Clinical trial NCT04678882: Dupilumab in Japanese Patients With Atopic Dermatitis
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 <18 Years Whose Disease is Not Adequately Controlled With Existing Therapies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Atopic Dermatitis
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2020-12-22
Enrollment: 62
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Proportion of participants with Eczema Area and Severity Index (EASI)-75 (≥75% improvement from baseline EASI)
timeFrame: At Week 16
Secondary outcomes:
measure: Percent change in EASI score
timeFrame: From baseline to week 16
measure: Percent change in weekly average of daily worst itch numerical rating scale (NRS) for participants aged ≥6 years to <12 years old
timeFrame: From baseline to week 16
measure: Proportion of participants with Investigator's Global Assessment (IGA) 0 or 1
timeFrame: At Week 16
measure: Percent change in weekly average of daily worst peak pruritus NRS for participants aged ≥12 years to <18 years old
timeFrame: From baseline to week 16
measure: Percent change in weekly average of daily worst scratch/itch NRS for participants aged ≥6 months to <6 years old
timeFrame: From baseline to week 16
measure: Percent change for intensity of pruritus
timeFrame: From baseline to week 16
measure: Proportion of participants with EASI-50 (≥50% improvement from baseline)
timeFrame: At Week 16
measure: Proportion of participants with EASI-90 (≥90% improvement from baseline)
timeFrame: At Week 16
measure: Change in percent body surface area (BSA) affected by atopic dermatitis (AD)
timeFrame: From baseline to week 16
measure: Change in Children's Dermatology Life Quality Index (CDLQI) (≥4 years)
timeFrame: From baseline to week 16
measure: Change in Infants' Dermatitis Quality of Life Index (IDQOL) (<4 years)
timeFrame: From baseline to week 16
measure: Change in Patient Oriented Eczema Measure (POEM)
timeFrame: From baseline to week 16
measure: Change in weekly average of daily worst peak pruritus NRS for participants aged ≥12 years to <18 years old
timeFrame: From baseline to week 16
measure: Change in weekly average of daily worst itch NRS for participants aged ≥6 years to <12 years old
timeFrame: From baseline to week 16
measure: Change in weekly average of daily worst scratch/itch NRS for participants aged ≥6 months to <6 years old
timeFrame: From baseline to week 16
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs), Serious Adverse Events (SAEs), and Adverse Event of Special Interest (AESI) From Baseline to 16 Weeks of Treatment
timeFrame: Baseline (Day 1) to Week 16
measure: Number of Participants With Skin-Infection TEAEs (Excluding Herpetic Infections) From Baseline to 16 Weeks of Treatment
timeFrame: Baseline (Day 1) to Week 16
measure: Number of Participants With TEAEs, SAEs, and AESI From Baseline of open-label extension (OLE) Through the Last Study Visit
timeFrame: Week 16 to Week 116
measure: Number of Participants With Treatment-emergent Anti-drug Antibody (ADA) to Dupilumab Over Time in Pediatric Participants with AD (Aged ≥6 Months to <18 Years old)
timeFrame: Baseline (Day 1) to Week 116
measure: Serum Concentration of Dupilumab up to Week 116
timeFrame: Pre-dose at Baseline (Day 1), and Weeks 4, 12, 16, 24, 32, 52, 68, 92, and 116
Other outcomes:
Locations:
city: Nagoya-shi
country: Japan
facility: Investigational Site Number : 3920011
state: Aichi
city: Toyoake-shi
country: Japan
facility: Investigational Site Number : 3920014
state: Aichi
city: Fukutsu-shi
country: Japan
facility: Investigational Site Number : 3920015
state: Fukuoka
city: Hiroshima-shi
country: Japan
facility: Investigational Site Number : 3920001
state: Hiroshima
city: Sapporo-shi
country: Japan
facility: Investigational Site Number : 3920013
state: Hokkaido
city: Sapporo-shi
country: Japan
facility: Investigational Site Number : 3920009
state: Hokkaido
city: Kobe-shi
country: Japan
facility: Investigational Site Number : 3920008
state: Hyogo
city: Kobe-shi
country: Japan
facility: Investigational Site Number : 3920007
state: Hyogo
city: Sagamihara-shi
country: Japan
facility: Investigational Site Number : 3920003
state: Kanagawa
city: Yokohama-Shi
country: Japan
facility: Investigational Site Number : 3920017
state: Kanagawa
city: Yokohama-shi
country: Japan
facility: Investigational Site Number : 3920010
state: Kanagawa
city: Tsu-shi
country: Japan
facility: Investigational Site Number : 3920006
state: Mie
city: Sakai-shi
country: Japan
facility: Investigational Site Number : 3920020
state: Osaka
city: Toyonaka-shi
country: Japan
facility: Investigational Site Number : 3920019
state: Osaka
city: Kumagaya-shi
country: Japan
facility: Investigational Site Number : 3920016
state: Saitama
city: Chuo-ku
country: Japan
facility: Investigational Site Number : 3920023
state: Tokyo
city: Koto-ku
country: Japan
facility: Investigational Site Number : 3920012
state: Tokyo
city: Toshima-ku
country: Japan
facility: Investigational Site Number : 3920022
state: Tokyo
city: Habikino-shi
country: Japan
facility: Investigational Site Number : 3920021
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: