Safety, Pharmacokinetics and Efficacy of Dupilumab in Patients ≥6 Months to <6 Years With Moderate-to-Severe Atopic Dermatitis (Liberty AD PRESCHOOL) (Liberty AD)
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| ClinicalTrials.gov Identifier: NCT03346434 |
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Recruitment Status :
Active, not recruiting
First Posted : November 17, 2017
Last Update Posted : April 12, 2021
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Sponsor:
Regeneron Pharmaceuticals
Collaborator:
Sanofi
Information provided by (Responsible Party):
Regeneron Pharmaceuticals
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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).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Dermatitis, Atopic | Drug: Dupilumab Drug: Matching placebo | Phase 2 Phase 3 |
Expanded Access : An investigational treatment associated with this study is temporarily not available outside the clinical trial. More info ...
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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.
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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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 162 participants |
| 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 |
| 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 |
| Actual Study Start Date : | November 30, 2017 |
| Estimated Primary Completion Date : | July 6, 2021 |
| Estimated Study Completion Date : | July 6, 2021 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Atopic dermatitis
MedlinePlus related topics:
Eczema
Drug Information available for:
Dupilumab
| Arm | Intervention/treatment |
|---|---|
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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 |
Drug: Dupilumab
Solution for injection, subcutaneous (SC)
Other Names:
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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.
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Drug: Dupilumab
Solution for injection, subcutaneous (SC)
Other Names:
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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.
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Drug: Dupilumab
Solution for injection, subcutaneous (SC)
Other Names:
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| Experimental: Part B (Double-Blind): Placebo |
Drug: Matching placebo
Solution for injection, subcutaneous (SC) |
Primary Outcome Measures :
- Part A: Concentration of total dupilumab in serum over time and pharmacokinetic (PK) parameters [ Time Frame: Baseline to week 4 ]Summary statistics of drug concentration and PK parameters
- Part A: Incidence of Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Baseline to week 4 ]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 [ Time Frame: At week 16 ]The Investigator's Global Assessment is a static 5-point measure of disease severity based on an overall assessment of the skin lesions. Scoring Ranges from 0 = Clear to 4 = severe disease
- Part B: For European Medicines Agency (EMA) only: Proportion of participants with Eczema Area and Severity Index (EASI) -75 (≥75% improvement from baseline) [ Time Frame: At week 16 ]The EASI is a validated measure used in clinical practice and clinical trials to assess the severity and extent of AD (Hanifin 2001). The EASI is a composite index with scores ranging from 0 to 72
- Part B: For EMA only: Proportion of participants with an IGA score of either 0 or 1 [ Time Frame: At week 16 ]
Secondary Outcome Measures :
- 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 ]SCORAD is a validated scoring index for AD, which combines A: extent (0-100), B: severity (0-18), and C: subjective symptoms (0-20) based on pruritus and sleep loss, each scored (0-10). The SCORAD for an individual is calculated by the formula: A/5 + 7B/2 + C (can range from 0 to 103).
- Part A: Proportion of participants with an IGA score of either 0 or 1 [ 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: Not applicable for EMA: 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: Percent change in weekly average of daily worst scratch/itch numeric rating score (NRS) [ Time Frame: Baseline to week 16 ]The NRS is an 11-point scale (0 to 10) in which 0 indicates no scratching/itching while 10 indicates worst scratching/itching possible
- 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 weekly average of daily worst scratch/itch NRS score [ Time Frame: Baseline to week 16 ]
- Part B: Proportion of participants with improvement (reduction) of weekly average of daily worst scratch/itch NRS score ≥4 [ Time Frame: Baseline to week 16 ]
- Part B: Proportion of participants with improvement (reduction) of weekly average of daily worst scratch/itch NRS score ≥3 [ Time Frame: Baseline to week 16 ]
- Part B: Change in skin pain NRS [ Time Frame: Baseline to week 16 ]
- Part B: Change in sleep quality NRS [ Time Frame: Baseline to week 16 ]
- Part B: Change in health-related quality of life, as measured by Childrens' Dermatology Life Quality Index (CDLQI) (participants ≥4 years of age) and Infants' Dermatology Quality of Life Index (IDQOL) (participants <4 years of age) [ Time Frame: Baseline to week 16 ]CDLQI is a quality of life questionnaire associated with atopic dermatitis (for participants <4 years of age). Scoring ranges from 0 = unanswered to 3 = very much. IDQOL is a quality of life questionnaire associated with atopic dermatitis (for patients <4 years of age). Scoring ranges from 0 (minimum impact) to 3 (maximum impact). The higher the sum of the scores, the greater the impact is on the QOL for CDLQI and IDQOL.
- Part B: Change in Dermatitis Family Index (DFI) [ Time Frame: Baseline to week 16 ]DFI is a 10-item quality of family life questionnaire associated with atopic dermatitis. Scores range from 0 - 3. The higher the sum of the scores the greater the impact in family QOL
- Part B: Change in Patient Oriented Eczema Measure (POEM) [ Time Frame: Baseline to week 16 ]POEM is a 7-item, validated questionnaire used in clinical practice and clinical trials to assess disease symptoms in children and adults. Scoring ranges from 0 = no days to 4 = all days. Scoring system of 0 to 28; the total score reflects disease-related morbidity.
- Part B: Topical treatment for AD - proportion of topical corticosteroids (TCS) medication-free days [ Time Frame: Baseline to week 16 ]
- Part B: Mean weekly dose of low potency TCS [ Time Frame: Up 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: Up to week 16 ]Excluding herpetic infections.
- Part B: Incidence of SAEs through week 16 [ Time Frame: Up to week 16 ]
Information from the National Library of Medicine
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| Ages Eligible for Study: | 6 Months to 5 Years (Child) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03346434
Locations
Show 48 study locations
Sponsors and Collaborators
Regeneron Pharmaceuticals
Sanofi
Investigators
| Study Director: | Clinical Trial Management | Regeneron Pharmaceuticals |
| Responsible Party: | Regeneron Pharmaceuticals |
| ClinicalTrials.gov Identifier: | NCT03346434 |
| Other Study ID Numbers: |
R668-AD-1539 2016-000955-28 ( EudraCT Number ) |
| First Posted: | November 17, 2017 Key Record Dates |
| Last Update Posted: | April 12, 2021 |
| Last Verified: | November 2020 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Regeneron Pharmaceuticals:
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Eczema |
Additional relevant MeSH terms:
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Dermatitis, Atopic Dermatitis Skin Diseases Skin Diseases, Genetic Genetic Diseases, Inborn |
Skin Diseases, Eczematous Hypersensitivity, Immediate Hypersensitivity Immune System Diseases |