Study to Assess the Long-term Safety of Dupilumab Administered in Participants ≥6 Months to <18 Years of Age With Atopic Dermatitis (AD)

Study Overview
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Brief Summary
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The primary objective of the study is to assess the long-term safety of dupilumab in pediatric participants with AD. The secondary objectives of the study are: To assess the long-term efficacy of dupilumab in pediatric participants with AD To assess the trough concentrations of functional dupilumab in serum and the immunogenicity in pediatric participants with AD after re-treatment with dupilumab Optional Pre-filled Pen (PFP) Sub-Study in pediatric patients ≥2 to <12 years of age with AD Co-Primary Objectives are: To evaluate the pharmacokinetic (PK) of dupilumab PFPs To evaluate the safety of dupilumab PFPs Secondary Objective is: - To evaluate the immunogenicity of dupilumab PFPs

Official Title
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An Open-Label Extension Study to Assess the Long-Term Safety and Efficacy of Dupilumab in Patients ≥6 Months to <18 Years of Age 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: Participated in a prior dupilumab study in pediatric participants with AD and adequately completed the visits and assessments required for both the treatment and follow-up periods, as defined in the prior study protocol PFP Sub-Study Only: Age ≥2 to <12 years at time of screening Body weight ≥5 kg and <60 kg at time of screening Must have received the same dupilumab dose regimen to be used in the PFP sub-study during the previous 12 weeks in the main OLE study using the prefilled syringe, as defined in the protocol Key Exclusion Criteria: Participants who, during their participation in a prior dupilumab study developed an adverse event (AE) or serious adverse event (SAE) deemed related to study drug which could indicate that continued treatment with study drug may present an unreasonable risk for the patient Participants, who during the participation in a prior Dupilumab study, developed an AE that was deemed related to study drug and led to study treatment discontinuation, which in the opinion of the investigator or medical monitor could indicate that continued treatment with study drug may present an unreasonable risk for the patient Treatment with an investigational drug, other than dupilumab, within 8 weeks or within 5 half-lives (if known), whichever is longer, before the baseline visit 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 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 participant's participation in the study PFP Sub-study Only: Poor compliance as defined by having missed 1 or more of the planned last 3 injections in the main OLE study prior to entering the sub-study Switched dupilumab doses within the past 12 weeks Meet criteria for temporary/permanent discontinuation of study drug at time of screening into PFP sub-study, as defined in the protocol. Note: Other protocol defined Inclusion / Exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 6 Months
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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Body weight ≥60 kg<br>Administered every two weeks (Q2W) | Drug: Dupilumab<br>* Weight-tiered dosing administered subcutaneous (SC)<br>* Other names: SAR231893;|
| Experimental: Body weight 30 kg to <60 kg<br>Administered Q2W | Drug: Dupilumab<br>* Weight-tiered dosing administered subcutaneous (SC)<br>* Other names: SAR231893;|
| Experimental: Body weight 15 kg to <30 kg<br>Administered every 4 weeks (Q4W) | Drug: Dupilumab<br>* Weight-tiered dosing administered subcutaneous (SC)<br>* Other names: SAR231893;|
| Experimental: Body weight 5 kg to <15 kg<br>Administered Q4W | Drug: Dupilumab<br>* Weight-tiered dosing administered subcutaneous (SC)<br>* Other names: SAR231893;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of treatment-emergent adverse events (TEAEs) per participant year from baseline through the last study visit |  | Baseline up to week 272 | 
| Number of participants with at least one TEAE per participant year from baseline through the last study visit |  | Baseline up to week 272 | 
| OPTIONAL SUB-STUDY: Pharmacokinetic (PK) of dupilumab: Peak concentration (Cmax) | Peak serum concentration after multiple doses of dupilumab administered using the PFP (test) relative to the prefilled syringe (reference) | Up to week 16 | 
| OPTIONAL SUB-STUDY: PK of dupilumab: Trough concentration (Ctrough) | Drug concentration in serum after multiple doses of dupilumab administered using the PFP (test) relative to the prefilled syringe (reference) | Up to week 16 | 
| OPTIONAL SUB-STUDY: Incidence of TEAEs during the 12-week PFP treatment period and during entire sub-study |  | Up to week 16 | 
| OPTIONAL SUB-STUDY: Incidence of SAEs during the 12-week PFP treatment period and during entire sub-study |  | Up to week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of treatment-emergent serious adverse events (SAEs) from baseline through the last study visit |  | Baseline up to week 272 | 
| Incidence of TEAEs of special interest from baseline through the last study visit |  | Baseline up to week 272 | 
| Proportion of participants with an Investigator Global Assessment (IGA) score of 0 or 1 (clear or almost clear) at all in-clinic visits post-baseline |  | Baseline up to week 272 | 
| Proportion of participants with Eczema Area and Severity Index (EASI)-75 (≥75% reduction in EASI from baseline of parent study) response at all in-clinic visits post-baseline |  | Baseline up to week 272 | 
| Change from baseline in EASI score at all in-clinic visits post-baseline |  | Baseline up to week 272 | 
| Percent change from baseline in EASI at all in-clinic visits post-baseline |  | Baseline up to week 272 | 
| Change from baseline in Body Surface Area (BSA) affected by AD (BSA) at all in-clinic visits post-baseline |  | Baseline up to week 272 | 
| Percent change from baseline in SCORing Atopic Dermatitis (SCORAD) at all in-clinic visits post-baseline |  | Baseline up to week 272 | 
| Change from baseline in Children's Dermatology Life Quality Index (CDLQI) for participants ≥4 years of age at all in-clinic visits post-baseline in which the assessments are planned to be performed |  | Baseline up to week 272 | 
| Change from baseline in Infants' Dermatology Quality of Life Index (IDQOL) for participants <4 years of age at all in-clinic visits post-baseline in which the assessments are planned to be performed |  | Baseline up to week 272 | 
| Proportion of responders (defined as participants with IGA 0 or 1) who maintain IGA 0 or 1 during at least 75% of the subsequent* visits during the treatment period | *Subsequent refers to the visits following the first visit at which IGA 0 or 1 is achieved. | Baseline to week 260 | 
| For responders (defined as participants with IGA 0 or 1), median percentage of subsequent* visits during the treatment period, at which IGA 0 or 1 is maintained | *Subsequent refers to the visits following the first visit at which IGA 0 or 1 is achieved. | Baseline to week 260 | 
| Number of AD flares during the study | AD flares are defined as worsening of the disease that requires escalation/intensification of AD treatment | Baseline to week 272 | 
| Annualize event rate of AD flares during the study | AD flares are defined as worsening of the disease that requires escalation/intensification of AD treatment | Baseline to week 272 | 
| Proportion of participants with at least one flare during the study | AD flares are defined as worsening of the disease that requires escalation/intensification of AD treatment | Baseline to week 272 | 
| Proportion of well-controlled weeks | Well-controlled weeks are those for which participants or parents/caregivers answer Yes AND during which no rescue treatments were administered | Baseline to week 272 | 
| OPTIONAL SUB-STUDY: Incidence and titer of treatment-emergent anti-drug antibodies (ADA) (PFP Sub-Study) |  | Up to 16 weeks | 

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