Safety, Pharmacokinetics and Efficacy of Dupilumab in Patients ≥6 Months to <6 Years With Moderate-to-Severe Atopic Dermatitis (Liberty AD PRESCHOOL)

Regeneron Pharmaceuticals

Status and phase: Completed; Phase 3; Phase 2

Conditions: Dermatitis, Atopic

Treatments: Drug: Matching placebo; Drug: Dupilumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT03346434

R668-AD-1539

2016-000955-28 (EudraCT Number)

Details and patient eligibility

About

This study is a 2-part (parts A and B) phase 2/3 study to evaluate the safety, pharmacokinetics (PK) and efficacy of dupilumab in participants 6 months to less than 6 years of age with moderate-to-severe atopic dermatitis (AD).

Full description

1. Part A (open-label, single-ascending-dose, sequential cohort phase 2 study):

   • Primary objective is to characterize the safety and PK of dupilumab administered as a single dose in pediatric participants, 6 months to less than 6 years of age, with severe AD.
   • Secondary objective is to evaluate the efficacy and immunogenicity of a single dose of dupilumab in participants 6 months to less than 6 years of age with severe AD.

2. Part B (randomized, double-blind, parallel-group, placebo-controlled phase 3 study):

   • Primary objective is to demonstrate the efficacy of multiple doses of dupilumab over 16 weeks of treatment when administered concomitantly with topical corticosteroids (TCS) in pediatric participants, 6 months to less than 6 years of age, with moderate-to-severe AD.
   • Secondary objective is to assess the safety and immunogenicity of multiple doses of dupilumab over 16 weeks of treatment when administered concomitantly with TCS in participants 6 months to less than 6 years of age with moderate-to-severe AD.

Enrollment: 202 patients

Sex: All

Ages: 6 months to 5 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria

• Diagnosis of atopic dermatitis (AD) according to the American Academy of Dermatology consensus criteria at the screening visit
• Participants with documented recent history (within 6 months before the screening visit) of inadequate response to topical AD medication(s)
• IGA score at screening and baseline visits
• part A: IGA = 4
• part B: IGA ≥3
• EASI score at screening and baseline visits
• part A: EASI ≥21
• part B: EASI ≥16
• Body Surface Area (BSA) involvement at screening and baseline visits
• part A: ≥15%
• part B: ≥10%
• At least 11 (of a total of 14*) applications of a topical emollient (moisturizer) during the 7 consecutive days immediately before the baseline visit (not including the day of randomization) (for part B of the study only)
• Baseline worst scratch/itch score weekly average score for maximum scratch/itch intensity ≥4 (for part B of the study only)
• At least 11 (of a total of 14) daily applications of low potency TCS during the 2-week TCS standardization period (beginning on day -14) leading up to the baseline visit (for part B of the study only).

Key Exclusion Criteria

• Prior treatment with dupilumab
• History of important side effects of low potency topical corticosteroids (only applicable for part B of the study)
• Having used immunosuppressive/immunomodulating drugs within 4 weeks before the baseline visit
• Treatment with a live (attenuated) vaccine within 4 weeks before the baseline visit
• 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 at any time before the baseline visit
• Diagnosed active endoparasitic infections or at high risk of these infections
• Severe concomitant illness(es) that, in the investigator's judgment, would adversely affect the patient's participation in the study
• Body weight <5 kg or ≥30 kg at baseline (only applicable part B of the study)

Note: Other protocol defined Inclusion/ Exclusion criteria apply

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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202 participants in 4 patient groups

Part A (Open label Dupilumab): Age cohorts 1 & 2

Experimental group

Description:

Age cohort 1: ≥2 years old to \<6 years old Age cohort 2: ≥6 months to \<2 years old

Treatment:

Drug: Dupilumab

Part B (Double-blind): Dupilumab dose 1

Experimental group

Description:

The results of part A will be used to guide the selection of dose levels and dosing frequency for part B.

Treatment:

Drug: Dupilumab

Part B (Double-blind): Dupilumab dose 2

Experimental group

Description:

The results of part A will be used to guide the selection of dose levels and dosing frequency for part B.

Treatment:

Drug: Dupilumab

Part B (Double-Blind): Placebo

Experimental group

Treatment:

Drug: Matching placebo