A Pharmacokinetic Study of Ruxolitinib Phosphate Cream in Pediatric Subjects With Atopic Dermatitis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, tolerability and the pharmacokinetics (PK) of topical ruxolitinib cream applied to pediatric subjects (age ≥ 2 to 17 years) with atopic dermatitis (AD).

Detailed Description
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Study has been modified to include younger pediatric subjects (age ≥2 to 11) in four additional cohorts.

Official Title
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An Open-Label, Pilot Pharmacokinetic Study of Ruxolitinib Phosphate Cream in Pediatric Subjects With Atopic Dermatitis

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Drug: Ruxolitinib phosphate cream


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pediatric subjects aged ≥ 2 to 17 years, inclusive Subjects diagnosed with AD as defined by the Hanifin and Rajka criteria. Subjects with active inflammation associated with AD. Subjects with an Investigator's Global Assessment (IGA) score of at least 2 at screening and baseline. Subjects with body surface area (BSA) of AD involvement of 8% to 20% at screening and baseline. Subjects who agree to discontinue all agents used to treat AD from screening through the final follow-up visit. Subjects of childbearing potential must agree to take appropriate precautions to avoid pregnancy or fathering a child for the duration of study participation. Written informed consent of the parent(s) or legal guardian and a verbal or written assent from the subject when possible. Exclusion Criteria: Unstable course of AD (spontaneously improving or rapidly deteriorating) as determined by the investigator over the previous 4 weeks before baseline. Use of topical treatments for AD (other than bland moisturizer such as Eucerin® cream) within 2 weeks of baseline. Concurrent conditions and history of other diseases: Presence of AD lesions only on the hands or feet without a history of involvement of other classical areas of involvement such as the face or the flexural folds. Other types of eczema. Any other concomitant skin disorder (eg, generalized erythroderma such as Netherton Syndrome, or psoriasis), pigmentation, or extensive scarring that in the opinion of the investigator may interfere with the evaluation of AD lesions or compromise subject safety. Immunocompromised (eg, lymphoma, acquired immunodeficiency syndrome, Wiskott-Aldrich syndrome) or have a history of malignant disease within 5 years before the baseline visit. Chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 4 weeks before the baseline visit. Active acute bacterial, fungal, or viral (eg, herpes simplex, herpes zoster, chicken pox) skin infection within 1 week before the baseline visit. Chronic asthma requiring more than 880 μg of inhaled budesonide or equivalent high dose of other inhaled corticosteroids. Subjects with cytopenias at screening per protocol-defined criteria. Use of the following medications: Systemic immunosuppressive or immunomodulating drugs (eg, oral or injectable corticosteroids, methotrexate, cyclosporine, mycophenolate mofetil, azathioprine) within 4 weeks or 5 half-lives of baseline (whichever is longer). Subjects taking potent systemic cytochrome P450 3A4 inhibitors or fluconazole within 2 weeks or 5 half lives, whichever is longer, before the baseline visit (topical agents with limited systemic availability are permitted). Subjects who have previously received JAK inhibitors, systemic or topical (eg, ruxolitinib, tofacitinib, baricitinib, filgotinib, lestaurtinib, pacritinib). 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. Use of any prohibited medications within 14 days or 5 half-lives (whichever is longer) of the baseline visit. Parent or legal guardian who, in the opinion of the investigator, is unable or unlikely to comply with the administration schedule and study evaluations or are unable or unwilling to apply the study drug.

Ages Eligible for Study
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Minimum Age: 2 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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Ruxolitinib phosphate cream 0.5%. | Drug: Ruxolitinib phosphate cream<br>* Ruxolitinib phosphate cream at the protocol-defined dose strength based on cohort assignment.<br>* Other names: INCB018424;|
| Experimental: Cohort 2<br>Ruxolitinib phosphate cream 1.5%. | Drug: Ruxolitinib phosphate cream<br>* Ruxolitinib phosphate cream at the protocol-defined dose strength based on cohort assignment.<br>* Other names: INCB018424;|
| Experimental: Cohort 3<br>Ruxolitinib phosphate cream 0.75%. | Drug: Ruxolitinib phosphate cream<br>* Ruxolitinib phosphate cream at the protocol-defined dose strength based on cohort assignment.<br>* Other names: INCB018424;|
| Experimental: Cohort 4<br>Ruxolitinib phosphate cream 1.5%. | Drug: Ruxolitinib phosphate cream<br>* Ruxolitinib phosphate cream at the protocol-defined dose strength based on cohort assignment.<br>* Other names: INCB018424;|
| Experimental: Cohort 5<br>Ruxolitinib phosphate cream 0.75%. | Drug: Ruxolitinib phosphate cream<br>* Ruxolitinib phosphate cream at the protocol-defined dose strength based on cohort assignment.<br>* Other names: INCB018424;|
| Experimental: Cohort 6<br>Ruxolitinib phosphate cream 1.5%. | Drug: Ruxolitinib phosphate cream<br>* Ruxolitinib phosphate cream at the protocol-defined dose strength based on cohort assignment.<br>* Other names: INCB018424;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participants with treatment-emergent adverse events (TEAEs) | A TEAE is any adverse event (AE) either reported for the first time or worsening of a pre-existing event after first application of study drug. | Screening through 30-37 days after end of treatment, up to approximately 12 weeks. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentrations of ruxolitinib for Cohorts 1 and 2 | Venous blood samples will be collected to assess the PK of ruxolitinib . | Day 1, Day 15, and Day 29 | 
| Plasma concentrations of ruxolitinib for Cohorts 3, 4, 5 and 6 | Venous blood samples will be collected to assess the PK of ruxolitinib . | Day 1, Day 10, and Day 29 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atopic dermatitis, Janus kinase (JAK) inhibitor, pediatric, inflammation