A Study of Ruxolitinib Phosphate Cream When Applied to Patients With Plaque Psoriasis

Study Overview
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Brief Summary
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The study is comprised of two parts. The first portion of this study will be a double-blind, Sponsor-unblinded, vehicle-controlled study with application of ruxolitinib or vehicle to paired lesions at least 15 cm apart in patients with active but stable plaque psoriasis. Part 2 of the study is a double-blind, sponsor unblinded, comparison of ruxolitinib with two FDA approved products in patients with active but stable plaque psoriasis.

Official Title
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A Double-Blind, Vehicle-Controlled, Rising Dose, Safety, Tolerability, Pharmacokinetic and Preliminary Efficacy Study of Ruxolitinib Phosphate Cream When Applied to Patients With Plaque Psoriasis

Conditions
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Psoriasis

Intervention / Treatment
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* Drug: Ruxolitinib phosphate cream
* Drug: Dovonex® calcipotriene 0.005%
* Drug: Diprolene® AF betamethasone dipropionate 0.05% cream.
* Drug: Placebo cream
* Drug: Ruxolitinib phosphate cream
* Drug: Ruxolitinib phosphate cream


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body Mass Index (BMI) of 17 to 40 kg/m2 Subjects must have two comparable psoriatic lesions measuring between 9 and 100 cm2 and these target lesions must be similar in size to each other, and separated by at least 15 cm. Exclusion Criteria: Subjects with lesions solely involving the palms of the hands or soles of the feet or intertriginous areas, the scalp or the face. Subjects with pustular psoriasis or erythroderma. Subjects currently on other topical agents or UVB therapy within 2 weeks of the first dose of study medication. Subjects receiving PUVA within 4 weeks of the first dose of study medication. Subjects receiving systemic retinoids, etanercept, adalimumab or efalizumab or oral immunosuppressives within 3 months prior to the first dose of study medication. Subjects receiving any other biological therapy (infliximab, alefacept, abatacept, etc) within 3 months of the first dose of study medication.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A: INCB018424 Ruxolitinib 0.5%<br>INCB018424 Ruxolitinib 0.5% vs vehicle applied once daily for 28 days | Drug: Ruxolitinib phosphate cream<br>* Ruxolitinib phosphate cream 0.5%<br>* Other names: INCB018424;Drug: Placebo cream<br>* Cream applied once or twice daily for 56 days<br>|
| Experimental: Cohort B: INCB018424 Ruxolitinib 1.0%<br>INCB018424 Ruxolitinib 1.0% vs vehicle applied once daily for 28 days | Drug: Placebo cream<br>* Cream applied once or twice daily for 56 days<br>Drug: Ruxolitinib phosphate cream<br>* Ruxolitinib phosphate cream 1.0%<br>* Other names: INCB018424;|
| Experimental: Cohort C: INCB018424 Ruxolitinib 1.5%<br>INCB018424 Ruxolitinib 1.5% vs vehicle applied twice for 28 days | Drug: Placebo cream<br>* Cream applied once or twice daily for 56 days<br>Drug: Ruxolitinib phosphate cream<br>* Ruxolitinib phosphate cream 1.5%<br>* Other names: INCB018424;|
| Experimental: Cohort D: 18424 Ruxolitinib vs Dovonex® calcipotriene<br>INCB018424 up to 1.5% versus Dovonex® calcipotriene 0.005% cream applied BID for 28 days | Drug: Dovonex® calcipotriene 0.005%<br>* Cream applied once or twice daily for up to 56 days.<br>|
| Experimental: Cohort E: 18424 Ruxolitinib vs Diprolene® AF betamethasone diproprionate<br>INCB018424 up to 1.5% versus Diprolene ® AF betamethasone dipropionate 0.05% cream applied twice a day for 28 days | Drug: Diprolene® AF betamethasone dipropionate 0.05% cream.<br>* Cream applied once or twice daily for up to 56 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Target Lesion Individual Component Scores for Erythema, Scaling and Thickness Compared to Baseline | The investigator assessed the severity of the clinical signs erythema, scaling, and thickness for each test site by using a 5-point scale from 0 (no evidence) to 4.0 (severe). | Baseline, Days 8, 15, 22, 28 and 56 | 
| Change in Target Lesion TOTAL Score (Sum of Erythema + Scaling + Thickness) Compared to Baseline | The total target lesion score was calculated by summing the scores for erythema, scaling, and thickness for that particular target lesion. The investigator assessed the severity of the clinical signs erythema, scaling, and thickness for each test site by using a 5-point scale from 0 (no evidence) to 4.0 (severe). | Baseline, Days 8, 15, 22, 28 and 56 | 
| Number of Participants With Treatment Emergent Adverse Events | A TEAE is any AE either reported for first time or worsening of a pre-existing event after first dose of study drug. | 3 months | 
| Pharmacokinetics Parameter : Skin Flux of INCB018424 | The INCB018424 skin flux was estimated from the overall mean steady-state plasma concentrations for each participant. | Days 8, 15, 22, and 28 | 
| Pharmacokinetics Parameter : Bioavailability of INCB018424 | The INCB018424 bioavailability will be estimated from the overall mean steady-state plasma concentrations for each subject in this study and the estimated systemic clearance of INCB018424 following oral-dose administration in another study. Bioavailability is defined as the proportion of a drug which enters the circulation when introduced into the body and so is able to have an active effect. | Days 8, 15, 22, and 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Target Lesion Area Compared to Baseline | Lesion area was estimated on Day 1 and Day 28 using a tracings of the lesion on transparency paper and measurement of the area. | Day 28 |