Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   42517   clinical trials with a EudraCT protocol, of which   7000   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).


    Phase 1 trials conducted solely in adults and that are not part of an agreed PIP are not public in the EU CTR (refer to European Guidance 2008/C 168/02   Art. 3 par. 2 and   Commission Guideline 2012/C 302/03,   Art. 5) .

    Clinical Trials marked as "Trial now transitioned" were transitioned to the Clinical Trial Regulation 536/2014 and can be further followed in the Clinical Trial Information System  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Phase 2/3 Study Investigating the Pharmacokinetics, Safety, and Efficacy of Dupilumab in Patients Aged ≥ 6 Months to < 6 Years with Moderate-to-Severe Atopic Dermatitis

    Summary
    EudraCT number
    2016-000955-28
    Trial protocol
    DE   GB   PL  
    Global end of trial date
    08 Jul 2021

    Results information
    Results version number
    v1(current)
    This version publication date
    22 Jan 2022
    First version publication date
    22 Jan 2022
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    R668-AD-1539
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT03346434
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Regeneron Pharmaceuticals, Inc.
    Sponsor organisation address
    777 Old Saw Mill River Rd., Tarrytown, NY, United States, 10591
    Public contact
    Clinical Trials Administrator, Regeneron Pharmaceuticals, Inc., clinicaltrials@regeneron.com
    Scientific contact
    Clinical Trials Administrator, Regeneron Pharmaceuticals, Inc., clinicaltrials@regeneron.com
    Paediatric regulatory details
    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?
    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
    08 Jul 2021
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    08 Jul 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main objective of Part A of this study was to characterize the safety and pharmacokinetics (PK) of dupilumab administered as a single dose in pediatric subjects, greater than or equal to (≥) 6 months to less than (<) 6 years of age with severe atopic dermatitis (AD). The main objective of Part B of this study was to demonstrate the efficacy of multiple doses of dupilumab over 16 weeks of treatment when administered concomitantly with topical corticosteroids (TCS) in pediatric subjects, greater than or equal to (≥) 6 months to less than (<) 6 years of age, with moderate-to-severe 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 Conference on Harmonisation (ICH) guidelines for Good Clinical Practice (GCP) and applicable regulatory requirements.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    30 Nov 2017
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Poland: 41
    Country: Number of subjects enrolled
    United Kingdom: 15
    Country: Number of subjects enrolled
    Germany: 8
    Country: Number of subjects enrolled
    United States: 138
    Worldwide total number of subjects
    202
    EEA total number of subjects
    49
    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)
    31
    Children (2-11 years)
    171
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    This study was conducted in 2 parts: Part A and Part B. Part A enrolled subjects in the United States, Germany, and the United Kingdom. Part B enrolled subjects in the United States, Germany, Poland, and the United Kingdom. Subjects who enrolled in Part A of study were not eligible to participate in Part B.

    Pre-assignment
    Screening details
    Subjects in Part A enrolled in 2 sequential age cohorts: Cohort 1 (≥2 to <6 yrs) and Cohort 2 (≥6 months to <2 yrs). Each age cohort received dupilumab in 1 of 2 doses: 3 milligrams per kilogram (mg/kg) or 6 mg/kg. Subjects in Part B were randomized to 1 of 2 treatment groups: placebo + TCS or dupilumab 200/300 mg every four weeks (Q4W) + TCS.

    Period 1
    Period 1 title
    Part A and Part B (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Not applicable
    Blinding used
    Not blinded
    Blinding implementation details
    Part A was an open-label, single ascending dose, sequential cohort study and Part B was a randomized, double-blind, placebo-controlled study.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Part A: Cohort 1 (≥2 to <6 years old): Dupilumab 3 mg/kg
    Arm description
    Subjects received a single subcutaneous (SC) injection of dupilumab at a dose of 3 mg/kg at Day 1. At week 4, subjects could roll over into an open-label extension (OLE) study (R668-AD-1434), if considered eligible. Subjects who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
    Arm type
    Experimental

    Investigational medicinal product name
    Dupilumab
    Investigational medicinal product code
    REGN668
    Other name
    DUPIXENT®
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects received SC injection of dupilumab on different quadrants of the abdomen (avoiding navel and waist areas), upper thighs, and upper arms.

    Arm title
    Part A: Cohort 1 (≥2 to <6 years old): Dupilumab 6 mg/kg
    Arm description
    Subjects received a single SC injection of dupilumab at a dose of 6 mg/kg at Day 1. At week 4, subjects could roll over into an OLE study (R668-AD-1434), if considered eligible. Subjects who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
    Arm type
    Experimental

    Investigational medicinal product name
    Dupilumab
    Investigational medicinal product code
    REGN668
    Other name
    DUPIXENT®
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects received SC injection of dupilumab on different quadrants of the abdomen (avoiding navel and waist areas), upper thighs, and upper arms.

    Arm title
    Part A: Cohort 2 (≥6 months to <2 years): Dupilumab 3 mg/kg
    Arm description
    Subjects received a single SC injection of dupilumab at a dose of 3 mg/kg at Day 1. At week 4, subjects could roll over into an OLE study (R668-AD-1434), if considered eligible. Subjects who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
    Arm type
    Experimental

    Investigational medicinal product name
    Dupilumab
    Investigational medicinal product code
    REGN668
    Other name
    DUPIXENT®
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects received SC injection of dupilumab on different quadrants of the abdomen (avoiding navel and waist areas), upper thighs, and upper arms.

    Arm title
    Part A: Cohort 2 (≥6 months to <2 years): Dupilumab 6 mg/kg
    Arm description
    Subjects received a single SC injection of dupilumab at a dose of 6 mg/kg at Day 1. At week 4, subjects could roll over into an OLE study (R668-AD-1434), if considered eligible. Subjects who did not enter the OLE study were followed for up to an additional 4 weeks for safety.
    Arm type
    Experimental

    Investigational medicinal product name
    Dupilumab
    Investigational medicinal product code
    REGN668
    Other name
    DUPIXENT®
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects received SC injection of dupilumab on different quadrants of the abdomen (avoiding navel and waist areas), upper thighs, and upper arms.

    Arm title
    Part B: Placebo + TCS
    Arm description
    Subjects received SC injection of placebo matched to dupilumab Q4W along with low potency TCS on areas of thin skin (face, neck, intertriginous, and genital areas, areas of skin atrophy) for 16 weeks. At week 16, subjects could roll over into an OLE study (R668-AD-1434), if considered eligible. Subjects who did not enter the OLE study were followed for up to an additional 12 weeks for safety ([Week 28, end of study (EOS) period]).
    Arm type
    Experimental

    Investigational medicinal product name
    TCS
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Cream
    Routes of administration
    Topical use
    Dosage and administration details
    Subjects applied low potency TCS once daily to areas with active lesions.

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects received SC injection placebo matched to dupilumab on different quadrants of the abdomen (avoiding navel and waist areas), upper thighs, and upper arms.

    Arm title
    Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
    Arm description
    Subjects with baseline weight of ≥ 5 to < 15 kilogram (kg) received SC injections of 200 mg or subjects with baseline weight ≥ 15 to < 30 kg received SC injections of 300 mg of dupilumab at Day 1 and Q4W from Week 4 to Week 12. Subjects applied daily low potency TCS on areas of thin skin (face, neck, intertriginous, and genital areas, areas of skin atrophy) for 16 weeks. At week 16, subjects could roll over into an OLE study (R668-AD-1434), if considered eligible. Subjects who did not enter the OLE study were followed for up to an additional 12 weeks for safety ([Week 28, EOS period].
    Arm type
    Experimental

    Investigational medicinal product name
    TCS
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Cream
    Routes of administration
    Topical use
    Dosage and administration details
    Subjects applied low potency TCS once daily to areas with active lesions.

    Investigational medicinal product name
    Dupilumab
    Investigational medicinal product code
    REGN668
    Other name
    DUPIXENT®
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects received SC injection of dupilumab on different quadrants of the abdomen (avoiding navel and waist areas), upper thighs, and upper arms

    Number of subjects in period 1
    Part A: Cohort 1 (≥2 to <6 years old): Dupilumab 3 mg/kg Part A: Cohort 1 (≥2 to <6 years old): Dupilumab 6 mg/kg Part A: Cohort 2 (≥6 months to <2 years): Dupilumab 3 mg/kg Part A: Cohort 2 (≥6 months to <2 years): Dupilumab 6 mg/kg Part B: Placebo + TCS Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
    Started
    10
    10
    10
    10
    79
    83
    Completed Part A
    10
    10
    9
    10
    0 [1]
    0 [2]
    Completed Part B
    0 [3]
    0 [4]
    0 [5]
    0 [6]
    1
    1
    Completed
    10
    10
    9
    10
    1
    1
    Not completed
    0
    0
    1
    0
    78
    82
         Subjects transitioned to OLE study
    -
    -
    -
    -
    75
    81
         Subject randomised in error
    -
    -
    -
    -
    1
    -
         Consent withdrawn by subject
    -
    -
    1
    -
    1
    -
         Lost to follow-up
    -
    -
    -
    -
    1
    1
    Notes
    [1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Subjects who completed Part B, thus not entering OLE period were reported in this milestone for more clarity of study design.
    [2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Subjects who completed Part B, thus not entering OLE period were reported in this milestone for more clarity of study design.
    [3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: 10 subjects completed Part A of the study and all subjects transitioned to OLE study at Week 4.
    [4] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: 10 subjects completed Part A of the study and all subjects transitioned to OLE study at Week 4.
    [5] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: 10 subjects completed Part A of the study, out of which 9 subjects transitioned to OLE study at Week 4.
    [6] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: 10 subjects completed Part A of the study and all subjects transitioned to OLE study at Week 4.

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Part A: Cohort 1 (≥2 to <6 years old): Dupilumab 3 mg/kg
    Reporting group description
    Subjects received a single subcutaneous (SC) injection of dupilumab at a dose of 3 mg/kg at Day 1. At week 4, subjects could roll over into an open-label extension (OLE) study (R668-AD-1434), if considered eligible. Subjects who did not enter the OLE study were followed for up to an additional 4 weeks for safety.

    Reporting group title
    Part A: Cohort 1 (≥2 to <6 years old): Dupilumab 6 mg/kg
    Reporting group description
    Subjects received a single SC injection of dupilumab at a dose of 6 mg/kg at Day 1. At week 4, subjects could roll over into an OLE study (R668-AD-1434), if considered eligible. Subjects who did not enter the OLE study were followed for up to an additional 4 weeks for safety.

    Reporting group title
    Part A: Cohort 2 (≥6 months to <2 years): Dupilumab 3 mg/kg
    Reporting group description
    Subjects received a single SC injection of dupilumab at a dose of 3 mg/kg at Day 1. At week 4, subjects could roll over into an OLE study (R668-AD-1434), if considered eligible. Subjects who did not enter the OLE study were followed for up to an additional 4 weeks for safety.

    Reporting group title
    Part A: Cohort 2 (≥6 months to <2 years): Dupilumab 6 mg/kg
    Reporting group description
    Subjects received a single SC injection of dupilumab at a dose of 6 mg/kg at Day 1. At week 4, subjects could roll over into an OLE study (R668-AD-1434), if considered eligible. Subjects who did not enter the OLE study were followed for up to an additional 4 weeks for safety.

    Reporting group title
    Part B: Placebo + TCS
    Reporting group description
    Subjects received SC injection of placebo matched to dupilumab Q4W along with low potency TCS on areas of thin skin (face, neck, intertriginous, and genital areas, areas of skin atrophy) for 16 weeks. At week 16, subjects could roll over into an OLE study (R668-AD-1434), if considered eligible. Subjects who did not enter the OLE study were followed for up to an additional 12 weeks for safety ([Week 28, end of study (EOS) period]).

    Reporting group title
    Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
    Reporting group description
    Subjects with baseline weight of ≥ 5 to < 15 kilogram (kg) received SC injections of 200 mg or subjects with baseline weight ≥ 15 to < 30 kg received SC injections of 300 mg of dupilumab at Day 1 and Q4W from Week 4 to Week 12. Subjects applied daily low potency TCS on areas of thin skin (face, neck, intertriginous, and genital areas, areas of skin atrophy) for 16 weeks. At week 16, subjects could roll over into an OLE study (R668-AD-1434), if considered eligible. Subjects who did not enter the OLE study were followed for up to an additional 12 weeks for safety ([Week 28, EOS period].

    Reporting group values
    Part A: Cohort 1 (≥2 to <6 years old): Dupilumab 3 mg/kg Part A: Cohort 1 (≥2 to <6 years old): Dupilumab 6 mg/kg Part A: Cohort 2 (≥6 months to <2 years): Dupilumab 3 mg/kg Part A: Cohort 2 (≥6 months to <2 years): Dupilumab 6 mg/kg Part B: Placebo + TCS Part B: Dupilumab 200 mg or 300 mg Q4W + TCS Total
    Number of subjects
    10 10 10 10 79 83 202
    Age categorical
    Units: Subjects
        6 months - <2 years
    0 0 10 10 5 6 31
        ≥2 years and <6 years
    10 10 0 0 74 77 171
    Gender categorical
    Units: Subjects
        Female
    4 3 1 2 24 39 73
        Male
    6 7 9 8 55 44 129
    Eczema Area and Severity Index (EASI)
    EASI score is used to measure severity and extent of AD and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of body: head, trunk, upper and lower extremities. Total EASI score ranges from 0 (minimum) to 72 (maximum) points, with higher scores indicating worse severity of AD. Part A: Safety analysis set (SAF) included all subjects who received any study drug and were analysed based on actual treatment received. Part B: Full analysis set (FAS) included all randomised subjects and analyses were based on treatment allocated at randomisation (as randomised).
    Units: Score on a Scale
        arithmetic mean (standard deviation)
    35.2 ± 9.21 40.2 ± 11.81 34.4 ± 14.25 36.1 ± 12.94 33.1 ± 12.18 35.1 ± 13.88 -

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    Part A: Cohort 1 (≥2 to <6 years old): Dupilumab 3 mg/kg
    Reporting group description
    Subjects received a single subcutaneous (SC) injection of dupilumab at a dose of 3 mg/kg at Day 1. At week 4, subjects could roll over into an open-label extension (OLE) study (R668-AD-1434), if considered eligible. Subjects who did not enter the OLE study were followed for up to an additional 4 weeks for safety.

    Reporting group title
    Part A: Cohort 1 (≥2 to <6 years old): Dupilumab 6 mg/kg
    Reporting group description
    Subjects received a single SC injection of dupilumab at a dose of 6 mg/kg at Day 1. At week 4, subjects could roll over into an OLE study (R668-AD-1434), if considered eligible. Subjects who did not enter the OLE study were followed for up to an additional 4 weeks for safety.

    Reporting group title
    Part A: Cohort 2 (≥6 months to <2 years): Dupilumab 3 mg/kg
    Reporting group description
    Subjects received a single SC injection of dupilumab at a dose of 3 mg/kg at Day 1. At week 4, subjects could roll over into an OLE study (R668-AD-1434), if considered eligible. Subjects who did not enter the OLE study were followed for up to an additional 4 weeks for safety.

    Reporting group title
    Part A: Cohort 2 (≥6 months to <2 years): Dupilumab 6 mg/kg
    Reporting group description
    Subjects received a single SC injection of dupilumab at a dose of 6 mg/kg at Day 1. At week 4, subjects could roll over into an OLE study (R668-AD-1434), if considered eligible. Subjects who did not enter the OLE study were followed for up to an additional 4 weeks for safety.

    Reporting group title
    Part B: Placebo + TCS
    Reporting group description
    Subjects received SC injection of placebo matched to dupilumab Q4W along with low potency TCS on areas of thin skin (face, neck, intertriginous, and genital areas, areas of skin atrophy) for 16 weeks. At week 16, subjects could roll over into an OLE study (R668-AD-1434), if considered eligible. Subjects who did not enter the OLE study were followed for up to an additional 12 weeks for safety ([Week 28, end of study (EOS) period]).

    Reporting group title
    Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
    Reporting group description
    Subjects with baseline weight of ≥ 5 to < 15 kilogram (kg) received SC injections of 200 mg or subjects with baseline weight ≥ 15 to < 30 kg received SC injections of 300 mg of dupilumab at Day 1 and Q4W from Week 4 to Week 12. Subjects applied daily low potency TCS on areas of thin skin (face, neck, intertriginous, and genital areas, areas of skin atrophy) for 16 weeks. At week 16, subjects could roll over into an OLE study (R668-AD-1434), if considered eligible. Subjects who did not enter the OLE study were followed for up to an additional 12 weeks for safety ([Week 28, EOS period].

    Primary: Part A: Maximum Observed Serum Concentration (Cmax) of Functional Dupilumab

    Close Top of page
    End point title
    Part A: Maximum Observed Serum Concentration (Cmax) of Functional Dupilumab [1] [2]
    End point description
    Serum concentration of functional dupilumab was reported. The Pharmacokinetic Analysis Set (PKAS) included all treated subjects who received any study drug (safety analysis set) and who had at least 1 non-missing functional dupilumab measurement following the administration of the first dose of study drug.
    End point type
    Primary
    End point timeframe
    Post-dose on Days 1, 3, 8, 18, and 29
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Data for this endpoint was planned to be reported for Part A arms only.
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data for this endpoint was planned to be reported for Part A arms only.
    End point values
    Part A: Cohort 1 (≥2 to <6 years old): Dupilumab 3 mg/kg Part A: Cohort 1 (≥2 to <6 years old): Dupilumab 6 mg/kg Part A: Cohort 2 (≥6 months to <2 years): Dupilumab 3 mg/kg Part A: Cohort 2 (≥6 months to <2 years): Dupilumab 6 mg/kg
    Number of subjects analysed
    9
    10
    10
    10
    Units: Milligrams per Liter (mg/L)
        arithmetic mean (standard deviation)
    25.2 ± 7.44
    49.8 ± 11.3
    20.1 ± 6.81
    46.1 ± 11.1
    No statistical analyses for this end point

    Primary: Part A: Dose Normalized Maximum Observed Serum Concentration (Cmax/Dose) of Dupilumab

    Close Top of page
    End point title
    Part A: Dose Normalized Maximum Observed Serum Concentration (Cmax/Dose) of Dupilumab [3] [4]
    End point description
    Dose normalized was calculated as Cmax obtained directly from the concentration versus time curve divided by dose. PKAS included all treated subjects who received any study drug (safety analysis set) and who had at least 1 non-missing functional dupilumab measurement following the administration of the first dose of study drug. Cmax/dose was measured in Milligrams per Liter/Milligrams per Kilogram ([mg/L]/[mg/kg]).
    End point type
    Primary
    End point timeframe
    Post-dose on Days 1, 3, 8, 18, and 29
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Data for this endpoint was planned to be reported for Part A arms only.
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data for this endpoint was planned to be reported for Part A arms only.
    End point values
    Part A: Cohort 1 (≥2 to <6 years old): Dupilumab 3 mg/kg Part A: Cohort 1 (≥2 to <6 years old): Dupilumab 6 mg/kg Part A: Cohort 2 (≥6 months to <2 years): Dupilumab 3 mg/kg Part A: Cohort 2 (≥6 months to <2 years): Dupilumab 6 mg/kg
    Number of subjects analysed
    9
    10
    10
    10
    Units: [mg/L]/[mg/kg]
        arithmetic mean (standard deviation)
    8.39 ± 2.48
    8.30 ± 1.89
    6.70 ± 2.27
    7.68 ± 1.86
    No statistical analyses for this end point

    Primary: Part A: Time to Reach the Maximum Serum Concentration (tmax) of Dupilumab

    Close Top of page
    End point title
    Part A: Time to Reach the Maximum Serum Concentration (tmax) of Dupilumab [5] [6]
    End point description
    Tmax was obtained directly from the concentration versus time curve. PKAS included all treated subjects who received any study drug (safety analysis set) and who had at least 1 non-missing functional dupilumab measurement following the administration of the first dose of study drug.
    End point type
    Primary
    End point timeframe
    Post-dose on Days 1, 3, 8, 18, and 29
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Data for this endpoint was planned to be reported for Part A arms only.
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data for this endpoint was planned to be reported for Part A arms only.
    End point values
    Part A: Cohort 1 (≥2 to <6 years old): Dupilumab 3 mg/kg Part A: Cohort 1 (≥2 to <6 years old): Dupilumab 6 mg/kg Part A: Cohort 2 (≥6 months to <2 years): Dupilumab 3 mg/kg Part A: Cohort 2 (≥6 months to <2 years): Dupilumab 6 mg/kg
    Number of subjects analysed
    9
    10
    10
    10
    Units: Days
        median (full range (min-max))
    1.92 (1.72 to 3.02)
    1.97 (1.87 to 7.82)
    1.95 (1.75 to 3.08)
    2.10 (1.80 to 7.99)
    No statistical analyses for this end point

    Primary: Part A: Last Quantifiable Serum Concentration (Clast) of Dupilumab

    Close Top of page
    End point title
    Part A: Last Quantifiable Serum Concentration (Clast) of Dupilumab [7] [8]
    End point description
    Clast is the last measurable serum concentration of dupilumab. PKAS included all treated subjects who received any study drug (safety analysis set) and who had at least 1 non-missing functional dupilumab measurement following the administration of the first dose of study drug.
    End point type
    Primary
    End point timeframe
    Post-dose on Days 1, 3, 8, 18, and 29
    Notes
    [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Data for this endpoint was planned to be reported for Part A arms only.
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data for this endpoint was planned to be reported for Part A arms only.
    End point values
    Part A: Cohort 1 (≥2 to <6 years old): Dupilumab 3 mg/kg Part A: Cohort 1 (≥2 to <6 years old): Dupilumab 6 mg/kg Part A: Cohort 2 (≥6 months to <2 years): Dupilumab 3 mg/kg Part A: Cohort 2 (≥6 months to <2 years): Dupilumab 6 mg/kg
    Number of subjects analysed
    9
    10
    10
    10
    Units: mg/L
        arithmetic mean (standard deviation)
    6.64 ± 6.16
    6.14 ± 4.69
    5.64 ± 4.52
    15.1 ± 9.48
    No statistical analyses for this end point

    Primary: Part A: Time of the Last Quantifiable Serum Concentration (tlast) of Dupilumab

    Close Top of page
    End point title
    Part A: Time of the Last Quantifiable Serum Concentration (tlast) of Dupilumab [9] [10]
    End point description
    Tlast was defined as the last time point with a measurable serum concentration of dupilumab. PKAS included all treated subjects who received any study drug (safety analysis set) and who had at least 1 non-missing functional dupilumab measurement following the administration of the first dose of study drug.
    End point type
    Primary
    End point timeframe
    Post-dose on Days 1, 3, 8, 18, and 29
    Notes
    [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Data for this endpoint was planned to be reported for Part A arms only.
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data for this endpoint was planned to be reported for Part A arms only.
    End point values
    Part A: Cohort 1 (≥2 to <6 years old): Dupilumab 3 mg/kg Part A: Cohort 1 (≥2 to <6 years old): Dupilumab 6 mg/kg Part A: Cohort 2 (≥6 months to <2 years): Dupilumab 3 mg/kg Part A: Cohort 2 (≥6 months to <2 years): Dupilumab 6 mg/kg
    Number of subjects analysed
    9
    10
    10
    10
    Units: Days
        median (full range (min-max))
    14.8 (6.79 to 28.0)
    26.5 (15.0 to 32.0)
    8.56 (6.88 to 16.9)
    16.0 (6.95 to 28.0)
    No statistical analyses for this end point

    Primary: Part A: Area Under the Serum Concentration-Time Curve from Time Zero to the Time of the Last Measurable Concentration (AUClast) of Dupilumab

    Close Top of page
    End point title
    Part A: Area Under the Serum Concentration-Time Curve from Time Zero to the Time of the Last Measurable Concentration (AUClast) of Dupilumab [11] [12]
    End point description
    AUClast was defined as area under the serum concentration time-curve from zero to the last measured concentration. PKAS included all treated subjects who received any study drug (safety analysis set) and who had at least 1 non-missing functional dupilumab measurement following the administration of the first dose of study drug.
    End point type
    Primary
    End point timeframe
    Post-dose on Days 1, 3, 8, 18, and 29
    Notes
    [11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Data for this endpoint was planned to be reported for Part A arms only.
    [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data for this endpoint was planned to be reported for Part A arms only.
    End point values
    Part A: Cohort 1 (≥2 to <6 years old): Dupilumab 3 mg/kg Part A: Cohort 1 (≥2 to <6 years old): Dupilumab 6 mg/kg Part A: Cohort 2 (≥6 months to <2 years): Dupilumab 3 mg/kg Part A: Cohort 2 (≥6 months to <2 years): Dupilumab 6 mg/kg
    Number of subjects analysed
    9
    10
    10
    10
    Units: Days*Milligrams per Liter (day*mg/L)
        arithmetic mean (standard deviation)
    198 ± 125
    622 ± 184
    123 ± 86.0
    493 ± 294
    No statistical analyses for this end point

    Primary: Part A: Dose Normalized Area Under the Serum Concentration-Time Curve from Time Zero to the Time of the Last Measurable Concentration (AUClast/Dose) of Dupilumab

    Close Top of page
    End point title
    Part A: Dose Normalized Area Under the Serum Concentration-Time Curve from Time Zero to the Time of the Last Measurable Concentration (AUClast/Dose) of Dupilumab [13] [14]
    End point description
    Dose normalized AUClast was calculated by AUClast/dose. PKAS included all treated subjects who received any study drug (safety analysis set) and who had at least 1 non-missing functional dupilumab measurement following the administration of the first dose of study drug.
    End point type
    Primary
    End point timeframe
    Post-dose on Days 1, 3, 8, 18, and 29
    Notes
    [13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was reported for this endpoint
    [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data for this endpoint was planned to be reported for Part A arms only.
    End point values
    Part A: Cohort 1 (≥2 to <6 years old): Dupilumab 3 mg/kg Part A: Cohort 1 (≥2 to <6 years old): Dupilumab 6 mg/kg Part A: Cohort 2 (≥6 months to <2 years): Dupilumab 3 mg/kg Part A: Cohort 2 (≥6 months to <2 years): Dupilumab 6 mg/kg
    Number of subjects analysed
    9
    10
    10
    10
    Units: [day*mg/L]/[mg/kg]
        arithmetic mean (standard deviation)
    66.0 ± 41.6
    104 ± 30.6
    41.0 ± 28.7
    82.1 ± 48.9
    No statistical analyses for this end point

    Primary: Part A: Number of Subjects with Treatment-Emergent Adverse Events (TEAEs)

    Close Top of page
    End point title
    Part A: Number of Subjects with Treatment-Emergent Adverse Events (TEAEs) [15] [16]
    End point description
    Adverse Event (AE) was defined as any untoward medical occurrence in a subject administered a study drug which may/may not have a causal relationship with study drug. Serious AE (SAE) was defined as any untoward medical occurrence that resulted in any of following outcomes: death, life-threatening, required initial/prolonged in-participant hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect/considered as medically important event. TEAE was defined as AE starting/worsening after first intake of study drug. TEAEs included subjects with both SAEs and non-SAEs. Number of subjects with TEAEs were reported. The safety analysis set (SAF) included all subjects who received any study drug and were analysed based on the actual treatment received.
    End point type
    Primary
    End point timeframe
    Baseline up to Week 4
    Notes
    [15] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was reported for this endpoint
    [16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data for this endpoint was planned to be reported for Part A arms only.
    End point values
    Part A: Cohort 1 (≥2 to <6 years old): Dupilumab 3 mg/kg Part A: Cohort 1 (≥2 to <6 years old): Dupilumab 6 mg/kg Part A: Cohort 2 (≥6 months to <2 years): Dupilumab 3 mg/kg Part A: Cohort 2 (≥6 months to <2 years): Dupilumab 6 mg/kg
    Number of subjects analysed
    10
    10
    10
    10
    Units: Subjects
    3
    2
    7
    7
    No statistical analyses for this end point

    Primary: Part A: Number of Subjects with TEAEs by Severity According to Qualitative Toxicity Scale

    Close Top of page
    End point title
    Part A: Number of Subjects with TEAEs by Severity According to Qualitative Toxicity Scale [17] [18]
    End point description
    Severity of TEAEs were graded using Qualitative Toxicity Scale, as follows: Mild: Subject is aware of the event or symptom, but the event or symptom is easily tolerated; Moderate: Subject experiences sufficient discomfort to interfere with or reduce his or her usual level of activity; Severe: Significant impairment of functioning: the Subject is unable to carry out his or her usual activities. Number of subjects with TEAEs by severity were reported. The SAF included all subjects who received any study drug and were analysed based on the actual treatment received.
    End point type
    Primary
    End point timeframe
    Baseline up to Week 4
    Notes
    [17] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was reported for this endpoint
    [18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data for this endpoint was planned to be reported for Part A arms only.
    End point values
    Part A: Cohort 1 (≥2 to <6 years old): Dupilumab 3 mg/kg Part A: Cohort 1 (≥2 to <6 years old): Dupilumab 6 mg/kg Part A: Cohort 2 (≥6 months to <2 years): Dupilumab 3 mg/kg Part A: Cohort 2 (≥6 months to <2 years): Dupilumab 6 mg/kg
    Number of subjects analysed
    10
    10
    10
    10
    Units: Subjects
        Mild
    1
    2
    4
    5
        Moderate
    2
    0
    2
    2
        Severe
    0
    0
    1
    0
    No statistical analyses for this end point

    Primary: Part B: Percentage of Subjects With Investigator's Global Assessment (IGA) Score 0 or 1 at Week 16

    Close Top of page
    End point title
    Part B: Percentage of Subjects With Investigator's Global Assessment (IGA) Score 0 or 1 at Week 16 [19]
    End point description
    The IGA is an assessment scale used in clinical studies to rate the severity of AD globally, based on a 5-point scale ranging from 0 to 4 where 0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe. A negative change from baseline indicated improvement. Percentage of subjects with IGA score of '0' or '1' is reported. The FAS included all randomised subjects. Efficacy analyses were based on the treatment allocated at randomisation (as randomised). Missing data due to withdrawn consent, adverse event (AE), lack of efficacy were imputed as non responder. Missing data due to any other reason including COVID-19 were imputed using multiple imputation (MI). Subjects were considered as non-responders after initiation of rescue treatment.
    End point type
    Primary
    End point timeframe
    Week 16
    Notes
    [19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data for this endpoint was planned to be reported for Part B arms only.
    End point values
    Part B: Placebo + TCS Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
    Number of subjects analysed
    79
    83
    Units: Percentage of Subjects
        number (confidence interval 95%)
    3.9 (-0.42 to 8.21)
    27.7 (18.45 to 38.62)
    Statistical analysis title
    Placebo + TCS vs Dupilumab 200/300 mg Q4W
    Comparison groups
    Part B: Dupilumab 200 mg or 300 mg Q4W + TCS v Part B: Placebo + TCS
    Number of subjects included in analysis
    162
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [20]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Percentage difference
    Point estimate
    23.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    13.27
         upper limit
    34.37
    Notes
    [20] - Threshold for significance at 0.05 level.

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

    Close Top of page
    End point title
    Part B: Percentage of Subjects with Eczema Area and Severity Index (EASI) -75 (EASI-75) (≥75% Improvement from Baseline) at Week 16 [21]
    End point description
    The EASI score is used to measure the severity and extent of AD and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper, and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores indicating the worse severity of AD. EASI-75 responders were the subjects who achieved ≥75% overall improvement in EASI score from baseline at Week 16. The FAS included all randomised subjects. Efficacy analyses were based on the treatment allocated at randomisation (as randomised). Missing data due to withdrawn consent, AE, lack of efficacy were imputed as non responder. Missing data due to any other reason including COVID-19 were imputed using MI. Subjects were considered as non-responders after initiation of rescue treatment.
    End point type
    Primary
    End point timeframe
    Week 16
    Notes
    [21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data for this endpoint was planned to be reported for Part B arms only.
    End point values
    Part B: Placebo + TCS Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
    Number of subjects analysed
    79
    83
    Units: Percentage of Subjects
        number (confidence interval 95%)
    10.7 (3.65 to 17.74)
    53.0 (41.74 to 64.07)
    Statistical analysis title
    Placebo + TCS vs Dupilumab 200/300 mg Q4W
    Comparison groups
    Part B: Placebo + TCS v Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
    Number of subjects included in analysis
    162
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [22]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Percentage difference
    Point estimate
    42.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    29.47
         upper limit
    55.16
    Notes
    [22] - Threshold for significance at 0.05 level.

    Secondary: Part A: Number of Subjects with Serious TEAEs and Severe TEAEs

    Close Top of page
    End point title
    Part A: Number of Subjects with Serious TEAEs and Severe TEAEs [23]
    End point description
    Adverse Event (AE) was defined as any untoward medical occurrence in a subject administered a study drug which may/may not have a causal relationship with study drug. A serious TEAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. Severe TEAE: significant impairment of functioning the subject is unable to carry out his or her usual activities. The SAF included all subjects who received any study drug and were analysed based on the actual treatment received.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 4
    Notes
    [23] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data for this endpoint was planned to be reported for Part A arms only.
    End point values
    Part A: Cohort 1 (≥2 to <6 years old): Dupilumab 3 mg/kg Part A: Cohort 1 (≥2 to <6 years old): Dupilumab 6 mg/kg Part A: Cohort 2 (≥6 months to <2 years): Dupilumab 3 mg/kg Part A: Cohort 2 (≥6 months to <2 years): Dupilumab 6 mg/kg
    Number of subjects analysed
    10
    10
    10
    10
    Units: Subjects
        Subjects with serious TEAEs
    1
    0
    1
    0
        Subjects with severe TEAEs
    0
    0
    1
    0
    No statistical analyses for this end point

    Secondary: Part A: Percent Change From Baseline in EASI Score at Week 4

    Close Top of page
    End point title
    Part A: Percent Change From Baseline in EASI Score at Week 4 [24]
    End point description
    The EASI score is used to measure the severity and extent of AD and measured erythema, infiltration, excoriation, and lichenification on 4 anatomic regions of the body: head, trunk, upper, and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores indicated the worse severity of AD. A negative change from baseline indicated improvement. The SAF included all subjects who received any study drug and was analysed based on the actual treatment received.
    End point type
    Secondary
    End point timeframe
    Week 4
    Notes
    [24] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data for this endpoint was planned to be reported for Part A arms only.
    End point values
    Part A: Cohort 1 (≥2 to <6 years old): Dupilumab 3 mg/kg Part A: Cohort 1 (≥2 to <6 years old): Dupilumab 6 mg/kg Part A: Cohort 2 (≥6 months to <2 years): Dupilumab 3 mg/kg Part A: Cohort 2 (≥6 months to <2 years): Dupilumab 6 mg/kg
    Number of subjects analysed
    10
    10
    10
    10
    Units: Percent Change
        arithmetic mean (standard deviation)
    -26.6 ± 47.37
    -48.7 ± 28.89
    -22.4 ± 42.52
    -43.2 ± 35.55
    No statistical analyses for this end point

    Secondary: Part A: Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score at Week 4

    Close Top of page
    End point title
    Part A: Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score at Week 4 [25]
    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). A negative change from baseline indicated improvement. SAF included all subjects who received any study drug and was analysed based on the actual treatment received.
    End point type
    Secondary
    End point timeframe
    Week 4
    Notes
    [25] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data for this endpoint was planned to be reported for Part A arms only.
    End point values
    Part A: Cohort 1 (≥2 to <6 years old): Dupilumab 3 mg/kg Part A: Cohort 1 (≥2 to <6 years old): Dupilumab 6 mg/kg Part A: Cohort 2 (≥6 months to <2 years): Dupilumab 3 mg/kg Part A: Cohort 2 (≥6 months to <2 years): Dupilumab 6 mg/kg
    Number of subjects analysed
    10
    10
    10
    10
    Units: Percent Change
        arithmetic mean (standard deviation)
    -18.6 ± 26.18
    -31.9 ± 17.45
    -22.4 ± 26.44
    -28.1 ± 27.84
    No statistical analyses for this end point

    Secondary: Part A: Percentage of Subjects with IGA Score 0 or 1 at Week 4

    Close Top of page
    End point title
    Part A: Percentage of Subjects with IGA Score 0 or 1 at Week 4 [26]
    End point description
    The IGA is an assessment scale used in clinical studies to rate the severity of AD globally, based on a 5-point scale ranging from 0 to 4 where 0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe. Percentage of subjects with IGA score of '0' or '1' were reported. SAF included all subjects who received any study drug and was analysed based on the actual treatment received.
    End point type
    Secondary
    End point timeframe
    Week 4
    Notes
    [26] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data for this endpoint was planned to be reported for Part A arms only.
    End point values
    Part A: Cohort 1 (≥2 to <6 years old): Dupilumab 3 mg/kg Part A: Cohort 1 (≥2 to <6 years old): Dupilumab 6 mg/kg Part A: Cohort 2 (≥6 months to <2 years): Dupilumab 3 mg/kg Part A: Cohort 2 (≥6 months to <2 years): Dupilumab 6 mg/kg
    Number of subjects analysed
    10
    10
    10
    10
    Units: Percentage of Subjects
        number (confidence interval 95%)
    10.0 (0.25 to 44.50)
    0.0 (0.00 to 30.85)
    10.0 (0.25 to 44.50)
    10.0 (0.25 to 44.50)
    No statistical analyses for this end point

    Secondary: Part A: Number of Subjects with At least One Positive Treatment-Emergent Anti-Drug Antibodies (ADA)

    Close Top of page
    End point title
    Part A: Number of Subjects with At least One Positive Treatment-Emergent Anti-Drug Antibodies (ADA) [27]
    End point description
    Treatment boosted (TB) Response: Any post-dose positive result at least 9-fold over the baseline level when baseline is positive; Treatment emergent (TE) Response: Post-dose positive result when baseline results were negative. The ADA Analysis Set (AAS) included all treated subjects who received any study drug and who had at least 1 non-missing ADA result following the first dose of study drug.
    End point type
    Secondary
    End point timeframe
    Baseline up to Day 57
    Notes
    [27] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data for this endpoint was planned to be reported for Part A arms only.
    End point values
    Part A: Cohort 1 (≥2 to <6 years old): Dupilumab 3 mg/kg Part A: Cohort 1 (≥2 to <6 years old): Dupilumab 6 mg/kg Part A: Cohort 2 (≥6 months to <2 years): Dupilumab 3 mg/kg Part A: Cohort 2 (≥6 months to <2 years): Dupilumab 6 mg/kg
    Number of subjects analysed
    10
    10
    10
    10
    Units: Subjects
        TB Response
    0
    0
    1
    0
        TE Response
    5
    4
    5
    5
    No statistical analyses for this end point

    Secondary: Part B: Number of Subjects with Serious TEAEs and Skin Infection TEAEs (Excluding Herpetic Infections) Through Week 16

    Close Top of page
    End point title
    Part B: Number of Subjects with Serious TEAEs and Skin Infection TEAEs (Excluding Herpetic Infections) Through Week 16 [28]
    End point description
    Adverse Event (AE) was defined as any untoward medical occurrence in a subject administered a study drug which may/may not have a causal relationship with study drug. A serious TEAE was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Skin infection TEAEs were identified based on blinded adjudication of all reported TEAEs under the 2 primary System Organ Classes (SOC): SOC = 'Infection and Infestations' or SOC = 'Skin and Subcutaneous Tissue Disorders.' SAF included all randomized subjects who received at least one dose of study drug and was analysed as treated.
    End point type
    Secondary
    End point timeframe
    Baseline through Week 16
    Notes
    [28] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data for this endpoint was planned to be reported for Part B arms only.
    End point values
    Part B: Placebo + TCS Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
    Number of subjects analysed
    78
    83
    Units: Subjects
        Subjects with serious TEAEs
    4
    0
        Subjects with skin infection TEAEs
    19
    10
    No statistical analyses for this end point

    Secondary: Part B: Number of Subjects with At least One Positive Treatment-Emergent ADA

    Close Top of page
    End point title
    Part B: Number of Subjects with At least One Positive Treatment-Emergent ADA [29]
    End point description
    Treatment emergent (TE): Post-dose positive result when baseline results were negative. AAS included all subjects who received any study drug and who had at least one non-missing ADA result after the first dose of the study drug.
    End point type
    Secondary
    End point timeframe
    Baseline up to Day 197
    Notes
    [29] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data for this endpoint was planned to be reported for Part B arms only.
    End point values
    Part B: Placebo + TCS Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
    Number of subjects analysed
    69
    74
    Units: Subjects
    0
    1
    No statistical analyses for this end point

    Secondary: Part B: Percent Change From Baseline in EASI Score at Week 16

    Close Top of page
    End point title
    Part B: Percent Change From Baseline in EASI Score at Week 16 [30]
    End point description
    The EASI score is used to measure the severity and extent of AD and measures erythema, infiltration, excoriation, and lichenification on 4 anatomic regions of the body: head, trunk, upper, and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores indicating the worse severity of AD. A negative change from baseline indicated improvement. FAS included all randomised subjects. Efficacy analyses were based on the treatment allocated at randomisation (as randomised). Missing data due to withdrawn consent, AE, or lack of efficacy and data after rescue were imputed by post baseline worst observation carried forward (WOCF). If there was no post baseline assessment, the baseline value was used. Missing values due to other reasons including COVID-19 were imputed by MI approach.
    End point type
    Secondary
    End point timeframe
    Week 16
    Notes
    [30] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data for this endpoint was planned to be reported for Part B arms only.
    End point values
    Part B: Placebo + TCS Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
    Number of subjects analysed
    79
    83
    Units: Percent Change
        least squares mean (standard error)
    -19.6 ± 5.13
    -70.0 ± 4.85
    Statistical analysis title
    Placebo + TCS vs Dupilumab 200/300 mg Q4W
    Comparison groups
    Part B: Placebo + TCS v Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
    Number of subjects included in analysis
    162
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [31]
    Method
    ANCOVA
    Parameter type
    Least Square (LS) Mean Difference
    Point estimate
    -50.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -62.38
         upper limit
    -38.4
    Notes
    [31] - Threshold for significance at 0.05 level.

    Secondary: Part B: Percent Change From Baseline in Weekly Average of Daily Worst Scratch/Itch/Numerical Rating Scale (NRS) at Week 16

    Close Top of page
    End point title
    Part B: Percent Change From Baseline in Weekly Average of Daily Worst Scratch/Itch/Numerical Rating Scale (NRS) at Week 16 [32]
    End point description
    Pruritus NRS is an assessment tool used to report intensity of subject’s pruritus (itch), both average & maximum intensity, during 24-hr recall period. Subjects were asked two questions: 1) For average itch intensity: how would you rate your itch overall (on average) during the previous 24 hrs; 2) For maximum itch intensity: How would you rate your itch at the worst moment during the previous 24 hrs? Both questions were rated on a scale: 0-10 with 0=no itch & 10=worst itch imaginable. A negative change from baseline indicated improvement. The FAS included all randomised subjects. Efficacy analyses were based on the treatment allocated at randomisation (as randomised). Missing data due to withdrawn consent, AE, or lack of efficacy and data after rescue were imputed by post baseline WOCF. If there was no post baseline assessment, the baseline value was used. Missing values due to other reasons including COVID-19 were imputed by MI approach.
    End point type
    Secondary
    End point timeframe
    Week 16
    Notes
    [32] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data for this endpoint was planned to be reported for Part B arms only.
    End point values
    Part B: Placebo + TCS Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
    Number of subjects analysed
    79
    83
    Units: Percent Change
        least squares mean (standard error)
    -2.2 ± 5.22
    -49.4 ± 5.03
    Statistical analysis title
    Placebo + TCS vs Dupilumab 200/300 mg Q4W
    Comparison groups
    Part B: Placebo + TCS v Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
    Number of subjects included in analysis
    162
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [33]
    Method
    ANCOVA
    Parameter type
    LS Mean Difference
    Point estimate
    -47.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -59.47
         upper limit
    -34.79
    Notes
    [33] - Threshold for significance at 0.05 level.

    Secondary: Part B: Percentage of Subjects with Improvement (Reduction From Baseline) of Weekly Average of Daily Worst Scratch/Itch/NRS ≥4 Points at Week 16

    Close Top of page
    End point title
    Part B: Percentage of Subjects with Improvement (Reduction From Baseline) of Weekly Average of Daily Worst Scratch/Itch/NRS ≥4 Points at Week 16 [34]
    End point description
    Pruritus NRS is an assessment tool used to report intensity of subject’s pruritus (itch), both average & maximum intensity, during 24-hr recall period. Subjects were asked two questions: 1) For average itch intensity: how would you rate your itch overall (on average) during the previous 24 hrs; & 2) For maximum itch intensity: How would you rate your itch at the worst moment during the previous 24 hrs? Both questions were rated on a scale: 0-10 with 0=no itch & 10=worst itch imaginable. The FAS included all randomised subjects. Efficacy analyses were based on the treatment allocated at randomisation (as randomised). Missing data due to withdrawn consent, AE, lack of efficacy were imputed as non responder. Missing data due to any other reason including COVID-19 were imputed using MI. Subjects were considered as non-responders after initiation of rescue treatment.
    End point type
    Secondary
    End point timeframe
    Week 16
    Notes
    [34] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data for this endpoint was planned to be reported for Part B arms only.
    End point values
    Part B: Placebo + TCS Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
    Number of subjects analysed
    78
    83
    Units: Percentage of Subjects
        number (confidence interval 95%)
    8.9 (2.25 to 15.51)
    48.1 (37.05 to 59.15)
    Statistical analysis title
    Placebo + TCS vs Dupilumab 200/300 mg Q4W
    Comparison groups
    Part B: Placebo + TCS v Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
    Number of subjects included in analysis
    161
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [35]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Percentage difference
    Point estimate
    39.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    26.18
         upper limit
    52.27
    Notes
    [35] - Threshold for significance at 0.05 level.

    Secondary: Part B: Percentage of Subjects with Improvement (Reduction From Baseline) of Weekly Average of Daily Worst Scratch/Itch/NRS ≥3 Points at Week 16

    Close Top of page
    End point title
    Part B: Percentage of Subjects with Improvement (Reduction From Baseline) of Weekly Average of Daily Worst Scratch/Itch/NRS ≥3 Points at Week 16 [36]
    End point description
    Pruritus NRS is an assessment tool used to report intensity of subject’s pruritus (itch), both average & maximum intensity, during 24-hr recall period. Subjects were asked two questions: 1) For average itch intensity: how would you rate your itch overall (on average) during the previous 24 hrs; & 2) For maximum itch intensity: How would you rate your itch at the worst moment during the previous 24 hrs? Both questions were rated on a scale: 0-10 with 0=no itch & 10=worst itch imaginable. The FAS included all randomised subjects. Efficacy analyses were based on the treatment allocated at randomisation (as randomised). Missing data due to withdrawn consent, AE, lack of efficacy were imputed as non responder. Missing data due to any other reason including COVID-19 were imputed using MI. Subjects were considered as non-responders after initiation of rescue treatment.
    End point type
    Secondary
    End point timeframe
    Week 16
    Notes
    [36] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data for this endpoint was planned to be reported for Part B arms only.
    End point values
    Part B: Placebo + TCS Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
    Number of subjects analysed
    78
    83
    Units: Percentage of Subjects
        number (confidence interval 95%)
    9.9 (2.59 to 17.22)
    53.3 (42.29 to 64.22)
    Statistical analysis title
    Placebo + TCS vs Dupilumab 200/300 mg Q4W
    Comparison groups
    Part B: Placebo + TCS v Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
    Number of subjects included in analysis
    161
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [37]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Percentage difference
    Point estimate
    43.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    30.03
         upper limit
    56.67
    Notes
    [37] - Threshold for significance at 0.05 level.

    Secondary: Part B: Percentage of Subjects Who Achieved EASI-50 (≥50% Improvement From Baseline) at Week 16

    Close Top of page
    End point title
    Part B: Percentage of Subjects Who Achieved EASI-50 (≥50% Improvement From Baseline) at Week 16 [38]
    End point description
    The EASI score is used to measure the severity and extent of AD and measured erythema, infiltration, excoriation, and lichenification on 4 anatomic regions of the body: head, trunk, upper, and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores indicating the worse severity of AD. EASI-50 responders were the subjects who achieved ≥50% overall improvement in EASI score from baseline at Week 16. The FAS included all randomised subjects. Efficacy analyses were based on the treatment allocated at randomisation (as randomised). Missing data due to withdrawn consent, AE, lack of efficacy were imputed as non responder. Missing data due to any other reason including COVID-19 were imputed using MI. Subjects were considered as non-responders after initiation of rescue treatment.
    End point type
    Secondary
    End point timeframe
    Week 16
    Notes
    [38] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data for this endpoint was planned to be reported for Part B arms only.
    End point values
    Part B: Placebo + TCS Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
    Number of subjects analysed
    79
    83
    Units: Percentage of Subjects
        number (confidence interval 95%)
    20.2 (11.09 to 29.23)
    68.7 (57.56 to 78.41)
    Statistical analysis title
    Placebo + TCS vs Dupilumab 200/300 mg Q4W
    Comparison groups
    Part B: Dupilumab 200 mg or 300 mg Q4W + TCS v Part B: Placebo + TCS
    Number of subjects included in analysis
    162
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [39]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Percentage difference
    Point estimate
    48.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    35.03
         upper limit
    62
    Notes
    [39] - Threshold for significance at 0.05 level.

    Secondary: Part B: Percentage of Subjects Who Achieved EASI-90 (≥90% Improvement From Baseline) at Week 16

    Close Top of page
    End point title
    Part B: Percentage of Subjects Who Achieved EASI-90 (≥90% Improvement From Baseline) at Week 16 [40]
    End point description
    The EASI score is used to measure the severity and extent of AD and measured erythema, infiltration, excoriation, and lichenification on 4 anatomic regions of the body: head, trunk, upper, and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores indicating the worse severity of AD. EASI-90 responders were the subjects who achieved ≥90% overall improvement in EASI score from baseline at Week 16. The FAS included all randomised subjects. Efficacy analyses were based on the treatment allocated at randomisation (as randomised). Missing data due to withdrawn consent, AE, lack of efficacy were imputed as non responder. Missing data due to any other reason including COVID-19 were imputed using MI. Subjects were considered as non-responders after initiation of rescue treatment.
    End point type
    Secondary
    End point timeframe
    Week 16
    Notes
    [40] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data for this endpoint was planned to be reported for Part B arms only.
    End point values
    Part B: Placebo + TCS Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
    Number of subjects analysed
    79
    83
    Units: Percentage of Subjects
        number (confidence interval 95%)
    2.8 (-1.02 to 6.66)
    25.3 (16.39 to 36.04)
    Statistical analysis title
    Placebo + TCS vs Dupilumab 200/300 mg Q4W
    Comparison groups
    Part B: Placebo + TCS v Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
    Number of subjects included in analysis
    162
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0001 [41]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Percentage difference
    Point estimate
    22.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    12.37
         upper limit
    32.6
    Notes
    [41] - Threshold for significance at 0.05 level.

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

    Close Top of page
    End point title
    Part B: Change From Baseline in Percent Body Surface Area (BSA) Affected by Atopic Dermatitis (AD) at Week 16 [42]
    End point description
    BSA affected by AD was assessed for each section of the body (the possible highest score for each region was: head and neck [9%], anterior trunk [18%], back [18%], upper limbs [18%], lower limbs [36%], and genitals [1%]). It was reported as a percentage of all major body sections combined. A negative change from baseline indicated improvement. The FAS included all randomised subjects. Efficacy analyses were based on the treatment allocated at randomisation (as randomised). Missing data due to withdrawn consent, AE, or lack of efficacy and data after rescue were imputed by post baseline WOCF. If there was no post baseline assessment, the baseline value was used. Missing values due to other reasons including COVID-19 were imputed by MI approach.
    End point type
    Secondary
    End point timeframe
    Week 16
    Notes
    [42] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data for this endpoint was planned to be reported for Part B arms only.
    End point values
    Part B: Placebo + TCS Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
    Number of subjects analysed
    79
    83
    Units: Percent of BSA
        least squares mean (standard error)
    -10.74 ± 2.926
    -35.00 ± 2.815
    Statistical analysis title
    Placebo + TCS vs Dupilumab 200/300 mg Q4W
    Comparison groups
    Part B: Dupilumab 200 mg or 300 mg Q4W + TCS v Part B: Placebo + TCS
    Number of subjects included in analysis
    162
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [43]
    Method
    ANCOVA
    Parameter type
    LS Mean Difference
    Point estimate
    -24.27
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -31.204
         upper limit
    -17.329
    Notes
    [43] - Threshold for significance at 0.05 level.

    Secondary: Part B: Change From Baseline in Patient Oriented Eczema Measure (POEM) at Week 16

    Close Top of page
    End point title
    Part B: Change From Baseline in Patient Oriented Eczema Measure (POEM) at Week 16 [44]
    End point description
    The POEM is a 7-item questionnaire that assesses disease symptoms (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) with a scoring system of 0 (absent disease) to 28 (severe disease) (high score indicative of poor quality of life [QOL]). A negative change from baseline indicated improvement. The FAS included all randomised subjects. Efficacy analyses were based on the treatment allocated at randomisation (as randomised). Missing data due to withdrawn consent, AE, or lack of efficacy and data after rescue were imputed by post baseline WOCF. If there was no post baseline assessment, the baseline value was used. Missing values due to other reasons including COVID-19 were imputed by MI approach.
    End point type
    Secondary
    End point timeframe
    Week 16
    Notes
    [44] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data for this endpoint was planned to be reported for Part B arms only.
    End point values
    Part B: Placebo + TCS Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
    Number of subjects analysed
    79
    83
    Units: Score on a Scale
        least squares mean (standard error)
    -3.8 ± 0.92
    -12.9 ± 0.89
    Statistical analysis title
    Placebo + TCS vs Dupilumab 200/300 mg Q4W
    Comparison groups
    Part B: Placebo + TCS v Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
    Number of subjects included in analysis
    162
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [45]
    Method
    ANCOVA
    Parameter type
    LS Mean Difference
    Point estimate
    -9.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -11.26
         upper limit
    -6.89
    Notes
    [45] - Threshold for significance at 0.05 level.

    Secondary: Part B: Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) at Week 16

    Close Top of page
    End point title
    Part B: Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) at Week 16 [46]
    End point description
    The SCORAD index is a clinical tool for assessing the severity of atopic dermatitis (AD). Extent and intensity of eczema as well as subjective signs (insomnia, etc.) are assessed and scored. Total score ranges from 0 (absent disease) to 103 (severe disease). A negative change from baseline indicated improvement. The FAS included all randomised subjects. Efficacy analyses were based on the treatment allocated at randomisation (as randomised). Missing data due to withdrawn consent, AE, or lack of efficacy and data after rescue were imputed by post baseline WOCF. If there was no post baseline assessment, the baseline value was used. Missing values due to other reasons including COVID-19 were imputed by MI approach.
    End point type
    Secondary
    End point timeframe
    Week 16
    Notes
    [46] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data for this endpoint was planned to be reported for Part B arms only.
    End point values
    Part B: Placebo + TCS Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
    Number of subjects analysed
    79
    83
    Units: Percent Change
        least squares mean (standard error)
    -16.2 ± 3.54
    -54.7 ± 3.39
    Statistical analysis title
    Placebo + TCS vs Dupilumab 200/300 mg Q4W
    Comparison groups
    Part B: Placebo + TCS v Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
    Number of subjects included in analysis
    162
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [47]
    Method
    ANCOVA
    Parameter type
    LS Mean Difference
    Point estimate
    -38.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -46.65
         upper limit
    -30.21
    Notes
    [47] - Threshold for significance at 0.05 level.

    Secondary: Part B: Change from Baseline in Subject’s Sleep Quality NRS at Week 16

    Close Top of page
    End point title
    Part B: Change from Baseline in Subject’s Sleep Quality NRS at Week 16 [48]
    End point description
    A sleep diary was completed by the parent/caregiver, included 2 questions assessing the caregiver’s sleep, and 6 questions assessing the child’s sleep based on caregiver observation. Sleep diary items, either alone or in combination served as subjective measures of sleep quality, difficulty falling asleep, nighttime awakenings, and sleep duration. Sleep quality was measured using an 11-point NRS (0 to 10) in which 0 indicated worst possible sleep while 10 indicated best possible sleep. The FAS included all randomised subjects. Efficacy analyses were based on the treatment allocated at randomisation (as randomised). Missing data due to withdrawn consent, AE, or lack of efficacy and data after rescue were imputed by post baseline WOCF. If there was no post baseline assessment, the baseline value was used. Missing values due to other reasons including COVID-19 were imputed by MI approach.
    End point type
    Secondary
    End point timeframe
    Week 16
    Notes
    [48] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data for this endpoint was planned to be reported for Part B arms only.
    End point values
    Part B: Placebo + TCS Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
    Number of subjects analysed
    79
    83
    Units: Score on a Scale
        least squares mean (standard error)
    0.34 ± 0.256
    2.04 ± 0.251
    Statistical analysis title
    Placebo + TCS vs Dupilumab 200/300 mg Q4W
    Comparison groups
    Part B: Placebo + TCS v Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
    Number of subjects included in analysis
    162
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [49]
    Method
    ANCOVA
    Parameter type
    LS Mean Difference
    Point estimate
    1.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.093
         upper limit
    2.317
    Notes
    [49] - Threshold significance was at 0.05 level.

    Secondary: Part B: Change from Baseline in Subject’s Skin Pain NRS at Week 16

    Close Top of page
    End point title
    Part B: Change from Baseline in Subject’s Skin Pain NRS at Week 16 [50]
    End point description
    Skin pain was assessed by the parent/caregiver and measured using a 11-point scale (0 to 10) in which 0 indicated no pain while 10 indicated worst pain possible. A negative change from baseline indicated improvement. The FAS included all randomised subjects. Efficacy analyses were based on the treatment allocated at randomisation (as randomised). Missing data due to withdrawn consent, AE, or lack of efficacy and data after rescue were imputed by post baseline WOCF. If there was no post baseline assessment, the baseline value was used. Missing values due to other reasons including COVID-19 were imputed by MI approach.
    End point type
    Secondary
    End point timeframe
    Week 16
    Notes
    [50] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data for this endpoint was planned to be reported for Part B arms only.
    End point values
    Part B: Placebo + TCS Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
    Number of subjects analysed
    79
    83
    Units: Score on a Scale
        least squares mean (standard error)
    -0.62 ± 0.302
    -3.93 ± 0.295
    Statistical analysis title
    Placebo + TCS vs Dupilumab 200/300 mg Q4W
    Comparison groups
    Part B: Placebo + TCS v Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
    Number of subjects included in analysis
    162
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [51]
    Method
    ANCOVA
    Parameter type
    LS Mean Difference
    Point estimate
    -3.31
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4.029
         upper limit
    -2.6
    Notes
    [51] - Threshold significance at 0.05 level.

    Secondary: Part B: Change From Baseline in Dermatitis Family Index (DFI) at Week 16

    Close Top of page
    End point title
    Part B: Change From Baseline in Dermatitis Family Index (DFI) at Week 16 [52]
    End point description
    DFI is a 10-item questionnaire with items inquiring about housework, food preparation, sleep, family leisure activity, shopping, expenditure, tiredness, emotional distress, relationships, and impact of helping with treatment on the primary caregiver's life. 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. A negative change from baseline indicated improvement. FAS included all randomised subjects. Efficacy analyses were based on the treatment allocated at randomisation (as randomised). Missing data due to withdrawn consent, AE, or lack of efficacy and data after rescue were imputed by post baseline WOCF. If there was no post baseline assessment, the baseline value was used. Missing values due to other reasons including COVID-19 were imputed by MI approach.
    End point type
    Secondary
    End point timeframe
    Week 16
    Notes
    [52] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data for this endpoint was planned to be reported for Part B arms only.
    End point values
    Part B: Placebo + TCS Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
    Number of subjects analysed
    79
    83
    Units: Score on a Scale
        least squares mean (standard error)
    -2.68 ± 0.839
    -10.48 ± 0.806
    Statistical analysis title
    Placebo + TCS vs Dupilumab 200/300 mg Q4W
    Comparison groups
    Part B: Placebo + TCS v Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
    Number of subjects included in analysis
    162
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [53]
    Method
    ANCOVA
    Parameter type
    LS Mean Difference
    Point estimate
    -7.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -9.789
         upper limit
    -5.814
    Notes
    [53] - Threshold significance at 0.05 level.

    Secondary: Part B: Change From Baseline in Children's Dermatology Life Quality Index (CDLQI) at Week 16

    Close Top of page
    End point title
    Part B: Change From Baseline in Children's Dermatology Life Quality Index (CDLQI) at Week 16 [54]
    End point description
    CDLQI is a validated 10 question tool to measure impact of skin disease on QOL in children by assessing how much the skin problem has affected the subjects over 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 (max. = 30, min. = 0). Higher the score, the greater the impact on QOL. A negative change from baseline indicated improvement. FAS included all randomised subjects. Efficacy analyses were based on the treatment allocated at randomisation (as randomised). Subjects ≥4 years of age were evaluated for this endpoint. Missing data due to withdrawn consent, AE, or lack of efficacy and data after rescue were imputed by post baseline WOCF. If there was no post baseline assessment, the baseline value was used. Missing values due to other reasons including COVID-19 were imputed by MI approach.
    End point type
    Secondary
    End point timeframe
    Week 16
    Notes
    [54] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data for this endpoint was planned to be reported for Part B arms only.
    End point values
    Part B: Placebo + TCS Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
    Number of subjects analysed
    38
    47
    Units: Score on a Scale
        least squares mean (standard error)
    -2.5 ± 1.66
    -10.0 ± 1.56
    Statistical analysis title
    Placebo + TCS vs Dupilumab 200/300 mg Q4W
    Comparison groups
    Part B: Placebo + TCS v Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
    Number of subjects included in analysis
    85
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [55]
    Method
    ANCOVA
    Parameter type
    LS Mean Difference
    Point estimate
    -7.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -10.29
         upper limit
    -4.75
    Notes
    [55] - Threshold significance at 0.05 level.

    Secondary: Part B: Change from Baseline in Infants' Dermatology Quality of Life Index (IDQOL) at Week 16

    Close Top of page
    End point title
    Part B: Change from Baseline in Infants' Dermatology Quality of Life Index (IDQOL) at Week 16 [56]
    End point description
    Infants' Dermatitis Quality of Life Index (IDQOL) were used to evaluate quality of life for subjects of age less than 4 years. IDQOL questionnaires were designed for infants (below the age of 4 years) with atopic dermatitis. The IDQOL was calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score in each questionnaire, the more quality of life is impaired. A negative change from baseline indicated improvement. The FAS included all randomised subjects. Efficacy analyses were based on the treatment allocated at randomisation (as randomised). Missing data due to withdrawn consent, AE, or lack of efficacy and data after rescue were imputed by post baseline WOCF. If there was no post baseline assessment, the baseline value was used. Missing values due to other reasons including COVID-19 were imputed by MI approach.
    End point type
    Secondary
    End point timeframe
    Week 16
    Notes
    [56] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data for this endpoint was planned to be reported for Part B arms only.
    End point values
    Part B: Placebo + TCS Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
    Number of subjects analysed
    41
    36
    Units: Score on a Scale
        least squares mean (standard error)
    -1.95 ± 1.078
    -10.91 ± 1.159
    Statistical analysis title
    Placebo + TCS vs Dupilumab 200/300 mg Q4W
    Comparison groups
    Part B: Placebo + TCS v Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
    Number of subjects included in analysis
    77
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [57]
    Method
    ANCOVA
    Parameter type
    LS Mean Difference
    Point estimate
    -8.96
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -11.711
         upper limit
    -6.202
    Notes
    [57] - Threshold significance at 0.05 level.

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

    Close Top of page
    End point title
    Part B: Percentage of Topical Corticosteroid (TCS) Medication-free Days From Baseline to Week 16 [58]
    End point description
    Percentage of TCS medication-free days was calculated as the number of days that a subject used neither TCS/TCI nor system rescue therapy divided by the study days. The FAS included all randomised subjects. Efficacy analyses were based on the treatment allocated at randomisation (as randomised).
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 16
    Notes
    [58] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data for this endpoint was planned to be reported for Part B arms only.
    End point values
    Part B: Placebo + TCS Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
    Number of subjects analysed
    77
    82
    Units: Percentage of Days
        median (full range (min-max))
    0.04 (0.0 to 0.9)
    0.21 (0.0 to 1.0)
    Statistical analysis title
    Placebo + TCS vs Dupilumab 200/300 mg Q4W
    Comparison groups
    Part B: Placebo + TCS v Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
    Number of subjects included in analysis
    159
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0015 [59]
    Method
    ANCOVA
    Confidence interval
    Notes
    [59] - Threshold significance is at 0.05 level.

    Secondary: Part B: Mean Weekly Dose of Low Potency TCS in Grams From Baseline to Week 16

    Close Top of page
    End point title
    Part B: Mean Weekly Dose of Low Potency TCS in Grams From Baseline to Week 16 [60]
    End point description
    Mean weekly dose of TCS in grams/week for low potency TCS from baseline to Week 16 were reported. The FAS included all randomised subjects. Efficacy analyses were based on the treatment allocated at randomisation (as randomised).
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 16
    Notes
    [60] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data for this endpoint was planned to be reported for Part B arms only.
    End point values
    Part B: Placebo + TCS Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
    Number of subjects analysed
    78
    81
    Units: Grams per Week
        least squares mean (standard error)
    13.4 ± 1.44
    10.5 ± 1.39
    Statistical analysis title
    Placebo + TCS vs Dupilumab 200/300 mg Q4W
    Comparison groups
    Part B: Placebo + TCS v Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
    Number of subjects included in analysis
    159
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0997 [61]
    Method
    ANCOVA
    Parameter type
    LS Mean Difference
    Point estimate
    -2.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -6.35
         upper limit
    0.56
    Notes
    [61] - Threshold significance at 0.05 level.

    Secondary: Part B: Mean Weekly Dose of TCS in Grams for Medium or High Potency TCS From Baseline to Week 16

    Close Top of page
    End point title
    Part B: Mean Weekly Dose of TCS in Grams for Medium or High Potency TCS From Baseline to Week 16 [62]
    End point description
    Mean weekly dose of TCS in grams/week for medium or high potency TCS from baseline to Week 16 were reported. The FAS included all randomised subjects. Efficacy analyses were based on the treatment allocated at randomisation (as randomised).
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 16
    Notes
    [62] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data for this endpoint was planned to be reported for Part B arms only.
    End point values
    Part B: Placebo + TCS Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
    Number of subjects analysed
    43
    24
    Units: Grams per Week
        least squares mean (standard error)
    6.1 ± 1.70
    3.0 ± 1.54
    No statistical analyses for this end point

    Secondary: Part B: Mean of Caregiver Missed Work Days Through Week 16

    Close Top of page
    End point title
    Part B: Mean of Caregiver Missed Work Days Through Week 16 [63]
    End point description
    Mean of caregiver missed work days through Week 16 was reported. The FAS included all randomised subjects. Efficacy analyses were based on the treatment allocated at randomisation (as randomised).
    End point type
    Secondary
    End point timeframe
    Baseline through Week 16
    Notes
    [63] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data for this endpoint was planned to be reported for Part B arms only.
    End point values
    Part B: Placebo + TCS Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
    Number of subjects analysed
    57
    57
    Units: Days
        arithmetic mean (standard deviation)
    5.05 ± 8.975
    2.49 ± 5.524
    No statistical analyses for this end point

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    From day of first treatment until the end of study
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    21.1, 23.1
    Reporting groups
    Reporting group title
    Part A: Cohort 1 (≥2 to <6 years old): Dupilumab 3 mg/kg
    Reporting group description
    Subjects received a single subcutaneous (SC) injection of dupilumab at a dose of 3 mg/kg at Day 1. At week 4, subjects could roll over into an open-label extension (OLE) study (R668-AD-1434), if considered eligible. Subjects who did not enter the OLE study were followed for up to an additional 4 weeks for safety. (Part A: MedDRA version 21.1)

    Reporting group title
    Part B: Dupilumab 200 mg or 300 mg Q4W + TCS
    Reporting group description
    Subjects with baseline weight of ≥ 5 to < 15 kilogram (kg) received SC injections of 200 mg or subjects with baseline weight ≥ 15 to < 30 kg received SC injections of 300 mg of dupilumab at Day 1 and Q4W from Week 4 to Week 12. Subjects applied daily low potency TCS on areas of thin skin (face, neck, intertriginous, and genital areas, areas of skin atrophy) for 16 weeks. At week 16, subjects could roll over into an OLE study (R668-AD-1434), if considered eligible. Subjects who did not enter the OLE study were followed for up to an additional 12 weeks for safety ([Week 28, EOS period]. (Part B: MedDRA version 23.1)

    Reporting group title
    Part A: Cohort 2 (≥6 months to <2 years): Dupilumab 6 mg/kg
    Reporting group description
    Subjects received a single SC injection of dupilumab at a dose of 6 mg/kg at Day 1. At week 4, subjects could roll over into an OLE study (R668-AD-1434), if considered eligible. Subjects who did not enter the OLE study were followed for up to an additional 4 weeks for safety. (Part A: MedDRA version 21.1)

    Reporting group title
    Part B: Placebo + TCS
    Reporting group description
    Subjects received SC injection of placebo matched to dupilumab Q4W along with low potency TCS on areas of thin skin (face, neck, intertriginous, and genital areas, areas of skin atrophy) for 16 weeks. At week 16, subjects could roll over into an OLE study (R668-AD-1434), if considered eligible. Subjects who did not enter the OLE study were followed for up to an additional 12 weeks for safety ([Week 28, end of study (EOS) period]). (Part B: MedDRA version 23.1)

    Reporting group title
    Part A: Cohort 1 (≥2 to <6 years old): Dupilumab 6 mg/kg
    Reporting group description
    Subjects received a single SC injection of dupilumab at a dose of 6 mg/kg at Day 1. At week 4, subjects could roll over into an OLE study (R668-AD-1434), if considered eligible. Subjects who did not enter the OLE study were followed for up to an additional 4 weeks for safety. (Part A: MedDRA version 21.1)

    Reporting group title
    Part A: Cohort 2 (≥6 months to <2 years): Dupilumab 3 mg/kg
    Reporting group description
    Subjects received a single SC injection of dupilumab at a dose of 3 mg/kg at Day 1. At week 4, subjects could roll over into an OLE study (R668-AD-1434), if considered eligible. Subjects who did not enter the OLE study were followed for up to an additional 4 weeks for safety. (Part A: MedDRA version 21.1)

    Serious adverse events
    Part A: Cohort 1 (≥2 to <6 years old): Dupilumab 3 mg/kg Part B: Dupilumab 200 mg or 300 mg Q4W + TCS Part A: Cohort 2 (≥6 months to <2 years): Dupilumab 6 mg/kg Part B: Placebo + TCS Part A: Cohort 1 (≥2 to <6 years old): Dupilumab 6 mg/kg Part A: Cohort 2 (≥6 months to <2 years): Dupilumab 3 mg/kg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 83 (0.00%)
    0 / 10 (0.00%)
    4 / 78 (5.13%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    Immune system disorders
    Anaphylactic reaction
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 83 (0.00%)
    0 / 10 (0.00%)
    0 / 78 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypersensitivity
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 83 (0.00%)
    0 / 10 (0.00%)
    1 / 78 (1.28%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Dermatitis atopic
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 83 (0.00%)
    0 / 10 (0.00%)
    1 / 78 (1.28%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Cellulitis staphylococcal
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 83 (0.00%)
    0 / 10 (0.00%)
    1 / 78 (1.28%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dermatitis infected
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 83 (0.00%)
    0 / 10 (0.00%)
    1 / 78 (1.28%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal bacteraemia
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 83 (0.00%)
    0 / 10 (0.00%)
    1 / 78 (1.28%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Part A: Cohort 1 (≥2 to <6 years old): Dupilumab 3 mg/kg Part B: Dupilumab 200 mg or 300 mg Q4W + TCS Part A: Cohort 2 (≥6 months to <2 years): Dupilumab 6 mg/kg Part B: Placebo + TCS Part A: Cohort 1 (≥2 to <6 years old): Dupilumab 6 mg/kg Part A: Cohort 2 (≥6 months to <2 years): Dupilumab 3 mg/kg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    7 / 10 (70.00%)
    29 / 83 (34.94%)
    2 / 10 (20.00%)
    45 / 78 (57.69%)
    7 / 10 (70.00%)
    3 / 10 (30.00%)
    Injury, poisoning and procedural complications
    Skin abrasion
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 83 (0.00%)
    1 / 10 (10.00%)
    0 / 78 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    0 / 10 (0.00%)
    3 / 83 (3.61%)
    0 / 10 (0.00%)
    5 / 78 (6.41%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    3
    0
    8
    0
    0
    Cough
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 83 (0.00%)
    1 / 10 (10.00%)
    5 / 78 (6.41%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    1
    6
    1
    0
    Blood and lymphatic system disorders
    Lymphadenopathy
         subjects affected / exposed
    0 / 10 (0.00%)
    3 / 83 (3.61%)
    0 / 10 (0.00%)
    6 / 78 (7.69%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    3
    0
    9
    0
    0
    Thrombocytosis
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 83 (0.00%)
    0 / 10 (0.00%)
    0 / 78 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Eye disorders
    Lacrimation increased
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 83 (0.00%)
    0 / 10 (0.00%)
    0 / 78 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    General disorders and administration site conditions
    Injection site erythema
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 83 (1.20%)
    0 / 10 (0.00%)
    0 / 78 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    Pyrexia
         subjects affected / exposed
    2 / 10 (20.00%)
    1 / 83 (1.20%)
    0 / 10 (0.00%)
    7 / 78 (8.97%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    2
    1
    0
    9
    0
    1
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    1 / 10 (10.00%)
    2 / 83 (2.41%)
    0 / 10 (0.00%)
    0 / 78 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    3
    0
    0
    0
    0
    Diarrhoea
         subjects affected / exposed
    1 / 10 (10.00%)
    1 / 83 (1.20%)
    0 / 10 (0.00%)
    2 / 78 (2.56%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    1
    0
    2
    1
    0
    Teething
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 83 (0.00%)
    0 / 10 (0.00%)
    0 / 78 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Skin and subcutaneous tissue disorders
    Dermatitis atopic
         subjects affected / exposed
    0 / 10 (0.00%)
    12 / 83 (14.46%)
    0 / 10 (0.00%)
    24 / 78 (30.77%)
    1 / 10 (10.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    17
    0
    46
    1
    1
    Urticaria
         subjects affected / exposed
    1 / 10 (10.00%)
    1 / 83 (1.20%)
    0 / 10 (0.00%)
    4 / 78 (5.13%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    1
    0
    4
    1
    0
    Musculoskeletal and connective tissue disorders
    Joint swelling
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 83 (0.00%)
    0 / 10 (0.00%)
    0 / 78 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    1 / 10 (10.00%)
    7 / 83 (8.43%)
    1 / 10 (10.00%)
    7 / 78 (8.97%)
    2 / 10 (20.00%)
    1 / 10 (10.00%)
         occurrences all number
    1
    8
    1
    8
    2
    1
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 10 (10.00%)
    5 / 83 (6.02%)
    0 / 10 (0.00%)
    7 / 78 (8.97%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    5
    0
    9
    1
    0
    Impetigo
         subjects affected / exposed
    1 / 10 (10.00%)
    3 / 83 (3.61%)
    0 / 10 (0.00%)
    6 / 78 (7.69%)
    1 / 10 (10.00%)
    1 / 10 (10.00%)
         occurrences all number
    1
    3
    0
    7
    1
    1
    Folliculitis
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 83 (0.00%)
    0 / 10 (0.00%)
    0 / 78 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    05 Jul 2017
    The purpose of amendment 2 was to harmonize the protocol across regions and to simplify regulatory submissions.
    22 Nov 2019
    The purpose of amendment 3 was to seek approval of the dose regimens for part B of the study.

    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
    For support, visit the EMA Service Desk , log in using your EMA account and open a ticket specifying "EU CTR" in your request.
    If you do not have an account, please visit the EMA Account management page page click on "Create an EMA account" and follow the instructions.
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2022 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA