Clinical trial NCT03054428: Efficacy and Safety of Dupilumab in Participants ≥12 to <18 Years of Age, With Moderate-to-severe Atopic Dermatitis
Official title: A Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy and Safety of Dupilumab Monotherapy in Patients ≥12 to <18 Years of Age, With Moderate-to-severe Atopic Dermatitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Moderate-to-Severe Atopic Dermatitis
Dermatitis, Dermatitis Atopic
Eczema, Skin Diseases, Skin
Diseases Genetic, Genetic
Diseases Inborn, Skin
Disease, Eczematous Skin
Hypersensitivity, Immediate
Hypersensitivity, Immune System Diseases
Dermatitis, Atopic
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Sanofi
First posted: 2017-02-15
Enrollment: 251
Sex: ALL
Minimum age (years): 12
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of the study was to demonstrate the efficacy of dupilumab as a monotherapy in participants ≥12 years to \<18 years of age with moderate-to-severe atopic dermatitis (AD). The secondary objective of the study was to assess the safety of dupilumab as a monotherapy in participants ≥12 years to \<18 years of age with moderate-to-severe AD.


Eligibility criteria: Inclusion Criteria:

* Male or female ≥12 to \<18 years of age at time of screening visit
* Diagnosis of AD according to the American Academy of Dermatology consensus criteria at screening visit
* IGA ≥3 at screening and baseline visit
* EASI ≥16 at the screening and baseline visit
* Baseline Pruritus NRS average score for maximum itch intensity ≥4
* ≥10% BSA of AD involvement at the screening and baseline visits
* With documented recent history (within 6 months before the screening visit) of inadequate response to topical AD medication(s) or for whom topical treatments is medically inadvisable

Exclusion Criteria:

* Participation in a prior dupilumab clinical study
* Treatment with topical corticosteroids (TCS) or topical calcineurin inhibitors (TCI) within 2 weeks before the baseline visit
* Having used immunosuppressive/immunomodulating drugs within 4 weeks before the baseline visit
* Body weight \<30 kg at baseline
* Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiprotozoals, or antifungals within 2 weeks before the baseline visit
* Known or suspected immunodeficiency, known history of human immunodeficiency virus (HIV) infection or HIV seropositivity at the screening visit, established diagnosis of HBV infection or HBV seropositivity at screening, established diagnosis of HCV infection or HCV seropositivity at screening
* History of malignancy before the baseline visit
* Diagnosed active endoparasitic infections or at high risk of these infections
* Patient is female who is pregnant, breastfeeding, or planning to become pregnant or breastfeed during the study
* Patient is female of childbearing potential and sexually active, who is unwilling to use adequate methods of contraception throughout the duration of the study and for 120 days after the last dose of study drug

Other protocol-defined inclusion/exclusion criteria may apply

Primary outcomes:
measure: Percentage of Participants With Investigator's Global Assessment (IGA) 0 or 1 (and Reduction From Baseline of ≥2 Points) at Week 16
timeFrame: Baseline and Week 16
measure: Percentage of Participants With Eczema Area and Severity Index (EASI)-75 (≥75% Improvement From Baseline) at Week 16
timeFrame: Baseline and Week 16
Secondary outcomes:
measure: Percent Change From Baseline in EASI Score at Week 16
timeFrame: Baseline and Week 16
measure: Percent Change From Baseline in Weekly Average of Daily Peak Pruritus Numerical Rating Scale (NRS) Score at Week 16
timeFrame: Baseline and Week 16
measure: Percentage of Participants With Improvement (Reduction ≥3 Points) of Weekly Average of Daily Peak Pruritus NRS From Baseline to Week 16
timeFrame: Baseline to Week 16
measure: Percentage of Participants With Improvement (Reduction ≥4 Points) of Weekly Average of Daily Peak Pruritus NRS From Baseline to Week 16
timeFrame: Baseline to Week 16
measure: Percentage of Participants With EASI-50 (≥50% Improvement From Baseline) at Week 16
timeFrame: Baseline and Week 16
measure: Percentage of Participants With EASI-90 (≥90% Improvement From Baseline) at Week 16
timeFrame: Baeline and Week 16
measure: Time to Onset of Effect on Pruritus as Measured by Percentage of Participants With Improvement (Reduction ≥3 Points) of Weekly Average of Daily Peak Pruritus NRS From Baseline
timeFrame: Baseline up to week 16
measure: Time to Onset of Effect on Pruritus as Measured by Percentage of Participants With Improvement (Reduction ≥4 Points) of Weekly Average of Daily Peak Pruritus NRS From Baseline
timeFrame: Baseline up to Week 16
measure: Change From Baseline in Percent Body Surface Area (BSA) at Week 16
timeFrame: Baseline and Week 16
measure: Percent Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Score at Week 16
timeFrame: Baseline and Week 16
measure: Change From Baseline in Children's Dermatology Life Quality Index (CDLQI) Total Score at Week 16
timeFrame: Baseline and Week 16
measure: Change From Baseline in Patient Oriented Eczema Measure (POEM) at Week 16
timeFrame: Baseline and Week 16
measure: Change From Baseline in Weekly Average of Daily Peak Pruritus NRS at Week 16
timeFrame: Baseline and Week 16
measure: Percent Change From Baseline in Weekly Average of Daily Peak Pruritus NRS at Week 4
timeFrame: Baseline and Week 4
measure: Change From Baseline in Total Hospital Anxiety and Depression Scale (HADS) at Week 16
timeFrame: Baseline and Week 16
measure: Percentage of Participants With Improvement (Reduction ≥4 Points) of Weekly Average of Daily Peak Pruritus NRS From Baseline at Week 4
timeFrame: Baseline and Week 4
measure: Percentage of Participants With Skin-infection Treatment Emergent Adverse Events (TEAEs) (Excluding Herpetic Infections) Through Week 16
timeFrame: Baseline through Week 16
measure: Percentage of Participants With Serious TEAEs Through Week 16
timeFrame: Baseline through Week 16
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Regeneron Investigational Site
state: Alabama
city: Gilbert
country: United States
facility: Regeneron Investigational Site
state: Arizona
city: Bakersfield
country: United States
facility: Regeneron Investigational Site
state: California
city: Long Beach
country: United States
facility: Regeneron Investigational Site
state: California
city: Rolling Hills Estates
country: United States
facility: Regeneron Investigational Site
state: California
city: San Diego
country: United States
facility: Regeneron Investigational Site
state: California
city: Santa Rosa
country: United States
facility: Regeneron Investigational Site
state: California
city: Centennial
country: United States
facility: Regeneron Investigational Site
state: Colorado
city: Denver
country: United States
facility: Regeneron Investigational Site
state: Colorado
city: Washington
country: United States
facility: Regeneron Investigational Site
state: District of Columbia
city: Tampa
country: United States
facility: Regeneron Investigational Site
state: Florida
city: Macon
country: United States
facility: Regeneron Investigational Site
state: Georgia
city: Sandy Springs
country: United States
facility: Regeneron Investigational Site
state: Georgia
city: Chicago
country: United States
facility: Regeneron Investigational Site
state: Illinois
city: Evansville
country: United States
facility: Regeneron Investigational Site
state: Indiana
city: Indianapolis
country: United States
facility: Regeneron Investigational Site
state: Indiana
city: Plainfield
country: United States
facility: Regeneron Investigational Site
state: Indiana
city: Rockville
country: United States
facility: Regeneron Investigational Site
state: Maryland
city: Boston
country: United States
facility: Regeneron Investigational Site
state: Massachusetts
city: Boston
country: United States
facility: Regeneron Investigational Site
state: Massachusetts
city: Plymouth
country: United States
facility: Regeneron Investigational Site
state: Minnesota
city: Saint Louis
country: United States
facility: Regeneron Investigational Site
state: Missouri
city: Forest Hills
country: United States
facility: Regeneron Investigational Site
state: New York
city: New York
country: United States
facility: Regeneron Investigational Site
state: New York
city: Rochester
country: United States
facility: Regeneron Investigational Site
state: New York
city: Chapel Hill
country: United States
facility: Regeneron Investigational Site
state: North Carolina
city: Bexley
country: United States
facility: Regeneron Investigational Site
state: Ohio
city: Tulsa
country: United States
facility: Regeneron Investigational Site
state: Oklahoma
city: Portland
country: United States
facility: Regeneron Investigational Site
state: Oregon
city: Portland
country: United States
facility: Regeneron Investigational Site
state: Oregon
city: Philadelphia
country: United States
facility: Regeneron Investigational Site
state: Pennsylvania
city: Charleston
country: United States
facility: Regeneron Investigational Site
state: South Carolina
city: Bellaire
country: United States
facility: Regeneron Investigational Site
state: Texas
city: San Antonio
country: United States
facility: Regeneron Investigational Site
state: Texas
city: Norfolk
country: United States
facility: Regeneron Investigational Site
state: Virginia
city: Seattle
country: United States
facility: Regeneron Investigational Site
state: Washington
city: Calgary
country: Canada
facility: Regeneron Investigational Site
state: Alberta
city: Surrey
country: Canada
facility: Regeneron Investigational Site
state: British Columbia
city: Surrey
country: Canada
facility: Regeneron Investigational Site
state: British Columbia
city: Winnipeg
country: Canada
facility: Regeneron Investigational Site
state: Manitoba
city: Markham
country: Canada
facility: Regeneron Investigational Site
state: Ontario
city: Ottawa
country: Canada
facility: Regeneron Investigational Site
state: Ontario
city: Peterborough
country: Canada
facility: Regeneron Investigational Site
state: Ontario
city: Richmond Hill
country: Canada
facility: Regeneron Research Site
state: Ontario
city: Windsor
country: Canada
facility: Regeneron Investigational Site
state: Ontario
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References:
citation: Blauvelt A, Guttman-Yassky E, Paller AS, Simpson EL, Cork MJ, Weisman J, Browning J, Soong W, Sun X, Chen Z, Kosloski MP, Kamal MA, Delevry D, Chuang CC, O'Malley JT, Bansal A. Long-Term Efficacy and Safety of Dupilumab in Adolescents with Moderate-to-Severe Atopic Dermatitis: Results Through Week 52 from a Phase III Open-Label Extension Trial (LIBERTY AD PED-OLE). Am J Clin Dermatol. 2022 May;23(3):365-383. doi: 10.1007/s40257-022-00683-2. Epub 2022 May 14.
citation: 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.
citation: 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.
citation: Siegfried EC, Bieber T, Simpson EL, Paller AS, Beck LA, Boguniewicz M, Schneider LC, Khokhar FA, Chen Z, Prescilla R, Mina-Osorio P, Bansal A. Effect of Dupilumab on Laboratory Parameters in Adolescents with Atopic Dermatitis: Results from a Randomized, Placebo-Controlled, Phase 3 Clinical Trial. Am J Clin Dermatol. 2021 Mar;22(2):243-255. doi: 10.1007/s40257-020-00583-3. Epub 2021 Mar 3.
citation: Bansal A, Simpson EL, Paller AS, Siegfried EC, Blauvelt A, de Bruin-Weller M, Corren J, Sher L, Guttman-Yassky E, Chen Z, Daizadeh N, Kamal MA, Shumel B, Mina-Osorio P, Mannent L, Patel N, Graham NMH, Khokhar FA, Ardeleanu M. Conjunctivitis in Dupilumab Clinical Trials for Adolescents with Atopic Dermatitis or Asthma. Am J Clin Dermatol. 2021 Jan;22(1):101-115. doi: 10.1007/s40257-020-00577-1.
citation: Silverberg JI, Yosipovitch G, Simpson EL, Kim BS, Wu JJ, Eckert L, Guillemin I, Chen Z, Ardeleanu M, Bansal A, Kaur M, Rossi AB, Graham NMH, Patel N, Gadkari A. Dupilumab treatment results in early and sustained improvements in itch in adolescents and adults with moderate to severe atopic dermatitis: Analysis of the randomized phase 3 studies SOLO 1 and SOLO 2, AD ADOL, and CHRONOS. J Am Acad Dermatol. 2020 Jun;82(6):1328-1336. doi: 10.1016/j.jaad.2020.02.060. Epub 2020 Mar 3.
citation: Paller AS, Bansal A, Simpson EL, Boguniewicz M, Blauvelt A, Siegfried EC, Guttman-Yassky E, Hultsch T, Chen Z, Mina-Osorio P, Lu Y, Rossi AB, He X, Kamal M, Graham NMH, Pirozzi G, Ruddy M, Eckert L, Gadkari A. Clinically Meaningful Responses to Dupilumab in Adolescents with Uncontrolled Moderate-to-Severe Atopic Dermatitis: Post-hoc Analyses from a Randomized Clinical Trial. Am J Clin Dermatol. 2020 Feb;21(1):119-131. doi: 10.1007/s40257-019-00478-y.
citation: Simpson EL, Paller AS, Siegfried EC, Boguniewicz M, Sher L, Gooderham MJ, Beck LA, Guttman-Yassky E, Pariser D, Blauvelt A, Weisman J, Lockshin B, Hultsch T, Zhang Q, Kamal MA, Davis JD, Akinlade B, Staudinger H, Hamilton JD, Graham NMH, Pirozzi G, Gadkari A, Eckert L, Stahl N, Yancopoulos GD, Ruddy M, Bansal A. Efficacy and Safety of Dupilumab in Adolescents With Uncontrolled Moderate to Severe Atopic Dermatitis: A Phase 3 Randomized Clinical Trial. JAMA Dermatol. 2020 Jan 1;156(1):44-56. doi: 10.1001/jamadermatol.2019.3336.
citation: Simpson EL, de Bruin-Weller M, Eckert L, Whalley D, Guillemin I, Reaney M, Chen Z, Nelson L, Qin S, Bansal A, Gadkari A. Responder Threshold for Patient-Oriented Eczema Measure (POEM) and Children's Dermatology Life Quality Index (CDLQI) in Adolescents with Atopic Dermatitis. Dermatol Ther (Heidelb). 2019 Dec;9(4):799-805. doi: 10.1007/s13555-019-00333-2. Epub 2019 Oct 22.
citation: Cork MJ, Thaci D, Eichenfield LF, Arkwright PD, Hultsch T, Davis JD, Zhang Y, Zhu X, Chen Z, Li M, Ardeleanu M, Teper A, Akinlade B, Gadkari A, Eckert L, Kamal MA, Ruddy M, Graham NMH, Pirozzi G, Stahl N, DiCioccio AT, Bansal A. Dupilumab in adolescents with uncontrolled moderate-to-severe atopic dermatitis: results from a phase IIa open-label trial and subsequent phase III open-label extension. Br J Dermatol. 2020 Jan;182(1):85-96. doi: 10.1111/bjd.18476. Epub 2019 Oct 8.