Study to Evaluate the Safety and Efficacy of JTE-051 in Subjects With Moderate to Severe Plaque Psoriasis

Study Overview
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Brief Summary
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Study to evaluate the efficacy, safety, tolerability and pharmacokinetics of JTE-051 administered for 12 weeks in subjects with moderate to severe plaque psoriasis.

Official Title
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A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Safety and Efficacy of JTE-051 Administered for 12 Weeks in Subjects With Moderate to Severe Plaque Psoriasis (CLEAR-PS)

Conditions
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Plaque Psoriasis, Skin Diseases

Intervention / Treatment
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* Drug: JTE-051
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with moderate to severe plaque psoriasis at least 6 months prior to Visit 1 Plaque-type psoriasis covering ≥10% of body surface area (BSA) at Visit 1 and Visit 2; Psoriasis Area and Severity Index (PASI) score ≥12 at Visit 1 and Visit 2; Static Physician's Global Assessment (sPGA) score ≥3 at Visit 1 and Visit 2; Body Mass Index (BMI) ≤40 at Visit 1. Exclusion Criteria: Medical history of treatment failure to any systemic agents for plaque psoriasis; Presence of erythrodermic psoriasis, pustular psoriasis, guttate psoriasis, medication-induced psoriasis or other skin conditions at (e.g., clinically-significant eczema or severe acne) that could interfere with study evaluations at Visit 1; Presence or history of any itch due to underlying conditions other than plaque psoriasis which cause or influence pruritus of the skin (e.g., drug induced pruritus, significant other systemic diseases with itch) within 12 months prior to Visit 1; History of a clinically-significant infection (e.g., that required oral antimicrobial therapy) within 8 weeks prior to Visit 2; History of infections requiring hospitalization or parenteral antibiotic, antiviral, antifungal or antiparasitic therapy within 6 months prior to Visit 2 and no history of recurrent infections or conditions predisposing to chronic infections (e.g., bronchiectasis, chronic osteomyelitis);

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: JTE-051 Dose 1<br>One dose of study drug by mouth daily for 12 weeks | Drug: JTE-051<br>* Active drug tablets containing JTE-051<br>|
| Experimental: JTE-051 Dose 2<br>One dose of study drug by mouth daily for 12 weeks | Drug: JTE-051<br>* Active drug tablets containing JTE-051<br>|
| Experimental: JTE-051 Dose 3<br>One dose of study drug by mouth daily for 12 weeks | Drug: JTE-051<br>* Active drug tablets containing JTE-051<br>|
| Experimental: JTE-051 Dose 4<br>One dose of study drug by mouth daily for 12 weeks | Drug: JTE-051<br>* Active drug tablets containing JTE-051<br>|
| Experimental: Placebo<br>One dose of study drug by mouth daily for 12 weeks | Drug: Placebo<br>* Placebo tablets identical in appearance to the active drug tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Subjects Achieving a Minimum 75% Improvement From Baseline in the Psoriasis Area and Severity Index (PASI-75) by End-of-treatment (EOT). | The psoriasis area and severity index (PASI) combines the assessment of the severity of lesions (scaling, redness and plaque thickness) and the area affected into a single score in the range of 0.0 (no disease) to 72.0 (maximal disease). The body is divided into four sections: (1) Head and neck; (2) Upper limbs; (3) Trunk (including axillae and groin); and (4) Lower limbs (including buttocks). The PASI score can vary in increments of 0.1 and range from 0.0 to 72.0, with higher scores representing greater severity of psoriasis. The PASI-75 response rate is defined as at least 75 percent (%) reduction in PASI score relative to Baseline. | Up to 12 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in PASI Score | The psoriasis area and severity index (PASI) combines the assessment of the severity of lesions (scaling, redness and plaque thickness) and the area affected into a single score in the range of 0.0 (no disease) to 72.0 (maximal disease). The body is divided into four sections: (1) Head and neck; (2) Upper limbs; (3) Trunk (including axillae and groin); and (4) Lower limbs (including buttocks). The PASI score can vary in increments of 0.1 and range from 0.0 to 72.0, with higher scores representing greater severity of psoriasis. Percent change was calculated by taking the Week 12 PASI score and subtracting the baseline PASI, and dividing by the baseline PASI, then multiplying by 100 to get the percent change from baseline. | Week 12 | 
| Proportion of Subjects Achieving PASI-50 (50% Improvement From Baseline in PASI) | The psoriasis area and severity index (PASI) combines the assessment of the severity of lesions (scaling, redness and plaque thickness) and the area affected into a single score in the range of 0.0 (no disease) to 72.0 (maximal disease). The body is divided into four sections: (1) Head and neck; (2) Upper limbs; (3) Trunk (including axillae and groin); and (4) Lower limbs (including buttocks). The PASI score can vary in increments of 0.1 and range from 0.0 to 72.0, with higher scores representing greater severity of psoriasis. The PASI-50 response rate is defined as at least 50 percent (%) reduction in PASI score relative to Baseline. | Week 12 | 
| Proportion of Subjects Achieving PASI-90 (90% Improvement From Baseline in PASI) | The psoriasis area and severity index (PASI) combines the assessment of the severity of lesions (scaling, redness and plaque thickness) and the area affected into a single score in the range of 0.0 (no disease) to 72.0 (maximal disease). The body is divided into four sections: (1) Head and neck; (2) Upper limbs; (3) Trunk (including axillae and groin); and (4) Lower limbs (including buttocks). The PASI score can vary in increments of 0.1 and range from 0.0 to 72.0, with higher scores representing greater severity of psoriasis. The PASI-90 response rate is defined as at least 90 percent (%) reduction in PASI score relative to Baseline. | Week 12 | 
| Proportion of Subjects Achieving PASI-100 (100% Improvement From Baseline in PASI) | The psoriasis area and severity index (PASI) combines the assessment of the severity of lesions (scaling, redness and plaque thickness) and the area affected into a single score in the range of 0.0 (no disease) to 72.0 (maximal disease). The body is divided into four sections: (1) Head and neck; (2) Upper limbs; (3) Trunk (including axillae and groin); and (4) Lower limbs (including buttocks). The PASI score can vary in increments of 0.1 and range from 0.0 to 72.0, with higher scores representing greater severity of psoriasis. The PASI-100 response rate is defined as 100 percent (%) reduction in PASI score relative to Baseline. | Week 12 | 
| Proportion of Subjects Who Achieved Static Physician's Global Assessment (sPGA) Score of 0 or 1 | The sPGA of psoriasis is scored on a 5-point scale, reflecting a global consideration of the redness, thickness and scaling across all psoriatic lesions. Average redness, thickness and scaling are scored separately over the whole body according to a 5-point severity scale (0 [no symptom] to 4 [severe symptom]). The total score is calculated as average of the 3 severity (redness, thickness and scaling) scores and rounded to the nearest whole number score to determine the sPGA score (0=cleared; 1=minimal; 2=mild; 3=moderate; and 4=severe). For this outcome measure, a score of 0 means no symptoms of psoriasis and a score of 1 means minimal symptoms of psoriasis. | Week 12 | 
| Change From Baseline in Static Physician's Global Assessment (sPGA) Score | The sPGA of psoriasis is scored on a 5-point scale, reflecting a global consideration of the redness, thickness and scaling across all psoriatic lesions. Average redness, thickness and scaling are scored separately over the whole body according to a 5-point severity scale (0 [no symptom] to 4 [severe symptom]). The total score is calculated as average of the 3 severity (redness, thickness and scaling) scores and rounded to the nearest whole number score to determine the sPGA score (0=cleared; 1=minimal; 2=mild; 3=moderate; and 4=severe). Change from baseline to Week 12 in sPGA was calculated by taking the Week 12 sPGA and subtracting the baseline sPGA. | Week 12 | 
| Percent Change From Baseline in Psoriasis Body Surface Area (BSA) | The total body surface area (BSA) affected by plaque-type psoriasis was obtained from the percentages of areas affected, including head, trunk, upper limbs and lower limbs. Each reported percentage was multiplied by its respective body region corresponding factor (head=0.1, upper limbs=0.2, trunk=0.3, lower limbs=0.4) and the resulting 4 values were added up to obtain the total psoriasis BSA (Range: 0 to 100). BSA (%)=0.1Sh + 0.2Sh+0.3St+0.4Sl, where S=body region surface area with psoriasis: h=head; u=upper limbs; t=trunk; l=lower limbs. Percent change from baseline to Week 12 in BSA was calculated by taking the Week 12 BSA and subtracting the baseline BSA, then dividing by the baseline BSA and multiplying by 100. A negative change from baseline at Week 12 indicates a reduction in the Psoriasis BSA compared to the baseline. | Week 12 | 
| Change From Baseline in the Skindex-16 Overall Score | Skindex-16 questionnaire contains 16 questions related to quality of life in subjects with skin disease. It consists of a short 16-item assessment completed by the subject, with each item rated on a 7-point Likert scale (0=never bothered to 6=always bothered). Each raw score is multiplied by 16.667 to transform all responses to a linear scale from 0 (no effect) to 100 (effect experienced all the time). Responses to the Skindex-16 are categorized into 3 subscales: symptom, emotional & functional; their respective scores are expressed in a linear scale from 0 to 100. Overall scale score is an average of 16 items expressed in a linear scale from 0 to 100. Change from baseline to Week 12 in the Skindex-16 Overall Score was calculated by taking the Week 12 Skindex-16 Overall Score and subtracting the baseline Skindex-16 Overall Score. A negative change from baseline at Week 12 indicates an improvement in the subject's condition compared to the baseline. | Week 12 | 
| Change From Baseline in the Skindex-16 Symptoms Scale Score | Skindex-16 questionnaire contains 16 questions related to quality of life in subjects with skin disease. It consists of a short 16-item assessment completed by the subject, with each item rated on a 7-point Likert scale (0=never bothered to 6=always bothered). Each raw score is multiplied by 16.667 to transform all responses to a linear scale from 0 (no effect) to 100 (effect experienced all the time). Responses to the Skindex-16 are categorized into 3 subscales: symptom, emotional & functional; their respective scores are expressed in a linear scale from 0 to 100. Symptoms scale score is an average of items 1 to 4 expressed in a linear scale from 0 to 100. Change from baseline to Week 12 in the Skindex-16 Symptoms Scale Score was calculated by taking the Week 12 Skindex-16 Symptoms Scale Score and subtracting the baseline Skindex-16 Symptoms Scale Score. A negative change from baseline at Week 12 indicates an improvement in the subject's condition compared to the baseline. | Week 12 | 
| Change From Baseline in the Skindex-16 Emotions Scale Score | Skindex-16 questionnaire contains 16 questions related to quality of life in subjects with skin disease. It consists of a short 16-item assessment completed by the subject, with each item rated on a 7-point Likert scale (0=never bothered to 6=always bothered). Each raw score is multiplied by 16.667 to transform all responses to a linear scale from 0 (no effect) to 100 (effect experienced all the time). Responses to the Skindex-16 are categorized into 3 subscales: symptom, emotional & functional; their respective scores are expressed in a linear scale from 0 to 100. Emotions scale score is an average of items 5 to 11 expressed in a linear scale from 0 to 100. Change from baseline to Week 12 in the Skindex-16 Emotions Scale Score was calculated by taking the Week 12 Skindex-16 Emotions Scale Score and subtracting the baseline Skindex-16 Emotions Scale Score. A negative change from baseline at Week 12 indicates an improvement in the subject's condition compared to the baseline. | Week 12 | 
| Change From Baseline in the Skindex-16 Functioning Scale Score | Skindex-16 questionnaire contains 16 questions related to quality of life in subjects with skin disease. It consists of a short 16-item assessment completed by the subject, with each item rated on a 7-point Likert scale (0=never bothered to 6=always bothered). Each raw score is multiplied by 16.667 to transform responses to a linear scale from 0 (no effect) to 100 (effect experienced all the time). Responses to the Skindex-16 are categorized into 3 subscales: symptom, emotional & functional; their respective scores are expressed in a linear scale from 0 to 100. Functioning scale score is an average of items 12 to 16 expressed in a linear scale from 0 to 100. Change from baseline to Week 12 in the Skindex-16 Functioning Scale Score was calculated by taking the Week 12 Skindex-16 Functioning Scale Score and subtracting the baseline Skindex-16 Functioning Scale Score. A negative change from baseline at Week 12 indicates an improvement in the subject's condition compared to the baseline. | Week 12 | 
| Number of Subjects With Treatment-emergent Adverse Events | Subjects in the Safety Population (13, subjects who were randomly assigned to treatment and who received at least one dose of study drug). The study was terminated early as per the Sponsor decision. All randomized subjects were included in the Safety Population. | Up to 16 Weeks | 
| JTE-051 Trough Plasma Concentrations | Trough plasma concentration is the measured concentration at the end of a dosing interval at steady state (taken directly before next administration). Blood samples were collected at specific timepoints to measure trough plasma concentrations of JTE-051 in the subjects randomized to JTE-051 treatment groups. | Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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JTE-051, Psoriasis