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    Clinical Trial Results:
    A Randomized, Double-blind, Placebo-controlled, Multi-center, Parallel-group Study to Evaluate the Efficacy, Safety and Pharmacokinetics of Dupilumab Compared to Placebo in Japanese Patients With Atopic Dermatitis Aged 6 Months to <18 Years Whose Disease is not Adequately Controlled With Existing Therapies

    Summary
    EudraCT number
    		 2020-002601-26
    Trial protocol
    		 Outside EU/EEA  
    Global end of trial date
    28 Oct 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    12 May 2024
    First version publication date
    12 May 2024
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    EFC16823
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04678882
    WHO universal trial number (UTN)
    		 U1111-1301-1257
    Sponsors
    Sponsor organisation name
    Sanofi K.K.
    Sponsor organisation address
    3-20-2, Nishi Shinjuku, Shinjuku-ku, Tokyo, Japan, 163-1488
    Public contact
    Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.com
    Scientific contact
    Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    11 Dec 2023
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    28 Oct 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the efficacy of dupilumab administered concomitantly with topical corticosteroids (TCS).
    Protection of trial subjects
    The study was conducted by investigators experienced in the treatment of pediatric participants. The parent(s) or guardian(s) as well as the children were fully informed of all pertinent aspects of the clinical trial as well as the possibility to discontinue at any time. In addition to the consent form for the parent(s)/guardian(s), an assent form in child-appropriate language was provided and explained to the child. Repeated invasive procedures were minimized. The number of blood samples as well as the amount of blood drawn were adjusted according to age and weight. A topical anesthesia may have been used to minimize distress and discomfort.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    15 Jan 2021
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Japan: 62
    Worldwide total number of subjects
    62
    EEA total number of subjects
    0
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    1
    Children (2-11 years)
    44
    Adolescents (12-17 years)
    17
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 The study was conducted at 19 centers in Japan. A total of 75 participants were screened from 15 February 2021 to 02 August 2021, of which 13 were screen failures. Screen failures were mainly due to not meeting inclusion criteria.

    Pre-assignment
    Screening details
    		 62 participants were randomized in 1:1 ratio to receive dupilumab or placebo in randomization treatment period.Randomization was stratified by age categories:≥6 months-<6 years,≥6 years-<12 years,≥12 years.For age group of ≥6 years-<12 years,randomization was further stratified by baseline Investigator's Global Assessment(IGA) score(3 versus 4).

    Period 1
    Period 1 title
    Randomization Treatment Period(16 Weeks)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Assessor, Carer

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo (Randomization Treatment Period)
    Arm description
    		 Participants received placebo matched to dupilumab subcutaneously (SC) every 2 weeks (q2w) with placebo loading dose for ≥30 kilograms (kg) body weight at baseline; placebo matched to dupilumab SC every 4 weeks (q4w) for ≥5 to <30 kg body weight at baseline, for up to 16 weeks during the randomization treatment period.
    Arm type
    		 Placebo

    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
    Placebo was administered SC as an identical formulation to the active 200 or 300 mg formulation without dupilumab to deliver placebo in 1.14 or 2 milliliters (mL) respectively, up to 16 weeks during the randomization treatment period. SC injection sites were alternated among the 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.

    Arm title
    		 Dupilumab (Randomization Treatment Period)
    Arm description
    		 Participants received dupilumab 300 milligrams (mg) SC q2w with 600 mg loading dose for ≥60 kg body weight at baseline; dupilumab 200 mg SC q2w with 400 mg loading dose for ≥30 to <60 kg body weight at baseline; dupilumab 300 mg SC q4w for ≥15 to <30 kg body weight at baseline; and dupilumab 200 mg SC q4w for ≥5 to <15 kg body weight at baseline, for up to 16 weeks during the randomization treatment period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Dupilumab
    Investigational medicinal product code
    SAR231893
    Other name
    Dupixent
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Dupilumab was supplied as 175 or 150 milligram per milliliter (mg/mL) solution in prefilled syringes to deliver 200 mg in 1.14 mL or 300 mg in 2 mL respectively, and was administered SC up to 16 weeks during the randomization treatment period. SC injection sites were alternated among the 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.

    Number of subjects in period 1
    		Placebo (Randomization Treatment Period) Dupilumab (Randomization Treatment Period)
    Started
    32
    30
    Completed
    32
    28
    Not completed
    0
    2
         Adverse Event: Not Related to COVID-19
    -
    1
         Withdrawal by Subject
    -
    1
    Period 2
    Period 2 title
    Open-label Extension Period(Week 17-EOS)
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo/Dupilumab (Open-label Extension Period)
    Arm description
    		 Participants who received placebo during the randomization treatment period and who entered the open-label extension (OLE) period, received dupilumab 300 mg SC q2w with 600 mg loading dose for ≥60 kg body weight; dupilumab 200 mg SC q2w with 400 mg loading dose for ≥30 to <60 kg body weight; dupilumab 300 mg SC q4w for ≥15 to <30 kg body weight; and dupilumab 200 mg SC q4w for ≥5 to <15 kg body weight, for 3 years or until approval of the indication in Japan.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Dupilumab
    Investigational medicinal product code
    SAR231893
    Other name
    Dupixent
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Dupilumab was supplied as 175 or 150 mg/mL solution in prefilled syringes to deliver 200 mg in 1.14 mL or 300 mg in 2 mL respectively, and was administered SC during the OLE period for 3 years or until approval of the indication in Japan. SC injection sites were alternated among the 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.

    Arm title
    		 Dupilumab/Dupilumab (Open-label Extension Period)
    Arm description
    		 Participants who received dupilumab during the randomization treatment period and who entered the OLE period, received dupilumab 300 mg SC q2w with 300 mg loading dose for ≥60 kg body weight; dupilumab 200 mg SC q2w with 200 mg loading dose for ≥30 to <60 kg body weight; dupilumab 300 mg SC q4w for ≥15 to <30 kg body weight; and dupilumab 200 mg SC q4w for ≥5 to <15 kg body weight, for 3 years or until approval of the indication in Japan.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Dupilumab
    Investigational medicinal product code
    SAR231893
    Other name
    Dupixent
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Dupilumab was supplied as 175 or 150 mg/mL solution in prefilled syringes to deliver 200 mg in 1.14 mL or 300 mg in 2 mL respectively, and was administered SC during the OLE period for 3 years or until approval of the indication in Japan. SC injection sites were alternated among the 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.

    Number of subjects in period 2
    		Placebo/Dupilumab (Open-label Extension Period) Dupilumab/Dupilumab (Open-label Extension Period)
    Started
    32
    28
    Completed
    30
    26
    Not completed
    2
    2
         Not Related to COVID-19
    1
    1
         Withdrawal by Subject
    1
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo (Randomization Treatment Period)
    Reporting group description
    		 Participants received placebo matched to dupilumab subcutaneously (SC) every 2 weeks (q2w) with placebo loading dose for ≥30 kilograms (kg) body weight at baseline; placebo matched to dupilumab SC every 4 weeks (q4w) for ≥5 to <30 kg body weight at baseline, for up to 16 weeks during the randomization treatment period.

    Reporting group title
    Dupilumab (Randomization Treatment Period)
    Reporting group description
    		 Participants received dupilumab 300 milligrams (mg) SC q2w with 600 mg loading dose for ≥60 kg body weight at baseline; dupilumab 200 mg SC q2w with 400 mg loading dose for ≥30 to <60 kg body weight at baseline; dupilumab 300 mg SC q4w for ≥15 to <30 kg body weight at baseline; and dupilumab 200 mg SC q4w for ≥5 to <15 kg body weight at baseline, for up to 16 weeks during the randomization treatment period.

    Reporting group values
    		 Placebo (Randomization Treatment Period) Dupilumab (Randomization Treatment Period) Total
    Number of subjects
    		 32 30 62
    Age Categorical
    Units: Subjects
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 9.6 ± 4.2 10.0 ± 4.1 -
    Gender Categorical
    Units: Subjects
        Female
    		 11 12 23
        Male
    		 21 18 39

    End points

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    End points reporting groups
    Reporting group title
    Placebo (Randomization Treatment Period)
    Reporting group description
    		 Participants received placebo matched to dupilumab subcutaneously (SC) every 2 weeks (q2w) with placebo loading dose for ≥30 kilograms (kg) body weight at baseline; placebo matched to dupilumab SC every 4 weeks (q4w) for ≥5 to <30 kg body weight at baseline, for up to 16 weeks during the randomization treatment period.

    Reporting group title
    Dupilumab (Randomization Treatment Period)
    Reporting group description
    		 Participants received dupilumab 300 milligrams (mg) SC q2w with 600 mg loading dose for ≥60 kg body weight at baseline; dupilumab 200 mg SC q2w with 400 mg loading dose for ≥30 to <60 kg body weight at baseline; dupilumab 300 mg SC q4w for ≥15 to <30 kg body weight at baseline; and dupilumab 200 mg SC q4w for ≥5 to <15 kg body weight at baseline, for up to 16 weeks during the randomization treatment period.
    Reporting group title
    Placebo/Dupilumab (Open-label Extension Period)
    Reporting group description
    		 Participants who received placebo during the randomization treatment period and who entered the open-label extension (OLE) period, received dupilumab 300 mg SC q2w with 600 mg loading dose for ≥60 kg body weight; dupilumab 200 mg SC q2w with 400 mg loading dose for ≥30 to <60 kg body weight; dupilumab 300 mg SC q4w for ≥15 to <30 kg body weight; and dupilumab 200 mg SC q4w for ≥5 to <15 kg body weight, for 3 years or until approval of the indication in Japan.

    Reporting group title
    Dupilumab/Dupilumab (Open-label Extension Period)
    Reporting group description
    		 Participants who received dupilumab during the randomization treatment period and who entered the OLE period, received dupilumab 300 mg SC q2w with 300 mg loading dose for ≥60 kg body weight; dupilumab 200 mg SC q2w with 200 mg loading dose for ≥30 to <60 kg body weight; dupilumab 300 mg SC q4w for ≥15 to <30 kg body weight; and dupilumab 200 mg SC q4w for ≥5 to <15 kg body weight, for 3 years or until approval of the indication in Japan.

    Subject analysis set title
    Placebo/Dupilumab (Dupilumab Exposure Period)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received placebo matched to dupilumab SC q2w with placebo loading dose for ≥30 kg body weight at baseline; placebo matched to dupilumab SC q4w for ≥5 to <30 kg body weight at baseline, for up to 16 weeks during the randomization treatment period. Participants then entered the OLE period and received dupilumab 300 mg SC q2w with 600 mg loading dose for ≥60 kg body weight; dupilumab 200 mg SC q2w with 400 mg loading dose for ≥30 to <60 kg body weight; dupilumab 300 mg SC q4w for ≥15 to <30 kg body weight; and dupilumab 200 mg SC q4w for ≥5 to <15 kg body weight, for 3 years or until approval of the indication in Japan.

    Subject analysis set title
    Dupilumab /Dupilumab (Dupilumab Exposure Period)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received dupilumab 300 mg SC q2w with 600 mg loading dose for ≥60 kg body weight at baseline; dupilumab 200 mg SC q2w with 400 mg loading dose for ≥30 to <60 kg body weight at baseline; dupilumab 300 mg SC q4w for ≥15 to <30 kg body weight at baseline; and dupilumab 200 mg SC q4w for ≥5 to <15 kg body weight at baseline, for up to 16 weeks during the randomization treatment period. Participants then entered the OLE period and received dupilumab 300 mg SC q2w with 300 mg loading dose for ≥60 kg body weight; dupilumab 200 mg SC q2w with 200 mg loading dose for ≥30 to <60 kg body weight; dupilumab 300 mg SC q4w for ≥15 to <30 kg body weight; and dupilumab 200 mg SC q4w for ≥5 to <15 kg body weight, for 3 years or until approval of the indication in Japan.

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

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    End point title
    		 Percentage of Participants With Eczema Area and Severity Index (EASI)-75 (≥75% Improvement From Baseline EASI) at Week 16
    End point description
    EASI score was a validated measure used to assess severity and extent of atopic dermatitis (AD). The 4 AD disease characteristics (erythema, thickness [induration, papulation, edema], scratching [excoriation], lichenification) were assessed for severity on scale of 0 (absent) to 3 (severe). Area of AD involvement was assessed as percentage by body area of head, trunk, upper limbs, lower limbs, and converted to score of 0 to 6. In each body region, area was expressed as 0, 1 (1% to 9%), 2 (10% to 29%), 3 (30% to 49%), 4 (50% to 69%), 5 (70% to 89%), or 6 (90% to 100%). For each body region, EASI score = (sum of the 4 AD disease characteristics scores) multiplied by (area of AD involvement score). Total EASI score ranged from 0 to 72, higher scores indicated increased extent and severity of AD. The Intent-to-treat (ITT) population included all randomized participants analyzed according to treatment group allocated by randomization regardless if the treatment kit was used or not.
    End point type
    Primary
    End point timeframe
    Week 16
    End point values
    		 Placebo (Randomization Treatment Period) Dupilumab (Randomization Treatment Period)
    Number of subjects analysed
    32
    30
    Units: percentage of participants
        number (not applicable)
    18.8
    43.3
    Statistical analysis title
    		 Dupilumab versus Placebo
    Comparison groups
    Placebo (Randomization Treatment Period) v Dupilumab (Randomization Treatment Period)
    Number of subjects included in analysis
    62
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [1]
    P-value
    		 = 0.0304 [2]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Response rate difference
    Point estimate
    25.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.26
         upper limit
    		 46.9
    Notes
    [1] - A hierarchical testing procedure was used to control the overall type-I error. Testing was then performed sequentially in order the outcome measure is reported and continued when previous outcome measure was statistically significant at two-sided 0.05.
    [2] - Cochran-Mantel-Haenszel(CMH) test was performed on association between responder status and intervention group, adjusted by randomization strata(≥6 months-<6 years,≥6 years-<12 years and IGA=3, ≥6 years-<12 years and IGA=4, and ≥12years at baseline).

    Secondary: Percent Change in EASI Score From Baseline to Week 16

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    End point title
    		 Percent Change in EASI Score From Baseline to Week 16
    End point description
    EASI score was validated measure used to assess severity and extent of AD.The 4 AD disease characteristics (erythema,thickness[induration,papulation,edema],scratching[excoriation],lichenification) were assessed for severity on scale of 0(absent) to 3(severe). Area of AD involvement was assessed as percentage by body area of head,trunk,upper limbs,lower limbs, and converted to score of 0-6. In each body region, area was expressed as 0,1(1%-9%),2(10%-29%),3(30%-49%),4(50%-69%),5(70%-89%), or 6(90%-100%). For each body region, EASI score=(sum of the 4 AD disease characteristics scores) multiplied by (area of AD involvement score). Total EASI score ranged 0-72, higher scores=increased extent and severity of AD. Baseline value=last available value before study drug administration. ITT population=all randomized participants analyzed according to treatment group allocated by randomization regardless if treatment kit was used or not. Only those participants with data available were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) to Week 16
    End point values
    		 Placebo (Randomization Treatment Period) Dupilumab (Randomization Treatment Period)
    Number of subjects analysed
    32
    29
    Units: percent change
        least squares mean (standard error)
    -23.27 ± 7.81
    -62.65 ± 7.87
    Statistical analysis title
    		 Dupilumab Versus Placebo
    Comparison groups
    Placebo (Randomization Treatment Period) v Dupilumab (Randomization Treatment Period)
    Number of subjects included in analysis
    61
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [3]
    P-value
    		 = 0.0003 [4]
    Method
    		 ANCOVA
    Parameter type
    		 Least Square (LS) Mean Difference
    Point estimate
    -39.38
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -60.57
         upper limit
    		 -18.19
    Notes
    [3] - A hierarchical testing procedure was used to control the overall type-I error. Testing was then performed sequentially in order the outcome measure is reported and continued when previous outcome measure was statistically significant at two-sided 0.05.
    [4] - Covariance model with treatment group (placebo vs pooled dupilumab), randomization strata defined as (≥6 months to <6 years, ≥6 years to <12 years and IGA=3, ≥6 years to <12 years and IGA=4, and ≥12 years), and baseline EASI score as covariates.

    Secondary: Percent Change From Baseline to Week 16 in Weekly Average of Daily Worst Itch Numerical Rating Scale (NRS) for Participants Aged ≥6 Years to <12 Years old

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    End point title
    		 Percent Change From Baseline to Week 16 in Weekly Average of Daily Worst Itch Numerical Rating Scale (NRS) for Participants Aged ≥6 Years to <12 Years old
    End point description
    The worst itch scale was a simple assessment tool used to report the intensity of their pruritus (itch). This was a 11-point scale (0 to 10) in which 0 indicated no itching while 10 indicated worst itching possible, and higher scores indicated greater severity. Participants were asked the following 2 questions: “What was the worst itch you had today?” and “What was the worst itch you had last night?”. The daily worst itch score was calculated as the worse of the scores for the 2 questions. Baseline worst itch average score for maximum itch intensity was determined based on the average of daily worst itch scores for maximum itch intensity during the 7 days immediately preceding randomization. The baseline value was defined as the last available value before study drug administration. Only participants from ITT population aged ≥6 years to <12 years old with data available were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) to Week 16
    End point values
    		 Placebo (Randomization Treatment Period) Dupilumab (Randomization Treatment Period)
    Number of subjects analysed
    18
    14
    Units: percent change
        least squares mean (standard error)
    -6.16 ± 9.65
    -39.45 ± 10.14
    Statistical analysis title
    		 Dupilumab Versus Placebo
    Comparison groups
    Placebo (Randomization Treatment Period) v Dupilumab (Randomization Treatment Period)
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [5]
    P-value
    		 = 0.0117 [6]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -33.28
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -59.15
         upper limit
    		 -7.42
    Notes
    [5] - A hierarchical testing procedure was used to control the overall type-I error. Testing was then performed sequentially in order the outcome measure is reported and continued when previous outcome measure was statistically significant at two-sided 0.05.
    [6] - Covariance model with treatment group (placebo vs pooled dupilumab), randomization strata defined as (IGA=3 vs 4), and baseline NRS score as covariates.

    Secondary: Percentage of Participants With Investigator’s Global Assessment (IGA) 0 or 1 at Week 16

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    End point title
    		 Percentage of Participants With Investigator’s Global Assessment (IGA) 0 or 1 at Week 16
    End point description
    The IGA was a static 5-point assessment instrument used in clinical studies to rate the severity of AD globally. The ratings (0 = clear, 1 = almost clear, 2 = mild, 3 = moderate, 4 = severe) were an overall assessment of the skin lesions based on erythema and papulation/infiltration. Higher score indicated more severe disease. The ITT population included all randomized participants analyzed according to the treatment group allocated by randomization regardless if the treatment kit was used or not.
    End point type
    Secondary
    End point timeframe
    Week 16
    End point values
    		 Placebo (Randomization Treatment Period) Dupilumab (Randomization Treatment Period)
    Number of subjects analysed
    32
    30
    Units: percentage of participants
        number (not applicable)
    9.4
    10.0
    Statistical analysis title
    		 Dupilumab Versus Placebo
    Comparison groups
    Placebo (Randomization Treatment Period) v Dupilumab (Randomization Treatment Period)
    Number of subjects included in analysis
    62
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [7]
    P-value
    		 = 0.8476 [8]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Response rate difference
    Point estimate
    1.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -13.73
         upper limit
    		 16.66
    Notes
    [7] - A hierarchical testing procedure was used to control the overall type-I error. Testing was then performed sequentially in order the outcome measure is reported and continued when previous outcome measure was statistically significant at two-sided 0.05.
    [8] - CMH test was performed on association between responder status and intervention group, adjusted by randomization strata (≥6 months to <6 years, ≥6 years to <12 years old and IGA=3, ≥6 years to <12 years old and IGA=4, and ≥12 years at baseline).

    Secondary: Percent Change From Baseline to Week 16 in Weekly Average of Daily Worst Pruritus Using the Peak Pruritus NRS for Participants Aged ≥12 Years to <18 Years old

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    End point title
    		 Percent Change From Baseline to Week 16 in Weekly Average of Daily Worst Pruritus Using the Peak Pruritus NRS for Participants Aged ≥12 Years to <18 Years old
    End point description
    The peak pruritus NRS was a simple assessment tool used report the intensity of their pruritus (itch) during a 24-hour recall period. Participants were asked the following question: For maximum itch intensity: “On a scale of 0 to 10, with 0 being ‘no itch’ and 10 being the ‘worst itch imaginable’, how would you rate your itch at the worst moment during the previous 24 hours?”. Participants answered the question on the scale of 0 (no itch) to 10 (worst itch imaginable), where higher scores indicated greater severity. Baseline pruritus NRS average score for maximum itch intensity was determined based on the average of daily NRS scores for maximum itch intensity during the 7 days immediately preceding randomization. The baseline value was defined as the last available value before study drug administration. Only participants from ITT population aged ≥12 years to <18 years old were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) to Week 16
    End point values
    		 Placebo (Randomization Treatment Period) Dupilumab (Randomization Treatment Period)
    Number of subjects analysed
    8
    9
    Units: percent change
        least squares mean (standard error)
    -22.20 ± 6.73
    -20.91 ± 6.33
    No statistical analyses for this end point

    Secondary: Percent Change From Baseline to Week 16 in Weekly Average of Daily Worst Scratch/Itch NRS for Participants Aged ≥6 Months to <6 Years old

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    End point title
    		 Percent Change From Baseline to Week 16 in Weekly Average of Daily Worst Scratch/Itch NRS for Participants Aged ≥6 Months to <6 Years old
    End point description
    The worst scratch/itch scale was an assessment tool that parents/caregivers of children aged ≥6 months to <6 years old used to report intensity of their child pruritus(scratch/itch) on 11-point scale (0-10) in which 0=no scratching/itching while 10=worst scratching/itching possible; higher scores indicated greater severity. Parents/caregivers were asked following instructions: “Answer the question below based on what you observe and what your child tells you (if applicable)”, and following question: “How would you rate your child’s scratching/itching at its worst in past 24 hours?”. Baseline worst itch scratch/itch average score for maximum itch intensity was determined based on average of daily worst scratch/itch scores for maximum itch intensity during 7 days immediately preceding randomization. The baseline value was defined as the last available value before study drug administration. Only participants from ITT population aged ≥6 months to <6 years old were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) to Week 16
    End point values
    		 Placebo (Randomization Treatment Period) Dupilumab (Randomization Treatment Period)
    Number of subjects analysed
    6
    4
    Units: percent change
        least squares mean (standard error)
    -10.88 ± 6.38
    -16.53 ± 7.93
    No statistical analyses for this end point

    Secondary: Percent Change From Baseline to Week 16 in Weekly Average of Daily Worst Pruritus Using Peak Pruritus NRS (Participants Aged ≥12Years[Yr]-<18Yr), Worst Itch NRS (Participants Aged ≥6Yr-<12Yr), and Worst Scratch/Itch NRS (Participants Aged ≥6 Months-<6Yr)

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    End point title
    		 Percent Change From Baseline to Week 16 in Weekly Average of Daily Worst Pruritus Using Peak Pruritus NRS (Participants Aged ≥12Years[Yr]-<18Yr), Worst Itch NRS (Participants Aged ≥6Yr-<12Yr), and Worst Scratch/Itch NRS (Participants Aged ≥6 Months-<6Yr)
    End point description
    Participants were asked certain questions for each scale that was used to report the intensity of pruritus (scratch/itch): the peak pruritus NRS for participants aged ≥12 years to <18 years old, the worst itch scale for participants aged ≥6 years to <12 years old, and the worst scratch/itch scale for participants aged ≥6 months to <6 years old. Participants or their parents/caregivers answered the questions on the scale of 0 (no itch) to 10 (worst itch imaginable), where higher scores indicated greater severity. The results of worst pruritus NRS across 3 age categories were pooled as a single indicator. The baseline value was defined as the last available value before study drug administration. The ITT population included all randomized participants analyzed according to the treatment group allocated by randomization regardless if the treatment kit was used or not. Only those participants with data available were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) to Week 16
    End point values
    		 Placebo (Randomization Treatment Period) Dupilumab (Randomization Treatment Period)
    Number of subjects analysed
    32
    27
    Units: percent change
        least squares mean (standard error)
    -10.38 ± 5.83
    -31.85 ± 6.25
    No statistical analyses for this end point

    Secondary: Percentage of Participants With EASI-50 (≥50% Improvement From Baseline) and EASI-90 (≥90% Improvement From Baseline) at Week 16

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    End point title
    		 Percentage of Participants With EASI-50 (≥50% Improvement From Baseline) and EASI-90 (≥90% Improvement From Baseline) at Week 16
    End point description
    EASI score was a validated measure used to assess severity and extent of AD. The 4 AD disease characteristics (erythema, thickness [induration, papulation, edema], scratching [excoriation], lichenification) were assessed for severity on scale of 0 (absent) to 3 (severe). Area of AD involvement was assessed as percentage by body area of head, trunk, upper limbs, lower limbs, and converted to score of 0 to 6. In each body region, area was expressed as 0, 1 (1% to 9%), 2 (10% to 29%), 3 (30% to 49%), 4 (50% to 69%), 5 (70% to 89%), or 6 (90% to 100%). For each body region, EASI score = (sum of the 4 AD disease characteristics scores) multiplied by (area of AD involvement score). Total EASI score ranged from 0 to 72, higher scores indicated increased extent and severity of AD. The ITT population included all randomized participants analyzed according to the treatment group allocated by randomization regardless if the treatment kit was used or not.
    End point type
    Secondary
    End point timeframe
    Week 16
    End point values
    		 Placebo (Randomization Treatment Period) Dupilumab (Randomization Treatment Period)
    Number of subjects analysed
    32
    30
    Units: percentage of participants
    number (not applicable)
        EASI-50
    31.3
    73.3
        EASI-90
    12.5
    6.7
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline to Week 16 in Percent Body Surface Area (BSA) Affected by Atopic Dermatitis
    End point description
    Body surface area 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 was reported as a percentage of all major body sections combined. The baseline value was defined as the last available value before study drug administration. The ITT population included all randomized participants analyzed according to the treatment group allocated by randomization regardless if the treatment kit was used or not. Only those participants with data available were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) to Week 16
    End point values
    		 Placebo (Randomization Treatment Period) Dupilumab (Randomization Treatment Period)
    Number of subjects analysed
    32
    29
    Units: percent BSA
        least squares mean (standard error)
    -8.56 ± 3.85
    -27.28 ± 3.84
    No statistical analyses for this end point

    Secondary: Change from Baseline to Week 16 in Children's Dermatology Life Quality Index (CDLQI) (≥4 years)

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    End point title
    		 Change from Baseline to Week 16 in Children's Dermatology Life Quality Index (CDLQI) (≥4 years)
    End point description
    CDLQI was a validated questionnaire designed to measure impact of skin disease on Quality of Life (QOL) in children aged ≥4 years of age. To complete the questionnaire, participants provided responses to 10 questions that focused on domains such as symptoms feelings associated with disease, impact of disease on leisure, school or holidays, personal relationships, sleep, and side effects of treatment for the skin disease. 9 questions were scored as follows: Very much = 3, Quite a lot = 2, Only a little = 1, Not at all or unanswered = 0. Question 7 had an added possible response, which was scored as 3. CDLQI for a participant is sum of score of each question with maximum of 30 and minimum of 0. Higher score indicated greater impact on the QOL. The baseline value was defined as the last available value before study drug administration. Only participants from ITT population aged ≥4 years old with data available were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) to Week 16
    End point values
    		 Placebo (Randomization Treatment Period) Dupilumab (Randomization Treatment Period)
    Number of subjects analysed
    26
    25
    Units: score on a scale
        least squares mean (standard error)
    0.44 ± 0.77
    -2.81 ± 0.76
    No statistical analyses for this end point

    Secondary: Change from Baseline to Week 16 in Infants' Dermatitis Quality of Life Index (IDQOL) (<4 years)

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    End point title
    		 Change from Baseline to Week 16 in Infants' Dermatitis Quality of Life Index (IDQOL) (<4 years)
    End point description
    IDQOL was a validated questionnaire developed to measure the impact of skin disease on QOL of infants and preschool children <4 years of age. IDQOL was completed by child’s parent or caregiver. The questionnaire consisted of 10 questions related to itching and scratching; mood of the child; how long it took for the child to get to sleep; whether the eczema had interfered with the child’s playing, swimming or participation in other family activities; problems during mealtimes; problems caused by treatment; level of comfort while dressing or undressing the child; and problems during bathing. Each question asked about the impact over the previous week and was scored on a scale of 0 (minimum impact) to 3 (maximum impact). The higher the score, the greater was the impact on QOL. The baseline value was defined as the last available value before study drug administration. Only participants from ITT population aged <4 years old were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) to Week 16
    End point values
    		 Placebo (Randomization Treatment Period) Dupilumab (Randomization Treatment Period)
    Number of subjects analysed
    2
    2
    Units: score on a scale
        least squares mean (standard error)
    0.27 ± 3.46
    -9.27 ± 3.46
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline to Week 16 in Patient Oriented Eczema Measure (POEM)
    End point description
    The POEM was a 7-item, validated PRO questionnaire used in clinical practice and clinical trials 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 (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 disease-related morbidity. Higher scores indicated more severe disease. The baseline value was defined as the last available value before study drug administration. The ITT population included all randomized participants analyzed according to the treatment group allocated by randomization regardless if the treatment kit was used or not. Only those participants with data available were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) to Week 16
    End point values
    		 Placebo (Randomization Treatment Period) Dupilumab (Randomization Treatment Period)
    Number of subjects analysed
    32
    29
    Units: score on a scale
        least squares mean (standard error)
    -0.89 ± 1.29
    -8.45 ± 1.36
    No statistical analyses for this end point

    Secondary: Change from Baseline to Week 16 in Weekly Average of Daily Worst Pruritus Using the Peak Pruritus NRS for Participants Aged ≥12 Years to <18 Years old

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    End point title
    		 Change from Baseline to Week 16 in Weekly Average of Daily Worst Pruritus Using the Peak Pruritus NRS for Participants Aged ≥12 Years to <18 Years old
    End point description
    The peak pruritus NRS was a simple assessment tool used report the intensity of their pruritus (itch) during a 24-hour recall period. Participants were asked the following question: For maximum itch intensity: “On a scale of 0 to 10, with 0 being ‘no itch’ and 10 being the ‘worst itch imaginable’, how would you rate your itch at the worst moment during the previous 24 hours?”. Participants answered the question on the scale of 0 (no itch) to 10 (worst itch imaginable), where higher scores indicated greater severity. Baseline pruritus NRS average score for maximum itch intensity was determined based on the average of daily NRS scores for maximum itch intensity during the 7 days immediately preceding randomization. The baseline value was defined as the last available value before study drug administration. Only participants from ITT population aged ≥12 years to <18 years old were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) to Week 16
    End point values
    		 Placebo (Randomization Treatment Period) Dupilumab (Randomization Treatment Period)
    Number of subjects analysed
    8
    9
    Units: score on a scale
        least squares mean (standard error)
    -1.38 ± 0.46
    -1.32 ± 0.43
    No statistical analyses for this end point

    Secondary: Change from Baseline to Week 16 in Weekly Average of Daily Worst Itch NRS for Participants Aged ≥6 Years to <12 Years old

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    End point title
    		 Change from Baseline to Week 16 in Weekly Average of Daily Worst Itch NRS for Participants Aged ≥6 Years to <12 Years old
    End point description
    The worst itch scale was a simple assessment tool used to report the intensity of their pruritus (itch). This was a 11-point scale (0 to 10) in which 0 indicated no itching while 10 indicated worst itching possible, and higher scores indicated greater severity. Participants were asked the following 2 questions: “What was the worst itch you had today?” and “What was the worst itch you had last night?”. The daily worst itch score was calculated as the worse of the scores for the 2 questions. Baseline worst itch average score for maximum itch intensity was determined based on the average of daily worst itch scores for maximum itch intensity during the 7 days immediately preceding randomization. The baseline value was defined as the last available value before study drug administration. Only participants from ITT population aged ≥6 years to <12 years old with data available were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) to Week 16
    End point values
    		 Placebo (Randomization Treatment Period) Dupilumab (Randomization Treatment Period)
    Number of subjects analysed
    18
    14
    Units: score on a scale
        least squares mean (standard error)
    -0.77 ± 0.68
    -2.95 ± 0.72
    No statistical analyses for this end point

    Secondary: Change from Baseline to Week 16 in Weekly Average of Daily Worst Scratch/Itch NRS for Participants Aged ≥6 Months to <6 Years old

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    End point title
    		 Change from Baseline to Week 16 in Weekly Average of Daily Worst Scratch/Itch NRS for Participants Aged ≥6 Months to <6 Years old
    End point description
    The worst scratch/itch scale was an assessment tool that parents/caregivers of children aged ≥6 months to <6 years old used to report intensity of their child pruritus(scratch/itch) on 11-point scale (0-10) in which 0=no scratching/itching while 10=worst scratching/itching possible; higher scores indicated greater severity. Parents/caregivers were asked following instructions: “Answer the question below based on what you observe and what your child tells you (if applicable)”, and following question: “How would you rate your child’s scratching/itching at its worst in past 24 hours?”. Baseline worst itch scratch/itch average score for maximum itch intensity was determined based on average of daily worst scratch/itch scores for maximum itch intensity during 7 days immediately preceding randomization. The baseline value was defined as the last available value before study drug administration. Only participants from ITT population aged ≥6 months to <6 years old were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) to Week 16
    End point values
    		 Placebo (Randomization Treatment Period) Dupilumab (Randomization Treatment Period)
    Number of subjects analysed
    6
    4
    Units: score on a scale
        least squares mean (standard error)
    -0.80 ± 0.49
    -1.24 ± 0.61
    No statistical analyses for this end point

    Secondary: Number of Participants With Skin-Infection TEAEs (Excluding Herpetic Infections) From Baseline to 16 Weeks of Treatment

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    End point title
    		 Number of Participants With Skin-Infection TEAEs (Excluding Herpetic Infections) From Baseline to 16 Weeks of Treatment
    End point description
    AE: Any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs: AEs that developed, worsened or became serious during the treatment-emergent period. The baseline value was defined as the last available value before study drug administration. Safety population included all participants randomly assigned to study intervention and who received at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) to Week 16
    End point values
    		 Placebo (Randomization Treatment Period) Dupilumab (Randomization Treatment Period)
    Number of subjects analysed
    32
    30
    Units: partcipants
    2
    2
    No statistical analyses for this end point

    Secondary: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs), Serious Adverse Events (SAEs), and Adverse Event of Special Interest (AESI) From Baseline to 16 Weeks of Treatment

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    End point title
    		 Number of Participants With Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs), Serious Adverse Events (SAEs), and Adverse Event of Special Interest (AESI) From Baseline to 16 Weeks of Treatment
    End point description
    Adverse event(AE): Any untoward medical occurrence in participant or clinical study participant, temporally associated with use of study intervention, whether or not considered related to study intervention. SAE: Any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, was congenital anomaly/birth defect, was medically important event. TEAEs: AEs that developed, worsened or became serious during treatment-emergent period. AESI: an AE(serious or nonserious) of scientific and medical concern specific to Sponsor’s product or program, for which ongoing monitoring and immediate notification by Investigator to Sponsor was required. Baseline value=as last available value before study drug administration. Safety population=all participants randomly assigned to study intervention and who received at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) to Week 16
    End point values
    		 Placebo (Randomization Treatment Period) Dupilumab (Randomization Treatment Period)
    Number of subjects analysed
    32
    30
    Units: participants
        Any TEAE
    19
    19
        Any TESAE
    1
    1
        Any SAE
    1
    1
        Any AESI
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Participants With Treatment-emergent Anti-drug Antibody (ADA) to Dupilumab Over Time in Pediatric Participants with AD (Aged ≥6 Months to <18 Years old)

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    End point title
    		 Number of Participants With Treatment-emergent Anti-drug Antibody (ADA) to Dupilumab Over Time in Pediatric Participants with AD (Aged ≥6 Months to <18 Years old)
    End point description
    Treatment-emergent ADA were defined as a positive response in the ADA assay post first dose, when baseline results are negative or missing. ADA population included all participants in the safety population who had at least 1 non-missing result in the ADA assay after first dose of the study treatment.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) to Week 116
    End point values
    		 Placebo (Randomization Treatment Period) Placebo/Dupilumab (Open-label Extension Period) Dupilumab (Randomization Treatment Period) Dupilumab/Dupilumab (Open-label Extension Period)
    Number of subjects analysed
    32
    32
    30
    28
    Units: participants
    2
    1
    2
    0
    No statistical analyses for this end point

    Secondary: Number of Participants With TEAEs, SAEs, and AESI From Baseline of OLE Through the Last Study Visit

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    End point title
    		 Number of Participants With TEAEs, SAEs, and AESI From Baseline of OLE Through the Last Study Visit
    End point description
    AE: Any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. SAE: Any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs: AEs that developed, worsened or became serious during the treatment-emergent period. AESI: an AE (serious or nonserious) of scientific and medical concern specific to the Sponsor’s product or program, for which ongoing monitoring and immediate notification by the Investigator to the Sponsor was required. Safety population included all participants randomly assigned to study intervention and who received at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    Week 16 to Week 116
    End point values
    		 Placebo/Dupilumab (Open-label Extension Period) Dupilumab/Dupilumab (Open-label Extension Period)
    Number of subjects analysed
    32
    28
    Units: participants
        Any TEAE
    30
    25
        Any SAE
    1
    2
        Any AESI
    0
    1
    No statistical analyses for this end point

    Secondary: Serum Concentration of Dupilumab up to Week 116

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    End point title
    		 Serum Concentration of Dupilumab up to Week 116
    End point description
    Serum samples were collected at specified timepoints. The PK population included all participants in the safety population with at least 1 non-missing result for functional dupilumab concentration in serum after first dose of the study treatment. Participants were analyzed according to the intervention actually received. Only those participants with data available were analyzed. Here, n=number of participants analyzed at the specified timepoint. 9999=parameter was not estimable as no participants were analyzed.
    End point type
    Secondary
    End point timeframe
    Pre-dose at Baseline (Day 1), and Weeks 4, 12, 16, 24, 32, 52, 68, 92, and 116
    End point values
    		 Placebo/Dupilumab (Dupilumab Exposure Period) Dupilumab /Dupilumab (Dupilumab Exposure Period)
    Number of subjects analysed
    30
    30
    Units: nanogram per milliliter (ng/mL)
    arithmetic mean (standard deviation)
        Baseline (n=0, 30)
    9999 ± 9999
    0.000 ± 0.000
        Week 4 (n=0, 29)
    9999 ± 9999
    52439.45 ± 24687.36
        Week 12 (n=0, 25)
    9999 ± 9999
    70160.00 ± 28052.67
        Week 16 (n=0, 27)
    9999 ± 9999
    75525.93 ± 31785.13
        Week 24 (n=30, 23)
    47883.33 ± 15953.99
    86665.22 ± 45997.76
        Week 32 (n=29, 20)
    58496.55 ± 25001.72
    84075.00 ± 49956.25
        Week 52 (n=23, 22)
    61856.52 ± 20717.49
    78286.36 ± 42318.32
        Week 68 (n=27, 24)
    62133.33 ± 18267.44
    77916.67 ± 41003.26
        Week 92 (n=26, 25)
    57373.08 ± 19790.96
    70153.56 ± 31250.06
        Week 116 (n=17, 17)
    51405.88 ± 16209.85
    64294.12 ± 24337.07
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Baseline to Week 16 (randomization treatment period) and Week 16 to end of study (EOS) (OLE period), up to approximately 140 weeks
    Adverse event reporting additional description
    Analysis was performed on safety population.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    26.1
    Reporting groups
    Reporting group title
    Placebo (Randomization Treatment Period)
    Reporting group description
    		 Participants received placebo matched to dupilumab SC q2w with placebo loading dose for ≥30 kg body weight at baseline; placebo matched to dupilumab SC q4w for ≥5 to <30 kg body weight at baseline, for up to 16 weeks during the randomization treatment period.

    Reporting group title
    Dupilumab (Randomization Treatment Period)
    Reporting group description
    		 Participants received dupilumab 300 mg SC q2w with 600 mg loading dose for ≥60 kg body weight at baseline; dupilumab 200 mg SC q2w with 400 mg loading dose for ≥30 to <60 kg body weight at baseline; dupilumab 300 mg SC q4w for ≥15 to <30 kg body weight at baseline; and dupilumab 200 mg SC q4w for ≥5 to <15 kg body weight at baseline, for up to 16 weeks during the randomization treatment period.

    Reporting group title
    Placebo/Dupilumab (Open-label Extension Period)
    Reporting group description
    		 Participants who received placebo during the randomization treatment period and who entered the OLE period, received dupilumab 300 mg SC q2w with 600 mg loading dose for ≥60 kg body weight; dupilumab 200 mg SC q2w with 400 mg loading dose for ≥30 to <60 kg body weight; dupilumab 300 mg SC q4w for ≥15 to <30 kg body weight; and dupilumab 200 mg SC q4w for ≥5 to <15 kg body weight, for 3 years or until approval of the indication in Japan.

    Reporting group title
    Dupilumab/Dupilumab (Open-label Extension Period)
    Reporting group description
    		 Participants who received dupilumab during the randomization treatment period and who entered the OLE period, received dupilumab 300 mg SC q2w with 300 mg loading dose for ≥60 kg body weight; dupilumab 200 mg SC q2w with 200 mg loading dose for ≥30 to <60 kg body weight; dupilumab 300 mg SC q4w for ≥15 to <30 kg body weight; and dupilumab 200 mg SC q4w for ≥5 to <15 kg body weight, for 3 years or until approval of the indication in Japan.

    Serious adverse events
    		 Placebo (Randomization Treatment Period) Dupilumab (Randomization Treatment Period) Placebo/Dupilumab (Open-label Extension Period) Dupilumab/Dupilumab (Open-label Extension Period)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 32 (3.13%)
    1 / 30 (3.33%)
    1 / 32 (3.13%)
    2 / 28 (7.14%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Injury, poisoning and procedural complications
    Skin Laceration
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
    1 / 28 (3.57%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Febrile Convulsion
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
    1 / 28 (3.57%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
    1 / 28 (3.57%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Terminal Ileitis
         subjects affected / exposed
    0 / 32 (0.00%)
    1 / 30 (3.33%)
    0 / 32 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Attention Deficit Hyperactivity Disorder
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 30 (0.00%)
    1 / 32 (3.13%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Covid-19
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo (Randomization Treatment Period) Dupilumab (Randomization Treatment Period) Placebo/Dupilumab (Open-label Extension Period) Dupilumab/Dupilumab (Open-label Extension Period)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    12 / 32 (37.50%)
    14 / 30 (46.67%)
    28 / 32 (87.50%)
    23 / 28 (82.14%)
    Injury, poisoning and procedural complications
    Wound
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 30 (0.00%)
    2 / 32 (6.25%)
    1 / 28 (3.57%)
         occurrences all number
    0
    0
    2
    1
    Ligament Sprain
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 30 (0.00%)
    3 / 32 (9.38%)
    1 / 28 (3.57%)
         occurrences all number
    1
    0
    3
    1
    Hand Fracture
         subjects affected / exposed
    0 / 32 (0.00%)
    1 / 30 (3.33%)
    1 / 32 (3.13%)
    2 / 28 (7.14%)
         occurrences all number
    0
    1
    1
    2
    Foot Fracture
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 30 (0.00%)
    1 / 32 (3.13%)
    3 / 28 (10.71%)
         occurrences all number
    0
    0
    1
    3
    Arthropod Bite
         subjects affected / exposed
    2 / 32 (6.25%)
    0 / 30 (0.00%)
    2 / 32 (6.25%)
    1 / 28 (3.57%)
         occurrences all number
    2
    0
    2
    1
    Nervous system disorders
    Headache
         subjects affected / exposed
    1 / 32 (3.13%)
    1 / 30 (3.33%)
    1 / 32 (3.13%)
    2 / 28 (7.14%)
         occurrences all number
    1
    1
    1
    2
    Syncope
         subjects affected / exposed
    0 / 32 (0.00%)
    2 / 30 (6.67%)
    0 / 32 (0.00%)
    2 / 28 (7.14%)
         occurrences all number
    0
    2
    0
    2
    Blood and lymphatic system disorders
    Neutropenia
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 30 (0.00%)
    1 / 32 (3.13%)
    2 / 28 (7.14%)
         occurrences all number
    0
    0
    2
    3
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    0 / 32 (0.00%)
    3 / 30 (10.00%)
    6 / 32 (18.75%)
    11 / 28 (39.29%)
         occurrences all number
    0
    3
    7
    15
    Injection Site Reaction
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
    2 / 28 (7.14%)
         occurrences all number
    0
    0
    0
    2
    Eye disorders
    Conjunctivitis Allergic
         subjects affected / exposed
    0 / 32 (0.00%)
    4 / 30 (13.33%)
    6 / 32 (18.75%)
    4 / 28 (14.29%)
         occurrences all number
    0
    4
    9
    5
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    0 / 32 (0.00%)
    2 / 30 (6.67%)
    0 / 32 (0.00%)
    2 / 28 (7.14%)
         occurrences all number
    0
    5
    0
    2
    Enteritis
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
    2 / 28 (7.14%)
         occurrences all number
    0
    0
    0
    3
    Dental Caries
         subjects affected / exposed
    2 / 32 (6.25%)
    1 / 30 (3.33%)
    4 / 32 (12.50%)
    3 / 28 (10.71%)
         occurrences all number
    2
    1
    8
    3
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 30 (0.00%)
    1 / 32 (3.13%)
    2 / 28 (7.14%)
         occurrences all number
    0
    0
    1
    3
    Skin and subcutaneous tissue disorders
    Dermatitis Contact
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 30 (0.00%)
    4 / 32 (12.50%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    4
    0
    Dermatitis Atopic
         subjects affected / exposed
    2 / 32 (6.25%)
    0 / 30 (0.00%)
    1 / 32 (3.13%)
    0 / 28 (0.00%)
         occurrences all number
    2
    0
    1
    0
    Acne
         subjects affected / exposed
    0 / 32 (0.00%)
    1 / 30 (3.33%)
    4 / 32 (12.50%)
    2 / 28 (7.14%)
         occurrences all number
    0
    1
    7
    3
    Urticaria
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 30 (0.00%)
    2 / 32 (6.25%)
    3 / 28 (10.71%)
         occurrences all number
    0
    0
    2
    4
    Psychiatric disorders
    Autism Spectrum Disorder
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
    2 / 28 (7.14%)
         occurrences all number
    0
    0
    0
    2
    Musculoskeletal and connective tissue disorders
    Myalgia
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 30 (0.00%)
    2 / 32 (6.25%)
    1 / 28 (3.57%)
         occurrences all number
    0
    0
    3
    1
    Back Pain
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 30 (0.00%)
    1 / 32 (3.13%)
    2 / 28 (7.14%)
         occurrences all number
    0
    0
    1
    3
    Arthralgia
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 30 (0.00%)
    1 / 32 (3.13%)
    2 / 28 (7.14%)
         occurrences all number
    0
    0
    2
    2
    Infections and infestations
    Impetigo
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 30 (0.00%)
    2 / 32 (6.25%)
    1 / 28 (3.57%)
         occurrences all number
    1
    0
    3
    1
    Hordeolum
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 30 (0.00%)
    2 / 32 (6.25%)
    2 / 28 (7.14%)
         occurrences all number
    0
    0
    2
    2
    Gastroenteritis
         subjects affected / exposed
    1 / 32 (3.13%)
    1 / 30 (3.33%)
    5 / 32 (15.63%)
    1 / 28 (3.57%)
         occurrences all number
    4
    1
    5
    1
    Covid-19
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 30 (0.00%)
    14 / 32 (43.75%)
    15 / 28 (53.57%)
         occurrences all number
    0
    0
    15
    17
    Bronchitis
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 30 (0.00%)
    1 / 32 (3.13%)
    2 / 28 (7.14%)
         occurrences all number
    0
    0
    1
    2
    Sinusitis
         subjects affected / exposed
    0 / 32 (0.00%)
    1 / 30 (3.33%)
    0 / 32 (0.00%)
    3 / 28 (10.71%)
         occurrences all number
    0
    1
    0
    5
    Oral Herpes
         subjects affected / exposed
    0 / 32 (0.00%)
    2 / 30 (6.67%)
    1 / 32 (3.13%)
    1 / 28 (3.57%)
         occurrences all number
    0
    2
    1
    3
    Nasopharyngitis
         subjects affected / exposed
    7 / 32 (21.88%)
    3 / 30 (10.00%)
    19 / 32 (59.38%)
    11 / 28 (39.29%)
         occurrences all number
    7
    3
    49
    18
    Influenza
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 30 (0.00%)
    2 / 32 (6.25%)
    3 / 28 (10.71%)
         occurrences all number
    0
    0
    3
    3

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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