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Clinical Trial Results:
A Randomized, Double-Blind, Placebo-Controlled Study to Investigate The Efficacy and Safety of Dupilumab Administered Concomitantly With Topical Corticosteroids in Patients, ≥ 6 Years to < 12 Years of Age, With Severe Atopic Dermatitis

Summary
EudraCT number	2016-004997-16
Trial protocol	CZ DE GB PL
Global end of trial date	28 Jun 2019

Results information
Results version number	v2
This version publication date	20 Jun 2020
First version publication date	26 Mar 2020
Other versions	v1 , v3
Version creation reason

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-1652

ISRCTN number

US NCT number

NCT03345914

WHO universal trial number (UTN)

Other trial identifiers

IND Number: 107969

Sponsor organisation name

Regeneron Pharmaceuticals, Inc.

Sponsor organisation address

777 Old Saw Mill River Road, Tarrytown, United States, 10591

Public contact

Clinical Trial Administrator, Regeneron Pharmaceuticals, Inc., clinicaltrials@regeneron.com

Scientific contact

Clinical Trial Administrator, Regeneron Pharmaceuticals, Inc., clinicaltrials@regeneron.com

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

Yes

EMA paediatric investigation plan number(s)

EMEA-001501-PIP01-13

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?

Yes

Analysis stage

Final

Date of interim/final analysis

28 Jun 2019

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

28 Jun 2019

Was the trial ended prematurely?

Main objective of the trial

The primary objective of this study was to assess the efficacy of dupilumab administered concomitantly with topical corticosteroids (TCS) in subjects greater than or equal to (≥) 6 years to less than (<) 12 years of age with severe atopic dermatitis (AD).

Protection of trial subjects

This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with the International Council for Harmonisation (ICH) guidelines for Good Clinical Practice (GCP) and applicable regulatory requirements.

Background therapy

Evidence for comparator

Actual start date of recruitment

17 Nov 2017

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Poland: 93

Country: Number of subjects enrolled

United Kingdom: 17

Country: Number of subjects enrolled

Czech Republic: 10

Country: Number of subjects enrolled

Germany: 10

Country: Number of subjects enrolled

Canada: 16

Country: Number of subjects enrolled

United States: 221

Worldwide total number of subjects

367

EEA total number of subjects

130

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)

367

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

A total of 474 subjects were screened for study eligibility at multiple sites in the United States and Europe. Screen failure was mostly due to inclusion/exclusion criteria not met and “other” reasons. The majority of subjects (221/367) were enrolled at study sites in the United States.

Screening details

A total of 474 subjects were screened, of which 367 subjects randomized in 1:1:1 ratio to 1 of 3 treatment groups. 5 randomized subjects were not treated (2 in the placebo + TCS group and 3 in the combined dupilumab + TCS group). Subjects randomized to receive Dupilumab 100 mg or 200 mg Q2W + TCS, Dupilumab 300 mg Q4W + TCS or matching placebo.

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, Monitor, Data analyst, Carer, Assessor

Are arms mutually exclusive

Yes

Placebo + TCS

Arm description

Subjects received matching placebo every 2 weeks (Q2W) or every 4 weeks (Q4W) during the 16-week double-blind treatment phase. Matching placebo was administered concomitantly with topical corticosteroids (TCS), including doubling the amount of placebo on Day 1 to match the loading dose.

Arm type

Experimental

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Subjects received subcutaneous injection of the study drug on different quadrants of the abdomen avoiding navel and waist areas), upper thighs, and upper arms so that the same site was not injected for 2 consecutive administrations.

Dupilumab 300 mg Q4W + TCS

Arm description

Subjects received subcutaneous injections of 600 milligrams (mg) loading dose on Day 1, then 300 mg of Dupilumab every 4 weeks (Q4W) from Week 4 to Week 12. Topical corticosteroids (TCS) were administered concomitantly during the 16-week double-blind treatment phase.

Arm type

Experimental

Investigational medicinal product name

Dupilumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Subjects received subcutaneous injection of the study drug on different quadrants of the abdomen (avoiding navel and waist areas), upper thighs, and upper arms so that the same site was not injected for 2 consecutive administrations.

Dupilumab 100 mg or 200 mg Q2W + TCS

Arm description

Subjects received subcutaneous injections of 100 milligrams (mg) or 200 mg of Dupilumab every 2 weeks (Q2W). For 100 mg Q2W treatment group, subjects received a 200 mg loading dose on Day 1, then 100 mg Q2W from Week 2 to Week 14. For 200 mg Q2W treatment group, subjects received a 400 mg loading dose on Day 1, then 200 mg Q2W from Week 2 to Week 14. Topical corticosteroids (TCS) were administered concomitantly in all groups during the 16-week double-blind treatment phase.

Arm type

Experimental

Investigational medicinal product name

Dupilumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Number of subjects in period 1	Placebo + TCS	Dupilumab 300 mg Q4W + TCS	Dupilumab 100 mg or 200 mg Q2W + TCS
Started	123	122	122
Completed Week 16 Study Treatment	114	118	119
Completed Week 28 End of Study	0	0	0
Completed	0	0	0
Not completed	123	122	122
Physician decision	-	1	1
Not Specified	1	1	1
Ongoing	-	-	1
Transition to another study at week 16	80	86	78
Transition to another study during follow-up	37	33	39
Withdrawal by subject	5	1	2

Baseline characteristics

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Reporting group title

Placebo + TCS

Reporting group description

Reporting group title

Dupilumab 300 mg Q4W + TCS

Reporting group description

Reporting group title

Dupilumab 100 mg or 200 mg Q2W + TCS

Reporting group description

Reporting group values	Placebo + TCS	Dupilumab 300 mg Q4W + TCS	Dupilumab 100 mg or 200 mg Q2W + TCS	Total
Number of subjects	123	122	122	367
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	8.3 ± 1.76	8.5 ± 1.74	8.5 ± 1.68	-
Gender categorical
Units: Subjects
Female	62	65	57	184
Male	61	57	65	183
Ethnicity
Units: Subjects
Not Hispanic or Latino	110	106	106	322
Hispanic or Latino	13	16	16	45
Race
Units: Subjects
White	77	89	88	254
Black or African American	23	19	20	62
Asian	13	5	10	28
Other	9	8	2	19
Not Reported/Missing	1	1	2	4
Eczema Area and Severity Index (EASI) Score
The EASI assesses severity and extent of atopic dermatitis. Scores range from 0-72. Four AD disease characteristics (erythema, thickness, scratching, and lichenification) are assessed for severity on a scale of “0” (absent) through “3” (severe). Area of involvement assessed as a percentage by body area of head, trunk, upper limbs and lower limbs and converted to a score of 0 to 6.
Units: Score on a Scale
arithmetic mean (standard deviation)	39.0 ± 12.01	37.4 ± 12.45	37.3 ± 10.86	-
Investigator’s Global Assessment (IGA) Score
IGA is an assessment instrument used in clinical studies to rate the severity of AD globally, based on a 5-point scale ranging from 0 (clear) to 4 (severe).
Units: Score on a Scale
arithmetic mean (standard deviation)	4.0 ± 0.00	4.0 ± 0.09	4.0 ± 0.00	-
Weekly Average of Daily Worst Itch Score
The worst itch scale is a simple assessment tool that subjects will use to report the intensity of their pruritus (itch). This is an 11-point scale (0 to 10) in which 0 indicates no itching while 10 indicates worst itching possible. Subjects will be asked to answer 2 questions daily throughout the entire study (screening period, treatment period, and follow-up period). The daily worst itch score will be calculated as the worse of the scores for the 2 questions.
Units: Score on a Scale
arithmetic mean (standard deviation)	7.7 ± 1.54	7.8 ± 1.58	7.8 ± 1.52	-
Body Surface Area (BSA) of Atopic Dermatitis
BSA affected by AD will be assessed for each section of the body using the rule of nines (the possible highest score for each region is: head and neck [9%], anterior trunk [18%], back [18%], upper limbs [18%], lower limbs [36%], and genitals [1%]) and will be reported as a percentage of all major body sections combined. The proportion assigned to different body regions is different in younger children as compared to older children (head and neck area is assigned a higher proportion in younger children as compared to older children).
Units: Percentage of BSA
arithmetic mean (standard deviation)	60.2 ± 21.46	54.8 ± 21.58	57.8 ± 20.04	-
SCORing Atopic Dermatitis (SCORAD) Score
SCORAD is used to assess the extent and severity of AD. Extent and severity of eczema as well as subjective symptoms (insomnia, etc) were assessed and scored. SCORAD total score range is from 0 (absent disease) to 103 (severe disease).
Units: Score on a Scale
arithmetic mean (standard deviation)	72.9 ± 12.01	75.6 ± 11.71	72.3 ± 10.83	-
Patient Oriented Eczema Measure (POEM)
POEM is a 7-item, validated questionnaire used to assess disease symptoms in children and adults. The format is a response to 7 items (dryness, itching, flaking, cracking, sleep loss, bleeding, and weeping) based on frequency of these disease symptoms during the past week (ie, 0 = no days, 1 = 1 to 2 days, 2 = 3 to 4 days, 3 = 5 to 6 days, and 4 = all days) with a scoring system of 0 to 28; the total score reflects disease-related morbidity.
Units: Score on a Scale
arithmetic mean (standard deviation)	20.7 ± 5.48	21.3 ± 5.51	20.5 ± 5.50	-
Children's Dermatology Life Quality Index (CDLQI) Total Score
CDLQI is a validated 10 question tool to measure the impact of skin disease on the quality of life (QOL) in children by assessing how much the skin problem has affected the subject over the past week. Nine questions are scored as follows: Very much = 3, Quite a lot = 2, Only a little = 1, Not at all or unanswered = 0. Question 7 has an added possible response, which is scored as 3. CDLQI equals the sum of the score of each question (maximum = 30, minimum = 0). Higher the score, the greater the impact on QOL. It can also be expressed as a percentage of the maximum possible score of 30.
Units: Score on a Scale
arithmetic mean (standard deviation)	14.6 ± 7.41	16.2 ± 7.85	14.5 ± 6.78	-
Dermatitis Family Index (DFI)
DFI is a 10-item questionnaire with items inquiring about housework, food preparation, sleep, family leisure activity, shopping, expenditure, tiredness, emotional distress, relationships and the impact of helping with treatment on the primary caregiver’s life. The DFI questions are scored on a four-point Likert scale ranging from 0 to 3, so that the total DFI score ranges from 0 to 30. Timeframe of reference is the past week. A higher DFI score indicates greater impairment in family QOL as affected by atopic dermatitis.
Units: Score on a Scale
arithmetic mean (standard deviation)	15.0 ± 7.54	16.9 ± 8.65	14.9 ± 7.05	-
Patient Reported Outcomes Measurements Information Systems (PROMIS) Anxiety Scale
The PROMIS Anxiety instrument measures self-reported fear (fearfulness, panic), anxious misery (worry, dread), hyperarousal (tension, nervousness, restlessness), & somatic symptoms related to arousal (racing heart, dizziness). Each question has five response options ranging in value from 1 to 5 (1 = Never, 2 = Almost never, 3 = Sometimes, 4 = Often, 5 = Almost Always). For an 8-item form, the lowest possible total raw score is 8; the highest possible total raw score is 40. For a 6-item form, the lowest possible total raw score is 6; the highest possible total raw score is 30.
Units: Score on a Scale
arithmetic mean (standard deviation)	57.3 ± 11.62	59.8 ± 13.66	58.6 ± 11.32	-
Patient Reported Outcomes Measurements Information Systems (PROMIS) Depression Scale
PROMIS Depression instrument assesses: self-reported negative mood (sadness, guilt), views of self (self-criticism, worthlessness) & social cognition (loneliness, interpersonal alienation), and decreased positive affect & engagement (loss of interest, meaning & purpose). Each question has 5 response options ranging in value from 1 to 5 (1=Never, 2=Almost never, 3=Sometimes, 4=Often, 5= Almost Always). For an 8-item form, lowest possible total raw score is 8; highest possible total raw score is 40. For a 6-item form, lowest possible total raw score is 6; highest possible total raw score is 30.
Units: Score on a Scale
arithmetic mean (standard deviation)	55.0 ± 12.05	58.1 ± 12.77	56.3 ± 11.22	-

End points

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Reporting group title

Placebo + TCS

Reporting group description

Reporting group title

Dupilumab 300 mg Q4W + TCS

Reporting group description

Reporting group title

Dupilumab 100 mg or 200 mg Q2W + TCS

Reporting group description

Primary: Percentage of Subjects with Investigator’s Global Assessment (IGA) 0 or 1 at Week 16

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End point title

Percentage of Subjects with Investigator’s Global Assessment (IGA) 0 or 1 at Week 16

End point description

The IGA was an assessment instrument used in clinical studies to rate the severity of AD globally, based on a 5-point scale ranging from 0 (clear) to 4 (severe). The full analysis set (FAS) included all randomized subjects. Efficacy analyses were based on the treatment allocated at randomization (as randomized). Values after first rescue treatment used were set to missing. Subjects with missing score at Week 16 were considered as a non-responder.

End point type

Primary

End point timeframe

Week 16

End point values	Placebo + TCS	Dupilumab 300 mg Q4W + TCS	Dupilumab 100 mg or 200 mg Q2W + TCS
Number of subjects analysed	123	122	122
Units: Percentage of Subjects
number (not applicable)	11.4	32.8	29.5

Dupilumab 100 mg/200 mg Q2W + TCS vs Placebo + TCS

Statistical analysis description

A 2-sided hierarchical testing procedure was used for the primary and secondary endpoints in a pre-specified order. Testing was then performed sequentially in the order the endpoints are reported. The hierarchical testing sequence continued only when the previous endpoint was statistically significant at 0.05 level.

Comparison groups

Placebo + TCS v Dupilumab 100 mg or 200 mg Q2W + TCS

Number of subjects included in analysis

245

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0004 ^[1]

Method

Cochran-Mantel-Haenszel

Parameter type

Percentage difference

Point estimate

18.1

Confidence interval

level

95%

sides

2-sided

lower limit

8.28

upper limit

27.97

Notes
[1] - The Cochran-Mantel-Haenszel (CMH) test adjusted by randomization strata (baseline weight group (< 30 kilograms (kg) or ≥ 30 kg) and region (North America or Europe) was used for the analysis of percentage of subjects with IGA 0 or 1 at Week 16.

Dupilumab 300 mg Q4W + TCS vs Placebo + TCS

Statistical analysis description

Comparison groups

Placebo + TCS v Dupilumab 300 mg Q4W + TCS

Number of subjects included in analysis

245

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[2]

Method

Cochran-Mantel-Haenszel

Parameter type

Percentage difference

Point estimate

21.4

Confidence interval

level

95%

sides

2-sided

lower limit

11.36

upper limit

31.45

Notes
[2] - The Cochran-Mantel-Haenszel (CMH) test adjusted by randomization strata (baseline weight group (< 30 kg or ≥ 30 kg) and region (North America or Europe) was used for the analysis of percentage of subjects with IGA 0 or 1 at Week 16.

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

End point description

The EASI assesses severity and extent of atopic dermatitis (AD). Scores range from 0-72. Four AD disease characteristics (erythema, thickness, scratching, and lichenification) were assessed for severity on a scale of “0” (absent) through “3” (severe). Area of involvement assessed as a percentage by body area of head, trunk, upper limbs, and lower limbs, and converted to a score of 0 to 6. The FAS included all randomized subjects. Efficacy analyses were based on the treatment allocated at randomization (as randomized). Values after first rescue treatment used were set to missing. Subjects with missing score at week 16 were considered as a non-responder.

End point type

Primary

End point timeframe

Week 16

End point values	Placebo + TCS	Dupilumab 300 mg Q4W + TCS	Dupilumab 100 mg or 200 mg Q2W + TCS
Number of subjects analysed	123	122	122
Units: Percentage of Subjects
number (not applicable)	26.8	69.7	67.2

Dupilumab 100 mg/200 mg Q2W + TCS vs Placebo + TCS

Statistical analysis description

Comparison groups

Placebo + TCS v Dupilumab 100 mg or 200 mg Q2W + TCS

Number of subjects included in analysis

245

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[3]

Method

Cochran-Mantel-Haenszel

Parameter type

Percentage difference

Point estimate

40.4

Confidence interval

level

95%

sides

2-sided

lower limit

28.95

upper limit

51.82

Notes
[3] - The Cochran-Mantel-Haenszel (CMH) test adjusted by randomization strata (baseline weight group (< 30 kg or ≥ 30 kg) and region (North America or Europe) was used for the analysis of percentage of subjects with EASI-75 at Week 16.

Dupilumab 300 mg Q4W + TCS vs Placebo + TCS

Statistical analysis description

Comparison groups

Placebo + TCS v Dupilumab 300 mg Q4W + TCS

Number of subjects included in analysis

245

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[4]

Method

Cochran-Mantel-Haenszel

Parameter type

Percentage difference

Point estimate

42.8

Confidence interval

level

95%

sides

2-sided

lower limit

31.54

upper limit

54.15

Notes
[4] - The Cochran-Mantel-Haenszel (CMH) test adjusted by randomization strata (baseline weight group (< 30 kg or ≥ 30 kg) and region (North America or Europe) was used for the analysis of percentage of subjects with EASI-75 at Week 16.

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

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End point title

Percent Change from Baseline in Eczema Area and Severity Index (EASI) Score at Week 16

End point description

The EASI assesses severity and extent of AD. Scores range from 0-72. Four AD disease characteristics (erythema, thickness, scratching, and lichenification) were assessed for severity on a scale of “0” (absent) through “3” (severe). Area of involvement assessed as a percentage by body area of head, trunk, upper limbs, and lower limbs, and converted to a score of 0 to 6. FAS included all randomized subjects. Efficacy analyses were based on the treatment allocated at randomization (as randomized).

End point type

Secondary

End point timeframe

Baseline (Day 1), Week 16

End point values	Placebo + TCS	Dupilumab 300 mg Q4W + TCS	Dupilumab 100 mg or 200 mg Q2W + TCS
Number of subjects analysed	123	122	122
Units: Percent change
least squares mean (standard error)	-48.6 ± 2.46	-82.1 ± 2.37	-78.4 ± 2.35

Dupilumab 100 mg/200 mg Q2W + TCS vs Placebo + TCS

Statistical analysis description

Comparison groups

Placebo + TCS v Dupilumab 100 mg or 200 mg Q2W + TCS

Number of subjects included in analysis

245

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[5]

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-29.8

Confidence interval

level

95%

sides

2-sided

lower limit

-36.33

upper limit

-23.24

Notes
[5] - The confidence interval (CI) with p-value was based on treatment difference (Dupilumab group vs placebo) of the LS mean percent change using ANCOVA model with baseline measurement as covariate and the treatment, randomization strata as fixed factors.

Dupilumab 300 mg Q4W + TCS vs Placebo + TCS

Statistical analysis description

Comparison groups

Placebo + TCS v Dupilumab 300 mg Q4W + TCS

Number of subjects included in analysis

245

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[6]

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-33.4

Confidence interval

level

95%

sides

2-sided

lower limit

-40.06

upper limit

-26.82

Notes
[6] - The confidence interval (CI) with p-value was based on treatment difference (Dupilumab group vs placebo) of the LS mean percent change using ANCOVA model with baseline measurement as covariate and the treatment, randomization strata as fixed factors.

Secondary: Percent Change from Baseline in Weekly Average of Daily Worst Itch Score at Week 16

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End point title

Percent Change from Baseline in Weekly Average of Daily Worst Itch Score at Week 16

End point description

The worst itch scale was a simple assessment tool that subjects used to report the intensity of their pruritus (itch). This was an 11-point scale (0 to 10) in which 0 indicated no itching while 10 indicated worst itching possible. Subjects were asked to answer 2 questions daily throughout the entire study (screening period, treatment period, and follow-up period). The daily worst itch score was calculated as the worse of the scores for the 2 questions. The FAS included all randomized subjects. Efficacy analyses were based on the treatment allocated at randomization (as randomized).

End point type

Secondary

End point timeframe

Baseline (Day 1), Week 16

End point values	Placebo + TCS	Dupilumab 300 mg Q4W + TCS	Dupilumab 100 mg or 200 mg Q2W + TCS
Number of subjects analysed	123	122	122
Units: Percent change
least squares mean (standard error)	-25.9 ± 2.90	-54.6 ± 2.89	-57.0 ± 2.77

Dupilumab 100 mg/200 mg Q2W + TCS vs Placebo + TCS

Statistical analysis description

Comparison groups

Placebo + TCS v Dupilumab 100 mg or 200 mg Q2W + TCS

Number of subjects included in analysis

245

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[7]

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-31

Confidence interval

level

95%

sides

2-sided

lower limit

-38.76

upper limit

-23.26

Notes
[7] - The confidence interval (CI) with p-value was based on treatment difference (Dupilumab group vs placebo) of the LS mean percent change using ANCOVA model with baseline measurement as covariate and the treatment, randomization strata as fixed factors.

Dupilumab 300 mg Q4W + TCS vs Placebo + TCS

Statistical analysis description

Comparison groups

Placebo + TCS v Dupilumab 300 mg Q4W + TCS

Number of subjects included in analysis

245

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[8]

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-28.6

Confidence interval

level

95%

sides

2-sided

lower limit

-36.47

upper limit

-20.82

Notes
[8] - The confidence interval (CI) with p-value was based on treatment difference (Dupilumab group vs placebo) of the LS mean percent change using ANCOVA model with baseline measurement as covariate and the treatment, randomization strata as fixed factors.

Secondary: Percentage of Subjects with Improvement (Reduction from Baseline) of Weekly Average of Daily Worst Itch Score ≥3 Points at Week 16

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End point title

Percentage of Subjects with Improvement (Reduction from Baseline) of Weekly Average of Daily Worst Itch Score ≥3 Points at Week 16

End point description

End point type

Secondary

End point timeframe

Week 16

End point values	Placebo + TCS	Dupilumab 300 mg Q4W + TCS	Dupilumab 100 mg or 200 mg Q2W + TCS
Number of subjects analysed	123	121	120
Units: Percentage of Subjects
number (not applicable)	21.1	60.3	67.5

Dupilumab 100 mg/200 mg Q2W + TCS vs Placebo + TCS

Statistical analysis description

Comparison groups

Placebo + TCS v Dupilumab 100 mg or 200 mg Q2W + TCS

Number of subjects included in analysis

243

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[9]

Method

Cochran-Mantel-Haenszel

Parameter type

Percentage difference

Point estimate

46.4

Confidence interval

level

95%

sides

2-sided

lower limit

35.3

upper limit

57.42

Notes
[9] - P-values were derived by Cochran-Mantel-Haenszel (CMH) test stratified by region [North America vs Europe] and baseline weight group [< 30 kg vs ≥ 30 kg].

Dupilumab 300 mg Q4W + TCS vs Placebo + TCS

Statistical analysis description

Comparison groups

Placebo + TCS v Dupilumab 300 mg Q4W + TCS

Number of subjects included in analysis

244

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[10]

Method

Cochran-Mantel-Haenszel

Parameter type

Percentage difference

Point estimate

39.2

Confidence interval

level

95%

sides

2-sided

lower limit

27.88

upper limit

50.51

Notes
[10] - P-values were derived by Cochran-Mantel-Haenszel (CMH) test stratified by region [North America vs Europe] and baseline weight group [< 30 kg vs ≥ 30 kg].

Secondary: Percentage of Subjects with Improvement (Reduction from Baseline) of Weekly Average of Daily Worst Itch Score ≥4 Points at Week 16

Top of page

End point title

Percentage of Subjects with Improvement (Reduction from Baseline) of Weekly Average of Daily Worst Itch Score ≥4 Points at Week 16

End point description

End point type

Secondary

End point timeframe

Week 16

End point values	Placebo + TCS	Dupilumab 300 mg Q4W + TCS	Dupilumab 100 mg or 200 mg Q2W + TCS
Number of subjects analysed	122	120	120
Units: Percentage of Subjects
number (not applicable)	12.3	50.8	58.3

Dupilumab 100 mg/200 mg Q2W + TCS vs Placebo + TCS

Statistical analysis description

Comparison groups

Placebo + TCS v Dupilumab 100 mg or 200 mg Q2W + TCS

Number of subjects included in analysis

242

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[11]

Method

Cochran-Mantel-Haenszel

Parameter type

Percentage difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

35.47

upper limit

56.61

Notes
[11] - P-values were derived by Cochran-Mantel-Haenszel (CMH) test stratified by region [North America vs Europe] and baseline weight group [< 30 kg vs ≥ 30 kg].

Dupilumab 300 mg Q4W + TCS vs Placebo + TCS

Statistical analysis description

Comparison groups

Placebo + TCS v Dupilumab 300 mg Q4W + TCS

Number of subjects included in analysis

242

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[12]

Method

Cochran-Mantel-Haenszel

Parameter type

Percentage difference

Point estimate

38.5

Confidence interval

level

95%

sides

2-sided

lower limit

27.86

upper limit

49.21

Notes
[12] - P-values were derived by Cochran-Mantel-Haenszel (CMH) test stratified by region [North America vs Europe] and baseline weight group [< 30 kg vs ≥ 30 kg].

Secondary: Percentage of Subjects Achieving Eczema Area and Severity Index - 50 (EASI-50) (≥ 50% Improvement from Baseline) at Week 16

Top of page

End point title

Percentage of Subjects Achieving Eczema Area and Severity Index - 50 (EASI-50) (≥ 50% Improvement from Baseline) at Week 16

End point description

The EASI assessed severity and extent of AD. Scores range from 0-72. Four AD disease characteristics (erythema, thickness, scratching, and lichenification) were assessed for severity on a scale of “0” (absent) through “3” (severe). Area of involvement assessed as a percentage by body area of head, trunk, upper limbs, and lower limbs, and converted to a score of 0 to 6. The FAS included all randomized subjects. Efficacy analyses were based on the treatment allocated at randomization (as randomized). Values after first rescue treatment used were set to missing. Subjects with missing score at week 16 were considered as a non-responder.

End point type

Secondary

End point timeframe

Week 16

End point values	Placebo + TCS	Dupilumab 300 mg Q4W + TCS	Dupilumab 100 mg or 200 mg Q2W + TCS
Number of subjects analysed	123	122	122
Units: Percentage of Subjects
number (not applicable)	43.1	91.0	82.8

Dupilumab 100 mg/200 mg Q2W + TCS vs Placebo + TCS

Statistical analysis description

Comparison groups

Placebo + TCS v Dupilumab 100 mg or 200 mg Q2W + TCS

Number of subjects included in analysis

245

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[13]

Method

Cochran-Mantel-Haenszel

Parameter type

Percentage difference

Point estimate

39.7

Confidence interval

level

95%

sides

2-sided

lower limit

28.68

upper limit

50.72

Notes
[13] - P-values were derived by Cochran-Mantel-Haenszel (CMH) test stratified by region [North America vs Europe] and baseline weight group [< 30 kg vs ≥ 30 kg].

Dupilumab 300 mg Q4W + TCS vs Placebo + TCS

Statistical analysis description

Comparison groups

Dupilumab 300 mg Q4W + TCS v Placebo + TCS

Number of subjects included in analysis

245

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[14]

Method

Cochran-Mantel-Haenszel

Parameter type

Percentage difference

Point estimate

47.9

Confidence interval

level

95%

sides

2-sided

lower limit

37.77

upper limit

58.01

Notes
[14] - P-values were derived by Cochran-Mantel-Haenszel (CMH) test stratified by region [North America vs Europe] and baseline weight group [< 30 kg vs ≥ 30 kg].

Secondary: Percentage of Subjects Achieving Eczema Area and Severity Index - 90 (EASI - 90) (≥ 90% Improvement from Baseline) at Week 16

Top of page

End point title

Percentage of Subjects Achieving Eczema Area and Severity Index - 90 (EASI - 90) (≥ 90% Improvement from Baseline) at Week 16

End point description

The EASI assessed the severity and extent of atopic dermatitis (AD). Scores range from 0-72. Four AD disease characteristics (erythema, thickness, scratching, and lichenification) were assessed for severity on a scale of “0” (absent) through “3” (severe). Area of involvement assessed as a percentage by body area of head, trunk, upper limbs, and lower limbs, and converted to a score of 0 to 6. The FAS included all randomized subjects. Efficacy analyses were based on the treatment allocated at randomization (as randomized). Values after first rescue treatment used were set to missing. Subjects with missing score at week 16 were considered as a non-responder.

End point type

Secondary

End point timeframe

Week 16

End point values	Placebo + TCS	Dupilumab 300 mg Q4W + TCS	Dupilumab 100 mg or 200 mg Q2W + TCS
Number of subjects analysed	123	122	122
Units: Percentage of Subjects
number (not applicable)	7.3	41.8	30.3

Dupilumab 100 mg/200 mg Q2W + TCS vs Placebo + TCS

Statistical analysis description

Comparison groups

Placebo + TCS v Dupilumab 100 mg or 200 mg Q2W + TCS

Number of subjects included in analysis

245

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[15]

Method

Cochran-Mantel-Haenszel

Parameter type

Percentage difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

13.65

upper limit

32.38

Notes
[15] - P-values were derived by Cochran-Mantel-Haenszel (CMH) test stratified by region [North America vs Europe] and baseline weight group [< 30 kg vs ≥ 30 kg].

Dupilumab 300 mg Q4W + TCS vs Placebo + TCS

Statistical analysis description

Comparison groups

Placebo + TCS v Dupilumab 300 mg Q4W + TCS

Number of subjects included in analysis

245

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[16]

Method

Cochran-Mantel-Haenszel

Parameter type

Percentage difference

Point estimate

34.5

Confidence interval

level

95%

sides

2-sided

lower limit

24.6

upper limit

44.37

Notes
[16] - P-values were derived by Cochran-Mantel-Haenszel (CMH) test stratified by region [North America vs Europe] and baseline weight group [< 30 kg vs ≥ 30 kg].

Secondary: Time to Achieve ≥ 4 Point Reduction of Weekly Average of Daily Worst Itch Score from Baseline during the 16-week Treatment Period

Top of page

End point title

Time to Achieve ≥ 4 Point Reduction of Weekly Average of Daily Worst Itch Score from Baseline during the 16-week Treatment Period

End point description

The worst itch scale: a simple assessment tool that subjects used to report intensity of their pruritus (itch). This was an 11-point scale (0 to 10) where 0 (no itching) and 10 (worst itching) possible. Subjects were asked to answer 2 questions daily throughout the entire study (screening period, treatment period, and follow-up period). The daily worst itch score was calculated as worse of scores for 2 questions. FAS was used. Time to event is calculated in weeks as (date of first event - date of first dose)/7. The event of NRS reduction ≥ 4 was based on observed data without setting data to be non-responder after rescue treatment use. Here "Number of subjects analyzed" = number of subjects who were evaluated for this specific endpoint and "99999" represents "Not computable" as only 12.3% of subjects achieved NRS reduction during 16-week treatment period & hence median time to achieve ≥ 4-point reduction of NRS for placebo +TCS treated subjects could not be reported.

End point type

Secondary

End point timeframe

Baseline (Day 1) up to Week 16

End point values	Placebo + TCS	Dupilumab 300 mg Q4W + TCS	Dupilumab 100 mg or 200 mg Q2W + TCS
Number of subjects analysed	122	120	120
Units: Weeks
median (confidence interval 95%)	99999 (99999 to 99999)	10.0 (7 to 13)	10.0 (8 to 12)

Dupilumab 100 mg/200 mg Q2W + TCS vs Placebo + TCS

Statistical analysis description

Comparison groups

Placebo + TCS v Dupilumab 100 mg or 200 mg Q2W + TCS

Number of subjects included in analysis

242

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[17]

Method

Cox model

Parameter type

Hazard ratios

Point estimate

3.114

Confidence interval

level

95%

sides

2-sided

lower limit

2.097

upper limit

4.624

Notes
[17] - P-values were derived by Cochran-Mantel-Haenszel (CMH) test stratified by region [North America vs Europe] and baseline weight group [< 30 kg vs ≥ 30 kg].

Dupilumab 300 mg Q4W + TCS vs Placebo + TCS

Statistical analysis description

Comparison groups

Placebo + TCS v Dupilumab 300 mg Q4W + TCS

Number of subjects included in analysis

242

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[18]

Method

Cox model

Parameter type

Hazard ratios

Point estimate

2.921

Confidence interval

level

95%

sides

2-sided

lower limit

1.957

upper limit

4.36

Notes
[18] - P-values were derived by Cochran-Mantel-Haenszel (CMH) test stratified by region [North America vs Europe] and baseline weight group [< 30 kg vs ≥ 30 kg].

Secondary: Time to Achieve ≥ 3 Point Reduction of Weekly Average of Daily Worst Itch Score from Baseline during the 16-week Treatment Period

Top of page

End point title

Time to Achieve ≥ 3 Point Reduction of Weekly Average of Daily Worst Itch Score from Baseline during the 16-week Treatment Period

End point description

The worst itch scale: a simple assessment tool that subjects used to report intensity of their pruritus (itch). This was an 11-point scale (0 to 10) where 0 (no itching) and 10 (worst itching) possible. Subjects were asked to answer 2 questions daily throughout the entire study (screening period, treatment period, and follow-up period). The daily worst itch score was calculated as worse of scores for 2 questions. FAS was used. Time to event is calculated in weeks as (date of first event - date of first dose)/7. The event of NRS reduction ≥ 3 was based on observed data without setting data to be non-responder after rescue treatment use. Here "Number of subjects analyzed" = number of subjects who were evaluated for this specific endpoint and "99999" represents "Not computable" as only 21.1% of subjects achieved NRS reduction during 16-week treatment period & hence median time to achieve ≥ 3-point reduction of NRS for placebo +TCS treated subjects could not be reported.

End point type

Secondary

End point timeframe

Baseline (Day 1) up to Week 16

End point values	Placebo + TCS	Dupilumab 300 mg Q4W + TCS	Dupilumab 100 mg or 200 mg Q2W + TCS
Number of subjects analysed	123	121	120
Units: Weeks
median (confidence interval 95%)	99999 (11 to 99999)	6.0 (5 to 9)	5.0 (5 to 7)

Dupilumab 100 mg/200 mg Q2W + TCS vs Placebo + TCS

Statistical analysis description

Comparison groups

Placebo + TCS v Dupilumab 100 mg or 200 mg Q2W + TCS

Number of subjects included in analysis

243

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[19]

Method

Cox model

Parameter type

Hazard ratios

Point estimate

2.278

Confidence interval

level

95%

sides

2-sided

lower limit

1.631

upper limit

3.182

Notes
[19] - P-values were derived by Cochran-Mantel-Haenszel (CMH) test stratified by region [North America vs Europe] and baseline weight group [< 30 kg vs ≥ 30 kg].

Dupilumab 300 mg Q4W + TCS vs Placebo + TCS

Statistical analysis description

Comparison groups

Placebo + TCS v Dupilumab 300 mg Q4W + TCS

Number of subjects included in analysis

244

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[20]

Method

Cox model

Parameter type

Hazard ratios

Point estimate

2.075

Confidence interval

level

95%

sides

2-sided

lower limit

1.481

upper limit

2.908

Notes
[20] - P-values were derived by Cochran-Mantel-Haenszel (CMH) test stratified by region [North America vs Europe] and baseline weight group [< 30 kg vs ≥ 30 kg].

Secondary: Change from Baseline in Percent Body Surface Area (BSA) Affected by Atopic Dermatitis (AD) at Week 16

Top of page

End point title

Change from Baseline in Percent Body Surface Area (BSA) Affected by Atopic Dermatitis (AD) at Week 16

End point description

BSA affected by AD was assessed for each section of the body using the rule of nines (the possible highest score for each region is: head and neck [9%], anterior trunk [18%], back [18%], upper limbs [18%], lower limbs [36%], and genitals [1%]) and were reported as a percentage of all major body sections combined. The proportion assigned to different body regions were different in younger children as compared to older children (head and neck area is assigned a higher proportion in younger children as compared to older children). The FAS included all randomized subjects. Efficacy analyses were based on the treatment allocated at randomization (as randomized).

End point type

Secondary

End point timeframe

Baseline (Day 1), Week 16

End point values	Placebo + TCS	Dupilumab 300 mg Q4W + TCS	Dupilumab 100 mg or 200 mg Q2W + TCS
Number of subjects analysed	123	122	122
Units: Percentage of BSA
least squares mean (standard error)	-21.65 ± 1.721	-40.53 ± 1.648	-39.37 ± 1.629

Dupilumab 100 mg/200 mg Q2W + TCS vs Placebo + TCS

Statistical analysis description

Comparison groups

Dupilumab 100 mg or 200 mg Q2W + TCS v Placebo + TCS

Number of subjects included in analysis

245

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[21]

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-17.72

Confidence interval

level

95%

sides

2-sided

lower limit

-22.272

upper limit

-13.161

Notes
[21] - The confidence interval (CI) with p-value was based on treatment difference (Dupilumab group vs placebo) of the LS mean percent change using ANCOVA model with baseline measurement as covariate and the treatment, randomization strata as fixed factors.

Dupilumab 300 mg Q4W + TCS vs Placebo + TCS

Statistical analysis description

Comparison groups

Placebo + TCS v Dupilumab 300 mg Q4W + TCS

Number of subjects included in analysis

245

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[22]

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-18.88

Confidence interval

level

95%

sides

2-sided

lower limit

-23.479

upper limit

-14.289

Notes
[22] - The confidence interval (CI) with p-value was based on treatment difference (Dupilumab group vs placebo) of the LS mean percent change using ANCOVA model with baseline measurement as covariate and the treatment, randomization strata as fixed factors.

Secondary: Percent Change from Baseline in SCORing Atopic Dermatitis (SCORAD) at Week 16

Top of page

End point title

Percent Change from Baseline in SCORing Atopic Dermatitis (SCORAD) at Week 16

End point description

SCORAD was used to assess the extent and severity of AD. Extent and severity of eczema as well as subjective symptoms (insomnia, etc) were assessed and scored. SCORAD total score ranges from 0 (absent disease) to 103 (severe disease). The FAS included all randomized subjects. Efficacy analyses were based on the treatment allocated at randomization (as randomized).

End point type

Secondary

End point timeframe

Baseline (Day 1), Week 16

End point values	Placebo + TCS	Dupilumab 300 mg Q4W + TCS	Dupilumab 100 mg or 200 mg Q2W + TCS
Number of subjects analysed	123	122	122
Units: Percent change
least squares mean (standard error)	-29.8 ± 2.26	-62.4 ± 2.13	-60.2 ± 2.11

Dupilumab 100 mg/200 mg Q2W + TCS vs Placebo + TCS

Statistical analysis description

Comparison groups

Placebo + TCS v Dupilumab 100 mg or 200 mg Q2W + TCS

Number of subjects included in analysis

245

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[23]

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-30.4

Confidence interval

level

95%

sides

2-sided

lower limit

-36.3

upper limit

-24.48

Notes
[23] - The confidence interval (CI) with p-value was based on treatment difference (Dupilumab group vs placebo) of the LS mean percent change using ANCOVA model with baseline measurement as covariate and the treatment, randomization strata as fixed factors.

Dupilumab 300 mg Q4W + TCS vs Placebo + TCS

Statistical analysis description

Comparison groups

Placebo + TCS v Dupilumab 300 mg Q4W + TCS

Number of subjects included in analysis

245

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[24]

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-32.6

Confidence interval

level

95%

sides

2-sided

lower limit

-38.57

upper limit

-26.59

Notes
[24] - The confidence interval (CI) with p-value was based on treatment difference (Dupilumab group vs placebo) of the LS mean percent change using ANCOVA model with baseline measurement as covariate and the treatment, randomization strata as fixed factors.

Secondary: Change from Baseline in Children’s Dermatology Life Quality Index (CDLQI) at Week 16

Top of page

End point title

Change from Baseline in Children’s Dermatology Life Quality Index (CDLQI) at Week 16

End point description

CDLQI was a validated 10 question tool to measure the impact of skin disease on the quality of life (QOL) in children by assessing how much the skin problem has affected the subject over the past week. Nine questions were scored as follows: Very much = 3, Quite a lot = 2, Only a little = 1, Not at all or unanswered = 0. Question 7 has an added possible response, which was scored as 3. CDLQI equals the sum of the score of each question (maximum = 30, minimum = 0). Higher the score, the greater the impact on QOL. It can also be expressed as a percentage of the maximum possible score of 30. The FAS included all randomized subjects. Efficacy analyses were based on the treatment allocated at randomization (as randomized).

End point type

Secondary

End point timeframe

Baseline (Day 1), Week 16

End point values	Placebo + TCS	Dupilumab 300 mg Q4W + TCS	Dupilumab 100 mg or 200 mg Q2W + TCS
Number of subjects analysed	123	122	122
Units: Score on a Scale
least squares mean (standard error)	-6.4 ± 0.51	-10.6 ± 0.47	-10.7 ± 0.46

Dupilumab 100 mg/200 mg Q2W + TCS vs Placebo + TCS

Statistical analysis description

Comparison groups

Placebo + TCS v Dupilumab 100 mg or 200 mg Q2W + TCS

Number of subjects included in analysis

245

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[25]

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-4.3

Confidence interval

level

95%

sides

2-sided

lower limit

-5.62

upper limit

-2.99

Notes
[25] - The confidence interval (CI) with p-value was based on treatment difference (Dupilumab group vs placebo) of the LS mean percent change using ANCOVA model with baseline measurement as covariate and the treatment, randomization strata as fixed factors.

Dupilumab 300 mg Q4W + TCS vs Placebo + TCS

Statistical analysis description

Comparison groups

Placebo + TCS v Dupilumab 300 mg Q4W + TCS

Number of subjects included in analysis

245

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[26]

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-4.2

Confidence interval

level

95%

sides

2-sided

lower limit

-5.57

upper limit

-2.89

Notes
[26] - The confidence interval (CI) with p-value was based on treatment difference (dupilumab group vs placebo) of the LS mean percent change using ANCOVA model with baseline measurement as covariate and the treatment, randomization strata as fixed factors.

Secondary: Change from Baseline in Patient Oriented Eczema Measure (POEM) at Week 16

Top of page

End point title

Change from Baseline in Patient Oriented Eczema Measure (POEM) at Week 16

End point description

POEM was a 7-item, validated questionnaire used to assess disease symptoms in children and adults. The format was a response to 7 items (dryness, itching, flaking, cracking, sleep loss, bleeding, and weeping) based on frequency of these disease symptoms during the past week (ie, 0 = no days, 1 = 1 to 2 days, 2 = 3 to 4 days, 3 = 5 to 6 days, and 4 = all days) with a scoring system of 0 to 28; the total score reflected the disease-related morbidity. The FAS included all randomized subjects. Efficacy analyses were based on the treatment allocated at randomization (as randomized).

End point type

Secondary

End point timeframe

Baseline (Day 1), Week 16

End point values	Placebo + TCS	Dupilumab 300 mg Q4W + TCS	Dupilumab 100 mg or 200 mg Q2W + TCS
Number of subjects analysed	123	122	122
Units: Score on a Scale
least squares mean (standard error)	-5.3 ± 0.69	-13.6 ± 0.65	-13.4 ± 0.65

Dupilumab 100 mg/200 mg Q2W + TCS vs Placebo + TCS

Statistical analysis description

Comparison groups

Placebo + TCS v Dupilumab 100 mg or 200 mg Q2W + TCS

Number of subjects included in analysis

245

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[27]

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-9.96

upper limit

-6.31

Notes
[27] - The confidence interval (CI) with p-value was based on treatment difference (Dupilumab group vs placebo) of the LS mean percent change using ANCOVA model with baseline measurement as covariate and the treatment, randomization strata as fixed factors.

Dupilumab 300 mg Q4W + TCS vs Placebo + TCS

Statistical analysis description

Comparison groups

Placebo + TCS v Dupilumab 300 mg Q4W + TCS

Number of subjects included in analysis

245

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[28]

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-8.3

Confidence interval

level

95%

sides

2-sided

lower limit

-10.13

upper limit

-6.43

Notes
[28] - The confidence interval (CI) with p-value was based on treatment difference (Dupilumab group vs placebo) of the LS mean percent change using ANCOVA model with baseline measurement as covariate and the treatment, randomization strata as fixed factors.

Secondary: Change from Baseline in Weekly Average of Daily Worst Itch Score at Week 16

Top of page

End point title

Change from Baseline in Weekly Average of Daily Worst Itch Score at Week 16

End point description

End point type

Secondary

End point timeframe

Baseline (Day 1), Week 16

End point values	Placebo + TCS	Dupilumab 300 mg Q4W + TCS	Dupilumab 100 mg or 200 mg Q2W + TCS
Number of subjects analysed	123	122	122
Units: Score on a Scale
least squares mean (standard error)	-2.05 ± 0.215	-4.22 ± 0.207	-4.45 ± 0.206

Dupilumab 100 mg/200 mg Q2W + TCS vs Placebo + TCS

Statistical analysis description

Comparison groups

Placebo + TCS v Dupilumab 100 mg or 200 mg Q2W + TCS

Number of subjects included in analysis

245

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[29]

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-2.41

Confidence interval

level

95%

sides

2-sided

lower limit

-2.984

upper limit

-1.831

Notes
[29] - The confidence interval (CI) with p-value was based on treatment difference (Dupilumab group vs placebo) of the LS mean percent change using ANCOVA model with baseline measurement as covariate and the treatment, randomization strata as fixed factors.

Dupilumab 300 mg Q4W + TCS vs Placebo + TCS

Statistical analysis description

Comparison groups

Placebo + TCS v Dupilumab 300 mg Q4W + TCS

Number of subjects included in analysis

245

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[30]

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-2.18

Confidence interval

level

95%

sides

2-sided

lower limit

-2.754

upper limit

-1.599

Notes
[30] - The confidence interval (CI) with p-value was based on treatment difference (Dupilumab group vs placebo) of the LS mean percent change using ANCOVA model with baseline measurement as covariate and the treatment, randomization strata as fixed factors.

Secondary: Change from Baseline in Dermatitis Family Index (DFI) at Week 16

Top of page

End point title

Change from Baseline in Dermatitis Family Index (DFI) at Week 16

End point description

DFI was a 10-item questionnaire with items inquiring about housework, food preparation, sleep, family leisure activity, shopping, expenditure, tiredness, emotional distress, relationships and the impact of helping with treatment on the primary caregiver’s life. The DFI questions were scored on a four-point Likert scale ranging from 0 to 3, so that the total DFI score ranges from 0 to 30. Timeframe of reference was the past week. A higher DFI score indicated greater impairment in family Quality of life (QOL) as affected by atopic dermatitis. The FAS included all randomized subjects. Efficacy analyses were based on the treatment allocated at randomization (as randomized).

End point type

Secondary

End point timeframe

Baseline (Day 1) , Week 16

End point values	Placebo + TCS	Dupilumab 300 mg Q4W + TCS	Dupilumab 100 mg or 200 mg Q2W + TCS
Number of subjects analysed	123	122	122
Units: Score on a Scale
least squares mean (standard error)	-6.77 ± 0.497	-10.75 ± 0.476	-10.89 ± 0.469

Dupilumab 100 mg/200 mg Q2W + TCS vs Placebo + TCS

Statistical analysis description

Comparison groups

Placebo + TCS v Dupilumab 100 mg or 200 mg Q2W + TCS

Number of subjects included in analysis

245

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[31]

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-4.11

Confidence interval

level

95%

sides

2-sided

lower limit

-5.434

upper limit

-2.796

Notes
[31] - The confidence interval (CI) with p-value was based on treatment difference (Dupilumab group vs placebo) of the LS mean percent change using ANCOVA model with baseline measurement as covariate and the treatment, randomization strata as fixed factors.

Dupilumab 300 mg Q4W + TCS vs Placebo + TCS

Statistical analysis description

Comparison groups

Placebo + TCS v Dupilumab 300 mg Q4W + TCS

Number of subjects included in analysis

245

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[32]

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-3.98

Confidence interval

level

95%

sides

2-sided

lower limit

-5.298

upper limit

-2.657

Notes
[32] - The confidence interval (CI) with p-value was based on treatment difference (Dupilumab group vs placebo) of the LS mean percent change using ANCOVA model with baseline measurement as covariate and the treatment, randomization strata as fixed factors.

Secondary: Change from Baseline in Patient Reported Outcomes Measurements Information Systems (PROMIS) Pediatric Anxiety Short Form Scale Total Score at Week 16

Top of page

End point title

Change from Baseline in Patient Reported Outcomes Measurements Information Systems (PROMIS) Pediatric Anxiety Short Form Scale Total Score at Week 16

End point description

The PROMIS Anxiety instrument measures self-reported fear (fearfulness, panic), anxious misery (worry, dread), hyperarousal (tension, nervousness, restlessness), and somatic symptoms related to arousal (racing heart, dizziness). The FAS included all randomized subjects. Efficacy analyses were based on the treatment allocated at randomization (as randomized).

End point type

Secondary

End point timeframe

Baseline (Day 1), Week 16

End point values	Placebo + TCS	Dupilumab 300 mg Q4W + TCS	Dupilumab 100 mg or 200 mg Q2W + TCS
Number of subjects analysed	123	122	122
Units: Score on a Scale
least squares mean (standard error)	-10.17 ± 0.912	-13.19 ± 0.861	-13.54 ± 0.860

Dupilumab 100 mg/200 mg Q2W + TCS vs Placebo + TCS

Statistical analysis description

Comparison groups

Placebo + TCS v Dupilumab 100 mg or 200 mg Q2W + TCS

Number of subjects included in analysis

245

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0061 ^[33]

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-3.37

Confidence interval

level

95%

sides

2-sided

lower limit

-5.779

upper limit

-0.962

Notes
[33] - The confidence interval (CI) with p-value was based on treatment difference (Dupilumab group vs placebo) of the LS mean percent change using ANCOVA model with baseline measurement as covariate and the treatment, randomization strata as fixed factors.

Dupilumab 300 mg Q4W + TCS vs Placebo + TCS

Statistical analysis description

Comparison groups

Placebo + TCS v Dupilumab 300 mg Q4W + TCS

Number of subjects included in analysis

245

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0133 ^[34]

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-3.02

Confidence interval

level

95%

sides

2-sided

lower limit

-5.414

upper limit

-0.629

Notes
[34] - The confidence interval (CI) with p-value was based on treatment difference (Dupilumab group vs placebo) of the LS mean percent change using ANCOVA model with baseline measurement as covariate and the treatment, randomization strata as fixed factors.

Secondary: Change from Baseline in Patient Reported Outcomes Measurements Information Systems (PROMIS) Pediatric Depressive Symptoms Short Form Scale Score at Week 16

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End point title

Change from Baseline in Patient Reported Outcomes Measurements Information Systems (PROMIS) Pediatric Depressive Symptoms Short Form Scale Score at Week 16

End point description

The PROMIS Depression instrument assesses self-reported negative mood (sadness, guilt), views of self (self-criticism, worthlessness), and social cognition (loneliness, interpersonal alienation), as well as decreased positive affect and engagement (loss of interest, meaning, and purpose). The FAS included all randomized subjects. Efficacy analyses were based on the treatment allocated at randomization (as randomized).

End point type

Secondary

End point timeframe

Baseline (Day 1), Week 16

End point values	Placebo + TCS	Dupilumab 300 mg Q4W + TCS	Dupilumab 100 mg or 200 mg Q2W + TCS
Number of subjects analysed	123	122	122
Units: Score on a Scale
least squares mean (standard error)	-7.42 ± 0.848	-12.84 ± 0.793	-11.92 ± 0.790

Dupilumab 100 mg/200 mg Q2W + TCS vs Placebo + TCS

Statistical analysis description

Comparison groups

Placebo + TCS v Dupilumab 100 mg or 200 mg Q2W + TCS

Number of subjects included in analysis

245

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[35]

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-4.5

Confidence interval

level

95%

sides

2-sided

lower limit

-6.734

upper limit

-2.272

Notes
[35] - The confidence interval (CI) with p-value was based on treatment difference (Dupilumab group vs placebo) of the LS mean percent change using ANCOVA model with baseline measurement as covariate and the treatment, randomization strata as fixed factors.

Dupilumab 300 mg Q4W + TCS vs Placebo + TCS

Statistical analysis description

Comparison groups

Placebo + TCS v Dupilumab 300 mg Q4W + TCS

Number of subjects included in analysis

245

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[36]

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-5.42

Confidence interval

level

95%

sides

2-sided

lower limit

-7.641

upper limit

-3.207

Notes
[36] - The confidence interval (CI) with p-value was based on treatment difference (Dupilumab group vs placebo) of the LS mean percent change using ANCOVA model with baseline measurement as covariate and the treatment, randomization strata as fixed factors.

Secondary: Percentage of Subjects Having at Least One Skin Infection Treatment Emergent Adverse Event (TEAE) (Excluding Herpetic Infections) through Week 16

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End point title

Percentage of Subjects Having at Least One Skin Infection Treatment Emergent Adverse Event (TEAE) (Excluding Herpetic Infections) through Week 16

End point description

Treatment-emergent adverse events (TEAEs) were defined as adverse events (AEs) that developed or worsened or became serious during on-treatment period (time from the first dose of study drug up to the end of study. 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-subjects hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included subjects with both serious and non-serious AEs. Percentage of subjects having at least one skin infection TEAE (Excluding Herpetic Infections) through Week 16 were reported. The FAS included all randomized subjects. Efficacy analyses were based on the treatment allocated at randomization (as randomized).

End point type

Secondary

End point timeframe

Baseline through Week 16

End point values	Placebo + TCS	Dupilumab 300 mg Q4W + TCS	Dupilumab 100 mg or 200 mg Q2W + TCS
Number of subjects analysed	123	122	122
Units: Percentage of Subjects
number (not applicable)	13.0	5.7	8.2

Dupilumab 100 mg/200 mg Q2W + TCS vs Placebo + TCS

Statistical analysis description

Comparison groups

Placebo + TCS v Dupilumab 100 mg or 200 mg Q2W + TCS

Number of subjects included in analysis

245

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.222 ^[37]

Method

Cochran-Mantel-Haenszel

Parameter type

Percentage Differenece

Point estimate

-4.8

Confidence interval

level

95%

sides

2-sided

lower limit

-12.49

upper limit

2.87

Notes
[37] - P-values were derived by Cochran-Mantel-Haenszel (CMH) test stratified by region [North America vs Europe] and baseline weight group [< 30 kg vs ≥ 30 kg].

Dupilumab 300 mg Q4W + TCS vs Placebo + TCS

Statistical analysis description

Comparison groups

Placebo + TCS v Dupilumab 300 mg Q4W + TCS

Number of subjects included in analysis

245

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0508 ^[38]

Method

Cochran-Mantel-Haenszel

Parameter type

Percentage Differenece

Point estimate

-7.3

Confidence interval

level

95%

sides

2-sided

lower limit

-14.51

upper limit

-0.03

Notes
[38] - P-values were derived by Cochran-Mantel-Haenszel (CMH) test stratified by region [North America vs Europe] and baseline weight group [< 30 kg vs ≥ 30 kg].

Secondary: Percentage of Subjects Having at Least One Serious Treatment Emergent Adverse Event (TEAE) through Week 16

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End point title

Percentage of Subjects Having at Least One Serious Treatment Emergent Adverse Event (TEAE) through Week 16

End point description

Treatment-emergent adverse events (TEAEs) were defined as adverse events (AEs) that developed or worsened or became serious during on-treatment period (time from the first dose of study drug up to the end of study. 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-subjects hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included subjects with both serious and non-serious AEs. The FAS included all randomized subjects. Efficacy analyses were based on the treatment allocated at randomization (as randomized).

End point type

Secondary

End point timeframe

Baseline (Day 1) through Week 16

End point values	Placebo + TCS	Dupilumab 300 mg Q4W + TCS	Dupilumab 100 mg or 200 mg Q2W + TCS
Number of subjects analysed	123	122	122
Units: Percentage of Subjects
number (not applicable)	1.6	1.6	0

No statistical analyses for this end point

Secondary: Percentage of Topical Corticosteroid (TCS) Medication-free Days from Baseline to Week 16

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End point title

Percentage of Topical Corticosteroid (TCS) Medication-free Days from Baseline to Week 16

End point description

Percentage of TCS medication-free days is calculated as the number of days that a patient used neither TCS/TCI nor system rescue therapy divided by the study days of each period. The FAS included all randomized subjects. Efficacy analyses were based on the treatment allocated at randomization (as randomized). Here "Number of subjects analyzed" = number of subjects who were evaluated for this specific endpoint.

End point type

Secondary

End point timeframe

Baseline (Day 1), Week 16

End point values	Placebo + TCS	Dupilumab 300 mg Q4W + TCS	Dupilumab 100 mg or 200 mg Q2W + TCS
Number of subjects analysed	123	122	121
Units: Days
arithmetic mean (standard deviation)	0.11 ± 0.185	0.20 ± 0.230	0.19 ± 0.207

No statistical analyses for this end point

Secondary: Mean Weekly Dose of Topical Corticosteroid (TCS) in Grams for Low or Medium Potency TCS from Baseline to Week 16

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End point title

Mean Weekly Dose of Topical Corticosteroid (TCS) in Grams for Low or Medium Potency TCS from Baseline to Week 16

End point description

Mean weekly dose of TCS in grams for low or medium potency TCS from baseline to Week 16 were reported. The FAS included all randomized subjects. Efficacy analyses were based on the treatment allocated at randomization (as randomized). Here "Number of subjects analyzed" = number of subjects who were evaluated for this specific endpoint.

End point type

Secondary

End point timeframe

Baseline (Day 1), Week 16

End point values	Placebo + TCS	Dupilumab 300 mg Q4W + TCS	Dupilumab 100 mg or 200 mg Q2W + TCS
Number of subjects analysed	120	120	120
Units: Grams
least squares mean (standard error)	20.1 ± 1.37	15.0 ± 1.36	14.4 ± 1.38

Dupilumab100 mg/ 200 mg Q2W + TCS vs Placebo + TCS

Statistical analysis description

Comparison groups

Placebo + TCS v Dupilumab 100 mg or 200 mg Q2W + TCS

Number of subjects included in analysis

240

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.003 ^[39]

Method

ANOVA

Parameter type

Least Square Mean Difference

Point estimate

-5.7

Confidence interval

level

95%

sides

2-sided

lower limit

-9.49

upper limit

-1.96

Notes
[39] - The confidence interval (CI) with p-value was based on treatment difference (Dupilumab group vs placebo) of the LS mean percent change using ANOVA model with the treatment, randomization strata as fixed factors.

Dupilumab 300 mg Q4W + TCS vs Placebo + TCS

Comparison groups

Placebo + TCS v Dupilumab 300 mg Q4W + TCS

Number of subjects included in analysis

240

Analysis specification

Pre-specified

Analysis type

superiority ^[40]

P-value

= 0.0082 ^[41]

Method

ANOVA

Parameter type

Least Square Mean Difference

Point estimate

-5.1

Confidence interval

level

95%

sides

2-sided

lower limit

-8.8

upper limit

-1.31

Notes
[40] - A 2-sided hierarchical testing procedure was used for the primary and secondary endpoints in a pre-specified order. Testing was then performed sequentially in the order the endpoints are reported. The hierarchical testing sequence continued only when the previous endpoint was statistically significant at 0.05 level
[41] - The confidence interval (CI) with p-value was based on treatment difference (Dupilumab group vs placebo) of the LS mean percent change using ANOVA model with the treatment, randomization strata as fixed factors.

Adverse events

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Timeframe for reporting adverse events

Reported AEs are treatment-emergent adverse events which were collected for both the 16-week treatment period and the follow-up period for as long as 12 weeks.

Adverse event reporting additional description

The safety analysis set (SAF) includes all randomized subjects who received at least one injection of study drug and were analyzed as treated. Treatment compliance/administration and all clinical safety variables were summarized based on the SAF.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

22.0

Reporting group title

Placebo + TCS

Reporting group description

Reporting group title

Dupilumab 300 mg Q4W + TCS

Reporting group description

Reporting group title

Dupilumab 100 mg or 200 mg Q2W + TCS

Reporting group description

Serious adverse events	Placebo + TCS	Dupilumab 300 mg Q4W + TCS	Dupilumab 100 mg or 200 mg Q2W + TCS
Total subjects affected by serious adverse events
subjects affected / exposed	2 / 120 (1.67%)	3 / 120 (2.50%)	0 / 122 (0.00%)
number of deaths (all causes)	0	0	0
number of deaths resulting from adverse events	0	0	0
Injury, poisoning and procedural complications
Bone contusion
subjects affected / exposed	0 / 120 (0.00%)	1 / 120 (0.83%)	0 / 122 (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
Immune system disorders
Food allergy
subjects affected / exposed	0 / 120 (0.00%)	1 / 120 (0.83%)	0 / 122 (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
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	1 / 120 (0.83%)	0 / 120 (0.00%)	0 / 122 (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
Skin and subcutaneous tissue disorders
Dermatitis atopic
subjects affected / exposed	1 / 120 (0.83%)	0 / 120 (0.00%)	0 / 122 (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
Infections and infestations
Urinary tract infection
subjects affected / exposed	0 / 120 (0.00%)	1 / 120 (0.83%)	0 / 122 (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

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

Non-serious adverse events	Placebo + TCS	Dupilumab 300 mg Q4W + TCS	Dupilumab 100 mg or 200 mg Q2W + TCS
Total subjects affected by non serious adverse events
subjects affected / exposed	57 / 120 (47.50%)	47 / 120 (39.17%)	50 / 122 (40.98%)
Nervous system disorders
Headache
subjects affected / exposed	10 / 120 (8.33%)	6 / 120 (5.00%)	7 / 122 (5.74%)
occurrences all number	11	7	10
General disorders and administration site conditions
Injection site erythema
subjects affected / exposed	2 / 120 (1.67%)	5 / 120 (4.17%)	7 / 122 (5.74%)
occurrences all number	3	5	9
Gastrointestinal disorders
Vomiting
subjects affected / exposed	8 / 120 (6.67%)	6 / 120 (5.00%)	6 / 122 (4.92%)
occurrences all number	9	7	8
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	11 / 120 (9.17%)	2 / 120 (1.67%)	4 / 122 (3.28%)
occurrences all number	12	2	4
Cough
subjects affected / exposed	9 / 120 (7.50%)	3 / 120 (2.50%)	5 / 122 (4.10%)
occurrences all number	13	3	5
Skin and subcutaneous tissue disorders
Dermatitis atopic
subjects affected / exposed	17 / 120 (14.17%)	8 / 120 (6.67%)	10 / 122 (8.20%)
occurrences all number	25	12	10
Infections and infestations
Conjunctivitis
subjects affected / exposed	3 / 120 (2.50%)	5 / 120 (4.17%)	7 / 122 (5.74%)
occurrences all number	3	5	8
Nasopharyngitis
subjects affected / exposed	8 / 120 (6.67%)	15 / 120 (12.50%)	8 / 122 (6.56%)
occurrences all number	11	16	10
Upper respiratory tract infection
subjects affected / exposed	12 / 120 (10.00%)	14 / 120 (11.67%)	12 / 122 (9.84%)
occurrences all number	12	19	16
Viral upper respiratory tract infection
subjects affected / exposed	6 / 120 (5.00%)	2 / 120 (1.67%)	1 / 122 (0.82%)
occurrences all number	6	2	1

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

31 Aug 2017

• Children who are engaging in heavy exercise can have transient increases in CPK that are not clinically relevant • Added an Ophthalmological Examination section for subjects who have history of certain eye disorders (conjunctivitis, blepharitis or keratitis) within the last 12 months and subjects who experience adverse events of special interest related to eye disorders • Modified the reporting schedule for subjects assessment of pruritus. Subjects will answer both questions in the evening

20 Nov 2018

• Included introduction of the modified full analysis set (mFAS), which excludes potentially unblinded subjects, and will be used for sensitivity analysis • Extended the duration of the visit window between Visit 1 and Visit 2 from 21 days to 63 days (ie, changed start of Visit 1 from -35 days to -77 days) and removed the limit of rescreen once to allow for the seamless screening/enrolment of all new subjects into the study • Added rationale for the inclusion of a placebo treatment group in the study design and a description of the risks and benefits to subjects assigned to the placebo treatment group • Corrected the description of age limit of the study population from “aged ≥ 6 to < 12 years at the time of baseline” to “aged ≥ 6 to < 12 years at the time of screening” to be consistent with the wording in the Inclusion Criteria and other sections of the protocol. • Revised language for accelerated reporting of pregnancy to sponsor and the duration subjects who are female of childbearing potential and sexually active are required to use highly effective methods of contraception after the last dose of study drug, to align with the current dupilumab label • Revised text to emphasize that the use of very-highpotency topical corticosteroids (TCS) is prohibited during the study, as their use is not recommended in subjects under 12 years of age. Also included examples of very-high-potency TCS • Included “injection observation” for the every 4 week regimen in the Schedule of Events table, to identify the visits at which the observation occurs • Revised the adverse events of special interest definition for conjunctivitis, keratitis, and blepharitis • Specified the list of potential major protocol violation types for the PPS, per request from the United States Food and Drug Administration

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 Investigate The Efficacy and Safety of Dupilumab Administered Concomitantly With Topical Corticosteroids in Patients, ≥ 6 Years to < 12 Years of Age, With Severe Atopic Dermatitis

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Subjects with Investigator’s Global Assessment (IGA) 0 or 1 at Week 16

Primary: Percentage of Subjects with Investigator’s Global Assessment (IGA) 0 or 1 at Week 16

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

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

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

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

Secondary: Percent Change from Baseline in Weekly Average of Daily Worst Itch Score at Week 16

Secondary: Percent Change from Baseline in Weekly Average of Daily Worst Itch Score at Week 16

Secondary: Percentage of Subjects with Improvement (Reduction from Baseline) of Weekly Average of Daily Worst Itch Score ≥3 Points at Week 16

Secondary: Percentage of Subjects with Improvement (Reduction from Baseline) of Weekly Average of Daily Worst Itch Score ≥3 Points at Week 16

Secondary: Percentage of Subjects with Improvement (Reduction from Baseline) of Weekly Average of Daily Worst Itch Score ≥4 Points at Week 16

Secondary: Percentage of Subjects with Improvement (Reduction from Baseline) of Weekly Average of Daily Worst Itch Score ≥4 Points at Week 16

Secondary: Percentage of Subjects Achieving Eczema Area and Severity Index - 50 (EASI-50) (≥ 50% Improvement from Baseline) at Week 16

Secondary: Percentage of Subjects Achieving Eczema Area and Severity Index - 50 (EASI-50) (≥ 50% Improvement from Baseline) at Week 16

Secondary: Percentage of Subjects Achieving Eczema Area and Severity Index - 90 (EASI - 90) (≥ 90% Improvement from Baseline) at Week 16

Secondary: Percentage of Subjects Achieving Eczema Area and Severity Index - 90 (EASI - 90) (≥ 90% Improvement from Baseline) at Week 16

Secondary: Time to Achieve ≥ 4 Point Reduction of Weekly Average of Daily Worst Itch Score from Baseline during the 16-week Treatment Period

Secondary: Time to Achieve ≥ 4 Point Reduction of Weekly Average of Daily Worst Itch Score from Baseline during the 16-week Treatment Period

Secondary: Time to Achieve ≥ 3 Point Reduction of Weekly Average of Daily Worst Itch Score from Baseline during the 16-week Treatment Period

Secondary: Time to Achieve ≥ 3 Point Reduction of Weekly Average of Daily Worst Itch Score from Baseline during the 16-week Treatment Period

Secondary: Change from Baseline in Percent Body Surface Area (BSA) Affected by Atopic Dermatitis (AD) at Week 16

Secondary: Change from Baseline in Percent Body Surface Area (BSA) Affected by Atopic Dermatitis (AD) at Week 16

Secondary: Percent Change from Baseline in SCORing Atopic Dermatitis (SCORAD) at Week 16

Secondary: Percent Change from Baseline in SCORing Atopic Dermatitis (SCORAD) at Week 16

Secondary: Change from Baseline in Children’s Dermatology Life Quality Index (CDLQI) at Week 16

Secondary: Change from Baseline in Children’s Dermatology Life Quality Index (CDLQI) at Week 16

Secondary: Change from Baseline in Patient Oriented Eczema Measure (POEM) at Week 16

Secondary: Change from Baseline in Patient Oriented Eczema Measure (POEM) at Week 16

Secondary: Change from Baseline in Weekly Average of Daily Worst Itch Score at Week 16

Secondary: Change from Baseline in Weekly Average of Daily Worst Itch Score at Week 16

Secondary: Change from Baseline in Dermatitis Family Index (DFI) at Week 16

Secondary: Change from Baseline in Dermatitis Family Index (DFI) at Week 16

Secondary: Change from Baseline in Patient Reported Outcomes Measurements Information Systems (PROMIS) Pediatric Anxiety Short Form Scale Total Score at Week 16

Secondary: Change from Baseline in Patient Reported Outcomes Measurements Information Systems (PROMIS) Pediatric Anxiety Short Form Scale Total Score at Week 16

Secondary: Change from Baseline in Patient Reported Outcomes Measurements Information Systems (PROMIS) Pediatric Depressive Symptoms Short Form Scale Score at Week 16

Secondary: Change from Baseline in Patient Reported Outcomes Measurements Information Systems (PROMIS) Pediatric Depressive Symptoms Short Form Scale Score at Week 16

Secondary: Percentage of Subjects Having at Least One Skin Infection Treatment Emergent Adverse Event (TEAE) (Excluding Herpetic Infections) through Week 16

Secondary: Percentage of Subjects Having at Least One Skin Infection Treatment Emergent Adverse Event (TEAE) (Excluding Herpetic Infections) through Week 16

Secondary: Percentage of Subjects Having at Least One Serious Treatment Emergent Adverse Event (TEAE) through Week 16

Secondary: Percentage of Subjects Having at Least One Serious Treatment Emergent Adverse Event (TEAE) through Week 16

Secondary: Percentage of Topical Corticosteroid (TCS) Medication-free Days from Baseline to Week 16

Secondary: Percentage of Topical Corticosteroid (TCS) Medication-free Days from Baseline to Week 16

Secondary: Mean Weekly Dose of Topical Corticosteroid (TCS) in Grams for Low or Medium Potency TCS from Baseline to Week 16

Secondary: Mean Weekly Dose of Topical Corticosteroid (TCS) in Grams for Low or Medium Potency TCS from Baseline to Week 16

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Randomized, Double-Blind, Placebo-Controlled Study to Investigate The Efficacy and Safety of Dupilumab Administered Concomitantly With Topical Corticosteroids in Patients, ≥ 6 Years to < 12 Years of Age, With Severe Atopic Dermatitis