A Study to Evaluate the Mechanism of Action of Ruxolitinib Cream in Subjects With Vitiligo (TRuE-V MOA)

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the Mechanism Of Action (MOA) of ruxolitinib cream in vitiligo by assessing the change in biomarkers.

Official Title
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A Randomized, Double-Blind, Vehicle-Controlled Study to Evaluate the Mechanism of Action of Ruxolitinib Cream for Vitiligo

Conditions
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Vitiligo

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria A clinical diagnosis of nonsegmental vitiligo with depigmented areas including ≥ 0.5% BSA on the face, ≥ 0.5 F-VASI, ≥ 3% BSA on nonfacial areas, and ≥ 3 T-VASI; total body vitiligo area (facial and nonfacial) should not exceed 50% BSA. At least 1 active vitiligo lesion (eg, such as confetti lesion, trichrome appearance, pinkish rim, or other evidence of inflammatory activity) at the site for skin biopsy. Agree to discontinue all agents used to treat vitiligo from screening through the final safety follow-up visit. Over-the-counter preparations deemed acceptable by the investigator and camouflage makeups are permitted. Exclusion Criteria No pigmented hair within any of the vitiligo areas on the face. Other forms of vitiligo (eg, segmental) or other differential diagnosis of vitiligo or other skin depigmentation disorders (eg, piebaldism, pityriasis alba, leprosy, postinflammatory hypopigmentation, progressive macule hypomelanosis, nevus anemicus, chemical leukoderma, and tinea versicolor). Used depigmentation treatments (eg, monobenzone) for past treatment of vitiligo or other pigmented areas except hydroquinone. Any other skin disease that, in the opinion of the investigator, would interfere with the study medication application or study assessments. Conditions at baseline that would interfere with evaluation of vitiligo. Use of any protocol-defined treatments within the indicated washout period before baseline.

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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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: Crossover Assignment
Interventional Model Description: Randomized, double-blind, vehicle-controlled, with an open-label treatment extension.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ruxolitinib cream<br>Ruxolitinib cream will be administered twice a day (BID) for 24 weeks | Drug: Ruxolitinib cream<br>* Ruxolitinib cream is a topical formulation applied as a thin film to affected areas.<br>* Other names: INCB018424 cream;|
| Placebo Comparator: Vehicle Cream<br>Vehicle cream is matching in appearance to ruxolitinib cream and is to be applied in the same manner as ruxolitinib cream. | Drug: Vehicle Cream<br>* Vehicle cream is matching in appearance to ruxolitinib cream and is to be applied in the same manner as ruxolitinib cream.<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change From Baseline in Chemokine (C-X-C Motif) Ligand 10 (CXCL10), an Immune Biomarker, at Week 4, Week 12, and Week 24 | Baseline was defined as the last non-missing measurement obtained on or before the first application of study drug. Percentage change from Baseline was calculated as the ([post-Baseline value minus the Baseline value] / Baseline value)*100. | Baseline; Week 4, Week 12, and Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation of Key Skin Inflammatory Biomarkers of Vitiligo in Target Lesions to Efficacy Readouts | Clinical scores (facial Vitiligo Area Scoring Index [F-VASI] and total body Vitiligo Area Scoring Index [T-VASI]) were evaluated for correlation with skin CXCL10 levels. | Baseline, Week 12, and Week 24 | 
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Double-Blind Period | An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. An AE could have been any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study drug. A TEAE was defined as any AE reported for the first time or the worsening of a pre-existing event after the first application of study drug. | from the time of Informed Consent Form signing until at least 30 days after the last application of study drug (up to Week 24 + 30 days) | 
| Number of Participants With TEAEs During the Treatment-Extension Period | An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. An AE could have been any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study drug. A TEAE was defined as any AE reported for the first time or the worsening of a pre-existing event after the first application of study drug. | from the completion of the Week 24 assessments until at least 30 days after the last application of study drug at Week 52 + 30 days | 
| Number of Participants With a Grade 3 or Higher TEAE During the Double-Blind Period | An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. A TEAE was defined as any AE reported for the first time or the worsening of a pre-existing event after the first application of study drug. AE severity was assessed per the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0: 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. | from the time of Informed Consent Form signing until at least 30 days after the last application of study drug (up to Week 24 + 30 days) | 
| Number of Participants With a Grade 3 or Higher TEAE During the Treatment-Extension Period | An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. A TEAE was defined as any AE reported for the first time or the worsening of a pre-existing event after the first application of study drug. AE severity was assessed per the CTCAE, version 5.0: 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. | from the completion of the Week 24 assessments until at least 30 days after the last application of study drug at Week 52 + 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vitiligo, depigmenting disorder, topical JAK inhibitor