Study of Ruxolitinib Cream in Adolescents With Atopic Dermatitis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the long-term safety and tolerability of ruxolitinib cream in adolescents with Atopic Dermatitis (AD).

Detailed Description
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The study comprises of a 8 week continuous treatment period followed by 44 week Long Term Safety (LTS) period and 30 days safety follow up period. During Continuous treatment period all lesions identified at baseline will be treated and during LTS period only active lesions will be treated.

Official Title
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A Phase 3, Open-Label, One-Year Safety Study of Ruxolitinib Cream in Adolescents (Ages ≥ 12 Years to < 18 Years) With Atopic Dermatitis

Conditions
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Atopic Dermatitis (AD)

Intervention / Treatment
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* Drug: Ruxolitinib Cream


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A diagnosis of Atopic Dermatitis (AD) as defined by the Hanifin and Rajka (1980) criteria. Duration of AD of at least 2 years. Total IGA score of 2 to 3 at the screening and baseline visits. Percent BSA (excluding the scalp) with AD involvement of 3% to 20% at the screening and baseline visits. Atopic dermatitis not adequately controlled with other topical prescription therapies or when those therapies are not advisable. Agree to discontinue all agents used to treat AD from screening through the final follow up visit. Willingness to avoid pregnancy or fathering children. Exclusion Criteria: An unstable course of AD (spontaneously improving or rapidly deteriorating) as determined by the investigator in the 4 weeks prior to baseline. Concurrent conditions and history of other diseases Any current and/or history of serious illness or medical, physical, or psychiatric condition(s) that, in the investigator's opinion, would interfere with full participation in the study, including application of study cream and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data. For example: Clinically significant or uncontrolled cardiovascular disease, including unstable angina, acute myocardial infarction or stroke within 6 months from Day 1 of study cream application, New York Heart Association Class III or IV congestive heart failure, and arrhythmia requiring therapy or uncontrolled hypertension (blood pressure > 150/90 mm Hg) unless approved by the medical monitor/sponsor. Current and/or history of malignancy in the 5 years preceding the baseline visit, except for adequately treated, nonmetastatic nonmelanoma skin cancer. Current and/or history of arterial or venous thrombosis, including DVT and PE. Current and/or history of active tuberculosis or current and/or history of latent tuberculosis unless adequately treated. Any of the following clinical laboratory test results at screening: Hemoglobin < 100 g/L (< 10 g/dL) Liver function tests: AST or ALT ≥ 2.5 × ULN Total bilirubin > 1.5 × ULN with the exception of Gilbert disease. c. Estimated glomerular filtration rate < 30 mL/min/1.73 m2 (using the CKD Epidemiology Collaboration equation). d. Positive serology test results for HIV antibody. e. Any other clinically significant laboratory result that, in the opinion of the investigator, poses a significant risk to the participant. Use of any of the following treatments within the indicated washout period before baseline: 5 half-lives or 12 weeks, whichever is longer - biologic agents (eg, dupilumab). 4 weeks - systemic corticosteroids or adrenocorticotropic hormone analogues, cyclosporine, methotrexate, azathioprine, or other systemic immunosuppressive or immunomodulating agents (eg, mycophenolate or tacrolimus). 2 weeks - immunizations with live-attenuated vaccines; sedating antihistamines, unless on long-term stable regimen (nonsedating antihistamines are permitted). Note: Live-attenuated vaccines are not recommended during the CT period. Note: COVID-19 vaccination is allowed. 1 week - use of other topical treatments for AD (other than bland emollients, eg, Aveeno® creams, ointments, sprays, soap substitutes), such as topical antipruritics (eg, doxepin cream), corticosteroids, calcineurin inhibitors, PDE4 inhibitors, coal tar (shampoo), 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 and their frequency remains the same throughout the study. Previously received systemic or topical JAK inhibitors (eg, ruxolitinib, tofacitinib, baricitinib, filgotinib, lestaurtinib, pacritinib). 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. Current treatment or treatment within 30 days or 5 half-lives (whichever is longer) before baseline with another investigational medication or current enrollment in another investigational drug protocol. Current treatment or treatment within 30 days or 5 half-lives (whichever is longer) before baseline with a strong CYP3A4 inhibitor. Inability to draw blood for PK analysis from any nonlesional areas. Known allergy or reaction to any component of the study cream formulation. In the opinion of the investigator unable or unlikely to comply with the administration schedule and study evaluations. Further exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 12 Years
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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ruxolitinib<br>Ruxolitinib cream 1.5% twice daily (BID) during the continuous and LTS treatment period. | Drug: Ruxolitinib Cream<br>* Ruxolitinib cream 1.5% twice daily (BID) during the continuous and LTS treatment period.<br>* Other names: INCB18424 cream;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Treatment-emergent adverse events (TEAEs) | TEAE defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug. | Baseline up to 56 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with clinically notable vital sign changes from baseline | Changes in vital signs assessment of blood pressure, pulse, respiration rate, and body temperature. | Baseline up to week 52 | 
| Number of participants with clinically significant changes from Baseline in height | Changes in height will be assessed. | Baseline up to week 52 | 
| Number of participants with clinically significant changes from Baseline in weight | Changes in weight will be assessed. | Baseline up to week 52 | 
| Number of participants with changes from baseline outside the normal range for clinically laboratory parameter values | Laboratory test values outside the normal range will be assessed for severity based on the normal ranges for the clinical reference laboratory. | Baseline up to week 52 | 
| Pharmacokinetic (PK) of Ruxolitinib: Trough concentrations | Trough concentration is defined as drug concentration in blood and/or saliva sampling. | Predose at weeks 2, 4, 8 followed by every 8 weeks through end of treatment (weeks 12, 20, 28, 36, 44 and 52) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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atopic dermatitis (AD), adolescents, pruritus, eczema, topical therapy, JAK inhibitor