Ruxolitinib in Seborrheic Dermatitis

Study Overview
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Brief Summary
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This study is an open-label prospective interventional trial that will assess the efficacy of ruxolitinib in the treatment of seborrheic dermatitis. It will also attempt to characterize the molecular immune profiles of patients with SD at week 0 and week 4, with comparison to baseline profiles in healthy control subjects.

Detailed Description
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The study will include 25 adult patients with moderate-to-severe-SD as well as 20 age- and gender-matched healthy control subjects for comparison. The SD patients will have baseline clinical score of at least 6 using the SD Severity Score in Appendix 1, or an Investigator Global Assessment (IGA) score of at least 3. Enrolled SD subjects will apply topical ruxolitinib 1.5% cream twice daily for 4 weeks. They will return for visits at weeks 2, 4, and 6 following study treatment initiation for repeat clinical assessments, medication reviews, tape-strip, blood and urine sample collections, and monitoring for adverse events.

Official Title
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Characterizing the Molecular Cutaneous Phenotype of Seborrheic Dermatitis and Treatment Response to Ruxolitinib 1.5% Cream

Conditions
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Seborrheic Dermatitis

Intervention / Treatment
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* Drug: Ruxolitinib 1.5% Cream


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria For SD Subjects: Male or female subjects ≥ 18 years of age at the time of signing the informed consent document. Subject is able to understand and voluntarily sign an informed consent document prior to participation in any study assessments or procedures. Subject is able to adhere to the study visit schedule and other protocol requirements. Baseline SD score of IGA ≥ 3 with facial involvement Subject agrees to discontinue all treatments for SD from screening through study completion aside from the study drug Subject has failed an adequate course of treatment with at least one available therapy (topical antifungals or low-potency topical corticosteroids) Subject is judged to be in otherwise good overall health as judged by the investigator, based on medical history, physical examination, and laboratory testing. (NOTE: The definition of good health means a subject does not have uncontrolled significant co-morbid conditions). Females of childbearing potential (FCBP) must have a negative pregnancy test at Screening and Baseline. While on the study drug and for at least 90 days after the last application of the study drug, male and female participants must be willing to take appropriate contraceptive measures to avoid pregnancy or fathering a child. FCBP who engage in activity in which conception is possible must use one of the approved contraceptive options described below: Option 1: Any one of the following highly effective contraceptive methods: hormonal contraception (oral, injection, implant, transdermal patch, vaginal ring); intrauterine device (IUD); tubal ligation; or partner's vasectomy, OR: Option 2: Male or female condom (latex condom or nonlatex condom NOT made out of natural [animal] membrane [for example, polyurethane]); PLUS one additional barrier method: (a) diaphragm with spermicide; (b) cervical cap with spermicide; or (c) contraceptive sponge with spermicide. The female subject's chosen form of contraception must be effective by the time the female subject is enrolled into the study. Inclusion Criteria For Control Subjects: Male or female subjects ≥ 18 years of age at the time of signing the informed consent document. Subject is able to understand and voluntarily sign an informed consent document prior to participation in any study assessments or procedures. Subject does not currently have and does not have a history of SD. Female of childbearing potential (FCBP) must have a negative pregnancy test at Screening and Baseline Exclusion Criteria For SD Subjects: The presence of any of the following will exclude a subject from enrollment: SD clinical severity of IGA <3 and SD Severity Score <6. Subjects with other skin diseases that would interfere with the study assessment in the opinion of the investigator. Active bacterial, fungal, or viral skin infection within 2 weeks from study initiation. Subject has clinically significant (as determined by the investigator) renal, hepatic, hematologic, intestinal, endocrine, pulmonary, cardiovascular, neurological, psychiatric, immunologic, or other major uncontrolled diseases (e.g., malignancy, TB, HIV, HBV, HCV, thromboembolic events) that will affect the health of the subject during the study, or interfere with the interpretation of study results. Subject has previously received treatment with oral or topical JAK inhibitors Current other topical treatments (e.g., topical corticosteroids, topical calcineurin inhibitors) within 1 week of baseline Use of systemic immunosuppressive medications, including, but not limited to, cyclosporine, systemic or intralesional corticosteroids, mycophenolate mofetil, azathioprine, methotrexate, tacrolimus within 4 weeks of study initiation Concurrent use of strong CYP3A4 inhibitors within 7 days or 5 half-lives (whichever is longer). A list of CYP3A4 inhibiting medications can be found in Appendix 3. History of adverse systemic or allergic reactions to any component of the study drug. Current participation in any other study with an investigational medication Subject who is pregnant or breast feeding Exclusion Criteria For Control Subjects: Active bacterial, fungal, or viral skin infection within 2 weeks from Screening/Baseline visit. Subject has uncontrolled clinically significant (as determined by the investigator) renal, hepatic, hematologic, intestinal, endocrine, pulmonary, cardiovascular, neurological, psychiatric, immunologic, or other disease. Subject has previously received treatment with oral or topical JAK inhibitors Current other topical treatments (e.g., topical corticosteroids, topical calcineurin inhibitors) within 1 week of baseline Use of systemic immunosuppressive medications, including, but not limited to, cyclosporine, systemic or intralesional corticosteroids, mycophenolate mofetil, azathioprine, methotrexate, tacrolimus within 4 weeks of study initiation Current participation in any other study with an investigational medication Subject who is pregnant or breast feeding

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Single Group Assignment
Interventional Model Description: Open-Label Trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ruxolitinib Cream<br>Participants will receive topical ruxolitinib 1.5% cream | Drug: Ruxolitinib 1.5% Cream<br>* topical ruxolitinib 1.5% cream twice daily for 4 weeks<br>|
| No Intervention: Healthy Control Subjects<br>Age- and gender-matched healthy control subjects | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigator Global Assessment of 0 or 1 at Week 4 | IGA Scale from 0-4 Clear 0 No signs of SD Almost Clear 1 Just perceptible erythema and just perceptible scaling Mild 2 Mild erythema and mild scaling Moderate 3 Moderate erythema and moderate scaling Severe 4 Severe erythema and severe scaling | At end of Treatment, Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Investigator Global Assessment from baseline to week 4 | IGA Scale from 0-4 Clear 0 No signs of SD Almost Clear 1 Just perceptible erythema and just perceptible scaling Mild 2 Mild erythema and mild scaling Moderate 3 Moderate erythema and moderate scaling Severe 4 Severe erythema and severe scaling | Baseline and Week 4 | 
| Change in seborrheic dermatitis severity score from baseline to week 4 | SD Severity Score (the sum of the three clinical features for a total score ranging from 0-12), where higher scores indicate more severe outcomes. Scale 0-4 Erythema 0-4 Pruritus 0-4 (0 = absence, 1 = mild, 2 = moderate, 3 = significant, 4 = severe) | Baseline and Week 4 | 
| Change in seborrheic dermatitis severity score for Scale from baseline to week 4 | Scale 0-4, where higher scores indicate more severe outcomes. (0 = absence, 1 = mild, 2 = moderate, 3 = significant, 4 = severe) | Baseline and Week 4 | 
| Change in seborrheic dermatitis severity score for Erythema from baseline to week 4 | Erythema 0-4, where higher scores indicate more severe outcomes. (0 = absence, 1 = mild, 2 = moderate, 3 = significant, 4 = severe) | Baseline and Week 4 | 
| Change in seborrheic dermatitis severity score for Pruritus from baseline to week 4 | Pruritus 0-4, where higher scores indicate more severe outcomes. (0 = absence, 1 = mild, 2 = moderate, 3 = significant, 4 = severe) | Baseline and Week 4 | 
| Change in seborrheic dermatitis severity score from baseline to week 6 | SD Severity Score (the sum of the three clinical features for a total score ranging from 0-12), where higher scores indicate more severe outcomes. Scale 0-4 Erythema 0-4 Pruritus 0-4 (0 = absence, 1 = mild, 2 = moderate, 3 = significant, 4 = severe) | Baseline to Week 6 | 
| Change in seborrheic dermatitis severity score from week 4 to week 6 | SD Severity Score (the sum of the three clinical features for a total score ranging from 0-12), where higher scores indicate more severe outcomes. Scale 0-4 Erythema 0-4 Pruritus 0-4 (0 = absence, 1 = mild, 2 = moderate, 3 = significant, 4 = severe) | Week 4 and Week 6 | 
| Frequency of Adverse Events |  | Baseline to Week 6 | 
| Duration of Adverse Events |  | Baseline to Week 6 | 
| Severity of Adverse Events | Severity will be measured as a category (mild, moderate, or severe). | Baseline to Week 6 |