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

Study Overview
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Brief Summary
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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%).

Official Title
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A Phase 3, Double-Blind, Randomized, Vehicle-Controlled, Efficacy and Safety Study of Ruxolitinib Cream Followed by a Long-Term Safety Extension Period in Children (Ages≥ 2 Years to < 12 Years) With Atopic Dermatitis ((TRuE-AD3)

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Drug: Ruxolitinib
* Drug: Vehicle Cream


Participation Criteria
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Eligibility Criteria
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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: Immunocompromised Chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 2 weeks before the baseline visit. Active acute bacterial, fungal, or viral skin infection within 1 week before the baseline visit. 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. 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. Other types of eczema. 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: 5 half-lives or 12 weeks, whichever is longer - biologic agents (eg, dupilumab). 4 weeks - systemic corticosteroids or adrenocorticotropic hormone analogues, cyclosporin, methotrexate, azathioprine, or other systemic immunosuppressive or immunomodulating agents (eg, mycophenolate or tacrolimus). 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. 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.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 11 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: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ruxolitinib (1.5% Cream)<br>Study drug will be administered twice daiily. | Drug: Ruxolitinib<br>* The study cream will be applied topically twice a day for up to 52 weeks.<br>* Other names: Jakafi;|
| Experimental: Ruxolitinib (0.75% cream)<br>Study drug will be administered twice daily. | Drug: Ruxolitinib<br>* The study cream will be applied topically twice a day for up to 52 weeks.<br>* Other names: Jakafi;|
| Placebo Comparator: Vehicle Cream<br>Vehicle cream will be administered twice daily. | Drug: Vehicle Cream<br>* Matching vehicle cream will be applied topically twice a day for up to 8 weeks.<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants who achieve Investigator's Global Assessment Treatment Success (IGA-TS) | Defined as Investigator's Global Assessment (IGA) score of 0 or 1 with ≥ 2 grade improvement from baseline. | Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with a ≥ 4-point improvement in Itch Numerical Rating Scale (NRS) score from baseline to Week 8 | NRS assessments will be reported by the participants ≥6 years of age, via Diary once daily beginning on the day of screening through the last application of study drug during the VC period. The Itch NRS is a validated, self reported, instrument for measurement of itch intensity and participants were asked to rate the intensity of their itch on an 11- point scale ranging from 0 (no itch) to 10 (worst itch imaginable); higher scores indicated greater itch intensity. A participant was a 4-point responder if their change from baseline is ≤ -4 (i.e. a decrease of at least 4). | Week 8 | 
| Proportion of participants with a ≥ 4-point improvement in Itch NRS score from baseline to Day 7 (Week 1) | NRS assessments will be reported by the participants ≥6 years of age, via Diary once daily beginning on the day of screening through the last application of study drug during the VC period. The Itch NRS is a validated, self reported, instrument for measurement of itch intensity and participants were asked to rate the intensity of their itch on an 11- point scale ranging from 0 (no itch) to 10 (worst itch imaginable); higher scores indicated greater itch intensity. A participant was a 4-point responder if their change from baseline is ≤ -4 (i.e. a decrease of at least 4). | Day 7 (Week 1) | 
| Proportion of participants with a ≥ 4-point improvement in Itch NRS score from baseline to Day 3 | NRS assessments will be reported by the participants ≥6 years of age, via Diary once daily beginning on the day of screening through the last application of study drug during the VC period. The Itch NRS is a validated, self reported, instrument for measurement of itch intensity and participants were asked to rate the intensity of their itch on an 11- point scale ranging from 0 (no itch) to 10 (worst itch imaginable); higher scores indicated greater itch intensity. A participant was a 4-point responder if their change from baseline is ≤ -4 (i.e. a decrease of at least 4). | Day 3 | 
| Number of Treatment Emergent Adverse Events (TEAEs) | Adverse events reported for the first time or worsening of a pre-existing event after the first application of study drug/treatment. | Up to 61 weeks | 
| Proportion of participants who achieve IGA-TS at Weeks 2 and 4 | Defined as Investigator's Global Assessment (IGA) score of 0 or 1 with ≥ 2 grade improvement from baseline. | Week 2 and 4 | 
| Proportion of participants with a ≥ 4-point improvement in Itch NRS score from baseline to Weeks 2 and 4 | NRS assessments will be reported by the participants ≥6 years of age, via Diary once daily beginning on the day of screening through the last application of study drug during the VC period. The Itch NRS is a validated, self reported, instrument for measurement of itch intensity and participants were asked to rate the intensity of their itch on an 11- point scale ranging from 0 (no itch) to 10 (worst itch imaginable); higher scores indicated greater itch intensity. A participant was a 4-point responder if their change from baseline is ≤ -4 (i.e. a decrease of at least 4). | Weeks 2 and 4 | 
| Proportion of participants who achieve EASI75 at Weeks 2, 4 and 8 | Defined as ≥ 75% improvement in Eczema Area and Severity Index (EASI) score. | Weeks 2, 4 and 8 | 
| Time to achieve Itch NRS score improvement of at least 2 or 4 points | Defined as time taken by participants to achieve a 2 or 4 point improvement on itch NRS scale. The Itch NRS is a validated, self reported, instrument for measurement of itch intensity and participants were asked to rate the intensity of their itch on an 11- point scale ranging from 0 (no itch) to 10 (worst itch imaginable); higher scores indicated greater itch intensity. | Week 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atopic Dermatitis, Ruxolitinib