A Study to Determine the Safety and Tolerability of Dupilumab (REGN668/SAR231893) in Patients Aged ≥6 to <18 Years With Atopic Dermatitis (Eczema)

Study Overview
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Brief Summary
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The primary objective of the study is to characterize the safety and pharmacokinetics (PK) of dupilumab in pediatric patients with moderate-to-severe atopic dermatitis (AD) (for adolescents ≥12 to <18 years of age) or severe AD (for children ≥6 to <12 years of age). The secondary objective of the study is to explore the immunogenicity and efficacy of dupilumab in pediatric patients with moderate-to-severe AD (for adolescents ≥12 to <18 years of age) or severe AD (for children ≥6 to <12 years of age).

Official Title
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A Phase 2a Study Investigating the Safety, Pharmacokinetics, Immunogenicity, and Exploratory Efficacy of Dupilumab in Patients Aged ≥6 to <18 Years With Atopic Dermatitis

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Drug: Dupilumab


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Male or female patients ≥6 to <18 years of age with a diagnosis of 1. Atopic Dermatitis whose disease cannot be adequately controlled with topical medications Minimum disease severity, as defined by Investigator's Global Assessment (IGA) IGA = 3 or 4 in adolescents ≥12 to <18 year of age IGA = 4 in children ≥6 to <12 years of age Key Exclusion Criteria: Recent treatment (within specific time windows before the baseline visit) with systemic immunosuppressive agents for eg. Systemic corticosteroids, live (attenuated) vaccines and other investigational drugs including biologics History of any of the following infections: Any systemic infection requiring treatment within 4 weeks before the baseline visit Superficial skin infections within 1 week before the baseline visit Known history of HIV infection History of seropositivity to hepatitis B or C screening tests History of clinical endoparasitosis (ie, helminthic infection) within 12 months before the baseline visit, or high risk of helminthic infection, unless subsequent medical assessments (e.g. stool exam, blood tests, etc.) have ruled out the possibility of parasite infection/infestation History of malignancy within 5 years before the baseline visit Persistent (confirmed by repeated tests ≥2 weeks apart) elevated transaminases (alanine aminotransferase [ALT] and/or aspartate aminotransferase [AST]) more than 3 times the upper limit of normal (ULN) during the screening period Presence of any severe concomitant illness(es) that, in the investigator's judgment, would adversely affect the patient's participation in the study Presence of skin comorbidities that may interfere with study assessments Females patients who are pregnant or breastfeeding Female patients who are of reproductive potential and are sexually active, who are unwilling to use adequate methods of contraception

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Cohort 1 will receive dupilumab dosing regimen 1 | Drug: Dupilumab<br> <br> * Other names: REGN668(SAR231893);|
| Experimental: Cohort 2<br>Cohort 2 will receive dupilumab dosing regimen 2 | Drug: Dupilumab<br> <br> * Other names: REGN668(SAR231893);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK) of Dupilumab: Maximum Plasma Concentration Observed (Cmax) After Single Administration | Peak dupilumab concentration in serum following single dose administration. Analysis was performed on PK analysis set that included all treated subjects who received the study medication and had at least 1 quantified (non-missing) result for dupilumab concentration following the first dose of the study drug. | Day 2, 4, 8, 15, 22, 29, 36, 43, and 50 | 
| PK of Dupilumab: Area Under the Plasma Concentration Versus Time Curve (AUClast) After Single Administration | Mean AUC estimates were calculated using mean concentration data at each time point, using a non-compartmental approach (NCA). Calculated AUClast (computed from time zero to the time of the last positive concentration) are presented. Analysis was performed on PK analysis set that included all treated subjects who received the study medication and had at least 1 quantified (non-missing) result for dupilumab concentration following the first dose of the study drug. | Day 2, 4, 8, 15, 22, 29, 36, 43, and 50 | 
| PK of Dupilumab: Trough Dupilumab Concentration in Serum (Ctrough) Before 3rd and 4th Repeated Dose | Analysis was performed on PK analysis set that included all treated subjects who received the study medication and had at least 1 quantified (non-missing) result for dupilumab concentration following the first dose of study drug. | Pre-dose on Day 71 and Day 85 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Reduction From Baseline in Eczema Area and Severity Index (EASI) at Week 12 | The EASI score was used to measure the severity and extent of atopic dermatitis (AD) and measures erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 to 72 points, with the higher scores reflecting the worse severity of AD. Analysis was performed on safety analysis set (SAF) that included all subjects who received any study drug. Data after rescue treatment use during the Part B period were set to missing, then missing values were imputed by last observation carried forward (LOCF). | Baseline to Week 12 (one week after last dose) | 
| Percent Reduction From Baseline in SCORing Atopic Dermatitis (SCORAD) Score at Week 12 | SCORAD is a clinical tool for assessing the severity of atopic dermatitis developed by the European Task Force on Atopic Dermatitis (Severity scoring of atopic dermatitis: the SCORAD index. Consensus Report of the European Task Force on Atopic Dermatitis. Dermatology (Basel) 186 (1): 23-31. 1993). Extent and intensity of eczema as well as subjective signs (insomnia, etc.) are assessed and scored. Total score ranges from 0 [absent disease] to 103 [severe disease]). Analysis was performed on SAF. Data after rescue treatment use during the Part B period were set to missing, then missing values were imputed by LOCF. | Baseline to Week 12 (one week after last dose) | 
| Percent Reduction From Baseline in Pruritus Numerical Rating Scale (NRS) at Week 12 | Pruritus NRS scale is an assessment tool that is used to report the intensity of subject's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Subjects were asked the following question: how would a subject rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 [0 = no itch; 10 = worst itch imaginable]). Analysis was performed on SAF. Data after rescue treatment use during the Part B period were set to missing, then missing values were imputed by LOCF. | Baseline to Week 12 (one week after last dose) | 
| Percentage of Subjects With Investigator Global Assessment (IGA) Score of 0 or 1 (Clear or Almost Clear) at Week 12 | IGA is an assessment scale used to determine severity of AD and clinical response to treatment on a 5-point scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe) based on erythema and papulation/infiltration. Therapeutic response is an IGA score of 0 (clear) or 1 (almost clear). Analysis was performed on SAF. Subjects with rescue treatment usage during the Part B period were specified as non-responders from the time the rescue was used. | Week 12 | 
| Percent Reduction From Baseline in Body Surface Area (BSA) at Week 12 | Body surface area affected by AD was assessed for each section of the body (the possible highest score for each region was: head and neck [9%], anterior trunk [18%], back [18%], upper limbs [18%], lower limbs [36%], and genitals [1%]). It was reported as a percentage of all major body sections combined. Analysis was performed on SAF. | Baseline to Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Eczema