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

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ClinicalTrials.gov Identifier: NCT03346434
Recruitment Status : Recruiting
First Posted : November 17, 2017
Last Update Posted : June 14, 2019
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
Regeneron Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE February 6, 2017
First Posted Date  ICMJE November 17, 2017
Last Update Posted Date June 14, 2019
Actual Study Start Date  ICMJE November 30, 2017
Estimated Primary Completion Date June 3, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 29, 2018)
  • Part A: Pharmacokinetic (PK) parameter - Maximum observed concentration (Cmax) [ Time Frame: Baseline to week 4 ]
    Peak dupilumab concentration in serum following single-dose administration
  • Part A: PK parameter - Time to reach maximum observed concentration (Tmax) time [ Time Frame: Baseline to week 4 ]
  • Part A: PK parameter - Area under the concentration-time curve (AUC) from time zero to the time of the last measurable concentration (AUClast) [ Time Frame: Baseline to week 4 ]
    AUC computed from time zero to the time of the last positive concentration
  • Part A: Incidence of Treatment-Emergent Adverse Events (TEAEs) [Safety and Tolerability] [ Time Frame: Baseline to week 8 ]
    TEAEs include adverse events (AEs), serious adverse events (SAEs), deaths, and laboratory abnormalities
  • Part B: Proportion of participants with an Investigator Global Assessment (IGA) score of 0 to 1 (on a 5-point scale) at week 16 [ Time Frame: At week 16 ]
Original Primary Outcome Measures  ICMJE
 (submitted: November 14, 2017)
  • Part A: Pharmacokinetic (PK) parameter - Maximum observed concentration (Cmax) [ Time Frame: Baseline to week 4 ]
    Peak dupilumab concentration in serum following single-dose administration
  • Part A: PK parameter - Time to reach maximum observed concentration (Tmax) time [ Time Frame: Baseline to week 4 ]
  • Part A: PK parameter - Area under the concentration-time curve (AUC) from time zero to the time of the last measurable concentration (AUClast) [ Time Frame: Baseline to week 4 ]
    AUC computed from time zero to the time of the last positive concentration
  • Part A: Incidence of Treatment-Emergent Adverse Events (TEAEs) [Safety and Tolerability] [ Time Frame: Baseline to week 8 ]
    TEAEs include adverse events (AEs), serious adverse events (SAEs), deaths, and laboratory abnormalities
  • Part B: Proportion of patients with an Investigator Global Assessment (IGA) score of 0 to 1 (on a 5-point scale) at week 16 [ Time Frame: At week 16 ]
Change History Complete list of historical versions of study NCT03346434 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 29, 2018)
  • Part A: Incidence of Serious Adverse Events (SAEs) [ Time Frame: Baseline to week 4 ]
  • Part A: Incidence of severe TEAEs [ Time Frame: Baseline to week 4 ]
  • Part A: Percent change in EASI score [ Time Frame: Baseline to week 4 ]
  • Part A: Percent change in SCORing Atopic Dermatitis (SCORAD) score [ Time Frame: Baseline to week 4 ]
  • Part A: Proportion of participants with an IGA score of either 0 or 1 (on a 5-point scale) [ Time Frame: At week 4 ]
  • Part A: Determine immunogenicity titer [ Time Frame: Baseline to week 4 ]
    Assessed by measurement of anti-drug antibodies
  • Part B: Proportion of participants with EASI-75 (≥75% improvement from baseline) [ Time Frame: At week 16 ]
  • Part B: Percent change in EASI score [ Time Frame: Baseline to week 16 ]
  • Part B: Reduction in pruritus (appropriate measure and endpoint definition in this patient population to be determined) [ Time Frame: At week 16 ]
  • Part B: Proportion of participants with EASI-50 (≥50% improvement from baseline) [ Time Frame: At week 16 ]
  • Part B: Proportion of participants with EASI-90 (≥90% improvement from baseline) [ Time Frame: At week 16 ]
  • Part B: Change in percent Body Surface Area (BSA) affected by AD [ Time Frame: Baseline to week 16 ]
  • Part B: Percent change in SCORAD [ Time Frame: Baseline to week 16 ]
  • Part B: Change in Children's Dermatology Life Quality Index (CDLQI) for participants ≥4 years of age [ Time Frame: Baseline to week 16 ]
  • Part B: Change in Infants' Dermatology Quality of Life Index (IDQOL) for participants <4 years of age [ Time Frame: Baseline to week 16 ]
  • Part B: Change in Dermatitis Family Index (DFI) [ Time Frame: Baseline to week 16 ]
  • Part B: Change in Patient Oriented Eczema Measure (POEM) [ Time Frame: Baseline to week 16 ]
  • Part B: Topical treatment for AD - proportion of medication-free days [ Time Frame: Baseline to week 16 ]
  • Part B: Mean weekly dose of topical corticosteroids (TCS) [ Time Frame: Baseline to week 16 ]
  • Part B: Mean of caregiver missed workdays [ Time Frame: Baseline to week 16 ]
  • Part B: Incidence of skin infection TEAEs [ Time Frame: Baseline to week 16 ]
  • Part B: Incidence of SAEs through week 16 [ Time Frame: Baseline to week 16 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: November 14, 2017)
  • Part A: Incidence of Serious Adverse Events (SAEs) [ Time Frame: Baseline to week 4 ]
  • Part A: Incidence of severe TEAEs [ Time Frame: Baseline to week 4 ]
  • Part A: Percent change in EASI score [ Time Frame: Baseline to week 4 ]
  • Part A: Percent change in SCORing Atopic Dermatitis (SCORAD) score [ Time Frame: Baseline to week 4 ]
  • Part A: Proportion of patients with an IGA score of either 0 or 1 (on a 5-point scale) [ Time Frame: At week 4 ]
  • Part A: Determine immunogenicity titer [ Time Frame: Baseline to week 4 ]
    Assessed by measurement of anti-drug antibodies
  • Part B: Proportion of patients with EASI-75 (≥75% improvement from baseline) [ Time Frame: At week 16 ]
  • Part B: Percent change in EASI score [ Time Frame: Baseline to week 16 ]
  • Part B: Reduction in pruritus (appropriate measure and endpoint definition in this patient population to be determined) [ Time Frame: At week 16 ]
  • Part B: Proportion of patients with EASI-50 (≥50% improvement from baseline) [ Time Frame: At week 16 ]
  • Part B: Proportion of patients with EASI-90 (≥90% improvement from baseline) [ Time Frame: At week 16 ]
  • Part B: Change in percent Body Surface Area (BSA) affected by AD [ Time Frame: Baseline to week 16 ]
  • Part B: Percent change in SCORAD [ Time Frame: Baseline to week 16 ]
  • Part B: Change in Children's Dermatology Life Quality Index (CDLQI) for patients ≥4 years of age [ Time Frame: Baseline to week 16 ]
  • Part B: Change in Infants' Dermatology Quality of Life Index (IDQOL) for patients <4 years of age [ Time Frame: Baseline to week 16 ]
  • Part B: Change in Dermatitis Family Index (DFI) [ Time Frame: Baseline to week 16 ]
  • Part B: Change in Patient Oriented Eczema Measure (POEM) [ Time Frame: Baseline to week 16 ]
  • Part B: Topical treatment for AD - proportion of medication-free days [ Time Frame: Baseline to week 16 ]
  • Part B: Mean weekly dose of Topical corticosteroids [ Time Frame: Baseline to week 16 ]
  • Part B: Mean of caregiver missed workdays [ Time Frame: Baseline to week 16 ]
  • Part B: Incidence of skin infection TEAEs [ Time Frame: Baseline to week 16 ]
  • Part B: Incidence of SAEs through week 16 [ Time Frame: Baseline to week 16 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety, Pharmacokinetics and Efficacy of Dupilumab in Patients ≥6 Months to <6 Years With Severe Atopic Dermatitis (Liberty AD PRESCHOOL)
Official Title  ICMJE A Phase 2/3 Study Investigating the Pharmacokinetics, Safety, and Efficacy of Dupilumab in Patients Aged ≥6 Months to <6 Years With Severe Atopic Dermatitis
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 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 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 severe AD
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Intervention Model Description:

Part A: Single-ascending-dose cohorts staggered by age;

Part B: Parallel Group

Masking: None (Open Label)
Masking Description:

Part A: Open Label;

Part B: Masked, Randomized

Primary Purpose: Treatment
Condition  ICMJE Dermatitis, Atopic
Intervention  ICMJE
  • Drug: Dupilumab
    Solution for injection, subcutaneous (SC)
    Other Names:
    • DUPIXENT®
    • REGN668
    • SAR231893
  • Drug: Matching placebo
    Solution for injection, subcutaneous (SC)
Study Arms  ICMJE
  • Experimental: Part A (Open label Dupilumab): Age cohorts 1 & 2

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

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

    Intervention: Drug: Dupilumab
  • Experimental: Part B (Double-blind): Dupilumab dose 1
    The results of part A will be used to guide the selection of dose levels and dosing frequency for part B.
    Intervention: Drug: Dupilumab
  • Experimental: Part B (Double-blind): Dupilumab dose 2
    The results of part A will be used to guide the selection of dose levels and dosing frequency for part B.
    Intervention: Drug: Dupilumab
  • Experimental: Part B (Double-Blind): Placebo
    Intervention: Drug: Matching placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 14, 2017)
280
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 27, 2021
Estimated Primary Completion Date June 3, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria

  1. Diagnosis of AD according to the American Academy of Dermatology consensus criteria at the screening visit
  2. Participants with documented recent history (within 6 months before the screening visit) of inadequate response to topical AD medication(s)
  3. IGA = 4 at screening and baseline visits
  4. EASI ≥21 at screening and baseline visits
  5. Body Surface Area (BSA) ≥15% at screening and baseline visits

Key Exclusion Criteria

  1. Participation in a prior dupilumab clinical study
  2. History of important side effects of medium potency topical corticosteroids (only applicable for part B of the study)
  3. Having used immunosuppressive/immunomodulating drugs within 4 weeks before the baseline visit
  4. Treatment with a live (attenuated) vaccine within 4 weeks before the baseline visit
  5. Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiprotozoals, or antifungals within 2 weeks before the baseline visit.
  6. Known history of human immunodeficiency virus (HIV) infection or HIV seropositivity at the screening visit
  7. History of malignancy at any time before the baseline visit
  8. Diagnosed active endoparasitic infections or at high risk of these infections
  9. Severe concomitant illness(es) that, in the investigator's judgment, would adversely affect the patient's participation in the study

Note: Other protocol defined Inclusion/ Exclusion criteria apply

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Months to 5 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Clinical Trials Administrator 844-734-6643 clinicaltrials@regeneron.com
Listed Location Countries  ICMJE Germany,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03346434
Other Study ID Numbers  ICMJE R668-AD-1539
2016-000955-28 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Regeneron Pharmaceuticals
Study Sponsor  ICMJE Regeneron Pharmaceuticals
Collaborators  ICMJE Sanofi
Investigators  ICMJE
Study Director: Clinical Trial Management Regeneron Pharmaceuticals
PRS Account Regeneron Pharmaceuticals
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP