A Study to Assess the Efficacy and Safety of Ruxolitinib Cream in Children With Atopic Dermatitis (TRuE-AD3)

Phase 3CompletedNCT04921969

Incyte Corporation330 enrolled

Overview

The purpose of the study is to assess the efficacy and safety of ruxolitinib cream in children with Atopic Dermatitis. This is a randomized, double-blind, Vehicle Controlled study. Participants will be randomized 2:2:1 to blinded treatment with ruxolitinib cream 0.75% ,1.5% , or vehicle cream, with stratification by baseline IGA score and age. At Week 8, efficacy will be evaluated. Participants who complete Week 8 assessments with no additional safety concerns will continue into the 44-week Long Term Safety (LTS) period with the same treatment regimen, except those initially randomized to vehicle cream will be rerandomized (1:1) in a blinded manner to 1 of the 2 active treatment groups (ruxolitinib cream 0.75% or 1.5%).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

330

Conditions

Atopic Dermatitis

Interventions

Eligibility

Sex: ALLMin age: 2 YearsMax age: 11 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Participants diagnosed with Atopic Dermatitis (AD) as defined by the Hanifin and Rajka criteria. * Participants with AD duration of at least 3 months (participant/parent/guardian may verbally report signs and symptoms of AD with onset at least 3 months prior). * Participants with IGA score of 2 to 3 at the screening and baseline visits. * Participants with %BSA (excluding scalp) of AD involvement of 3% to 20% at screening and baseline visits. * For children aged 6 years to \< 12 years, baseline itch NRS score ≥ 4. * Participants/guardians who agree to discontinue all agents used by the participant to treat AD from the screening visit through the final safety follow-up visit. * Participants with at least 1 target lesion that measures at least 5 cm2 at the screening and baseline visits. The target lesion must be representative of the participant's disease state but not located on the hands, feet, or genitalia. * Willingness to avoid pregnancy or fathering a child for the duration of study participation. Exclusion Criteria: * An unstable course of AD (spontaneously improving or rapidly deteriorating) as determined by the investigator over the previous 4 weeks before the baseline visit. * Concurrent conditions and history of other diseases as follows: 1. Immunocompromised 2. Chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 2 weeks before the baseline visit. 3. Active acute bacterial, fungal, or viral skin infection within 1 week before the baseline visit. 4. Any other concomitant skin disorder, pigmentation, or extensive scarring that in the opinion of the investigator may interfere with the evaluation of AD lesions or compromise participant safety. 5. Presence of AD lesions only on the hands or feet without prior history of involvement of other classic areas of involvement such as the face or the flexural folds. 6. Other types of eczema. 7. Chronic asthma requiring more than 880 µg of inhaled budesonide or equivalent high dose of other inhaled corticosteroids. * Any serious illness or medical, physical, or psychiatric condition(s) that, in the investigator's opinion, would interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data. * Use of any of the following treatments within the indicated washout period before the baseline visit: 1. 5 half-lives or 12 weeks, whichever is longer - biologic agents (eg, dupilumab). 2. 4 weeks - systemic corticosteroids or adrenocorticotropic hormone analogues, cyclosporin, methotrexate, azathioprine, or other systemic immunosuppressive or immunomodulating agents (eg, mycophenolate or tacrolimus). 3. 2 weeks - immunizations with activated vaccines; sedating antihistamines unless on a long-term stable regimen (nonsedating antihistamines are permitted). Note: Live vaccines are not recommended during the VC period. 4. 1 week - use of topical treatments for AD (other than bland emollients, eg, Aveeno® creams, ointments, sprays, soap substitutes), such as corticosteroids, calcineurin inhibitors, PDE4 inhibitors, coal tar (shampoo), topical antibiotics, or antibacterial cleansing body wash/soap. Note: Diluted sodium hypochlorite "bleach" baths are allowed as long as they do not exceed 2 baths per week. * Participants who have previously received JAK inhibitors, systemic or topical. -Ultraviolet light therapy or prolonged exposure to natural or artificial sources of UV radiation (eg, sunlight or tanning booth) within 2 weeks prior to the baseline visit and/or intention to have such exposure during the study, which is thought by the investigator to potentially impact the participant's AD.- * Positive serology test results at screening for HIV antibody. * Current treatment or treatment within 30 days or 5 half-lives (whichever is longer) before the baseline visit with another investigational medication or current enrollment in another investigational drug protocol. * In the opinion of the investigator, unable or unlikely to comply with the administration schedule and study evaluations. * Employees of the sponsor or investigator or otherwise dependents of them.

Locations (67)

Clinical Research Center of Alabama

Birmingham, Alabama, United States

Cahaba Dermatology

Hoover, Alabama, United States

Physicians Research Group Ii

Gilbert, Arizona, United States

Cct Research With Center For Dermatology and Plastic Surgery

Scottsdale, Arizona, United States

Burke Pharmaceutical Research

Hot Springs, Arkansas, United States

Outcomes

Primary Outcomes

VC Period: Percentage of Participants Who Achieved Investigator's Global Assessment - Treatment Success (IGA-TS) at Week 8

The IGA is an overall eczema severity rating on a 5-point scale ranging from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, induration/papulation, and oozing/crusting. The IGA-TS is defined as an IGA score of 0 (clear skin) or 1 (almost clear skin) with ≥2 grade improvement from Baseline.

Time frame: Baseline to Week 8

Secondary Outcomes

VC Period: Percentage of Participants With a ≥4-Point Improvement in Itch Numerical Rating Scale (NRS) Score From Baseline to Week 8

The Itch NRS is a daily participant-reported measure (24-hour recall) of the worst level of itch intensity using a diary. Participants were asked to rate the itching severity because of their AD by selecting the number from 0 (no itch) to 10 (worst imaginable itch) that best described their worst level of itching in the past 24 hours.

Time frame: Baseline to Week 8

VC Period: Percentage of Participants With a ≥4-Point Improvement in Itch NRS Score From Baseline to Day 7 (Week 1)

Time frame: Baseline to Day 7 (Week 1)

VC Period: Percentage of Participants With a ≥4-Point Improvement in Itch NRS Score From Baseline to Day 3

Time frame: Baseline to Day 3

VC Period: Number of Participants With Any Treatment-emergent Adverse Event (TEAE)

An adverse event was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it was considered drug related. An AE could therefore be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study cream. A TEAE is defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug until the end of the safety follow-up.

Time frame: from Baseline up to Week 8

LTS Period: Number of Participants With Any TEAE

Time frame: From Week 8 up to Week 56

VC Period: Number of Participants With Any Grade 3 or Higher TEAE

A TEAE is defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug until the end of the safety follow-up. The severity of AEs will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Grades 1 through 5. The investigator made an assessment of intensity for each AE and SAE reported during the study and assigned it to 1 of the following categories: Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; treatment not indicated. Grade 2: moderate; minimal, local, or noninvasive treatment indicated; limiting age-appropriate activities of daily living. Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. Grade 4: life-threatening consequences; urgent treatment indicated; Grade 5: fatal.

Time frame: from Baseline up to Week 8

LTS Period: Number of Participants With Any Grade 3 or Higher TEAE

Time frame: From Week 12 up to Week 56

VC Period: Percentage of Participants Who Achieved IGA-TS at Weeks 2 and 4

Time frame: Baseline to Weeks 2 and 4

VC Period: Percentage of Participants With a ≥4-Point Improvement in Itch NRS Score From Baseline to Week 2 and 4

The Itch NRS is a daily participant-reported measure (24-hour recall) of the worst level of itch intensity using a diary. Participants were asked to rate the itching severity because of their AD by selecting a number from 0 (no itch) to 10 (worst imaginable itch) that best described their worst level of itching in the past 24 hours.

Time frame: Baseline to Weeks 2 and 4

VC Period: Percentage of Participants Who Achieved Eczema Area and Severity Index 75 (EASI75) at Weeks 2, 4, and 8

The EASI scoring system examines 4 areas of the body (head/neck, trunk, upper limbs, and lower limbs) and weights them for participants of ≥8 years of age. Each of the 4 body regions is assessed separately for erythema (E), induration/papulation/edema (I), excoriations (Ex), and lichenification (l), each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72; the severity strata are as follows: 0 = clear; 0.1 to 1.0 = almost clear; 1.1 to 7.0 = mild; 7.1 to 21.0 = moderate; 21.1 to 50.0 = severe; 50.1 to 72.0 = very severe. An EASI75 responder was defined as a participant achieving 75% or greater improvement from Baseline in EASI score.

Time frame: Baseline to Weeks 2, 4, and 8

VC Period: Time to Achieve Itch NRS Score Improvement of at Least 2 or 4 Points

The Itch NRS is a daily participant-reported measure (24-hour recall), of the worst level of itch intensity using a diary. Participants are asked to rate the itching severity because of their AD by selecting a number from 0 (no itch) to 10 (worst imaginable itch) that best describes their worst level of itching in the past 24 hours. Kaplan-Meier estimation method was used for analyses.

Time frame: up to Week 8