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Clinical Trial Results:
A Randomized, Double-Blind, Placebo-Controlled Study to Demonstrate the Efficacy and Long-Term Safety of Dupilumab in Adult Patients With Moderate-to-Severe Atopic Dermatitis

Summary
EudraCT number	2013-003254-24
Trial protocol	DE CZ IT HU NL LV BE PL ES RO FR
Global end of trial date	19 Oct 2016

Results information
Results version number	v1
This version publication date	24 Aug 2017
First version publication date	24 Aug 2017
Other versions	v2

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

R668-AD-1224

ISRCTN number

US NCT number

NCT02260986

WHO universal trial number (UTN)

Sponsor organisation name

Regeneron Pharmaceuticals, Inc.

Sponsor organisation address

777 Old Saw Mill River Rd., Tarrytown, United States,

Public contact

Clinical Trials information, Regeneron Pharmaceuticals, Inc., clinicaltrials@regeneron.com

Scientific contact

Clinical Trials information, Regeneron Pharmaceuticals, Inc., clinicaltrials@regeneron.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Interim

Date of interim/final analysis

27 Apr 2016

Is this the analysis of the primary completion data?

Yes

Primary completion date

17 Aug 2015

Global end of trial reached?

Yes

Global end of trial date

19 Oct 2016

Was the trial ended prematurely?

Main objective of the trial

The primary objective of the study was to demonstrate the efficacy of Dupilumab administered concomitantly with topical corticosteroid (TCS) through Week 16 in adult subjects with moderate-to-severe atopic dermatitis (AD) compared to placebo administered concomitantly with TCS.

Protection of trial subjects

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Council for Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.

Background therapy

All subjects were required to apply moisturizers (emollients) at least twice daily for at least 7 consecutive days immediately before randomization and to continue throughout the study. Starting on Day 1/baseline, all subjects were required to initiate treatment with a TCS using a standardized regimen. The type and amount of topical products (TCS and topical calcineurin inhibitors [TCI]) used during the study were recorded. It was recommended that subjects use triamcinolone acetonide 0.1% cream or fluocinolone acetonide 0.025% ointment for medium potency, and hydrocortisone 1% cream for low potency.

Evidence for comparator

Actual start date of recruitment

16 Sep 2014

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Netherlands: 43

Country: Number of subjects enrolled

Poland: 144

Country: Number of subjects enrolled

Romania: 4

Country: Number of subjects enrolled

Spain: 10

Country: Number of subjects enrolled

United Kingdom: 36

Country: Number of subjects enrolled

Czech Republic: 20

Country: Number of subjects enrolled

Hungary: 27

Country: Number of subjects enrolled

Italy: 13

Country: Number of subjects enrolled

Australia: 41

Country: Number of subjects enrolled

Canada: 115

Country: Number of subjects enrolled

Japan: 117

Country: Number of subjects enrolled

New Zealand: 5

Country: Number of subjects enrolled

Korea, Republic of: 26

Country: Number of subjects enrolled

United States: 139

Worldwide total number of subjects

740

EEA total number of subjects

297

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

713

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

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

Screening details

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

Period 1 title

Overall Study (Overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Assessor

Are arms mutually exclusive

Yes

Placebo qw

Arm 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 51.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Subcutaneous injection among the different quadrants of the abdomen (avoiding navel and waist areas), upper thighs, and upper arms.

Dupilumab 300 mg q2w

Arm description

Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, subjects received placebo.

Arm type

Experimental

Investigational medicinal product name

Dupilumab 300 mg q2w

Investigational medicinal product code

REGN668; SAR231893

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Subcutaneous injection among the different quadrants of the abdomen (avoiding navel and waist areas), upper thighs, and upper arms.

Dupilumab 300 mg qw

Arm description

Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 51.

Arm type

Experimental

Investigational medicinal product name

Dupilumab 300 mg qw

Investigational medicinal product code

REGN668; SAR231893

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Subcutaneous injection among the different quadrants of the abdomen (avoiding navel and waist areas), upper thighs, and upper arms.

Number of subjects in period 1	Placebo qw	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Started	315	106	319
Completed	225	93	278
Not completed	90	13	41
Consent withdrawn by subject	17	4	9
Car accident	-	-	1
Pregnancy	2	-	-
Adverse event	24	-	11
Lack of investigation product supply	2	-	1
Lost to follow-up	4	-	3
Lack of efficacy	27	3	-
Protocol deviation	14	5	16
Incorrect randomization	-	1	-

Baseline characteristics

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Reporting group title

Placebo qw

Reporting 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 51.

Reporting group title

Dupilumab 300 mg q2w

Reporting group description

Reporting group title

Dupilumab 300 mg qw

Reporting group description

Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 51.

Reporting group values	Placebo qw	Dupilumab 300 mg q2w	Dupilumab 300 mg qw	Total
Number of subjects	315	106	319	740
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	36.6 ( 13.01 )	39.6 ( 13.98 )	36.9 ( 13.67 )	-
Gender categorical
Units: Subjects
Female	122	44	128	294
Male	193	62	191	446
Ethnicity
Units: Subjects
Hispanic or Latino	10	2	5	17
Not Hispanic or Latino	299	103	309	711
Unknown or Not Reported	6	1	5	12
Race
Units: Subjects
American Indian or Alaska Native	0	0	0	0
Asian	83	29	89	201
Native Hawaiian or Other Pacific Islander	0	0	0	0
Black or African American	19	2	13	34
White	208	74	208	490
More than one race	0	0	0	0
Unknown or Not Reported	5	1	9	15
Eczema Area and Severity Index (EASI) Score
The EASI score was used to measure the severity and extent of AD and measures erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD.
Units: units on scale
arithmetic mean (standard deviation)	32.6 ( 12.93 )	33.6 ( 13.3 )	32.1 ( 12.76 )	-
Investigator Global Assessment (IGA) Score
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).
Units: units on scale
arithmetic mean (standard deviation)	3.5 ( 0.5 )	3.5 ( 0.5 )	3.5 ( 0.5 )	-
Weekly Peak Averaged Pruritus Numeric Rating Scale (NRS)
Pruritus NRS was an assessment tool that was used to report the intensity of subject’s pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Subjects were asked the following question: how would a subject rate his itch at worst moment during previous 24 hours (for maximum itch intensity on a scale of 0–10 [0=no itch;10=worst itch imaginable]).
Units: units on scale
arithmetic mean (standard deviation)	7.3 ( 1.84 )	7.4 ( 1.66 )	7.1 ( 1.9 )	-
Body Surface Area (BSA) Involvement with Atopic Dermatitis (AD)
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.
Units: percentage of BSA
arithmetic mean (standard deviation)	56.9 ( 21.69 )	59.5 ( 20.84 )	54.1 ( 21.76 )	-
SCORing Atopic Dermatitis (SCORAD) Score
SCORAD was a clinical tool for assessing the severity of AD developed by the European Task Force on Atopic Dermatitis (Severity scoring of atopic dermatitis: the SCORAD index). Consensus Report of the European Task Force on Atopic Dermatitis. Dermatology (Basel) 186 (1): 23–31. 1993. Extent and intensity of eczema as well as subjective signs (insomnia, etc.) are assessed and scored. Total score ranges from 0 (absent disease) to 103 (severe disease). Data for SCORAD score was reported for a total of 734 subjects (Placebo qw: 313; Dupilumab 300 mg q2w: 105 and Dupilumab 300 mg qw: 316).
Units: units on a scale
arithmetic mean (standard deviation)	66 ( 13.53 )	69.3 ( 15.24 )	65.9 ( 13.63 )	-
Dermatology Life Quality Index (DLQI) Total Score
DLQI was a 10-item, validated questionnaire used in clinical practice and clinical trials to assess the impact of AD disease symptoms and treatment on quality of life (QOL). The 10 questions assessed QOL over the past week, with an overall scoring of 0 (absent disease) to 30 (severe disease); a high score was indicative of a poor QOL.
Units: units on scale
arithmetic mean (standard deviation)	14.7 ( 7.37 )	14.5 ( 7.31 )	14.4 ( 7.17 )	-
Patient Oriented Eczema Measure (POEM)
The POEM was a 7-item questionnaire that assessed disease symptoms (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) with a scoring system of 0 (absent disease) to 28 (severe disease) (high score indicative of poor quality of life [QOL]). Data for POEM score was reported for a total of 739 subjects (Placebo qw: 314; Dupilumab 300 mg q2w: 106 and Dupilumab 300 mg qw: 319).
Units: units on a scale
arithmetic mean (standard deviation)	20 ( 5.99 )	20.3 ( 5.68 )	20.1 ( 6.05 )	-
Global Individual Signs Score (GISS)
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).
Units: units on scale
arithmetic mean (standard deviation)	8.7 ( 1.84 )	8.9 ( 2.04 )	8.9 ( 1.8 )	-
Total Hospital Anxiety Depression Scale (HADS)
The HADS is a fourteen item scale. Seven of the items relate to anxiety and seven relate to depression. Each item on the questionnaire is scored from 0-3 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.
Units: units on scale
arithmetic mean (standard deviation)	12.6 ( 8.06 )	12.9 ( 7.73 )	12.8 ( 8.01 )	-

End points

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Reporting group title

Placebo qw

Reporting 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 51.

Reporting group title

Dupilumab 300 mg q2w

Reporting group description

Reporting group title

Dupilumab 300 mg qw

Reporting group description

Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 51.

Subject analysis set title

Placebo qw

Subject analysis set type

Safety analysis

Subject analysis set 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 51.

Subject analysis set title

Dupilumab 300 mg q2w

Subject analysis set type

Safety analysis

Subject analysis set description

Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, subjects received placebo. Four subjects received fewer injections of Dupilumab 300 mg in Dupilumab 300 qw arm, were analyzed in Dupilumab 300 mg q2w arm.

Subject analysis set title

Dupilumab 300 mg qw

Subject analysis set type

Safety analysis

Subject analysis set description

Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 51. Four subjects received fewer injections of Dupilumab 300 mg in Dupilumab 300 qw arm, were analyzed in Dupilumab 300 mg q2w arm.

Primary: Percentage of Subjects With Eczema Area and Severity Index-75 (EASI-75) (≥75% Improvement From Baseline) at Week 16

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End point title

Percentage of Subjects With Eczema Area and Severity Index-75 (EASI-75) (≥75% Improvement From Baseline) at Week 16

End point description

The EASI score was used to measure the severity and extent of atopic dermatitis (AD) and measures erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI-75 responders were the subjects who achieved ≥75% overall improvement in EASI score from baseline to Week 16. All efficacy analyses were performed on the Full Analysis Set (FAS), which included all randomized subjects. Efficacy analyses were based on the treatment allocated by interactive voice response system/ interactive web response system (IVRS/IWRS) at randomization (as randomized).

End point type

Primary

End point timeframe

Baseline to Week 16

End point values	Placebo qw	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Number of subjects analysed	315	106	319
Units: percentage of subjects
number (not applicable)	23.2	68.9	63.9

Dupilumab 300 mg q2w vs Placebo

Statistical analysis description

Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity (IGA baseline values: IGA=3 vs IGA=4). Values after first rescue treatment use were set to missing and subjects with missing EASI score at Week 16 were considered as non-responders.

Comparison groups

Dupilumab 300 mg q2w v Placebo qw

Number of subjects included in analysis

421

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[1]

Method

Cochran-Mantel-Haenszel

Parameter type

difference in percentages

Point estimate

45.7

Confidence interval

level

95%

sides

2-sided

lower limit

35.72

upper limit

55.66

Notes
[1] - Threshold for significance at 0.025 level.

Dupilumab 300 mg qw vs Placebo

Statistical analysis description

Comparison groups

Dupilumab 300 mg qw v Placebo qw

Number of subjects included in analysis

634

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[2]

Method

Cochran-Mantel-Haenszel

Parameter type

difference in percentages

Point estimate

40.8

Confidence interval

level

95%

sides

2-sided

lower limit

33.74

upper limit

47.81

Notes
[2] - Threshold for significance at 0.025 level.

Primary: Percentage of Subjects With Investigator’s Global Assessment (IGA) Score of “0” or “1” and Reduction From Baseline of ≥2 Points at Week 16

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End point title

Percentage of Subjects With Investigator’s Global Assessment (IGA) Score of “0” or “1” and Reduction From Baseline of ≥2 Points at Week 16

End point description

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 is an IGA score of 0 (clear) or 1 (almost clear). Subjects with IGA score “0” or “1” and a reduction from baseline of ≥2 points at Week 16 were reported. All efficacy analyses were performed on the FAS, which included all randomized subjects. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). (Co-primary efficacy endpoints are for the European Union [EU], EU reference market countries, and Japan only).

End point type

Primary

End point timeframe

Baseline to Week 16

End point values	Placebo qw	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Number of subjects analysed	315	106	319
Units: percentage of subjects
number (not applicable)	12.4	38.7	39.2

Dupilumab 300 mg q2w vs Placebo

Statistical analysis description

Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity (IGA baseline values: IGA=3 vs IGA=4). Values after first rescue treatment were set to missing and subjects with missing IGA scores at Week 16 were considered as non-responders.

Comparison groups

Dupilumab 300 mg q2w v Placebo qw

Number of subjects included in analysis

421

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[3]

Method

Cochran-Mantel-Haenszel

Parameter type

difference in percentages

Point estimate

26.3

Confidence interval

level

95%

sides

2-sided

lower limit

16.34

upper limit

36.26

Notes
[3] - Threshold for significance at 0.025 level.

Dupilumab 300 mg qw vs Placebo

Statistical analysis description

Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity (IGA baseline values: IGA=3 vs IGA=4). Values after first rescue treatment were set to missing and subjects with missing IGA scores at Week 16 were considered as non-responders.

Comparison groups

Dupilumab 300 mg qw v Placebo qw

Number of subjects included in analysis

634

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[4]

Method

Cochran-Mantel-Haenszel

Parameter type

difference in percentages

Point estimate

26.8

Confidence interval

level

95%

sides

2-sided

lower limit

20.33

upper limit

33.28

Notes
[4] - Threshold for significance at 0.025 level.

Secondary: Percentage of Subjects With Improvement (Reduction ≥4 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 16

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End point title

Percentage of Subjects With Improvement (Reduction ≥4 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 16

End point description

Pruritus NRS was an assessment tool that was used to report the intensity of a subject’s pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Subjects were asked the following question: how would a subject 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]). Subjects achieving a reduction of ≥4 points from baseline in weekly average of peak daily pruritus NRS score at Week 16 were reported. All efficacy analyses were performed on the FAS, which included all randomized subjects. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of subjects analyzed = subjects with baseline peak pruritus NRS score ≥4.

End point type

Secondary

End point timeframe

Baseline to Week 16

End point values	Placebo qw	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Number of subjects analysed	299	102	295
Units: percentage of subjects
number (not applicable)	19.7	58.8	50.8

Dupilumab 300 mg q2w vs Placebo

Statistical analysis description

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 previous endpoint was statistically significant at 0.025 level for both comparisons.

Comparison groups

Dupilumab 300 mg q2w v Placebo qw

Number of subjects included in analysis

401

Analysis specification

Pre-specified

Analysis type

superiority ^[5]

P-value

< 0.0001 ^[6]

Method

Cochran-Mantel-Haenszel

Parameter type

difference in percentages

Point estimate

39.1

Confidence interval

level

95%

sides

2-sided

lower limit

28.53

upper limit

49.65

Notes
[5] - Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity (IGA baseline values: IGA=3 vs IGA=4). Values after first rescue treatment use were set to missing and subjects with missing peak NRS at Week 16 were considered as non-responders.
[6] - Threshold for significance at 0.025 level.

Dupilumab 300 mg qw vs Placebo

Statistical analysis description

Comparison groups

Dupilumab 300 mg qw v Placebo qw

Number of subjects included in analysis

594

Analysis specification

Pre-specified

Analysis type

superiority ^[7]

P-value

< 0.0001 ^[8]

Method

Cochran-Mantel-Haenszel

Parameter type

difference in percentages

Point estimate

31.1

Confidence interval

level

95%

sides

2-sided

lower limit

23.84

upper limit

38.39

Notes
[7] - Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity (IGA baseline values: IGA=3 vs IGA=4). Values after first rescue treatment use were set to missing and subjects with missing peak NRS at Week 16 were considered as non-responders.
[8] - Threshold for significance at 0.025 level.

Secondary: Percentage of Subjects With Improvement (Reduction ≥3 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 16

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End point title

Percentage of Subjects With Improvement (Reduction ≥3 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 16

End point description

Pruritus NRS was an assessment tool that was used to report the intensity of a subject’s pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Subjects were asked the following question: how would a subject 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]). Subjects achieving a reduction of ≥3 points from baseline in weekly average of peak daily pruritus NRS score at Week 16 were reported. All efficacy analyses were performed on the FAS, which included all randomized subjects. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of subjects analyzed = subjects with baseline peak pruritus NRS score ≥3.

End point type

Secondary

End point timeframe

Baseline to Week 16

End point values	Placebo qw	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Number of subjects analysed	306	105	309
Units: percentage of subjects
number (not applicable)	27.8	65.7	62.5

Dupilumab 300 mg q2w vs Placebo

Statistical analysis description

Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity (IGA baseline values: IGA=3 vs IGA=4). Values after first rescue treatment use were set to missing and subjects with missing peak NRS at Week 16 were considered as non-responders.

Comparison groups

Dupilumab 300 mg q2w v Placebo qw

Number of subjects included in analysis

411

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[9]

Method

Cochran-Mantel-Haenszel

Parameter type

difference in percentages

Point estimate

37.9

Confidence interval

level

95%

sides

2-sided

lower limit

27.56

upper limit

48.31

Notes
[9] - Threshold for significance at 0.025 level.

Dupilumab 300 mg qw vs Placebo

Statistical analysis description

Comparison groups

Dupilumab 300 mg qw v Placebo qw

Number of subjects included in analysis

615

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[10]

Method

Cochran-Mantel-Haenszel

Parameter type

difference in percentages

Point estimate

34.7

Confidence interval

level

95%

sides

2-sided

lower limit

27.31

upper limit

42.05

Notes
[10] - Threshold for significance at 0.025 level.

Secondary: Percentage of Subjects With Investigator’s Global Assessment (IGA) Score of “0” or “1” and Reduction From Baseline of ≥2 Points at Week 52

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End point title

Percentage of Subjects With Investigator’s Global Assessment (IGA) Score of “0” or “1” and Reduction From Baseline of ≥2 Points at Week 52

End point 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). Subjects with IGA score of “0” or “1” and a reduction from baseline of ≥2 points at Week 52 were reported. All efficacy analyses were performed on the FAS, which included all randomized subjects. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of subjects analyzed = subjects with available data for this endpoint.

End point type

Secondary

End point timeframe

Baseline to Week 52

End point values	Placebo qw	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Number of subjects analysed	264	89	270
Units: percentage of subjects
number (not applicable)	12.5	36	40

Dupilumab 300 mg q2w vs Placebo

Statistical analysis description

Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity (IGA baseline values: IGA=3 vs IGA=4). Values after first rescue treatment were set to missing and subjects with missing IGA scores at Week 52 were considered as non-responders.

Comparison groups

Dupilumab 300 mg q2w v Placebo qw

Number of subjects included in analysis

353

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[11]

Method

Cochran-Mantel-Haenszel

Parameter type

difference in percentages

Point estimate

23.5

Confidence interval

level

95%

sides

2-sided

lower limit

12.72

upper limit

34.19

Notes
[11] - Threshold for significance at 0.025 level.

Dupilumab 300 mg qw vs Placebo

Statistical analysis description

Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity (IGA baseline values: IGA=3 vs IGA=4). Values after first rescue treatment were set to missing and subjects with missing IGA scores at Week 52 were considered as non-responders.

Comparison groups

Dupilumab 300 mg qw v Placebo qw

Number of subjects included in analysis

534

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[12]

Method

Cochran-Mantel-Haenszel

Parameter type

difference in percentages

Point estimate

27.5

Confidence interval

level

95%

sides

2-sided

lower limit

20.42

upper limit

34.58

Notes
[12] - Threshold for significance at 0.025 level.

Secondary: Percentage of Subjects With Eczema Area and Severity Index-75 (EASI-75) (≥75% Improvement From Baseline) at Week 52

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End point title

Percentage of Subjects With Eczema Area and Severity Index-75 (EASI-75) (≥75% Improvement From Baseline) at Week 52

End point 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 subjects who achieved ≥75% overall improvement in EASI score from baseline to Week 52. All efficacy analyses were performed on the FAS, which included all randomized subjects. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of subjects analyzed = subjects with available data for this endpoint.

End point type

Secondary

End point timeframe

Baseline to Week 52

End point values	Placebo qw	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Number of subjects analysed	264	89	270
Units: percentage of subjects
number (not applicable)	21.6	65.2	64.1

Dupilumab 300 mg q2w vs Placebo

Statistical analysis description

Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity (IGA baseline values: IGA=3 vs IGA=4). Values after first rescue treatment use were set to missing and subjects with missing EASI score at Week 52 were considered as non-responders.

Comparison groups

Dupilumab 300 mg q2w v Placebo qw

Number of subjects included in analysis

353

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[13]

Method

Cochran-Mantel-Haenszel

Parameter type

difference in percentages

Point estimate

43.6

Confidence interval

level

95%

sides

2-sided

lower limit

32.5

upper limit

54.65

Notes
[13] - Threshold for significance at 0.025 level.

Dupilumab 300 mg qw vs Placebo

Statistical analysis description

Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity (IGA baseline values: IGA=3 vs IGA=4). Values after first rescue treatment use were set to missing and subjects with missing EASI score at Week 52 were considered as non-responders.

Comparison groups

Dupilumab 300 mg qw v Placebo qw

Number of subjects included in analysis

534

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[14]

Method

Cochran-Mantel-Haenszel

Parameter type

difference in percentages

Point estimate

42.5

Confidence interval

level

95%

sides

2-sided

lower limit

34.91

upper limit

50.06

Notes
[14] - Threshold for significance at 0.025 level.

Secondary: Percent Change From Baseline in Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score to Week 16

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End point title

Percent Change From Baseline in Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score to Week 16

End point description

Pruritus NRS was an assessment tool that was used to report the intensity of a subject’s pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Subjects were asked the following question: how would a subject 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]). All efficacy analyses were performed on the FAS, which included all randomized subjects. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).

End point type

Secondary

End point timeframe

Baseline to Week 16

End point values	Placebo qw	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Number of subjects analysed	315	106	319
Units: percent change
least squares mean (standard error)	-30.3 ( 2.36 )	-56.6 ( 3.95 )	-57.1 ( 2.11 )

Dupilumab 300 mg q2w vs Placebo

Statistical analysis description

Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using ANCOVA model with baseline measurements as covariate and the treatment, region and baseline IGA strata as fixed factors.

Comparison groups

Dupilumab 300 mg q2w v Placebo qw

Number of subjects included in analysis

421

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[15]

Method

ANCOVA

Parameter type

Least square (LS) mean difference

Point estimate

-26.2

Confidence interval

level

95%

sides

2-sided

lower limit

-35.04

upper limit

-17.43

Notes
[15] - Threshold for significance at 0.025 level.

Dupilumab 300 mg qw vs Placebo

Statistical analysis description

Comparison groups

Dupilumab 300 mg qw v Placebo qw

Number of subjects included in analysis

634

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[16]

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

-26.8

Confidence interval

level

95%

sides

2-sided

lower limit

-32.83

upper limit

-20.73

Notes
[16] - Threshold for significance at 0.025 level.

Secondary: Percentage of Subjects With Improvement (Reduction ≥4 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 52

Top of page

End point title

Percentage of Subjects With Improvement (Reduction ≥4 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 52

End point description

Pruritus NRS was an assessment tool that was used to report the intensity of a subject's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Subjects were asked the following question: how would a subject 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]). Subjects achieving a reduction of ≥4 points from baseline in weekly average of peak daily pruritus NRS score at Week 52 were reported. All efficacy analyses were performed on the FAS, which included all randomized subjects. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of subjects analyzed = subjects with baseline peak pruritus NRS score ≥4.

End point type

Secondary

End point timeframe

Baseline to Week 52

End point values	Placebo qw	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Number of subjects analysed	249	86	249
Units: percentage of subjects
number (not applicable)	12.9	51.2	39

Dupilumab 300 mg q2w vs Placebo

Statistical analysis description

Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity (IGA baseline values: IGA=3 vs IGA=4). Values after first rescue treatment were set to missing and subjects with missing peak NRS at Week 52 were considered as non-responders.

Comparison groups

Dupilumab 300 mg q2w v Placebo qw

Number of subjects included in analysis

335

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[17]

Method

Cochran-Mantel-Haenszel

Parameter type

difference in percentages

Point estimate

38.3

Confidence interval

level

95%

sides

2-sided

lower limit

26.96

upper limit

49.66

Notes
[17] - Threshold for significance at 0.025 level.

Dupilumab 300 mg qw vs Placebo

Statistical analysis description

Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity (IGA baseline values: IGA=3 vs IGA=4). Values after first rescue treatment were set to missing and subjects with missing peak NRS at Week 52 were considered as non-responders.

Comparison groups

Dupilumab 300 mg qw v Placebo qw

Number of subjects included in analysis

498

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[18]

Method

Cochran-Mantel-Haenszel

Parameter type

difference in percentages

Point estimate

26.1

Confidence interval

level

95%

sides

2-sided

lower limit

18.76

upper limit

33.45

Notes
[18] - Threshold for significance at 0.025 level.

Secondary: Percentage of Subjects With Improvement (Reduction ≥3 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 52

Top of page

End point title

Percentage of Subjects With Improvement (Reduction ≥3 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 52

End point description

Pruritus NRS was an assessment tool that was used to report the intensity of a subject's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Subjects were asked the following question: how would a subject 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]). Subjects achieving a reduction of ≥3 points from baseline in weekly average of peak daily pruritus NRS score at Week 52 were reported. All efficacy analyses were performed on the FAS, which included all randomized subjects. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of subjects analyzed = subjects with baseline peak pruritus NRS score ≥3.

End point type

Secondary

End point timeframe

Baseline to Week 52

End point values	Placebo qw	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Number of subjects analysed	256	88	261
Units: percentage of subjects
number (not applicable)	15.6	55.7	42.9

Dupilumab 300 mg q2w vs Placebo

Statistical analysis description

Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity (IGA baseline values: IGA=3 vs IGA=4). Values after first rescue treatment were set to missing and subjects with missing peak NRS at Week 52 were considered as non-responders.

Comparison groups

Dupilumab 300 mg q2w v Placebo qw

Number of subjects included in analysis

344

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[19]

Method

Cochran-Mantel-Haenszel

Parameter type

difference in percentages

Point estimate

40.1

Confidence interval

level

95%

sides

2-sided

lower limit

28.76

upper limit

51.35

Notes
[19] - Threshold for significance at 0.025 level.

Dupilumab 300 mg qw vs Placebo

Statistical analysis description

Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity (IGA baseline values: IGA=3 vs IGA=4). Values after first rescue treatment were set to missing and subjects with missing peak NRS at Week 52 were considered as non-responders.

Comparison groups

Dupilumab 300 mg qw v Placebo qw

Number of subjects included in analysis

517

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[20]

Method

Cochran-Mantel-Haenszel

Parameter type

difference in percentages

Point estimate

27.3

Confidence interval

level

95%

sides

2-sided

lower limit

19.81

upper limit

34.76

Notes
[20] - Threshold for significance at 0.025 level.

Secondary: Percentage of Subjects With Improvement (Reduction ≥4 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 24

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End point title

Percentage of Subjects With Improvement (Reduction ≥4 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 24

End point description

Pruritus NRS was an assessment tool that was used to report the intensity of a subject’s pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Subjects were asked the following question: how would a subject 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]). Subjects achieving a reduction of ≥4 points from baseline in weekly average of peak daily pruritus NRS score at Week 24 were reported. All efficacy analyses were performed on the FAS, which included all randomized subjects. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of subjects analyzed = subjects with baseline peak pruritus NRS score ≥4.

End point type

Secondary

End point timeframe

Baseline to Week 24

End point values	Placebo qw	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Number of subjects analysed	299	102	295
Units: percentage of subjects
number (not applicable)	16.1	53.9	43.7

Dupilumab 300 mg q2w vs Placebo

Statistical analysis description

Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity (IGA baseline values: IGA=3 vs IGA=4). Values after first rescue treatment were set to missing and subjects with missing peak NRS at Week 24 were considered as non-responders.

Comparison groups

Dupilumab 300 mg q2w v Placebo qw

Number of subjects included in analysis

401

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[21]

Method

Cochran-Mantel-Haenszel

Parameter type

difference in percentages

Point estimate

37.9

Confidence interval

level

95%

sides

2-sided

lower limit

27.34

upper limit

48.4

Notes
[21] - Threshold for significance at 0.025 level.

Dupilumab 300 mg qw vs Placebo

Statistical analysis description

Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity (IGA baseline values: IGA=3 vs IGA=4). Values after first rescue treatment were set to missing and subjects with missing peak NRS at Week 24 were considered as non-responders.

Comparison groups

Dupilumab 300 mg qw v Placebo qw

Number of subjects included in analysis

594

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[22]

Method

Cochran-Mantel-Haenszel

Parameter type

difference in percentages

Point estimate

27.7

Confidence interval

level

95%

sides

2-sided

lower limit

20.65

upper limit

34.7

Notes
[22] - Threshold for significance at 0.025 level.

Secondary: Percentage of Subjects With Improvement (Reduction ≥4 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 4

Top of page

End point title

Percentage of Subjects With Improvement (Reduction ≥4 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 4

End point description

Pruritus NRS was an assessment tool that was used to report the intensity of a subject's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Subjects were asked the following question: how would a subject 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]). Subjects achieving a reduction of ≥4 points from baseline in weekly average of peak daily pruritus NRS score at Week 4 were reported. All efficacy analyses were performed on the FAS, which included all randomized subjects. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of subjects analyzed = subjects with baseline peak pruritus NRS score ≥4.

End point type

Secondary

End point timeframe

Baseline to Week 4

End point values	Placebo qw	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Number of subjects analysed	299	102	295
Units: percentage of subjects
number (not applicable)	16.4	37.3	27.1

Dupilumab 300 mg q2w vs Placebo

Statistical analysis description

Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity (IGA baseline values: IGA=3 vs IGA=4). Values after first rescue treatment were set to missing and subjects with missing peak NRS at Week 4 were considered as non-responders.

Comparison groups

Dupilumab 300 mg q2w v Placebo qw

Number of subjects included in analysis

401

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[23]

Method

Cochran-Mantel-Haenszel

Parameter type

difference in percentages

Point estimate

20.9

Confidence interval

level

95%

sides

2-sided

lower limit

10.59

upper limit

31.15

Notes
[23] - Threshold for significance at 0.025 level.

Dupilumab 300 mg qw vs Placebo

Statistical analysis description

Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity (IGA baseline values: IGA=3 vs IGA=4). Values after first rescue treatment were set to missing and subjects with missing peak NRS at Week 4 were considered as non-responders.

Comparison groups

Dupilumab 300 mg qw v Placebo qw

Number of subjects included in analysis

594

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0021 ^[24]

Method

Cochran-Mantel-Haenszel

Parameter type

difference in percentages

Point estimate

10.7

Confidence interval

level

95%

sides

2-sided

lower limit

4.15

upper limit

17.31

Notes
[24] - Threshold for significance at 0.025 level.

Secondary: Percentage of Subjects With Improvement (Reduction ≥4 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 2

Top of page

End point title

Percentage of Subjects With Improvement (Reduction ≥4 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 2

End point description

Pruritus NRS was an assessment tool that was used to report the intensity of a subject's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Subjects were asked the following question: how would a subject 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]). Subjects achieving a reduction of ≥4 points from baseline in weekly average of peak daily pruritus NRS score at Week 2 were reported. All efficacy analyses were performed on the FAS, which included all randomized subjects. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of subjects analyzed = subjects with baseline peak pruritus NRS score ≥4.

End point type

Secondary

End point timeframe

Baseline to Week 2

End point values	Placebo qw	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Number of subjects analysed	299	102	295
Units: percentage of subjects
number (not applicable)	8	17.6	13.6

Dupilumab 300 mg q2w vs Placebo

Statistical analysis description

Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity (IGA baseline values: IGA=3 vs IGA=4). Values after first rescue treatment were set to missing and subjects with missing peak NRS at Week 2 were considered as non-responders.

Comparison groups

Dupilumab 300 mg q2w v Placebo qw

Number of subjects included in analysis

401

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0062 ^[25]

Method

Cochran-Mantel-Haenszel

Parameter type

difference in percentages

Point estimate

9.6

Confidence interval

level

95%

sides

2-sided

lower limit

1.61

upper limit

17.63

Notes
[25] - Threshold for significance at 0.025 level.

Dupilumab 300 mg qw vs Placebo

Statistical analysis description

Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity (IGA baseline values: IGA=3 vs IGA=4). Values after first rescue treatment were set to missing and subjects with missing peak NRS at Week 2 were considered as non-responders.

Comparison groups

Dupilumab 300 mg qw v Placebo qw

Number of subjects included in analysis

594

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0344 ^[26]

Method

Cochran-Mantel-Haenszel

Parameter type

difference in percentages

Point estimate

5.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.56

upper limit

10.51

Notes
[26] - Threshold for significance at 0.025 level.

Secondary: Change From Baseline in Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score to Week 16

Top of page

End point title

Change From Baseline in Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score to Week 16

End point description

Pruritus NRS was an assessment tool that was used to report the intensity of a subject's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Subjects were asked the following question: how would a subject 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]). All efficacy analyses were performed on the FAS, which included all randomized subjects. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).

End point type

Secondary

End point timeframe

Baseline to Week 16

End point values	Placebo qw	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Number of subjects analysed	315	106	319
Units: units on a scale
least squares mean (standard error)	-2.36 ( 0.138 )	-4.17 ( 0.207 )	-4.27 ( 0.126 )

Dupilumab 300 mg q2w vs Placebo

Statistical analysis description

Comparison groups

Dupilumab 300 mg q2w v Placebo qw

Number of subjects included in analysis

421

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[27]

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

-1.81

Confidence interval

level

95%

sides

2-sided

lower limit

-2.297

upper limit

-1.322

Notes
[27] - Threshold for significance at 0.025 level.

Secondary: Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score to Week 16

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End point title

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

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

End point type

Secondary

End point timeframe

Baseline to Week 16

End point values	Placebo qw	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Number of subjects analysed	315	106	319
Units: percent change
least squares mean (standard error)	-48.4 ( 3.82 )	-80.5 ( 6.34 )	-81.5 ( 5.78 )

Dupilumab 300 mg q2w vs Placebo

Statistical analysis description

Comparison groups

Dupilumab 300 mg q2w v Placebo qw

Number of subjects included in analysis

421

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[28]

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

-32.1

Confidence interval

level

95%

sides

2-sided

lower limit

-46.37

upper limit

-17.82

Notes
[28] - Threshold for significance at 0.025 level.

Secondary: Change From Baseline in Percent Body Surface Area (BSA) Affected by AD to Week 16

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End point title

Change From Baseline in Percent Body Surface Area (BSA) Affected by AD to Week 16

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

End point type

Secondary

End point timeframe

Baseline to Week 16

End point values	Placebo qw	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Number of subjects analysed	315	106	319
Units: percentage of BSA
least squares mean (standard error)	-22.01 ( 1.158 )	-40.39 ( 1.844 )	-39.58 ( 1.065 )

Dupilumab 300 mg q2w vs Placebo

Statistical analysis description

Comparison groups

Dupilumab 300 mg q2w v Placebo qw

Number of subjects included in analysis

421

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[29]

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

-18.38

Confidence interval

level

95%

sides

2-sided

lower limit

-22.583

upper limit

-14.187

Notes
[29] - Threshold for significance at 0.025 level.

Secondary: Percent Change From Baseline in the SCORing Atopic Dermatitis (SCORAD) Score to Week 16

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End point title

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

End point description

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

End point type

Secondary

End point timeframe

Baseline to Week 16

End point values	Placebo qw	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Number of subjects analysed	315	106	319
Units: percent change
least squares mean (standard error)	-36.2 ( 1.66 )	-63.9 ( 2.52 )	-65.9 ( 1.49 )

Dupilumab 300 mg q2w vs Placebo

Statistical analysis description

Comparison groups

Dupilumab 300 mg q2w v Placebo qw

Number of subjects included in analysis

421

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[30]

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

-27.7

Confidence interval

level

95%

sides

2-sided

lower limit

-33.46

upper limit

-21.9

Notes
[30] - Threshold for significance at 0.025 level.

Secondary: Change From Baseline in Dermatology Life Quality Index (DLQI) to Week 16

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End point title

Change From Baseline in Dermatology Life Quality Index (DLQI) to Week 16

End point description

The DLQI was a 10-item, validated questionnaire used in clinical practice and clinical trials to assess the impact of AD disease symptoms and treatment on quality of life (QOL). The 10 questions assessed QOL over the past week, with an overall scoring of 0 (absent disease) to 30 (severe disease); a high score was indicative of a poor QOL. All efficacy analyses were performed on the FAS, which included all randomized subjects. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).

End point type

Secondary

End point timeframe

Baseline to Week 16

End point values	Placebo qw	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Number of subjects analysed	315	106	319
Units: units on a scale
least squares mean (standard error)	-5.8 ( 0.34 )	-10 ( 0.5 )	-10.7 ( 0.31 )

Dupilumab 300 mg q2w vs Placebo

Statistical analysis description

Comparison groups

Dupilumab 300 mg q2w v Placebo qw

Number of subjects included in analysis

421

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[31]

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

-4.2

Confidence interval

level

95%

sides

2-sided

lower limit

-5.31

upper limit

-3.02

Notes
[31] - Threshold for significance at 0.025 level.

Secondary: Change From Baseline in Patient Oriented Eczema Measure (POEM) to Week 16

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End point title

Change From Baseline in Patient Oriented Eczema Measure (POEM) to Week 16

End point description

The POEM was a 7-item questionnaire that assesses disease symptoms (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) with a scoring system of 0 (absent disease) to 28 (severe disease) (high score indicative of poor quality of life [QOL]). All efficacy analyses were performed on the FAS, which included all randomized subjects. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).

End point type

Secondary

End point timeframe

Baseline to Week 16

End point values	Placebo qw	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Number of subjects analysed	315	106	319
Units: units on a scale
least squares mean (standard error)	-5.3 ( 0.41 )	-12.7 ( 0.64 )	-12.9 ( 0.37 )

Dupilumab 300 mg q2w vs Placebo

Statistical analysis description

Comparison groups

Dupilumab 300 mg q2w v Placebo qw

Number of subjects included in analysis

421

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[32]

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

-7.4

Confidence interval

level

95%

sides

2-sided

lower limit

-8.85

upper limit

-5.93

Notes
[32] - Threshold for significance at 0.025 level.

Secondary: Change From Baseline in Hospital Anxiety Depression Scale (HADS) to Week 16

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End point title

Change From Baseline in Hospital Anxiety Depression Scale (HADS) to Week 16

End point description

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

End point type

Secondary

End point timeframe

Baseline to Week 16

End point values	Placebo qw	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Number of subjects analysed	315	106	319
Units: units on a scale
least squares mean (standard error)	-4 ( 0.37 )	-4.9 ( 0.58 )	-5.4 ( 0.35 )

Dupilumab 300 mg q2w vs Placebo

Statistical analysis description

Comparison groups

Dupilumab 300 mg q2w v Placebo qw

Number of subjects included in analysis

421

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1596 ^[33]

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-2.27

upper limit

0.37

Notes
[33] - Threshold for significance at 0.025 level.

Secondary: Percent Change From Baseline in Total Global Individual Signs Score (GISS) to Week 16

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End point title

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

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

End point type

Secondary

End point timeframe

Baseline to Week 16

End point values	Placebo qw	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Number of subjects analysed	315	106	319
Units: Percent Change
least squares mean (standard error)	-33.3 ( 1.89 )	-55.4 ( 2.69 )	-59.3 ( 1.64 )

No statistical analyses for this end point

Secondary: Proportion of Topical Atopic Dermatitis Medication-Free Days Through Week 52

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End point title

Proportion of Topical Atopic Dermatitis Medication-Free Days Through Week 52

End point description

Proportion of topical AD medication-free days through Week 52 was calculated as the number of days that a subject used neither topical corticosteroid (TCS)/ topical calcineurin inhibitors (TCI) nor system rescue therapy divided by the study days of each period. All efficacy analyses were performed on the FAS, which included all randomized subjects. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).

End point type

Secondary

End point timeframe

Baseline Up to Week 52

End point values	Placebo qw	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Number of subjects analysed	315	106	319
Units: days
arithmetic mean (standard deviation)	10.5 ( 23.68 )	16.6 ( 30.08 )	22.5 ( 33.69 )

No statistical analyses for this end point

Secondary: Percent Change From Baseline in Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score to Week 2

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End point title

Percent Change From Baseline in Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score to Week 2

End point description

Pruritus NRS was an assessment tool that was used to report the intensity of a subject’s pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Subjects were asked the following question: how would a subject 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]). All efficacy analyses were performed on the FAS, which included all randomized subjects. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).

End point type

Secondary

End point timeframe

Baseline to Week 2

End point values	Placebo qw	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Number of subjects analysed	315	106	319
Units: Percent Change
least squares mean (standard error)	-19.7 ( 1.58 )	-27.3 ( 2.67 )	-25.7 ( 1.57 )

No statistical analyses for this end point

Secondary: Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score to Week 52

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End point title

Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score to Week 52

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

End point type

Secondary

End point timeframe

Baseline to Week 52

End point values	Placebo qw	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Number of subjects analysed	264	89	270
Units: Percent Change
least squares mean (standard error)	-60.9 ( 4.29 )	-84.9 ( 6.73 )	-87.8 ( 6.19 )

No statistical analyses for this end point

Secondary: Change From Baseline in Percent Body Surface Area (BSA) Affected by AD to Week 52

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End point title

Change From Baseline in Percent Body Surface Area (BSA) Affected by AD to Week 52

End point description

End point type

Secondary

End point timeframe

Baseline to Week 52

End point values	Placebo qw	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Number of subjects analysed	264	89	270
Units: Percentage of BSA
least squares mean (standard error)	-29.41 ( 1.443 )	-43.75 ( 1.874 )	-43.67 ( 1.143 )

No statistical analyses for this end point

Secondary: Percent Change From Baseline in the SCORing Atopic Dermatitis (SCORAD) Score to Week 52

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End point title

Percent Change From Baseline in the SCORing Atopic Dermatitis (SCORAD) Score to Week 52

End point description

SCORAD was a clinical tool for assessing the severity of AD developed by the European Task Force on Atopic Dermatitis (Severity scoring of atopic dermatitis: the SCORAD index). Consensus Report of the European Task Force on Atopic Dermatitis. Dermatology (Basel) 186 (1): 23–31. 1993. Extent and intensity of eczema as well as subjective signs (insomnia, etc.) were assessed and scored. Total score ranges from 0 (absent disease) to 103 (severe disease). All efficacy analyses were performed on the FAS, which included all randomized subjects. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of subjects analyzed = subjects with available data for this endpoint.

End point type

Secondary

End point timeframe

Baseline to Week 52

End point values	Placebo qw	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Number of subjects analysed	264	89	270
Units: Percent Change
least squares mean (standard error)	-47.3 ( 2.18 )	-69.7 ( 3.06 )	-70.4 ( 1.72 )

No statistical analyses for this end point

Secondary: Percent Change From Baseline in Global Individual Signs Score (GISS) to Week 52

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End point title

Percent Change From Baseline in Global Individual Signs Score (GISS) to Week 52

End point description

End point type

Secondary

End point timeframe

Baseline to Week 52

End point values	Placebo qw	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Number of subjects analysed	264	89	270
Units: Percent Change
least squares mean (standard error)	-40.8 ( 2.72 )	-62.8 ( 3.35 )	-64.4 ( 2.13 )

No statistical analyses for this end point

Secondary: Change From Baseline in Dermatology Life Quality Index (DLQI) to Week 52

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End point title

Change From Baseline in Dermatology Life Quality Index (DLQI) to Week 52

End point description

End point type

Secondary

End point timeframe

Baseline to Week 52

End point values	Placebo qw	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Number of subjects analysed	264	89	270
Units: units on a scale
least squares mean (standard error)	-7.2 ( 0.4 )	-11.4 ( 0.57 )	-11.1 ( 0.36 )

No statistical analyses for this end point

Secondary: Change From Baseline in Patient Oriented Eczema Measure (POEM) to Week 52

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End point title

Change From Baseline in Patient Oriented Eczema Measure (POEM) to Week 52

End point description

End point type

Secondary

End point timeframe

Baseline to Week 52

End point values	Placebo qw	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Number of subjects analysed	264	89	270
Units: units on a scale
least squares mean (standard error)	-7 ( 0.57 )	-14.2 ( 0.78 )	-13.2 ( 0.45 )

No statistical analyses for this end point

Secondary: Change From Baseline in Hospital Anxiety Depression Scale (HADS) to Week 52

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End point title

Change From Baseline in Hospital Anxiety Depression Scale (HADS) to Week 52

End point description

End point type

Secondary

End point timeframe

Baseline to Week 52

End point values	Placebo qw	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Number of subjects analysed	264	89	270
Units: units on a scale
least squares mean (standard error)	-3.8 ( 0.47 )	-5.5 ( 0.71 )	-5.9 ( 0.42 )

No statistical analyses for this end point

Secondary: Number of Flares Through Week 52

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End point title

Number of Flares Through Week 52

End point description

AD flares were defined as worsening of the disease that required escalation/intensification of AD treatment. Number of flares occurred in the subjects from first dose through Week 52 were reported. All safety analysis were performed on safety analysis set (SAF) that included all randomized subjects who received any study drug, and were analyzed as-treated.

End point type

Secondary

End point timeframe

Baseline up to Week 52

End point values	Placebo qw	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Number of subjects analysed	315	110	315
Units: flares
number (not applicable)	216	20	51

No statistical analyses for this end point

Secondary: Number of Serious Treatment Emergent Adverse Events (TEAEs) Leading to Study Drug Discontinuation through Week 52

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End point title

Number of Serious Treatment Emergent Adverse Events (TEAEs) Leading to Study Drug Discontinuation through Week 52

End point description

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

End point type

Secondary

End point timeframe

Baseline up to Week 52

End point values	Placebo qw	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Number of subjects analysed	315	110	315
Units: events
number (not applicable)	28	2	10

No statistical analyses for this end point

Secondary: Percentage of Subjects With Skin Infection TEAEs (excluding Herpetic Infections) from Baseline through Week 52

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End point title

Percentage of Subjects With Skin Infection TEAEs (excluding Herpetic Infections) from Baseline through Week 52

End point description

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

End point type

Secondary

End point timeframe

Baseline up to Week 52

End point values	Placebo qw	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Number of subjects analysed	315	110	315
Units: percentage of subjects
number (not applicable)	17.8	10.9	8.3

No statistical analyses for this end point

Secondary: Number of Skin Infection TEAEs (excluding Herpetic Infections) from Baseline through Week 52

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End point title

Number of Skin Infection TEAEs (excluding Herpetic Infections) from Baseline through Week 52

End point description

End point type

Secondary

End point timeframe

Baseline up to Week 52

End point values	Placebo qw	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Number of subjects analysed	315	110	315
Units: events
number (not applicable)	80	15	29

No statistical analyses for this end point

Secondary: Percentage of Subjects With Skin Infection TEAEs (excluding Herpetic Infections) Requiring Systemic Treatment from Baseline through Week 52

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End point title

Percentage of Subjects With Skin Infection TEAEs (excluding Herpetic Infections) Requiring Systemic Treatment from Baseline through Week 52

End point description

End point type

Secondary

End point timeframe

Baseline up to Week 52

End point values	Placebo qw	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Number of subjects analysed	315	110	315
Units: percentage of subjects
number (not applicable)	9.5	5.5	3.8

No statistical analyses for this end point

Secondary: Number of Skin Infection TEAEs (excluding Herpetic Infections) Requiring Systemic Treatment from Baseline through Week 52

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End point title

Number of Skin Infection TEAEs (excluding Herpetic Infections) Requiring Systemic Treatment from Baseline through Week 52

End point description

End point type

Secondary

End point timeframe

Baseline up to Week 52

End point values	Placebo qw	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Number of subjects analysed	315	110	315
Units: events
number (not applicable)	44	7	13

No statistical analyses for this end point

Other pre-specified: Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score to Week 16

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End point title

Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score to Week 16

End point description

ACQ-5 questionnaire was a validated questionnaire comprising of 5 questions for asthma symptoms: woken at night by symptoms, wake in the mornings with symptoms, limitation of daily activities, shortness of breath, and wheeze. Subjects were asked to rate their asthma symptoms during the previous week on a 7-point scale as 0=no impairment, 6=maximum impairment. ACQ-5 score is the mean of the 5 questions and range between 0 (totally controlled) and 6 (severely uncontrolled) (a higher score indicated lower asthma control). All efficacy analyses were performed on the FAS, which included all randomized subjects. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of subjects analyzed = subjects with ACQ-5 value at baseline. The ACQ-5 questionnaire was administered only to the subjects with a medical history of asthma.

End point type

Other pre-specified

End point timeframe

Baseline to Week 16

End point values	Placebo qw	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Number of subjects analysed	154	48	145
Units: units on a scale
least squares mean (standard error)	-0.12 ( 0.082 )	-0.19 ( 0.113 )	-0.36 ( 0.068 )

No statistical analyses for this end point

Other pre-specified: Change From Baseline in Sinonasal Outcome Test (SNOT-22) Score to Week 16

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End point title

Change From Baseline in Sinonasal Outcome Test (SNOT-22) Score to Week 16

End point description

The SNOT 22 was a validated measure of health related quality of life in sinonasal disease. It is a 22 item questionnaire with each item assigned a score ranging from 0-5. The total score may range from 0 (no disease) -110 (worst disease) (lower scores represent better health related quality of life. All efficacy analyses were performed on the FAS, which included all randomized subjects. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). The SNOT-22 was administered only to subjects with chronic inflammatory conditions of the nasal mucosa and/or paranasal sinuses.

End point type

Other pre-specified

End point timeframe

Baseline to Week 16

End point values	Placebo qw	Dupilumab 300 mg q2w	Dupilumab 300 mg qw
Number of subjects analysed	99	45	99
Units: units on a scale
least squares mean (standard error)	-4.77 ( 1.903 )	-6.38 ( 2.445 )	-10.39 ( 1.63 )

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Time-frame was 'On treatment (Week 52) period' defined time from administration of first dose of study drug to study completion date of Week 52 visit (365 days starting from first dose of study drug if the date of Week 52 visit was unavailable).

Adverse event reporting additional description

All Adverse Events were collected from signature of informed consent form up to study completion date of the Week 52 visit regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment-emergent that is AEs developed/worsened and deaths that occurred during 'On treatment (Week 52) period'.SAF population.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

18.0

Reporting group title

Placebo qw

Reporting 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 51.

Reporting group title

Dupilumab 300 mg qw

Reporting group description

Reporting group title

Dupilumab 300 mg q2w

Reporting group description

Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with a single 300 mg injection of Dupilumab q2w from Week 1 to Week 51. During weeks in which Dupilumab was not administered, subjects received placebo. Four subjects received fewer injections of Dupilumab 300 mg in Dupilumab 300 qw arm, were analyzed in Dupilumab 300 mg q2w arm.

Serious adverse events	Placebo qw	Dupilumab 300 mg qw	Dupilumab 300 mg q2w
Total subjects affected by serious adverse events
subjects affected / exposed	20 / 315 (6.35%)	12 / 315 (3.81%)	4 / 110 (3.64%)
number of deaths (all causes)	0	1	0
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cervix carcinoma
subjects affected / exposed	1 / 315 (0.32%)	0 / 315 (0.00%)	0 / 110 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Penile squamous cell carcinoma
subjects affected / exposed	1 / 315 (0.32%)	0 / 315 (0.00%)	0 / 110 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Squamous cell carcinoma
subjects affected / exposed	1 / 315 (0.32%)	1 / 315 (0.32%)	0 / 110 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Squamous cell carcinoma of skin
subjects affected / exposed	0 / 315 (0.00%)	1 / 315 (0.32%)	1 / 110 (0.91%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Squamous cell carcinoma of the tongue
subjects affected / exposed	0 / 315 (0.00%)	1 / 315 (0.32%)	0 / 110 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Uterine leiomyoma
subjects affected / exposed	1 / 315 (0.32%)	0 / 315 (0.00%)	0 / 110 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vascular disorders
Hypertension
subjects affected / exposed	1 / 315 (0.32%)	0 / 315 (0.00%)	0 / 110 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Venous thrombosis limb
subjects affected / exposed	1 / 315 (0.32%)	0 / 315 (0.00%)	0 / 110 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Soft tissue inflammation
subjects affected / exposed	1 / 315 (0.32%)	0 / 315 (0.00%)	0 / 110 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Anxiety
subjects affected / exposed	0 / 315 (0.00%)	0 / 315 (0.00%)	1 / 110 (0.91%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Investigations
Liver function test abnormal
subjects affected / exposed	1 / 315 (0.32%)	0 / 315 (0.00%)	0 / 110 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Clavicle fracture
subjects affected / exposed	1 / 315 (0.32%)	0 / 315 (0.00%)	0 / 110 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Concussion
subjects affected / exposed	1 / 315 (0.32%)	0 / 315 (0.00%)	0 / 110 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Contusion
subjects affected / exposed	1 / 315 (0.32%)	0 / 315 (0.00%)	0 / 110 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ligament rupture
subjects affected / exposed	1 / 315 (0.32%)	0 / 315 (0.00%)	0 / 110 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Limb traumatic amputation
subjects affected / exposed	1 / 315 (0.32%)	0 / 315 (0.00%)	0 / 110 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Road traffic accident
subjects affected / exposed	0 / 315 (0.00%)	1 / 315 (0.32%)	0 / 110 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Spinal compression fracture
subjects affected / exposed	0 / 315 (0.00%)	1 / 315 (0.32%)	0 / 110 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac disorders
Acute myocardial infarction
subjects affected / exposed	1 / 315 (0.32%)	0 / 315 (0.00%)	0 / 110 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nervous system disorders
Carotid artery stenosis
subjects affected / exposed	1 / 315 (0.32%)	0 / 315 (0.00%)	0 / 110 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cerebral infarction
subjects affected / exposed	0 / 315 (0.00%)	0 / 315 (0.00%)	1 / 110 (0.91%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cerebrovascular accident
subjects affected / exposed	1 / 315 (0.32%)	0 / 315 (0.00%)	0 / 110 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Eye disorders
Cataract
subjects affected / exposed	1 / 315 (0.32%)	0 / 315 (0.00%)	0 / 110 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cystoid macular oedema
subjects affected / exposed	0 / 315 (0.00%)	1 / 315 (0.32%)	0 / 110 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Glaucoma
subjects affected / exposed	1 / 315 (0.32%)	0 / 315 (0.00%)	0 / 110 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Pancreatitis
subjects affected / exposed	1 / 315 (0.32%)	0 / 315 (0.00%)	0 / 110 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholelithiasis
subjects affected / exposed	0 / 315 (0.00%)	1 / 315 (0.32%)	0 / 110 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Dermatitis atopic
subjects affected / exposed	1 / 315 (0.32%)	1 / 315 (0.32%)	1 / 110 (0.91%)
occurrences causally related to treatment / all	0 / 1	0 / 2	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Rash maculo-papular
subjects affected / exposed	0 / 315 (0.00%)	1 / 315 (0.32%)	0 / 110 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Urticaria
subjects affected / exposed	1 / 315 (0.32%)	0 / 315 (0.00%)	0 / 110 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Pseudarthrosis
subjects affected / exposed	1 / 315 (0.32%)	0 / 315 (0.00%)	0 / 110 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Osteoarthritis
subjects affected / exposed	0 / 315 (0.00%)	1 / 315 (0.32%)	0 / 110 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Spondylolisthesis
subjects affected / exposed	0 / 315 (0.00%)	1 / 315 (0.32%)	0 / 110 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infections and infestations
Abdominal wall abscess
subjects affected / exposed	1 / 315 (0.32%)	0 / 315 (0.00%)	0 / 110 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Appendicitis
subjects affected / exposed	0 / 315 (0.00%)	1 / 315 (0.32%)	0 / 110 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bronchitis
subjects affected / exposed	1 / 315 (0.32%)	0 / 315 (0.00%)	0 / 110 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Eczema herpeticum
subjects affected / exposed	1 / 315 (0.32%)	0 / 315 (0.00%)	0 / 110 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	1 / 315 (0.32%)	0 / 315 (0.00%)	0 / 110 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Superinfection bacterial
subjects affected / exposed	0 / 315 (0.00%)	0 / 315 (0.00%)	1 / 110 (0.91%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Placebo qw	Dupilumab 300 mg qw	Dupilumab 300 mg q2w
Total subjects affected by non serious adverse events
subjects affected / exposed	216 / 315 (68.57%)	228 / 315 (72.38%)	74 / 110 (67.27%)
Nervous system disorders
Headache
subjects affected / exposed	19 / 315 (6.03%)	24 / 315 (7.62%)	5 / 110 (4.55%)
occurrences all number	30	48	5
General disorders and administration site conditions
Injection site reaction
subjects affected / exposed	24 / 315 (7.62%)	60 / 315 (19.05%)	16 / 110 (14.55%)
occurrences all number	102	224	34
Eye disorders
Blepharitis
subjects affected / exposed	3 / 315 (0.95%)	11 / 315 (3.49%)	6 / 110 (5.45%)
occurrences all number	3	14	7
Conjunctivitis allergic
subjects affected / exposed	19 / 315 (6.03%)	54 / 315 (17.14%)	13 / 110 (11.82%)
occurrences all number	22	74	20
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	19 / 315 (6.03%)	7 / 315 (2.22%)	5 / 110 (4.55%)
occurrences all number	23	7	5
Skin and subcutaneous tissue disorders
Dermatitis atopic
subjects affected / exposed	161 / 315 (51.11%)	91 / 315 (28.89%)	40 / 110 (36.36%)
occurrences all number	278	133	52
Infections and infestations
Influenza
subjects affected / exposed	17 / 315 (5.40%)	9 / 315 (2.86%)	4 / 110 (3.64%)
occurrences all number	25	13	4
Nasopharyngitis
subjects affected / exposed	62 / 315 (19.68%)	63 / 315 (20.00%)	26 / 110 (23.64%)
occurrences all number	89	88	40
Oral herpes
subjects affected / exposed	10 / 315 (3.17%)	17 / 315 (5.40%)	4 / 110 (3.64%)
occurrences all number	15	31	9
Sinusitis
subjects affected / exposed	9 / 315 (2.86%)	18 / 315 (5.71%)	2 / 110 (1.82%)
occurrences all number	11	20	2
Upper respiratory tract infection
subjects affected / exposed	34 / 315 (10.79%)	46 / 315 (14.60%)	11 / 110 (10.00%)
occurrences all number	52	78	21
Urinary tract infection
subjects affected / exposed	14 / 315 (4.44%)	16 / 315 (5.08%)	2 / 110 (1.82%)
occurrences all number	16	22	3

More information

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Were there any global substantial amendments to the protocol? Yes

07 Jul 2014

Modification of study design: Dupilumab to be administered concomitantly with TCS; Incorporated the doses selected for phase 3 studies based on results of an interim analysis of a phase 2b dose-ranging study. The doses selected were 300 mg qw and 300 mg q2w; Increased the number of subjects to 700 and randomized in a 3:1:3 ratio to Dupilumab 300 mg qw, Dupilumab 300 mg q2w and matching placebo; Changed time of the assessment of the efficacy endpoints to week 16 from week 12; Clarified that different health authorities requested different primary endpoints although the study was to be conducted the same in all countries; Modified secondary endpoints and added exploratory endpoints. Modified Inclusion/Exclusion Criteria; Expanded section on prohibited medications; Modified section on study drug continuation rules; Modified assessments (Added Patient Global Assessment of Treatment; added Atopic keratoconjunctivitis [AKC], ACQ-5 and SNOT-22; added a second question for subject assessment of pruritus; added Hemoglobin A1c [HbA1c] to study assessments; changed frequency and timing of some assessments).

22 Oct 2014

Incorporated changes concerning the concomitant use of dupilumab and systemic corticosteroids that had already been made in the US-specific protocol (for global [R668-AD-1224.01] and UK-specific [R668-AD-1224.01GB] protocols only); Added positive HBcAb as an exclusion; Updated prohibited medications; Removed “treatment with a live (attenuated) vaccine” from the list of events that would lead to temporary discontinuation of study drug; Added “rescue treatment prior to week 2” to the list of events that would lead to permanent discontinuation of study drug; Modified the AKC assessment schedule; Added % BSA to the assessments to be completed prior to escalation of TCS treatment; Specified that fasting was recommended prior to obtaining laboratory samples; Clarified the description of IGA; Clarified subject population for SNOT-22 assessment; -Included an assessment of vital signs at visit 3; Changed reporting time for AEs leading to study withdrawal; Clarified reporting requirements for pregnancy or a complication of pregnancy in a female partner of a male subject; Modified statistics section for greater clarity and to expand on MMRM; Updated the cut-off date for earlier studies.

24 Feb 2015

Added text to indicate that for background treatment with moisturizers (emollients), to allow adequate assessment of skin dryness, moisturizers should not be applied on the area(s) of non-lesional skin designated for such assessments for at least 8 hours before each clinic visit; Changed the terminology of “European Medicines Agency (EMA) reference market” to “European Union (EU) reference market”, and “reference market submissions” to “reference market countries”; Made revisions to indicate that Japan had been added to the countries that would use the co-primary endpoints; Separated the secondary endpoints into 2 parts: Key Secondary Endpoints and Other Secondary Endpoints; Moved some of the secondary endpoint to the “key secondary endpoints” section; Added some endpoints in the “other secondary endpoints” section; Moved the following endpoint to the end of “other secondary endpoints”: “incidence of skin-infection TEAEs requiring systemic treatment from baseline through Week 56; Revised the definition for the FAS and added per protocol set (PPS) for efficacy analysis; Added description of methods for missing data imputation and data analysis for continuous secondary endpoints to be used in US and US reference market countries; Added an inclusion criterion requiring a subject to have a baseline Pruritus NRS average score for maximum itch intensity ≥3 to be eligible to enroll in the study; Changed one of recommended super high potency TCS from “betamethasone dipropionate 0.05% cream” to “betamethasone dipropionate 0.05% optimized ointment” to be consistent with the study reference manual, and made revision to clarify that the standardized low or median potency TCS daily regimen was once daily; Added a statement in the “Rescue Medications” section for clarity and to be consistent with the section of Reasons for Permanent Discontinuation of study drug; Clarified that ECGs should be performed before blood was drawn during visits requiring blood draws.

02 Oct 2015

Removed the requirement that no subjects would receive study drug from both vials and prefilled syringes; Indicated that the primary analysis, which would include the Week 16 primary and key secondary endpoints for all randomized subjects, would also contain Week 52 efficacy endpoints, which at a minimum would include all subjects randomized by 27 April 2015 and whose pertinent data (i.e. data required for Week 52 analyses) had been collected and validated; Modified and reorder key secondary efficacy endpoints, other secondary endpoints, and exploratory endpoints to match the SAP; Modified the statement regarding subjects with anti-drug antibody (ADA) titer of ≥240 at their last study visit returning to the clinic for additional samples.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A Randomized, Double-Blind, Placebo-Controlled Study to Demonstrate the Efficacy and Long-Term Safety of Dupilumab in Adult Patients With Moderate-to-Severe Atopic Dermatitis

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Subjects With Eczema Area and Severity Index-75 (EASI-75) (≥75% Improvement From Baseline) at Week 16

Primary: Percentage of Subjects With Eczema Area and Severity Index-75 (EASI-75) (≥75% Improvement From Baseline) at Week 16

Primary: Percentage of Subjects With Investigator’s Global Assessment (IGA) Score of “0” or “1” and Reduction From Baseline of ≥2 Points at Week 16

Primary: Percentage of Subjects With Investigator’s Global Assessment (IGA) Score of “0” or “1” and Reduction From Baseline of ≥2 Points at Week 16

Secondary: Percentage of Subjects With Improvement (Reduction ≥4 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 16

Secondary: Percentage of Subjects With Improvement (Reduction ≥4 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 16

Secondary: Percentage of Subjects With Improvement (Reduction ≥3 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 16

Secondary: Percentage of Subjects With Improvement (Reduction ≥3 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 16

Secondary: Percentage of Subjects With Investigator’s Global Assessment (IGA) Score of “0” or “1” and Reduction From Baseline of ≥2 Points at Week 52

Secondary: Percentage of Subjects With Investigator’s Global Assessment (IGA) Score of “0” or “1” and Reduction From Baseline of ≥2 Points at Week 52

Secondary: Percentage of Subjects With Eczema Area and Severity Index-75 (EASI-75) (≥75% Improvement From Baseline) at Week 52

Secondary: Percentage of Subjects With Eczema Area and Severity Index-75 (EASI-75) (≥75% Improvement From Baseline) at Week 52

Secondary: Percent Change From Baseline in Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score to Week 16

Secondary: Percent Change From Baseline in Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score to Week 16

Secondary: Percentage of Subjects With Improvement (Reduction ≥4 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 52

Secondary: Percentage of Subjects With Improvement (Reduction ≥4 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 52

Secondary: Percentage of Subjects With Improvement (Reduction ≥3 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 52

Secondary: Percentage of Subjects With Improvement (Reduction ≥3 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 52

Secondary: Percentage of Subjects With Improvement (Reduction ≥4 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 24

Secondary: Percentage of Subjects With Improvement (Reduction ≥4 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 24

Secondary: Percentage of Subjects With Improvement (Reduction ≥4 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 4

Secondary: Percentage of Subjects With Improvement (Reduction ≥4 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 4

Secondary: Percentage of Subjects With Improvement (Reduction ≥4 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 2

Secondary: Percentage of Subjects With Improvement (Reduction ≥4 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 2

Secondary: Change From Baseline in Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score to Week 16

Secondary: Change From Baseline in Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score to Week 16

Secondary: Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score to Week 16

Secondary: Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score to Week 16

Secondary: Change From Baseline in Percent Body Surface Area (BSA) Affected by AD to Week 16

Secondary: Change From Baseline in Percent Body Surface Area (BSA) Affected by AD to Week 16

Secondary: Percent Change From Baseline in the SCORing Atopic Dermatitis (SCORAD) Score to Week 16

Secondary: Percent Change From Baseline in the SCORing Atopic Dermatitis (SCORAD) Score to Week 16

Secondary: Change From Baseline in Dermatology Life Quality Index (DLQI) to Week 16

Secondary: Change From Baseline in Dermatology Life Quality Index (DLQI) to Week 16

Secondary: Change From Baseline in Patient Oriented Eczema Measure (POEM) to Week 16

Secondary: Change From Baseline in Patient Oriented Eczema Measure (POEM) to Week 16

Secondary: Change From Baseline in Hospital Anxiety Depression Scale (HADS) to Week 16

Secondary: Change From Baseline in Hospital Anxiety Depression Scale (HADS) to Week 16

Secondary: Percent Change From Baseline in Total Global Individual Signs Score (GISS) to Week 16

Secondary: Percent Change From Baseline in Total Global Individual Signs Score (GISS) to Week 16

Secondary: Proportion of Topical Atopic Dermatitis Medication-Free Days Through Week 52

Secondary: Proportion of Topical Atopic Dermatitis Medication-Free Days Through Week 52

Secondary: Percent Change From Baseline in Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score to Week 2

Secondary: Percent Change From Baseline in Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score to Week 2

Secondary: Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score to Week 52

Secondary: Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score to Week 52

Secondary: Change From Baseline in Percent Body Surface Area (BSA) Affected by AD to Week 52

Secondary: Change From Baseline in Percent Body Surface Area (BSA) Affected by AD to Week 52

Secondary: Percent Change From Baseline in the SCORing Atopic Dermatitis (SCORAD) Score to Week 52

Secondary: Percent Change From Baseline in the SCORing Atopic Dermatitis (SCORAD) Score to Week 52

Secondary: Percent Change From Baseline in Global Individual Signs Score (GISS) to Week 52

Secondary: Percent Change From Baseline in Global Individual Signs Score (GISS) to Week 52

Secondary: Change From Baseline in Dermatology Life Quality Index (DLQI) to Week 52

Secondary: Change From Baseline in Dermatology Life Quality Index (DLQI) to Week 52

Secondary: Change From Baseline in Patient Oriented Eczema Measure (POEM) to Week 52

Secondary: Change From Baseline in Patient Oriented Eczema Measure (POEM) to Week 52

Secondary: Change From Baseline in Hospital Anxiety Depression Scale (HADS) to Week 52

Secondary: Change From Baseline in Hospital Anxiety Depression Scale (HADS) to Week 52

Secondary: Number of Flares Through Week 52

Secondary: Number of Flares Through Week 52

Secondary: Number of Serious Treatment Emergent Adverse Events (TEAEs) Leading to Study Drug Discontinuation through Week 52

Secondary: Number of Serious Treatment Emergent Adverse Events (TEAEs) Leading to Study Drug Discontinuation through Week 52

Secondary: Percentage of Subjects With Skin Infection TEAEs (excluding Herpetic Infections) from Baseline through Week 52

Secondary: Percentage of Subjects With Skin Infection TEAEs (excluding Herpetic Infections) from Baseline through Week 52

Secondary: Number of Skin Infection TEAEs (excluding Herpetic Infections) from Baseline through Week 52

Secondary: Number of Skin Infection TEAEs (excluding Herpetic Infections) from Baseline through Week 52

Secondary: Percentage of Subjects With Skin Infection TEAEs (excluding Herpetic Infections) Requiring Systemic Treatment from Baseline through Week 52

Secondary: Percentage of Subjects With Skin Infection TEAEs (excluding Herpetic Infections) Requiring Systemic Treatment from Baseline through Week 52

Secondary: Number of Skin Infection TEAEs (excluding Herpetic Infections) Requiring Systemic Treatment from Baseline through Week 52

Secondary: Number of Skin Infection TEAEs (excluding Herpetic Infections) Requiring Systemic Treatment from Baseline through Week 52

Clinical Trial Results:
A Randomized, Double-Blind, Placebo-Controlled Study to Demonstrate the Efficacy and Long-Term Safety of Dupilumab in Adult Patients With Moderate-to-Severe Atopic Dermatitis