Study to Evaluate the Efficacy and Safety of JTE-451 in Subjects With Moderate to Severe Plaque Psoriasis

Phase 2

Completed

Conditions: Psoriasis
Skin Diseases
Plaque Psoriasis

Interventions: Drug: JTE-451 Tablets
Drug: Placebo Tablets

Registration Number: NCT03832738

Lead Sponsor: Akros Pharma Inc.

Brief Summary: Study to evaluate the efficacy and safety of JTE-451 administered for 16 weeks in subjects with moderate to severe plaque psoriasis.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 152

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
JTE-451 Dose 1	JTE-451 Tablets	JTE-451 Tablets Dose 1 daily for 16 weeks.
JTE-451 Dose 2	JTE-451 Tablets	JTE-451 Tablets Dose 2 daily for 16 weeks.
Placebo	Placebo Tablets	Placebo Tablets daily for 16 weeks.

Primary Outcome Measures

Name	Time	Method
Percentage of Subjects Achieving a Minimum 75% Improvement From Baseline in the Psoriasis Area and Severity Index (PASI-75) at End-of-treatment (EOT)	End of Treatment (Up to 16 Weeks)	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.

Secondary Outcome Measures

Name	Time	Method
Percentage of Subjects Achieving a Minimum 50% Improvement From Baseline in the Psoriasis Area and Severity Index (PASI-50) at EOT	End of Treatment (Up to 16 Weeks)	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.
Percentage of Subjects Achieving a Minimum 90% Improvement From Baseline in the Psoriasis Area and Severity Index (PASI-90) at EOT	End of Treatment (Up to 16 Weeks)	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.
Percent Change From Baseline in Psoriasis Area and Severity Index (PASI) Score at EOT	End of Treatment (Up to 16 Weeks)	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.
Percentage of Subjects Who Achieved Static Physician's Global Assessment (sPGA) Score of 0 or 1 at EOT	End of Treatment (Up to 16 Weeks)	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.
Change From Baseline in Static Physician's Global Assessment (sPGA) Score at EOT	End of Treatment (Up to 16 Weeks)	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.
Percent Change From Baseline in Psoriasis Body Surface Area (BSA) at EOT	End of Treatment (Up to 16 Weeks)	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.
Change From Baseline in the Skindex-16 Overall Score at EOT	End of Treatment (Up to 16 Weeks)	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.
Change From Baseline in the Skindex-16 Symptom Scale Scores at EOT	End of Treatment (Up to 16 Weeks)	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.
Change From Baseline in the Skindex-16 Emotions Scale Scores at EOT	End of Treatment (Up to 16 Weeks)	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.
Change From Baseline in the Skindex-16 Functioning Scale Scores at EOT	End of Treatment (Up to 16 Weeks)	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.
Change From Baseline in Itch Numeric Rating Scale (NRS) at EOT	End of Treatment (Up to 16 Weeks)	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).
Number of Subjects With Treatment-emergent Adverse Events	Follow-up (Up to 20 Weeks)	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: 1. 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. 2. An AE present prior to the treatment period that worsened in severity during the treatment period or the follow-up period. 3. 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.
JTE-451 Trough Plasma Concentrations at Week 16	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.

Trial Locations

Locations (33): Research Toronto
🇨🇦
Toronto, Ontario, Canada
Dermoklinika - Centrum Medyczne s.c., M. Kierstan, J. Narbutt, A. Lesiak
🇵🇱
Lodz, Poland
ETG Siedlce
🇵🇱
Siedlce, Poland
Clinical Research Group Sp. z o.o.
🇵🇱
Warszawa, Poland
Dorota Bystrzanowska "High-Med" Przychodnia Specjalistyczna
🇵🇱
Warszawa, Poland
Centrum Medyczne Grunwald
🇵🇱
Poznan, Poland
Carpe Diem Centrum Medycyny Estetycznej
🇵🇱
Warszawa, Poland
Clinical Science Institute
🇺🇸
Santa Monica, California, United States
Advanced Dermatology and Skin Cancer Specialists
🇺🇸
Temecula, California, United States
Dawes Fretzin Clinical Research Group, LLC
🇺🇸
Indianapolis, Indiana, United States
Health Concepts
🇺🇸
Rapid City, South Dakota, United States
Central Sooner Research
🇺🇸
Norman, Oklahoma, United States
Wiseman Dermatology Research Inc.
🇨🇦
Winnipeg, Manitoba, Canada
SimcoDerm Medical and Surgical Dermatology Center
🇨🇦
Barrie, Ontario, Canada
SKiN Health
🇨🇦
Cobourg, Ontario, Canada
Diex Research Sherbrooke Inc.
🇨🇦
Sherbrooke, Quebec, Canada
Szpital Uniwersytecki nr 1 im. Dr. A. Jurasza w Bydgoszczy, Klinika Dermatologii, Chorob Prenoszonych Droga Plciowa
🇵🇱
Bydgoszcz, Poland
Prywatny Gabinet Dermatologiczny Elzbieta Klujszo
🇵🇱
Kielce, Poland
Copernicus Podmiot Leczniczy Sp. z o.o., Oddzial Dermatologii
🇵🇱
Gdansk, Poland
Centrum Nowoczesnych Terapii "Dobry Lekarz" Spolka z orgraniczona odpowiedzialnoscia
🇵🇱
Krakow, Poland
Centrum Terapii Wspolczesnej J.M. Jasnorzewska Spolka Komandytowo-Akeyjna
🇵🇱
Lodz, Poland
ETG Lodz
🇵🇱
Lodz, Poland
ETG Lublin
🇵🇱
Lublin, Poland
Solumed Centrum Medyczne
🇵🇱
Poznan, Poland
Kliniczny Szpital Wojewodzki nr 1 im. Fryderyka Chopina w Rzeszowie, Klinika Dermatologii
🇵🇱
Rzeszow, Poland
ETG Skierniewice
🇵🇱
Skierniewice, Poland
ETG Warszawa
🇵🇱
Warszawa, Poland
DERMMEDICA Sp. z o.o.
🇵🇱
Wrocław, Poland
Royalderm Agnieszka Nawrocka
🇵🇱
Warszawa, Poland
CITYCLINIC Przychodnia Psychologiczno-Lekarska Matusiak Spolka Partnerska
🇵🇱
Wroclaw, Poland
ETG Zamosc
🇵🇱
Zamosc, Poland
K. Papp Clinical Research
🇨🇦
Waterloo, Ontario, Canada
Rhode Island Hospital
🇺🇸
Providence, Rhode Island, United States