Clinical trial NCT03345914: 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)
Official title: A Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy and Safety of Dupilumab Administered Concomitantly With Topical Corticosteroids in Patients, ≥6 Years to <12 Years of Age, With Severe Atopic Dermatitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Dermatitis, Atopic
Keywords: Eczema
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Sanofi
First posted: 2017-11-17
Enrollment: 367
Sex: ALL
Minimum age (years): 6
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Key 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

Key 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

Note: Other Inclusion/ Exclusion criteria apply

Primary outcomes:
measure: Percentage of Participants With Investigator's Global Assessment (IGA) 0 or 1 at Week 16
timeFrame: Week 16
Secondary outcomes:
measure: Percentage of Participants With Eczema Area and Severity Index -75 (EASI-75) (≥ 75 Percent (%) Improvement From Baseline) at Week 16
timeFrame: Week 16
measure: Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score at Week 16
timeFrame: Baseline (Day 1), Week 16
measure: Percent Change From Baseline in Weekly Average of Daily Worst Itch Score at Week 16
timeFrame: Baseline (Day 1), Week 16
measure: Percentage of Participants With Improvement (Reduction From Baseline) of Weekly Average of Daily Worst Itch Score ≥3 Points at Week 16
timeFrame: Week 16
measure: Percentage of Participants With Improvement (Reduction From Baseline) of Weekly Average of Daily Worst Itch Score ≥4 Points at Week 16
timeFrame: Week 16
measure: Percentage of Participants Achieving Eczema Area and Severity Index - 50 (EASI-50) (≥ 50% Improvement From Baseline) at Week 16
timeFrame: Week 16
measure: Percentage of Participants Achieving Eczema Area and Severity Index - 90 (EASI - 90) (≥ 90% Improvement From Baseline) at Week 16
timeFrame: Week 16
measure: Time to Achieve ≥ 4 Point Reduction of Weekly Average of Daily Worst Itch Score From Baseline During the 16-week Treatment Period
timeFrame: Baseline (Day 1) up to Week 16
measure: Time to Achieve ≥ 3 Point Reduction of Weekly Average of Daily Worst Itch Score From Baseline During the 16-week Treatment Period
timeFrame: Baseline (Day 1) up to Week 16
measure: Change From Baseline in Percent Body Surface Area (BSA) Affected by Atopic Dermatitis (AD) at Week 16
timeFrame: Baseline (Day 1), Week 16
measure: Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) at Week 16
timeFrame: Baseline (Day 1), Week 16
measure: Change From Baseline in Children's Dermatology Life Quality Index (CDLQI) at Week 16
timeFrame: Baseline (Day 1), Week 16
measure: Change From Baseline in Patient Oriented Eczema Measure (POEM) at Week 16
timeFrame: Baseline (Day 1), Week 16
measure: Change From Baseline in Weekly Average of Daily Worst Itch Score at Week 16
timeFrame: Baseline (Day 1), Week 16
measure: Change From Baseline in Dermatitis Family Index (DFI) at Week 16
timeFrame: Baseline (Day 1) , Week 16
measure: Change From Baseline in Patient Reported Outcomes Measurements Information Systems (PROMIS) Pediatric Anxiety Short Form Scale Total Score at Week 16
timeFrame: Baseline (Day 1), Week 16
measure: Change From Baseline in Patient Reported Outcomes Measurements Information Systems (PROMIS) Pediatric Depressive Symptoms Short Form Scale Score at Week 16
timeFrame: Baseline (Day 1), Week 16
measure: Percentage of Participants Having at Least One Skin Infection Treatment Emergent Adverse Event (TEAE) (Excluding Herpetic Infections) Through Week 16
timeFrame: Baseline through Week 16
measure: Percentage of Participants Having at Least One Serious Treatment Emergent Adverse Event (TEAE) Through Week 16
timeFrame: Baseline (Day 1) through Week 16
measure: Proportion of Topical Corticosteroid (TCS) Medication-free Days From Baseline to Week 16
timeFrame: Baseline (Day 1), Week 16
measure: Mean Weekly Dose of Topical Corticosteroid (TCS) in Grams for Low or Medium Potency TCS From Baseline to Week 16
timeFrame: Baseline (Day 1), Week 16
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Regeneron Research Site
state: Alabama
city: Gilbert
country: United States
facility: Regeneron Research Site
state: Arizona
city: Bakersfield
country: United States
facility: Regeneron Research Site
state: California
city: Long Beach
country: United States
facility: Regeneron Research Site
state: California
city: Mission Viejo
country: United States
facility: Regeneron Research Site
state: California
city: Rolling Hills Estates
country: United States
facility: Regeneron Research Site
state: California
city: San Diego
country: United States
facility: Regeneron Research Site
state: California
city: Denver
country: United States
facility: Regeneron Research Site
state: Colorado
city: Coral Gables
country: United States
facility: Regeneron Research Site
state: Florida
city: Tampa
country: United States
facility: Regeneron Research Site
state: Florida
city: Tampa
country: United States
facility: Regeneron Research Site
state: Florida
city: Macon
country: United States
facility: Regeneron Research Site
state: Georgia
city: Sandy Springs
country: United States
facility: Regeneron Research Site
state: Georgia
city: Chicago
country: United States
facility: Regeneron Research Site
state: Illinois
city: Normal
country: United States
facility: Regeneron Research Site
state: Illinois
city: Rockville
country: United States
facility: Regeneron Research Site
state: Maryland
city: Ypsilanti
country: United States
facility: Regeneron Research Site
state: Michigan
city: Minneapolis
country: United States
facility: Regeneron Research Site
state: Minnesota
city: Saint Louis
country: United States
facility: Regeneron Research Site
state: Missouri
city: Forest Hills
country: United States
facility: Regeneron Research Site
state: New York
city: New York
country: United States
facility: Regeneron Research Site
state: New York
city: Rochester
country: United States
facility: Regeneron Research Site
state: New York
city: Gahanna
country: United States
facility: Regeneron Research Site
state: Ohio
city: Portland
country: United States
facility: Regeneron Research Site
state: Oregon
city: Philadelphia
country: United States
facility: Regeneron Research Site
state: Pennsylvania
city: Charleston
country: United States
facility: Regeneron Research Site
state: South Carolina
city: North Charleston
country: United States
facility: Regeneron Research Site
state: South Carolina
city: Bellaire
country: United States
facility: Regeneron Research Site
state: Texas
city: San Antonio
country: United States
facility: Regeneron Research Site
state: Texas
city: Norfolk
country: United States
facility: Regeneron Research Site
state: Virginia
city: Seattle
country: United States
facility: Regeneron Research Site
state: Washington
city: Calgary
country: Canada
facility: Regeneron Research Site
state: Alberta
city: Markham
country: Canada
facility: Regeneron Research Site
state: Ontario
city: Peterborough
country: Canada
facility: Regeneron Research Site
state: Ontario
city: Montréal
country: Canada
facility: Regeneron Research Site
state: Quebec
city: Kutná Hora
country: Czechia
facility: Regeneron Research Site
city: Ústí Nad Labem
country: Czechia
facility: Regeneron Research Site
city: Muenchen
country: Germany
facility: Regeneron Research Site
state: Bavaria
city: Osnabruck
country: Germany
facility: Regeneron Research Site
state: Lower Saxony
city: Munster
country: Germany
facility: Regeneron Research Site
state: Nordrhein-Westfalen
city: Dresden
country: Germany
facility: Regeneron Research Site
state: Sachsen
city: Gera
country: Germany
facility: Regeneron Research Site
state: Thuringen
city: Bad Bentheim
country: Germany
facility: Regeneron Research Site
city: Hamburg
country: Germany
facility: Regeneron Research Site
city: Wroclaw
country: Poland
facility: Regeneron Research Site
state: Dolnoslaskie
city: Krakow
country: Poland
facility: Regeneron Research Site
state: Malopolska
city: Białystok
country: Poland
facility: Regeneron Research Site
city: Bydgoszcz
country: Poland
facility: Regeneron Research Site
city: Gdańsk
country: Poland
facility: Regeneron Research Site
city: Katowice
country: Poland
facility: Regeneron Research Site
city: Katowice
country: Poland
facility: Regeneron Research Site
city: Katowice
country: Poland
facility: Regeneron Research Site
city: Warszawa
country: Poland
facility: Regeneron Research Site
city: Warszawa
country: Poland
facility: Regeneron Research Site
city: Warszawa
country: Poland
facility: Regeneron Research Site
city: Łódź
country: Poland
facility: Regeneron Research Site
city: Świętokrzyskie
country: Poland
facility: Regeneron Research Site
city: London
country: United Kingdom
facility: Regeneron Research Site
city: Manchester
country: United Kingdom
facility: Regeneron Research Site
city: Newcastle Upon Tyne
country: United Kingdom
facility: Regeneron Research Site
city: Sheffield
country: United Kingdom
facility: Regeneron Research Site
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
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: 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.