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dupilumab 300 mg q2w vs Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dupilumab 300 mg qw
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments	Threshold for significance at 0.025 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-2.2
	Confidence Interval	(2-Sided) 95%; -3.46 to -1.03
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dupilumab 300 mg qw vs Placebo

17. Secondary Outcome

Title	Percent Change From Baseline in Global Individual Signs Score (GISS) to Week 16
Description	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).
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) included all randomized participants. Here, number of participants analyzed = participants with available data for this endpoint.

Arm/Group Title	Placebo	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Arm/Group Description	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.	Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a placebo alternating with single 300 mg injection of Dupilumab qw from Week 1 to Week 15.	Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 15.
Measure Participants	97	173	162
Mean (Standard Deviation) [percent change]	-26.2 (25.70)	-52.5 (27.33)	-51.1 (26.58)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dupilumab 300 mg q2w
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Threshold for significance at 0.025 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-27.0
	Confidence Interval	(2-Sided) 95%; -35.04 to -18.91
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dupilumab 300 mg q2w vs Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dupilumab 300 mg qw
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Threshold for significance at 0.025 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-25.6
	Confidence Interval	(2-Sided) 95%; -33.06 to -18.12
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dupilumab 300 mg qw vs Placebo

18. Secondary Outcome

Title	Percent Change From Baseline in Peak Daily Pruritus NRS Score to Week 2
Description	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]).
Time Frame	Baseline to Week 2

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) included all randomized participants. Here, number of participants analyzed = participants with available data for this endpoint.

Arm/Group Title	Placebo	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Arm/Group Description	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.	Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a placebo alternating with single 300 mg injection of Dupilumab qw from Week 1 to Week 15.	Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 15.
Measure Participants	194	214	212
Mean (Standard Deviation) [percent change]	-4.2 (22.77)	-20.4 (21.40)	-18.9 (28.40)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dupilumab 300 mg q2w
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Threshold for significance at 0.025 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-16.5
	Confidence Interval	(2-Sided) 95%; -21.08 to -11.90
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dupilumab 300 mg q2w vs Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dupilumab 300 mg qw
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Threshold for significance at 0.025 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-15.1
	Confidence Interval	(2-Sided) 95%; -19.62 to -10.50
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dupilumab 300 mg qw vs Placebo

19. Secondary Outcome

Title	Percentage of Participants With Skin Infection Treatment Emergent Adverse Events (TEAEs) Requiring Systemic Treatment
Description	Treatment-emergent adverse events (TEAEs) were defined as AEs that developed or worsened or became serious during on-treatment period (time from the first dose of study drug up to the end of study [Week 28]). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs. Statistical significance in the hierarchical testing of secondary hypotheses was broken at this endpoint. Therefore, subsequent secondary efficacy endpoints were not tested for statistical significance.
Time Frame	Baseline up to Week 16

Outcome Measure Data

Analysis Population Description

Safety analysis set (SAF) which included all randomized participants who received any study drug, and was analyzed as treated.

Arm/Group Title	Placebo	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Arm/Group Description	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.	Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a placebo alternating with single 300 mg injection of Dupilumab qw from Week 1 to Week 15.	Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 15.
Measure Participants	222	229	218
Number [percentage of participants]	0 0%	0 0%	0 0%

20. Secondary Outcome

Title	Percentage of Participants With Treatment Emergent Serious Adverse Events (TESAEs) From Baseline Through Week 16
Description	Any untoward medical occurrence in a participant who received investigational medicinal product (IMP) was considered an AE without regard to possibility of causal relationship with this treatment. Treatment-emergent adverse events (TEAEs) were defined as AEs that developed or worsened or became serious during on-treatment period (time from the first dose of study drug up to the end of study [Week 28]). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs.
Time Frame	Baseline up to Week 16

Outcome Measure Data

Analysis Population Description

Safety analysis set (SAF) which included all randomized participants who received any study drug, and was analyzed as treated.

Arm/Group Title	Placebo	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Arm/Group Description	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.	Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a placebo alternating with single 300 mg injection of Dupilumab qw from Week 1 to Week 15.	Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 15.
Measure Participants	222	229	218
Number [percentage of participants]	5.0 2.2%	3.1 1.4%	0.9 0.4%

21. Secondary Outcome

Title	Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) Leading to Treatment Discontinuation From Baseline Through Week 16
Description	Any untoward medical occurrence in a participant who received investigational medicinal product (IMP) was considered an AE without regard to possibility of causal relationship with this treatment. Treatment-emergent adverse events (TEAEs) were defined as AEs that developed or worsened or became serious during on-treatment period (time from the first dose of study drug up to the end of study [Week 28]). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs.
Time Frame	Baseline up to Week 16

Outcome Measure Data

Analysis Population Description

Safety analysis set (SAF) which included all randomized participants who received any study drug, and was analyzed as treated.

Arm/Group Title	Placebo	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Arm/Group Description	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.	Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a placebo alternating with single 300 mg injection of Dupilumab qw from Week 1 to Week 15.	Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 15.
Measure Participants	222	229	218
Number [percentage of participants]	0.9 0.4%	1.7 0.8%	1.8 0.8%

Adverse Events

Time Frame	All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 28) regardless of seriousness or relationship to investigational product.
Adverse Event Reporting Description	Reported AEs are treatment-emergent adverse events that developed/worsened during the 'on-treatment period' (time form the first dose of study drug up to the end of study [Week 28]). Analysis was performed on safety population.
Arm/Group Title	Placebo		Dupilumab 300 mg q2w		Dupilumab 300 mg qw
Arm/Group Description	Participants exposed to Placebo (for Dupilumab) for 16 weeks (mean exposure of 14 weeks)		Participants exposed to Dupilumab 300 mg alternating with placebo qw for 16 weeks (mean exposure of 15 weeks).		Participants exposed to Dupilumab 300 mg qw for 16 weeks (mean exposure of 15 weeks).
All Cause Mortality
	Placebo		Dupilumab 300 mg q2w		Dupilumab 300 mg qw
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/222 (0%)		0/229 (0%)		0/218 (0%)
Serious Adverse Events
	Placebo		Dupilumab 300 mg q2w		Dupilumab 300 mg qw
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/222 (5.4%)		7/229 (3.1%)		2/218 (0.9%)
Blood and lymphatic system disorders
Anaemia	1/222 (0.5%)	1	0/229 (0%)	0	0/218 (0%)	0
Cardiac disorders
Acute myocardial infarction	0/222 (0%)	0	1/229 (0.4%)	1	0/218 (0%)	0
Coronary artery disease	1/222 (0.5%)	1	0/229 (0%)	0	0/218 (0%)	0
Myocardial infarction	0/222 (0%)	0	0/229 (0%)	0	1/218 (0.5%)	1
Infections and infestations
Abscess sweat gland	0/222 (0%)	0	1/229 (0.4%)	1	0/218 (0%)	0
Device related infection	1/222 (0.5%)	1	0/229 (0%)	0	0/218 (0%)	0
Kidney infection	0/222 (0%)	0	0/229 (0%)	0	1/218 (0.5%)	1
Mastitis	1/222 (0.5%)	1	0/229 (0%)	0	0/218 (0%)	0
Sepsis	1/222 (0.5%)	1	0/229 (0%)	0	0/218 (0%)	0
Staphylococcal infection	1/222 (0.5%)	1	0/229 (0%)	0	0/218 (0%)	0
Urinary tract infection bacterial	1/222 (0.5%)	1	0/229 (0%)	0	0/218 (0%)	0
Injury, poisoning and procedural complications
Clavicle fracture	0/222 (0%)	0	1/229 (0.4%)	1	0/218 (0%)	0
Laceration	0/222 (0%)	0	1/229 (0.4%)	1	0/218 (0%)	0
Metabolism and nutrition disorders
Hyperglycaemia	1/222 (0.5%)	1	0/229 (0%)	0	0/218 (0%)	0
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	1/222 (0.5%)	1	0/229 (0%)	0	0/218 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lipoma	0/222 (0%)	0	1/229 (0.4%)	1	0/218 (0%)	0
Psychiatric disorders
Depression	1/222 (0.5%)	1	0/229 (0%)	0	0/218 (0%)	0
Suicidal ideation	2/222 (0.9%)	2	0/229 (0%)	0	0/218 (0%)	0
Renal and urinary disorders
Nephrolithiasis	0/222 (0%)	0	0/229 (0%)	0	1/218 (0.5%)	1
Skin and subcutaneous tissue disorders
Dermatitis atopic	3/222 (1.4%)	3	2/229 (0.9%)	2	0/218 (0%)	0
Surgical and medical procedures
Limb operation	0/222 (0%)	0	1/229 (0.4%)	1	0/218 (0%)	0
Vascular disorders
Aortic stenosis	1/222 (0.5%)	1	0/229 (0%)	0	0/218 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo		Dupilumab 300 mg q2w		Dupilumab 300 mg qw
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	97/222 (43.7%)		92/229 (40.2%)		90/218 (41.3%)
Eye disorders
Conjunctivitis allergic	3/222 (1.4%)	3	12/229 (5.2%)	13	8/218 (3.7%)	11
General disorders
Injection site reaction	13/222 (5.9%)	18	19/229 (8.3%)	63	41/218 (18.8%)	111
Infections and infestations
Nasopharyngitis	22/222 (9.9%)	30	27/229 (11.8%)	32	26/218 (11.9%)	34
Upper respiratory tract infection	7/222 (3.2%)	7	7/229 (3.1%)	7	12/218 (5.5%)	14
Nervous system disorders
Headache	13/222 (5.9%)	16	21/229 (9.2%)	33	11/218 (5%)	15
Skin and subcutaneous tissue disorders
Dermatitis atopic	66/222 (29.7%)	77	35/229 (15.3%)	44	21/218 (9.6%)	26

Limitations/Caveats

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