A Dose Ranging Study of the Effect of Ruxolitinib Phosphate Cream When Applied to Participants With Plaque Psoriasis

Study Overview
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Brief Summary
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The study was double-blind, randomized, vehicle-controlled study with application of Ruxolitinib phosphate cream or vehicle cream in participants with stable plaque psoriasis applied once daily for 12 weeks without occlusive dressings. There were 4 treatment groups anticipated to have 50 participants in each.

Official Title
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A Double-Blind, Randomized, Vehicle-Controlled Dose Ranging Study of the Effect of INCB018424 Phosphate Cream When Applied to Patients With Plaque Psoriasis

Conditions
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Psoriasis

Intervention / Treatment
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* Other: Placebo Cream
* Drug: Ruxolitinib Phosphate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Plaque psoriasis involving up to 2 to 20% Body Surface Area Exclusion Criteria: Lesions solely involving intertriginous areas, the scalp or the face Systemic therapy for their psoriasis Pustular psoriasis or erythroderma Currently on other topical agents or Ultraviolet B (UVB) therapy within 2 weeks of the first dose of study medication Started or discontinued therapy within 2 months of Screening with agents that can exacerbate psoriasis Receiving systemic triazole antifungals except fluconazole

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 |
| --- | --- |
| Placebo Comparator: Vehicle Cream<br>Vehicle cream, applied topically, once daily from Day 1 to Week 12. | Other: Placebo Cream<br>* Cream with no active drug<br>|
| Experimental: Ruxolitinib Phosphate 0.5% Cream<br>Ruxolitinib phosphate 0.5% cream, applied topically, once daily from Day 1 to Week 12. | Drug: Ruxolitinib Phosphate<br>* Ruxolitinib phosphate cream<br>* Other names: INCB018424;|
| Experimental: Ruxolitinib Phosphate 1.0% Cream<br>Ruxolitinib phosphate 1.0% cream, applied topically, once daily from Day 1 to Week 12. | Drug: Ruxolitinib Phosphate<br>* Ruxolitinib phosphate cream<br>* Other names: INCB018424;|
| Experimental: Ruxolitinib Phosphate 1.5% Cream<br>Ruxolitinib phosphate 1.5% cream, applied topically, once daily from Day 1 to Week 12. | Drug: Ruxolitinib Phosphate<br>* Ruxolitinib phosphate cream<br>* Other names: INCB018424;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change From Baseline in Total Lesion Score for All Treatable Psoriatic Lesions to Day 84 | Total Lesion Score is calculated as the sum of component scores for erythema (E), scaling (S), and thickness (T) of the study-treated lesions taken together. Each component consists of ratings of 0=none, 1=mild, 2=moderate, 3=marked, and 4=severe such that total lesion score can vary in value from 0 to 12. A negative change from Baseline indicates improvement. | From Baseline (Day 1) to Day 84 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change From Baseline in the Individual Lesion Scores for Lesion Thickness | Lesion thickness was scored using a 5-point scale ranging from 0 to 4 where 0 is none or absent and 4 is severe lesion. A negative change from Baseline indicates improvement. | From Baseline (Day 1) to Day 84 | 
| Absolute Change From Baseline in the Individual Lesion Scores for Lesion Erythema | Lesion erythema was scored using a 5-point scale ranging from 0 to 4 where 0 is none or absent and 4 is severe lesion. A negative change from Baseline indicates improvement. | From Baseline (Day 1) to Day 84 | 
| Absolute Change From Baseline in the Individual Lesion Scores for Lesion Scaling | Lesion scaling was scored using a 5-point scale ranging from 0 to 4 where 0 is none or absent and 4 is severe lesion. A negative change from Baseline indicates improvement. | From Baseline (Day 1) to Day 84 | 
| Percent Change From Baseline in the Individual Lesion Scores of Lesion Thickness | Lesion thickness was scored using a 5-point scale ranging from 0 to 4 where 0 is none or absent and 4 is severe lesion. A negative percent change from Baseline indicates improvement in lesion. | From Baseline (Day 1) to Day 84 | 
| Percent Change From Baseline in the Individual Lesion Scores of Lesion Erythema | Lesion erythema was scored using a 5-point scale ranging from 0 to 4 where 0 is none or absent and 4 is severe lesion. A negative percent change from Baseline indicates improvement in lesion. | From Baseline (Day 1) to Day 84 | 
| Percent Change From Baseline in the Individual Lesion Scores of Lesion Scaling | Lesion scaling was scored using a 5-point scale ranging from 0 to 4 where 0 is none or absent and 4 is severe lesion. A negative percent change from Baseline indicates improvement in lesion. | From Baseline (Day 1) to Day 84 | 
| Percentage of Participants Achieving None (Score=0) and Mild (Score=1) in Lesion Thickness at Day 84 | Lesion thickness was scored using a 5-point scale ranging from 0 to 4 where 0 is none or absent and 4 is severe lesion. Participants with individual lesion scores 0 (none) and 1 (mild) are reported in this outcome measure. | Day 84 | 
| Percentage of Participants Achieving None (Score=0) and Mild (Score=1) in Lesion Erythema at Day 84 | The individual lesion scores were calculated individually for thickness, erythema, and scaling. Lesion erythema was scored using a 5-point scale ranging from 0 to 4 where 0 is none or absent and 4 is severe lesion. Participants with individual lesion scores 0 (none) and 1 (mild) are reported in this outcome measure. The LOCF method was used for analysis. | Day 84 | 
| Percentage of Participants Achieving None (Score=0) and Mild (Score=1) in Lesion Scaling at Day 84 | The individual lesion scores were calculated individually for thickness, erythema, and scaling. Lesion scaling was scored using a 5-point scale ranging from 0 to 4 where 0 is none or absent and 4 is severe lesion. Participants with individual lesion scores 0 (none) and 1 (mild) are reported in this outcome measure. The LOCF method was used for analysis. | Day 84 | 
| Absolute Change From Baseline in the Percent Treatable Body Surface Area (BSA) | The lesion areas were estimated based on the Rule of Nines method for the entire skin surface; psoriatic disease activity and the percent BSA were calculated for the treatable areas (i.e., areas that excluded the scalp, face, and intertriginous areas). The BSA is calculated as follows: BSA (m^²)=([Height(cm) x Weight(kg)]/3600 )^½. A negative change from Baseline indicates improvement. | Baseline (Day 1) to Day 84 | 
| Absolute Change From Baseline in the Physician's Global Assessment (PGA) Score | The overall disease activity in the participants, a measure of the overall quality (erythema, scaling, and thickness) and extent (BSA) of plaques, was measured using the PGA. The PGA was an overall assessment of each participant's plaque psoriasis. The assessment was recorded using a 6-point scale ranging from 0 to 5 where 0 is 'Clear' (no evidence of disease) and 5 is 'very Severe' lesion. A negative change from Baseline indicates improvement. The ANCOVA method was used for analyses. | Baseline (Day 1) to Day 84 | 
| Percent Change From Baseline in the PGA Score | The overall disease activity in the participants, a measure of the overall quality (erythema, scaling, and thickness) and extent (BSA) of plaques, was measured using the PGA. The PGA was an overall assessment of each participant's plaque psoriasis. The assessment was recorded using a 6-point scale ranging from 0 to 5 where 0 indicates 'Clear' (no evidence of disease) and 5 indicates 'very Severe' lesion. A negative percent change indicates improvement. The ANCOVA method was used for analyses. | Baseline (Day 1) to Day 84 | 
| Percentage of Participants Achieving Clear (Score=0) and Almost Clear (Score=1) on the PGA | The overall disease activity in the participants, a measure of the overall quality (erythema, scaling, and thickness) and extent (BSA) of plaques, was measured using the PGA. The PGA was an overall assessment of each participant's plaque psoriasis. The assessment was recorded using a 6-point scale ranging from 0 to 5 where 0 indicates 'Clear' (no evidence of disease) and 5 indicates 'very Severe' lesion. Participants with individual lesion scores 0 (clear) and 1 (almost clear) are reported in this outcome measure. | Day 84 | 
| Absolute Change From Baseline in the Psoriasis Area and Severity Index (PASI) Score | PASI is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). Body is divided into 4 areas for scoring [lower extremities, trunk (including stomach, chest, back), upper extremities, head]; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by scale 0 (none) to 4 (severe). Final PASI is the sum of severity score for each area multiplied coverage for each section multiplied by area score weight of section (lower extremities: 0.4, trunk: 0.3, upper extremities: 0.2, head: 0.1). A negative change from baseline indicates improvement. The ANCOVA method was used for analyses. | Baseline (Day 1) to Day 84 | 
| Percent Change From Baseline in the PASI Score | PASI is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). Body is divided into 4 areas for scoring [lower extremities, trunk (including stomach, chest, back), upper extremities, head]; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by scale 0 (none) to 4 (severe). Final PASI is the sum of severity score for each area multiplied by coverage for each section multiplied by area score weight of section (lower extremities: 0.4, trunk: 0.3, upper extremities: 0.2, head: 0.1). A percent negative change from baseline indicates improvement in disease. The ANCOVA method was used for analyses. | Baseline (Day 1) to Day 84 | 
| Percentage of Participants With Treatable Percent BSA ≥10% Achieving PASI 50%, PASI 75%, And PASI 90% Improvements From Baseline to Each Time Point | PASI is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). Body is divided into 4 areas for scoring [lower extremities, trunk (including stomach, chest, back), upper extremities, head]; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by scale 0 (none) to 4 (severe). Final PASI is the sum of severity score for each area* multiplied by coverage for each section* multiplied by area score weight of section (lower extremities: 0.4, trunk: 0.3, upper extremities: 0.2, head: 0.1). A negative percent change from Baseline indicates improvement. Data for Day 84 was imputed using the LOCF method. | Baseline (Day 1) and Days 15, 28, 56, 84, and 112 | 
| Trough Plasma Concentrations [Minimum Concentration at Steady-state (Css,Min)] of Ruxolitinib Phosphate Prior to Study Drug Application at Steady State |  | Pre-application on Days 1, 15, 28, 56, and 84 |