Dupilumab in Japanese Patients With Atopic Dermatitis

Study Overview
=================
Brief Summary
-----------------
Primary Objective: To evaluate the efficacy of dupilumab administered concomitantly with topical corticosteroids (TCS) Secondary Objective: To evaluate the efficacy of dupilumab administered concomitantly with TCS. To assess the safety of dupilumab over 16 weeks of treatment when administered concomitantly with TCS in participants. To assess immunogenicity as determined by the incidence, titer, and clinical impact of treatment-emergent anti-drug antibodies (ADA) to dupilumab over time in pediatric patients with atopic dermatitis (AD) (aged ≥6 months to <18 years old) To assess the concentration of dupilumab in serum following administration concomitantly with TCS.

Detailed Description
-----------------
For participant who declines to enter open-lebal extension (OLE), the duration of the study for each participant is approximately 33 weeks (including screening and follow-up) For participant choosing enter OLE, the duration is approximately 21 weeks (including screening) plus 3 years OLE period or until approval of the indication in Japan whichever is sooner.

Official Title
-----------------
A Randomized, Double-blind, Placebo-controlled, Multi-center, Parallel-group Study to Evaluate the Efficacy, Safety and Pharmacokinetics of Dupilumab Compared to Placebo in Japanese Patients With Atopic Dermatitis Aged 6 Months to

Conditions
-----------------
Atopic Dermatitis

Intervention / Treatment
-----------------
* Drug: Placebo
* Drug: Dupilumab SAR231893


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria : Japanese and ≥6 months to <18 years of age, at the time of signing the informed consent and/or assent. Diagnosis of AD according to the American Academy of Dermatology consensus criteria at screening visit. Chronic AD diagnosed at least 1 year prior to the screening visit (for participants between 6 months to <1 year of age, the requirement is to have had chronic AD for 3 months). (Investigator's Global Assessment) IGA ≥ 3 at screening and baseline visits. (Eczema Area and Severity Index) EASI ≥16 at screening and baseline visits. Baseline peak pruritus Numerical Rating Scale (NRS) average score for maximum itch intensity ≥4 for participants ≥12 to <18 years of age. Baseline worst itch NRS or worst scratch/itch NRS weekly average score for maximum itch or scratch/itch intensity ≥4 for participants ≥6 months to <12 years of age. Body surface area (BSA) of AD involvement >10% at screening and baseline visits. With documented recent history (within 6 months before the baseline visit) of inadequate response to topical AD medication(s). At least 11 (of a total of 14) applications of a stable dose of topical emollient (moisturizer) twice daily immediately before the baseline visit. Willing and able to comply with all clinic visits and study-related procedures. Participant, either alone or with help of parents/legal guardians (for 6 years old to less than18 years of age) or parents/caregiver or legal guardians (for 6 months to less than 6 years of age) as appropriate, must be able to understand and complete study-related questionnaires. Body weight ≥5 kg at baseline. Contraceptive use by female participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Exclusion criteria: Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiprotozoals, or antifungals within 2 weeks before the baseline visit or during the screening period. Known or suspected immunodeficiency, including history of invasive opportunistic infections Participants with active tuberculosis (TB) or non-tuberculous mycobacterial infection, or a history of incompletely treated TB will be excluded from the study unless it is well documented by a specialist that the participant has been adequately treated and can now start treatment with a biologic agent, in the medical judgment of the Investigator and/or infectious disease specialist. Known history of human immunodeficiency virus (HIV)-1 and HIV-2 infection or HIV seropositivity at the screening Participants with any of the following result at the screening: Positive (or indeterminate) Hepatitis B surface antigen (HBs Ag) or, Positive hepatitis B core antibody (HBc Ab) confirmed by positive hepatitis B virus (HBV) DNA or, Positive hepatitis C antibody (HCV Ab) confirmed by positive hepatitis C virus (HCV) RNA. Presence of skin comorbidities that may interfere with study assessments History of malignancy within 5 years before the baseline visit History of systemic hypersensitivity or anaphylaxis to dupilumab or any other biologic therapy. Known or suspected alcohol and/or drug abuse. Diagnosed active endoparasitic infections; suspected or high risk of endoparasitic infection. Severe concomitant illness(es) that, in the Investigator's judgment, would adversely affect the participant's participation in the study. Participant with any other medical or psychological condition including relevant laboratory or electrocardiogram (ECG) abnormalities at screening Exposure to another systemic or topical investigative drug within a certain time period prior to Visit 1 (screening), Having used any of immunosuppressive/immunomodulating drugs and phototherapy within 4 weeks before the screening visit. Past Treatment with biologics as follows: Any cell-depleting agents within 6 months before the screening visit. Anti-IgE therapy within 4 months before the screening visit. Other monoclonal antibodies (which are biological response modifiers): within 5 half-lives (if known) or 16 weeks before the screening visit (Visit 1), whichever is longer. History of important side effects to medium potency TCS Treatment with a live (attenuated) vaccine within 4 weeks before the baseline visit. Either intravenous immunoglobulin therapy and/or plasmapheresis within 30 days prior to screening visit. Planned or anticipated use of any prohibited medications and procedures during screening and study treatment period. Initiation of treatment of AD with prescription moisturizers or moisturizers containing additives such as ceramide, hyaluronic acid, urea, or filaggrin degradation products during the screening period Participation in a prior dupilumab clinical study or have been treated with commercially available dupilumab. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dupilumab<br>Double dose on day1 and followed by single dose every 2 weeks.Or single dose every 4 weeks | Drug: Dupilumab SAR231893<br>* Pharmaceutical form:solution for injection Route of administration: subcutaneous (SC)<br>|
| Placebo Comparator: Placebo<br>Double dose on day1 and followed by single dose every 2 weeks.Or single dose every 4 weeks | Drug: Placebo<br>* Pharmaceutical form:solution for injection Route of administration: subcutaneous (SC)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with Eczema Area and Severity Index (EASI)-75 (≥75% improvement from baseline EASI) | The EASI is a composite index with scores ranging from 0 to 72.Higher scores indicates worse condition | At Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change in EASI score | The EASI is a composite index with scores ranging from 0 to 72.Higher scores indicates worse condition | From baseline to week 16 | 
| Percent change in weekly average of daily worst itch numerical rating scale (NRS) for participants aged ≥6 years to <12 years old | The worst itch NRS is a simple assessment tool those participants ≥6 years old to <12 years old will use to report the intensity of their pruritus (itch). This is an 11-point scale (0 to 10) in which 0 indicates no itching while 10 indicate worst itching possible. | From baseline to week 16 | 
| Proportion of participants with Investigator's Global Assessment (IGA) 0 or 1 | The IGA is an assessment instrument used in clinical studies to rate the severity of AD globally, based on a 5-point scale ranging from 0 (clear) to 4 (severe) | At Week 16 | 
| Percent change in weekly average of daily worst peak pruritus NRS for participants aged ≥12 years to <18 years old | The peak pruritus NRS is a simple assessment tool that participants ≥ 12 to <18 years old will use to report the intensity of their pruritus (itch) ranges from 0 to 10 with 0 being 'no itch' and 10 being the' worst itch imaginable' | From baseline to week 16 | 
| Percent change in weekly average of daily worst scratch/itch NRS for participants aged ≥6 months to <6 years old | The worst scratch/itch NRS is a simple assessment tool those participants ≥6 years old to <6 years old range from 1 to 10 in which 0 indicates no itching while 10 indicate worst itching possible | From baseline to week 16 | 
| Percent change for intensity of pruritus | The intensity is assessed by numerical rating scale ranging from 0 to 10 which higher scale indicate worse itch condition | From baseline to week 16 | 
| Proportion of participants with EASI-50 (≥50% improvement from baseline) | The EASI is a composite index with scores ranging from 0 to 72.Higher scores is worse condition | At Week 16 | 
| Proportion of participants with EASI-90 (≥90% improvement from baseline) | The EASI is a composite index with scores ranging from 0 to 72.Higher scores is worse condition | At Week 16 | 
| Change in percent body surface area (BSA) affected by atopic dermatitis (AD) | BSA affected by atopic dermatitis will be assessed for each major section of the body (head, trunk, arms, and legs). | From baseline to week 16 | 
| Change in Children's Dermatology Life Quality Index (CDLQI) (≥4 years) | The CDLQI is a validated questionnaire designed to measure the impact of skin disease on the Quality of Life. The higher the score, the greater the impact is on the quality of life | From baseline to week 16 | 
| Change in Infants' Dermatitis Quality of Life Index (IDQOL) (<4 years) | The IDQOL is a validated questionnaire developed to measure the impact of skin disease on the QOL of infants and preschool children <4 years of age wil completed by the child's parent or caregiver. The higher the score, the greater the impact is on the quality of life. - | From baseline to week 16 | 
| Change in Patient Oriented Eczema Measure (POEM) | The POEM is a 7-item (dryness, itching, flaking, cracking, sleep loss, bleeding, and weeping) questionnaire used to assess disease symptoms with a scoring system of 1 to 28. The higher score, the higher morbidity | From baseline to week 16 | 
| Change in weekly average of daily worst peak pruritus NRS for participants aged ≥12 years to <18 years old | The peak pruritus NRS is a simple assessment tool that participants ≥ 12 to <18 years old will use to report the intensity of their pruritus (itch) ranges from 0 to 10 with 1 being 'no itch' and 10 being the' worst itch imaginable' | From baseline to week 16 | 
| Change in weekly average of daily worst itch NRS for participants aged ≥6 years to <12 years old | The worst itch NRS is a simple assessment tool those participants ≥6 years old to <12 years old range from 1 to 10 in which 1 indicates no itching while 10 indicate worst itching possible - | From baseline to week 16 | 
| Change in weekly average of daily worst scratch/itch NRS for participants aged ≥6 months to <6 years old | The worst scratch/itch NRS is a simple assessment tool those participants ≥6 years old to <12 years old range from 1 to 10 in which 1 indicates no itching while 10 indicate worst itching possible | From baseline to week 16 |