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

Psoriasis Clinical Trial

— IMPACT-PS  

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03832738
• Other study ID #: AE451-G-18-004
• Status: Completed
• Phase: Phase 2
• Start date: January 17, 2019
• Est. completion date: March 13, 2020

Study information

• Verified date: August 2021
• Source: Akros Pharma Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 152
• Est. completion date: March 13, 2020
• Est. primary completion date: March 13, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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)-? 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.

Related Conditions & MeSH terms

• Plaque Psoriasis
• Psoriasis
• Skin Diseases

Intervention

Drug:
• JTE-451 Tablets
Active drug tablets containing JTE-451
• Placebo Tablets
Placebo tablets matching in appearance to the active drug tablets

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Akros Pharma Inc.

Countries where clinical trial is conducted

United States,  Canada,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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