Study to Evaluate the Efficacy and Safety of JTE-451 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 and safety of JTE-451 administered for 16 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 Efficacy and Safety of JTE-451 Administered for 16 Weeks in Subjects With Moderate to Severe Plaque Psoriasis (IMPACT-PS)

Conditions
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Plaque Psoriasis, Psoriasis, Skin Diseases

Intervention / Treatment
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* Drug: JTE-451 Tablets
* Drug: Placebo Tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have had a history of moderate to severe plaque psoriasis for at least 6 months prior to Visit 1; Subjects with moderate to severe plaque psoriasis covering ≥10% body surface area (BSA), with a psoriasis area and severity index (PASI) ≥12 and static Physician's Global Assessment (sPGA) score ≥3 at Visit 1 and Visit 2 Exclusion Criteria: History of discontinuation of biologic therapies (including marketed and investigational drugs) directly targeting Interleukin (IL)-17A, IL-17A/F, IL-17 receptor A, IL-12/IL-23p40 or IL-23p19 due to lack of efficacy, according to the Investigator's judgment; Prior exposure to retinoid-related orphan receptor (ROR)-γ inhibitors; Presence of erythrodermic psoriasis, pustular psoriasis, guttate psoriasis, medication-induced psoriasis or other skin conditions (e.g., clinically-significant eczema or severe acne) at Visit 1; History or presence of itch due to underlying conditions other than plaque psoriasis which cause or influence pruritus of the skin within 12 months prior to Visit 1.

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-451 Dose 1<br>JTE-451 Tablets Dose 1 daily for 16 weeks. | Drug: JTE-451 Tablets<br>* Active drug tablets containing JTE-451<br>|
| Experimental: JTE-451 Dose 2<br>JTE-451 Tablets Dose 2 daily for 16 weeks. | Drug: JTE-451 Tablets<br>* Active drug tablets containing JTE-451<br>|
| Placebo Comparator: Placebo<br>Placebo Tablets daily for 16 weeks. | Drug: Placebo Tablets<br>* Placebo tablets matching 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 |
| --- | --- | --- |
| Percentage of Subjects Achieving a Minimum 75% Improvement From Baseline in the Psoriasis Area and Severity Index (PASI-75) at 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 at EOT (up to 16 weeks) relative to Baseline. | End of Treatment (Up to 16 Weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Achieving a Minimum 50% Improvement From Baseline in the Psoriasis Area and Severity Index (PASI-50) at EOT | The 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 at EOT (up to 16 weeks) relative to Baseline. | End of Treatment (Up to 16 Weeks) | 
| Percentage of Subjects Achieving a Minimum 90% Improvement From Baseline in the Psoriasis Area and Severity Index (PASI-90) at EOT | The 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 at EOT (up to 16 weeks) relative to Baseline. | End of Treatment (Up to 16 Weeks) | 
| Percent Change From Baseline in Psoriasis Area and Severity Index (PASI) Score at EOT | The 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 from baseline to EOT (up to 16 weeks) in PASI score was calculated by taking the PASI score at EOT and subtracting the baseline PASI score, then dividing by the baseline PASI score and multiplying by 100. | End of Treatment (Up to 16 Weeks) | 
| Percentage of Subjects Who Achieved Static Physician's Global Assessment (sPGA) Score of 0 or 1 at EOT | 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 symptoms] to 4 [severe symptoms]). 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, at EOT (up to 16 weeks), a score of 0 means no symptoms of psoriasis and a score of 1 means minimal symptoms of psoriasis. | End of Treatment (Up to 16 Weeks) | 
| Change From Baseline in Static Physician's Global Assessment (sPGA) Score at EOT | 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 symptoms] to 4 [severe symptoms]). 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 EOT (up to 16 weeks) in sPGA score was calculated by taking the sPGA score at EOT and subtracting the baseline sPGA score. | End of Treatment (Up to 16 Weeks) | 
| Percent Change From Baseline in Psoriasis Body Surface Area (BSA) at EOT | 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+0.2Su+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 EOT (up to 16 weeks) in BSA was calculated by taking the EOT BSA and subtracting the baseline BSA, then dividing by the baseline BSA and multiplying by 100. A negative change from baseline at EOT indicates a reduction in the Psoriasis BSA compared to the baseline. | End of Treatment (Up to 16 Weeks) | 
| Change From Baseline in the Skindex-16 Overall Score at EOT | 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 EOT (up to 16 weeks) in the Skindex-16 Overall Score was calculated by taking the EOT Skindex-16 Overall Score and subtracting the baseline Skindex-16 Overall Score. A negative change from baseline at EOT indicates an improvement in the subject's condition compared to the baseline. | End of Treatment (Up to 16 Weeks) | 
| Change From Baseline in the Skindex-16 Symptom Scale Scores at EOT | 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 EOT (up to 16 weeks) in the Skindex-16 Symptoms Scale Score was calculated by taking the EOT Skindex-16 Symptoms Scale Score and subtracting the baseline Skindex-16 Symptoms Scale Score. A negative change from baseline at EOT indicates an improvement in the subject's condition compared to the baseline. | End of Treatment (Up to 16 Weeks) | 
| Change From Baseline in the Skindex-16 Emotions Scale Scores at EOT | 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 EOT (up to 16 weeks) in the Skindex-16 Emotions Scale Score was calculated by taking the EOT Skindex-16 Emotions Scale Score and subtracting the baseline Skindex-16 Emotions Scale Score. A negative change from baseline at EOT indicates an improvement in the subject's condition compared to the baseline. | End of Treatment (Up to 16 Weeks) | 
| Change From Baseline in the Skindex-16 Functioning Scale Scores at EOT | 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 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 EOT (up to 16 weeks) in the Skindex-16 Functioning Scale Score was calculated by taking the EOT Skindex-16 Functioning Scale Score and subtracting the baseline Skindex-16 Functioning Scale Score. A negative change from baseline at EOT indicates an improvement in the subject's condition compared to the baseline. | End of Treatment (Up to 16 Weeks) | 
| Change From Baseline in Itch Numeric Rating Scale (NRS) at EOT | The Itch NRS is a validated, self-reported, instrument for measurement of itch intensity and subjects were asked to rate the intensity of their itch on an 11-point scale ranging from 0 (no itch) to 10 (worst itch imaginable); higher scores indicated greater itch intensity. The Itch NRS scores were recorded by the subject using the e-diary once daily from screening through the last visit. Change from baseline to EOT (up to 16 weeks) in the Itch NRS Score was calculated by taking the Itch NRS Score (weekly average) at EOT and subtracting the baseline Itch NRS Score (weekly average). | End of Treatment (Up to 16 Weeks) | 
| Number of Subjects With Treatment-emergent Adverse Events | Subjects in the Safety Population (151, randomized subjects who received at least one dose of study drug). The treatment-emergent adverse event (TEAE) is defined as one of the following: An adverse event (AE) that occurred during the treatment period or the follow-up period. In the process of collecting the onset dates of AEs, an AE that occurs after the initiation of trial medication on Day 1 (the first day of the treatment period) should be treated as a TEAE. All AEs occurring on the day of first dose will be considered as TEAE if the time of AE occurrence relative to the dosing is unknown. An AE present prior to the treatment period that worsened in severity during the treatment period or the follow-up period. Any events that are present prior to the treatment period and have recovered, but recurred during the treatment period or the follow-up period should be considered as new TEAEs. | Follow-up (Up to 20 Weeks) | 
| JTE-451 Trough Plasma Concentrations at Week 16 | 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 concentration of JTE-451 in the pharmacokinetic (PK) population. | Week 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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JTE-451, Psoriasis, Plaque psoriasis, IMPACT-PS