Study to Investigate the Efficacy and Safety of Dupilumab Administered With Topical Corticosteroids (TCS) in Participants ≥6 to <12 Years With Severe Atopic Dermatitis (AD)

NCT ID: NCT03345914

Last Updated: 2020-08-13

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

367 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-11-17

Study Completion Date

2019-09-10

Brief Summary

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The main objective of the trial is to demonstrate the efficacy of dupilumab administered concomitantly with topical corticosteroids (TCS) in participants ≥6 years to \<12 years of age with severe atopic dermatitis (AD).

The secondary objective is to assess the safety of dupilumab administered concomitantly with TCS in patients ≥6 years to \<12 years of age with severe AD.

Detailed Description

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Conditions

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Dermatitis, Atopic

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Group 1

Participants will receive dupilumab, dosing regimen 1

Group Type EXPERIMENTAL

Dupilumab

Intervention Type DRUG

Pharmaceutical form: Solution for injection in pre-filled syringe;

Route of administration: Subcutaneous (SC)

Background Treatment: Topical Corticosteroids

Intervention Type OTHER

All participants are required to initiate treatment with a medium potency TCS using a standardized regimen. It is recommended that participants use triamcinolone acetonide 0.1% cream, fluocinolone acetonide 0.025% cream, or clobetasone butyrate 0.05%.

Background Treatment: Moisturizers

Intervention Type OTHER

All participants should apply moisturizers throughout the study. All types of moisturizers are permitted, but participants may not initiate treatment with prescription moisturizers. Participants may continue using stable doses of such moisturizers if initiated before the screening visit.

Group 2

Participants will receive dupilumab, dosing regimen 2

Group Type EXPERIMENTAL

Dupilumab

Intervention Type DRUG

Pharmaceutical form: Solution for injection in pre-filled syringe;

Route of administration: Subcutaneous (SC)

Background Treatment: Topical Corticosteroids

Intervention Type OTHER

All participants are required to initiate treatment with a medium potency TCS using a standardized regimen. It is recommended that participants use triamcinolone acetonide 0.1% cream, fluocinolone acetonide 0.025% cream, or clobetasone butyrate 0.05%.

Background Treatment: Moisturizers

Intervention Type OTHER

All participants should apply moisturizers throughout the study. All types of moisturizers are permitted, but participants may not initiate treatment with prescription moisturizers. Participants may continue using stable doses of such moisturizers if initiated before the screening visit.

Group 3

Participants will receive matching placebo

Group Type EXPERIMENTAL

Matching Placebo

Intervention Type DRUG

Pharmaceutical form: Solution for injection;

Route of administration: Subcutaneous (SC)

Background Treatment: Topical Corticosteroids

Intervention Type OTHER

All participants are required to initiate treatment with a medium potency TCS using a standardized regimen. It is recommended that participants use triamcinolone acetonide 0.1% cream, fluocinolone acetonide 0.025% cream, or clobetasone butyrate 0.05%.

Background Treatment: Moisturizers

Intervention Type OTHER

All participants should apply moisturizers throughout the study. All types of moisturizers are permitted, but participants may not initiate treatment with prescription moisturizers. Participants may continue using stable doses of such moisturizers if initiated before the screening visit.

Interventions

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Dupilumab

Pharmaceutical form: Solution for injection in pre-filled syringe;

Route of administration: Subcutaneous (SC)

Intervention Type DRUG

Matching Placebo

Pharmaceutical form: Solution for injection;

Route of administration: Subcutaneous (SC)

Intervention Type DRUG

Background Treatment: Topical Corticosteroids

All participants are required to initiate treatment with a medium potency TCS using a standardized regimen. It is recommended that participants use triamcinolone acetonide 0.1% cream, fluocinolone acetonide 0.025% cream, or clobetasone butyrate 0.05%.

Intervention Type OTHER

Background Treatment: Moisturizers

All participants should apply moisturizers throughout the study. All types of moisturizers are permitted, but participants may not initiate treatment with prescription moisturizers. Participants may continue using stable doses of such moisturizers if initiated before the screening visit.

Intervention Type OTHER

Other Intervention Names

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DUPIXENT® REGN668 SAR231893

Eligibility Criteria

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Inclusion Criteria

1. Diagnosis of AD according to the American Academy of Dermatology consensus criteria (Eichenfield 2003) at screening visit
2. Chronic AD diagnosed at least 1 year prior to the screening visit
3. IGA = 4 at screening and baseline visits
4. EASI ≥21 at the screening and baseline visits
5. BSA ≥15% at screening and baseline visits
6. Documented recent history (within 6 months before the baseline visit) of inadequate response to topical AD medication(s)
7. At least 11 (of a total of 14) applications of a stable dose of topical emollient (moisturizer) twice daily during the 7 consecutive days immediately before the baseline visit

Exclusion Criteria

1. Participation in a prior dupilumab clinical study
2. Treatment with a systemic investigational drug before the baseline visit
3. Treatment with a topical investigational drug within 2 weeks prior to the baseline visit
4. Treatment with crisabarole within 2 weeks prior to the baseline visit
5. History of important side effects of medium potency topical corticosteroids (e.g, intolerance to treatment, hypersensitivity reactions, significant skin atrophy, systemic effects), as assessed by the investigator or patient's treating physician
6. Treatment with a topical calcineurin inhibitor (TCI) within 2 weeks prior to the baseline visit
7. Having used any of the following treatments within 4 weeks before the baseline visit, or any condition that, in the opinion of the investigator, is likely to require such treatment(s) during the first 4 weeks of study treatment:

1. Immunosuppressive/immunomodulating drugs (e.g, systemic corticosteroids, cyclosporine, mycophenolate-mofetil, interferon gamma, Janus kinase inhibitors, azathioprine, methotrexate, etc.)
2. Phototherapy for AD
8. Treatment with biologics, as follows:

1. Any cell-depleting agents including but not limited to rituximab:

within 6 months before the baseline visit, or until lymphocyte and CD 19+ lymphocyte count returns to normal, whichever is longer
2. Other biologics: within 5 half-lives (if known) or 16 weeks before the baseline visit, whichever is longer
9. Treatment with a live (attenuated) vaccine within 4 weeks before the baseline visit
10. Body weight \<15 kg at baseline
Minimum Eligible Age

6 Years

Maximum Eligible Age

11 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sanofi

INDUSTRY

Sponsor Role collaborator

Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trial Management

Role: STUDY_DIRECTOR

Regeneron Pharmaceuticals

Locations

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Regeneron Research Site

Birmingham, Alabama, United States

Site Status

Regeneron Research Site

Gilbert, Arizona, United States

Site Status

Regeneron Research Site

Bakersfield, California, United States

Site Status

Regeneron Research Site

Long Beach, California, United States

Site Status

Regeneron Research Site

Mission Viejo, California, United States

Site Status

Regeneron Research Site

Rolling Hills Estates, California, United States

Site Status

Regeneron Research Site

San Diego, California, United States

Site Status

Regeneron Research Site

Denver, Colorado, United States

Site Status

Regeneron Research Site

Coral Gables, Florida, United States

Site Status

Regeneron Research Site

Tampa, Florida, United States

Site Status

Regeneron Research Site

Tampa, Florida, United States

Site Status

Regeneron Research Site

Macon, Georgia, United States

Site Status

Regeneron Research Site

Sandy Springs, Georgia, United States

Site Status

Regeneron Research Site

Chicago, Illinois, United States

Site Status

Regeneron Research Site

Normal, Illinois, United States

Site Status

Regeneron Research Site

Rockville, Maryland, United States

Site Status

Regeneron Research Site

Ypsilanti, Michigan, United States

Site Status

Regeneron Research Site

Minneapolis, Minnesota, United States

Site Status

Regeneron Research Site

St Louis, Missouri, United States

Site Status

Regeneron Research Site

Forest Hills, New York, United States

Site Status

Regeneron Research Site

New York, New York, United States

Site Status

Regeneron Research Site

Rochester, New York, United States

Site Status

Regeneron Research Site

Gahanna, Ohio, United States

Site Status

Regeneron Research Site

Portland, Oregon, United States

Site Status

Regeneron Research Site

Philadelphia, Pennsylvania, United States

Site Status

Regeneron Research Site

Charleston, South Carolina, United States

Site Status

Regeneron Research Site

North Charleston, South Carolina, United States

Site Status

Regeneron Research Site

Bellaire, Texas, United States

Site Status

Regeneron Research Site

San Antonio, Texas, United States

Site Status

Regeneron Research Site

Norfolk, Virginia, United States

Site Status

Regeneron Research Site

Seattle, Washington, United States

Site Status

Regeneron Research Site

Calgary, Alberta, Canada

Site Status

Regeneron Research Site

Markham, Ontario, Canada

Site Status

Regeneron Research Site

Peterborough, Ontario, Canada

Site Status

Regeneron Research Site

Montreal, Quebec, Canada

Site Status

Regeneron Research Site

Kutná Hora, , Czechia

Site Status

Regeneron Research Site

Ústí nad Labem, , Czechia

Site Status

Regeneron Research Site

Munich, Bavaria, Germany

Site Status

Regeneron Research Site

Osnabrück, Lower Saxony, Germany

Site Status

Regeneron Research Site

Münster, North Rhine-Westphalia, Germany

Site Status

Regeneron Research Site

Dresden, Saxony, Germany

Site Status

Regeneron Research Site

Gera, Thuringia, Germany

Site Status

Regeneron Research Site

Bad Bentheim, , Germany

Site Status

Regeneron Research Site

Hamburg, , Germany

Site Status

Regeneron Research Site

Wroclaw, Lower Silesian Voivodeship, Poland

Site Status

Regeneron Research Site

Krakow, Malopolska, Poland

Site Status

Regeneron Research Site

Bialystok, , Poland

Site Status

Regeneron Research Site

Bydgoszcz, , Poland

Site Status

Regeneron Research Site

Gdansk, , Poland

Site Status

Regeneron Research Site

Katowice, , Poland

Site Status

Regeneron Research Site

Katowice, , Poland

Site Status

Regeneron Research Site

Katowice, , Poland

Site Status

Regeneron Research Site

Lodz, , Poland

Site Status

Regeneron Research Site

Świętokrzyskie, , Poland

Site Status

Regeneron Research Site

Warsaw, , Poland

Site Status

Regeneron Research Site

Warsaw, , Poland

Site Status

Regeneron Research Site

Warsaw, , Poland

Site Status

Regeneron Research Site

London, , United Kingdom

Site Status

Regeneron Research Site

Manchester, , United Kingdom

Site Status

Regeneron Research Site

Newcastle upon Tyne, , United Kingdom

Site Status

Regeneron Research Site

Sheffield, , United Kingdom

Site Status

Countries

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United States Canada Czechia Germany Poland United Kingdom

References

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Langley RG, Gherardi G, Coleman A, Ardeleanu M, Rodriguez-Marco A, Levy S, Bansal A, Chen Z, Rossi AB, Shumel B, Khokhar FA. The Safety Data of Dupilumab for the Treatment of Moderate-to-Severe Atopic Dermatitis in Infants, Children, Adolescents, and Adults. Am J Clin Dermatol. 2025 Sep 24. doi: 10.1007/s40257-025-00952-w. Online ahead of print.

Reference Type DERIVED
PMID: 40993471 (View on PubMed)

Kamal MA, Kosloski MP, Lai CH, Partridge MA, Rajadhyaksha M, Kanamaluru V, Bansal A, Shabbir A, Shumel B, Ardeleanu M, Richards SM, Yan H, Xu CR, Rodriguez-Marco A, Xiao J, Khokhar FA, Gherardi G, Babilonia E, Maloney J, Mortensen E, Akinlade B, Braunstein N, Stahl N, Torri A, Davis JD, DiCioccio AT. Immunogenicity of dupilumab in adult and pediatric patients with atopic dermatitis. Front Immunol. 2024 Nov 11;15:1466372. doi: 10.3389/fimmu.2024.1466372. eCollection 2024.

Reference Type DERIVED
PMID: 39588375 (View on PubMed)

Cork MJ, Thaci D, Eichenfield LF, Arkwright PD, Chen Z, Thomas RB, Kosloski MP, Dubost-Brama A, Prescilla R, Bansal A, Levit NA. Dupilumab Safety and Efficacy in a Phase III Open-Label Extension Trial in Children 6-11 Years of Age with Severe Atopic Dermatitis. Dermatol Ther (Heidelb). 2023 Nov;13(11):2697-2719. doi: 10.1007/s13555-023-01016-9. Epub 2023 Sep 26.

Reference Type DERIVED
PMID: 37750994 (View on PubMed)

Siegfried EC, Cork MJ, Katoh N, Zhang H, Chuang CC, Thomas RB, Rossi AB, Cyr SL, Zhang A. Dupilumab Provides Clinically Meaningful Responses in Children Aged 6-11 Years with Severe Atopic Dermatitis: Post Hoc Analysis Results from a Phase III Trial. Am J Clin Dermatol. 2023 Sep;24(5):787-798. doi: 10.1007/s40257-023-00791-7. Epub 2023 Jun 10.

Reference Type DERIVED
PMID: 37300760 (View on PubMed)

Paller AS, Yosipovitch G, Weidinger S, DiBenedetti D, Whalley D, Gadkari A, Guillemin I, Zhang H, Eckert L, Chao J, Bansal A, Chuang CC, Delevry D. Development, Psychometric Validation and Responder Definition of Worst Itch Scale in Children with Severe Atopic Dermatitis. Dermatol Ther (Heidelb). 2022 Dec;12(12):2839-2850. doi: 10.1007/s13555-022-00804-z. Epub 2022 Oct 21.

Reference Type DERIVED
PMID: 36269504 (View on PubMed)

Paller AS, Wollenberg A, Siegfried E, Thaci D, Cork MJ, Arkwright PD, Gooderham M, Sun X, O'Malley JT, Khokhar FA, Vakil J, Bansal A, Rosner K, Shumel B, Levit NA. Laboratory Safety of Dupilumab in Patients Aged 6-11 Years with Severe Atopic Dermatitis: Results from a Phase III Clinical Trial. Paediatr Drugs. 2021 Sep;23(5):515-527. doi: 10.1007/s40272-021-00459-x. Epub 2021 Aug 31.

Reference Type DERIVED
PMID: 34462864 (View on PubMed)

Simpson EL, Paller AS, Siegfried EC, Thaci D, Wollenberg A, Cork MJ, Marcoux D, Huang R, Chen Z, Rossi AB, Shumel B, Sierka D, Bansal A. Dupilumab Demonstrates Rapid and Consistent Improvement in Extent and Signs of Atopic Dermatitis Across All Anatomical Regions in Pediatric Patients 6 Years of Age and Older. Dermatol Ther (Heidelb). 2021 Oct;11(5):1643-1656. doi: 10.1007/s13555-021-00568-y. Epub 2021 Aug 24.

Reference Type DERIVED
PMID: 34427891 (View on PubMed)

Kamal MA, Kovalenko P, Kosloski MP, Srinivasan K, Zhang Y, Rajadhyaksha M, Lai CH, Kanamaluru V, Xu C, Sun X, Simpson EL, Paller AS, Siegfried EC, Shumel B, Bansal A, Al-Huniti N, Davis JD. The Posology of Dupilumab in Pediatric Patients With Atopic Dermatitis. Clin Pharmacol Ther. 2021 Nov;110(5):1318-1328. doi: 10.1002/cpt.2366. Epub 2021 Aug 24.

Reference Type DERIVED
PMID: 34270797 (View on PubMed)

Simpson EL, de Bruin-Weller M, Bansal A, Chen Z, Nelson L, Whalley D, Prescilla R, Guillemin I, Delevry D. Definition of Clinically Meaningful Within-Patient Changes in POEM and CDLQI in Children 6 to 11 Years of Age with Severe Atopic Dermatitis. Dermatol Ther (Heidelb). 2021 Aug;11(4):1415-1422. doi: 10.1007/s13555-021-00543-7. Epub 2021 May 27.

Reference Type DERIVED
PMID: 34046851 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2016-004997-16

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

R668-AD-1652

Identifier Type: -

Identifier Source: org_study_id

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