Clinical trial NCT03346434: Safety, Pharmacokinetics and Efficacy of Dupilumab in Patients ≥6 Months to <6 Years With Moderate-to-Severe Atopic Dermatitis (Liberty AD PRESCHOOL)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Dermatitis, Atopic
Keywords: Eczema
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Sanofi
First posted: 2017-11-17
Enrollment: 202
Sex: ALL
Minimum age (years): 6
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Part A: Single-ascending-dose cohorts staggered by age;

Part B: Parallel Group
Primary purpose: TREATMENT

Brief summary: 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).

Detailed 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.

Eligibility 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

Primary outcomes:
measure: Part A: Maximum Observed Serum Concentration (Cmax) of Functional Dupilumab
timeFrame: Post-dose on Days 1, 3, 8, 18, and 29
measure: Part A: Dose Normalized Maximum Observed Serum Concentration (Cmax/Dose) of Dupilumab
timeFrame: Post-dose on Days 1, 3, 8, 18, and 29
measure: Part A: Time to Reach the Maximum Serum Concentration (Tmax) of Dupilumab
timeFrame: Post-dose on Days 1, 3, 8, 18, and 29
measure: Part A: Last Quantifiable Serum Concentration (Clast) of Dupilumab
timeFrame: Post-dose on Days 1, 3, 8, 18, and 29
measure: Part A: Time of the Last Quantifiable Serum Concentration (Tlast) of Dupilumab
timeFrame: Post-dose on Days 1, 3, 8, 18, and 29
measure: Part A: Area Under the Serum Concentration-Time Curve From Time Zero to the Time of the Last Measurable Concentration (AUClast) of Dupilumab
timeFrame: Post-dose on Days 1, 3, 8, 18, and 29
measure: 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
timeFrame: Post-dose on Days 1, 3, 8, 18, and 29
measure: Part A: Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE)
timeFrame: Baseline up to Week 4
measure: Part A: Number of Participants With TEAEs by Severity According to Qualitative Toxicity Scale
timeFrame: Baseline up to Week 4
measure: Part B: Percentage of Participants With Investigator's Global Assessment (IGA) Score 0 or 1 at Week 16
timeFrame: Week 16
measure: Part B: Percentage of Participants With Eczema Area and Severity Index (EASI) -75 (EASI-75) (≥75% Improvement From Baseline) at Week 16
timeFrame: Week 16
Secondary outcomes:
measure: Part A: Number of Participants With Serious TEAEs and Severe TEAEs
timeFrame: Baseline up to Week 4
measure: Part A: Percent Change From Baseline in EASI Score at Week 4
timeFrame: Week 4
measure: Part A: Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score at Week 4
timeFrame: Week 4
measure: Part A: Percentage of Participants With IGA Score 0 or 1 at Week 4
timeFrame: Week 4
measure: Part A: Number of Participants With at Least One Positive Treatment-Emergent Anti-Drug Antibodies (ADA)
timeFrame: Baseline up to Day 57
measure: Part B: Number of Participants With at Least One Serious Adverse Event (SAE) Through Week 16
timeFrame: Baseline through Week 16
measure: Part B: Number of Participants With at Least One Skin Infection Treatment Emergent Adverse Event (TEAE) (Excluding Herpetic Infection) Through Week 16
timeFrame: Baseline through Week 16
measure: Part B: Number of Participants With at Least One Positive Treatment-Emergent ADA
timeFrame: Baseline up to Day 197
measure: Part B: Percent Change From Baseline in EASI Score at Week 16
timeFrame: Week 16
measure: Part B: Percent Change From Baseline in Weekly Average of Daily Worst Scratch/Itch/Numerical Rating Scale (NRS) at Week 16
timeFrame: Week 16
measure: Part B: Percentage of Participants With Improvement (Reduction From Baseline) of Weekly Average of Daily Worst Scratch/Itch/NRS ≥4 Points at Week 16
timeFrame: Week 16
measure: Part B: Percentage of Participants With Improvement (Reduction From Baseline) of Weekly Average of Daily Worst Scratch/Itch/NRS ≥3 Points at Week 16
timeFrame: Week 16
measure: Part B: Percentage of Participants Who Achieved EASI-50 (≥50% Improvement From Baseline) at Week 16
timeFrame: Week 16
measure: Part B: Percentage of Participants Who Achieved EASI-90 (≥90% Improvement From Baseline) at Week 16
timeFrame: Week 16
measure: Part B: Change From Baseline in Percent Body Surface Area (BSA) Affected by Atopic Dermatitis (AD) at Week 16
timeFrame: Week 16
measure: Part B: Change From Baseline in Patient Oriented Eczema Measure (POEM) at Week 16
timeFrame: Week 16
measure: Part B: Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) at Week 16
timeFrame: Week 16
measure: Part B: Change From Baseline in Participant's Sleep Quality NRS at Week 16
timeFrame: Week 16
measure: Part B: Change From Baseline in Participant's Skin Pain NRS at Week 16
timeFrame: Week 16
measure: Part B: Change From Baseline in Dermatitis Family Index (DFI) at Week 16
timeFrame: Week 16
measure: Part B: Change From Baseline in Children's Dermatology Life Quality Index (CDLQI) at Week 16
timeFrame: Week 16
measure: Part B: Change From Baseline in Infants' Dermatology Quality of Life Index (IDQOL) at Week 16
timeFrame: Week 16
measure: Part B: Percentage of Topical Corticosteroid (TCS) Medication-free Days From Baseline to Week 16
timeFrame: Baseline up to Week 16
measure: Part B: Mean Weekly Dose of Low Potency TCS in Grams From Baseline to Week 16
timeFrame: Baseline up to Week 16
measure: Part B: Mean Weekly Dose of TCS in Grams for Medium or High Potency TCS From Baseline to Week 16
timeFrame: Baseline up to Week 16
measure: Part B: Mean Number of Caregiver Missed Work Days 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: Long Beach
country: United States
facility: Regeneron Investigational Site
state: California
city: Los Angeles
country: United States
facility: Regeneron Investigational site
state: California
city: Palo Alto
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: Washington
country: United States
facility: Regeneron Investigational Site
state: District of Columbia
city: Coral Gables
country: United States
facility: Regeneron Investigational Site
state: Florida
city: Tampa
country: United States
facility: Regeneron Investigational Site
state: Florida
city: Columbus
country: United States
facility: Regeneron Investigational Site
state: Georgia
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: Rockville
country: United States
facility: Regeneron Investigational Site
state: Maryland
city: Boston
country: United States
facility: Regeneron Investigational Site
state: Massachusetts
city: Ann Arbor
country: United States
facility: Regeneron Investigational Site
state: Michigan
city: Ypsilanti
country: United States
facility: Regeneron Investigational Site
state: Michigan
city: Saint Louis
country: United States
facility: Regeneron Investigational Site
state: Missouri
city: Lincoln
country: United States
facility: Regeneron Investigational Site
state: Nebraska
city: Hackensack
country: United States
facility: Regeneron Investigational Site
state: New Jersey
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: 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: North Charleston
country: United States
facility: Regeneron Investigational Site
state: South Carolina
city: Austin
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: Milwaukee
country: United States
facility: Regeneron Investigational Site
state: Wisconsin
city: Osnabrück
country: Germany
facility: Regeneron Investigational Site
state: Lower Saxony
city: Muenster
country: Germany
facility: Regeneron Investigational site
state: North Rhine-Westphal
city: Dresden
country: Germany
facility: Regeneron Investigational Site
state: Sachsen
city: Frankfurt/ Main
country: Germany
facility: Regeneron Investigational site
city: Kiel
country: Germany
facility: Regeneron Investigational Site
city: Muenchen
country: Germany
facility: Regeneron Investigational Site
city: Muenchen
country: Germany
facility: Regeneron Investigational site
city: Bialystok
country: Poland
facility: Regeneron Investigational Site
city: Katowice
country: Poland
facility: Regeneron Investigational Site
city: Krakow
country: Poland
facility: Regeneron Investigational Site
city: Ostrowiec Swietokrzyski
country: Poland
facility: Regeneron Investigational Site
city: Warszawa
country: Poland
facility: Regeneron Investigational Site
city: Warszawa
country: Poland
facility: Regeneron Investigational Site
city: Manchester
country: United Kingdom
facility: Regeneron Investigational Site
state: Lancashire
city: Sheffield
country: United Kingdom
facility: Regeneron Investigational Site
state: South Yorkshire
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References:
citation: Paller AS, Simpson EL, Siegfried EC, Cork MJ, Wollenberg A, Arkwright PD, Soong W, Gonzalez ME, Schneider LC, Sidbury R, Lockshin B, Meltzer S, Wang Z, Mannent LP, Amin N, Sun Y, Laws E, Akinlade B, Dillon M, Kosloski MP, Kamal MA, Dubost-Brama A, Patel N, Weinreich DM, Yancopoulos GD, O'Malley JT, Bansal A; participating investigators. Dupilumab in children aged 6 months to younger than 6 years with uncontrolled atopic dermatitis: a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2022 Sep 17;400(10356):908-919. doi: 10.1016/S0140-6736(22)01539-2.