A Study of Zasocitinib in Adults With Psoriatic Arthritis Who Have or Have Not Been Treated With Biologic Medicines

Phase 3

Not yet recruiting

• Conditions: Psoriatic Arthritis
• Interventions: Drug: Zasocitinib; Drug: Placebo

• Registration Number: NCT06671496
• Lead Sponsor: Takeda

Brief Summary

Psoriatic arthritis (PsA) is a chronic inflammatory disease that affects the joints and skin in people who have psoriasis (PsO).

The main aim of the study is to know how well zasocitinib (TAK-279) works in participants with active PsA based on their previous experience with specific treatments.

The participants will be treated with either zasocitinib, or placebo. Participants will be in the study for up to 60 weeks.

Detailed Description

Not available

Basic Information
|
Recruitment & Eligibility
|
Study & Design

Study Timeline

• Study First Submitted: 2024-10-31
• Study First Submitted QC: 2024-10-31
• Status Verified: 2024-11
• Study First Posted: 2024-11-04
• Last Update Submitted: 2024-11-13
• Last Update Posted: 2024-11-15
• Study Start: 2025-03-06
• Primary Completion: 2027-05-18
• Study Completion: 2028-01-26

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 600

Inclusion Criteria

Age:

1. The participant is aged 18 years or older at the time of signing the informed consent form (ICF).

   Disease Characteristics:

2. The participant has had signs and symptoms consistent with PsA for at least 3 months.

3. The participant meets the Classification Criteria for Psoriatic Arthritis (CASPAR criteria).

4. The participant has active arthritis as shown by a minimum of >=3 tender joints in TJC68 and >=3 swollen joints in SJC66 at the screening and baseline (Day 1) visits.

5. The participant has at least 1 active lesion of plaque PsO >=2 cm in diameter, or any nail or nail bed changes characteristic of PsO.

   Medications for PsA:

6. The participant has had at least one of the following:

   1. Inadequate response to a nonsteroidal anti-inflammatory drug (NSAID), OR
   2. Inadequate response to a conventional synthetic disease-modifying antirheumatic drug (csDMARD), OR
   3. Biological disease-modifying antirheumatic drug (DMARD)-inadequate response (Bio-IR): Inadequate response to up to 2 biologic DMARDs.

Read More

Exclusion Criteria

PsA and PsO:

1. The participant has other disease(s) that might confound the evaluations of benefit of zasocitinib therapy, including but not limited to rheumatoid arthritis, axial spondyloarthritis, systemic lupus erythematosus, Lyme disease, gout, or fibromyalgia.
2. The participant has a concomitant comorbid skin condition that, in the opinion of the investigator, would interfere with the study assessments, such as evidence of non-plaque PsO (erythrodermic, pustular, predominately guttate PsO, inverse, or drug-induced PsO).

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo + Zasoctinib	Placebo	Participants will receive placebo, orally, QD for up to Week 16, followed by zasoctinib Dose A or Dose B, orally, QD, from Week 16 up to Week 52.
Zasocitinib Dose A	Zasocitinib	Participants will receive zasocitinib Dose A, tablets, orally, once daily (QD) for up to Week 52.
Zasocitinib Dose B	Zasocitinib	Participants will receive zasocitinib Dose B, tablets, orally, QD for up to Week 52.
Placebo + Zasoctinib	Zasocitinib	Participants will receive placebo, orally, QD for up to Week 16, followed by zasoctinib Dose A or Dose B, orally, QD, from Week 16 up to Week 52.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Achieving American College of Rheumatology 20 (ACR20) Response at Week 16 for Zasocitinib Dose A and B Compared to Placebo	At Week 16	ACR responses are the numerical measurement of improvement in multiple disease assessment criteria. It is a composite clinical outcome assessment (COA) measure that includes both clinician-reported outcome assessments (ClinROs) and patient-reported outcomes (PROs). An ACR20 response is defined as: greater than or equal to (\>=) 20 percent (%) improvement from baseline in both swollen joint count 66 joints (SJC66) and tender joint count 68 joints (TJC68), and \>=20% improvement from baseline in 3 of the following 5 assessments: Patient's global assessment (PtGA) of psoriatic arthritis (PsA) pain; PtGA of PsA; physician's global assessment of disease activity (PGA) of PsA; participant's assessment of physical function as measured by health assessment questionnaire-disability index (HAQ-DI); high-sensitivity C-reactive protein (hsCRP). Percentage of participants achieving ACR20 response at Week 16 for zasocitinib Dose A and B compared to placebo will be reported.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Achieving Minimal Disease Activity (MDA) at Week 16 for Zasocitinib Dose A and B Compared to Placebo	At Week 16	The MDA is defined as a composite outcome measure of 7 ClinROs and PROs used in PsA. Participants are classified as achieving MDA if they fulfil 5 of 7 outcome measures: TJC68 less than or equal to (\<=) 1, SJC66 \<=1, psoriasis area and severity index (PASI) score \<=1 or body surface area (BSA) affected by psoriasis \<=3%, PtGA of PsA Pain score \<=15, PtGA of PsA score \<=20, HAQ-DI \<=0.5, and Leeds Enthesitis Index (LEI) \<=1. Percentage of participants achieving MDA at Week 16 for zasocitinib Dose A and B compared to placebo will be reported.
Percentage of Participants Achieving PASI-75 Response (in Participants With a Baseline >=3% BSA) at Week 16 for Zasocitinib Dose A and B Compared to Placebo	Baseline, at Week 16	A PASI-75 response is defined as \>=75% improvement in the PASI score from baseline. It is a ClinRO used to measure psoriasis severity, combining the percent of affected skin surface area with the severity of erythema, induration, and desquamation across four body regions: head, upper extremities, trunk, and lower extremities. Severity is scored on a 0-4 scale, with 0 indicating no involvement and 4 indicating very marked involvement. PASI scores range from 0 to 72, with \<=3 representing mild disease, \>=3 to 15 representing moderate disease, and \>=15 indicating severe disease. Percentage of participants achieving PASI-75 response (in participants with a baseline \>=3% body surface area \[BSA\]) for zasocitinib Dose A and B compared to placebo at Week 16 will be reported.
Percentage of Participants Achieving ACR50 Response at Week 16 for Zasocitinib Dose A and B Compared to Placebo	At Week 16	ACR responses are the numerical measurement of improvement in multiple disease assessment criteria. It is a composite COA measure that includes both ClinROs and PROs. An ACR50 response is defined as: \>= 50% improvement from baseline in both SJC66 and TJC68, and \>=50% improvement from baseline in 3 of the following 5 assessments: PtGA of PsA pain; PtGA of PsA; PGA of PsA; participant's assessment of physical function as measured by HAQ-DI; hsCRP. Percentage of participants achieving ACR50 response at Week 16 for zasocitinib Dose A and B compared to placebo will be reported.
Change From Baseline in the HAQ-DI Score at Week 16 for Zasocitinib Dose A and B Compared to Placebo	Baseline, at Week 16	The HAQ-DI is defined as a 20-item PRO measure used to assess functional ability over the past week across 8 categories: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and common daily activities. For each of these categories, participant reports the amount of difficulty they have in performing 2 or 3 specific activities on a 4-point scale (0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty, 3 = unable to do) The use of assistive devices and personal assistance are also noted. The HAQ-DI score is calculated as the mean of the category scores (0 = no disability, 3 = completely disabled), with 0 being the most desirable outcome and 3 as the least desirable. Participants must have scores for at least 6 categories for the HAQ-DI to be computed. Change from baseline in the HAQ-DI score at Week 16 for zasocitinib Dose A and B compared to placebo will be reported.
Percentage of Participants Achieving ACR70 Response at Week 16 for Zasocitinib Dose A and B Compared to Placebo	At Week 16	ACR responses are the numerical measurement of improvement in multiple disease assessment criteria. It is a composite COA measure that includes both ClinROs and PROs. An ACR70 response is defined as: \>=70% improvement from baseline in both SJC66 and TJC68, and \>=70% improvement from baseline in 3 of the following 5 assessments: PtGA of PsA pain; PtGA of PsA; PGA of PsA; participant's assessment of physical function as measured by HAQ-DI; hsCRP. Percentage of participants achieving ACR70 response at Week 16 for zasocitinib Dose A and B compared to placebo will be reported.
Change From Baseline in the Short Form-36 Health Survey Version 2.0 (SF-36 v2.0) Physical Component Summary (PCS) Score at Week 16 for Zasocitinib Dose A Compared to Placebo	Baseline, at Week 16	The SF-36 v2.0 is defined as a self-administered, validated questionnaire designed to measure general health-related quality of life (QoL). This 36-item questionnaire measures 8 domains over the past 4 weeks, including physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health, physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. Summary score PCS, will be calculated ranging from 0 (worst) to 100 (best). Higher scores indicate better QoL. Change from baseline in the SF-36 v2.0 PCS score at Week 16 for zasocitinib Dose A compared to placebo will be reported.
Change From Baseline in the Functional Assessment of Chronic Illness Therapy (FACIT)- Fatigue Score at Week 16 for Zasocitinib Dose A Compared to Placebo	Baseline, at Week 16	The FACIT-fatigue score is defined as a 13-item PRO measure that assesses the severity of self-reported fatigue and its impact on daily functioning over the past 7 days. It includes items measuring tiredness, weakness, listlessness, lack of energy, and the effects on activities such as sleep and social interactions. Each item is rated on a 5-point scale (0 = not at all; 1 = a little bit; 2 = somewhat; 3 = quite a bit; 4 = very much). The total score ranges from 0 to 52, with higher scores indicating less fatigue. Change from baseline in the FACIT- fatigue score at Week 16 for zasocitinib Dose A compared to placebo will be reported.
Percentage of Participants Achieving PASI-90 Response (in Participants With a Baseline >=3% BSA) at Week 16 for Zasocitinib Dose A and B Compared to Placebo	Baseline, at Week 16	A PASI-90 response is defined as \>=90% improvement in the PASI score from baseline. It is a ClinRO used to measure psoriasis severity, combining the percent of affected skin surface area with the severity of erythema, induration, and desquamation across four body regions: head, upper extremities, trunk, and lower extremities. Severity is scored on a 0-4 scale, with 0 indicating no involvement and 4 indicating very marked involvement. PASI scores range from 0 to 72, with \<=3 representing mild disease, \>=3 to 15 representing moderate disease, and \>=15 indicating severe disease. Percentage of participants achieving PASI-90 response (in participants with a baseline \>=3% BSA) at Week 16 for zasocitinib Dose A and B compared to placebo will be reported.
Percentage of Participants Achieving LEI =0 (in Participants With a Baseline LEI >=1) at Week 16 for Zasocitinib Dose A and B Compared to Placebo	Baseline, at Week 16	The LEI is defined as a 6-item ClinRO measure specifically developed for PsA. It assesses the presence or absence of pain/tenderness when 4 kilograms per centimeter square (kg/cm\^2) of pressure is applied to 6 enthesial sites: the lateral epicondyles, medial femoral condyles, and Achilles tendon insertions on both sides of the body. Tenderness at each site is recorded on a dichotomous scale (0 = non-tender, 1 = tender). The total score is the sum of tender sites, ranging from 0 to 6, with a higher score indicating a greater enthesitis burden. Percentage of participants achieving LEI =0 (in participants with a baseline LEI \>=1) at Week 16 for zasocitinib Dose A and B compared to placebo will be reported.
Change From Baseline in Individual Components of ACR Response at Week 16 for Zasocitinib Dose A and B Compared to Placebo	Baseline, at Week 16	ACR responses are the numerical measurement of improvement in multiple disease assessment criteria. It is a composite COA measure that includes both ClinROs and PROs. An ACR response is defined as: improvement from baseline in both SJC66 and TJC68, and improvement from baseline in 3 of the following 5 assessments: PtGA of PsA pain (0-100 visual analogue scale \[VAS\]); PtGA of PsA (0-100 VAS); PGA of PsA (0-100 VAS); participant's assessment of physical function as measured by HAQ-DI (0-3 scale); hsCRP. Change from baseline in individual components of ACR response at Week 16 for zasocitinib Dose A and B compared to placebo will be reported.
Percentage of Participants Achieving Leeds Dactylitis Index (LDI) =0 (in Participants With a Baseline LDI >=1) at Week 16 for Zasocitinib Dose A and B Compared to Placebo	Baseline, at Week 16	The LDI is defined as a ClinRO measure use to assess the presence of dactylitis. It involves measuring the circumference of all 20 digits using a dactylometer, with measurements taken around the proximal phalanx as close to the web space as possible. Moderate pressure is applied to assess tenderness or pain in the affected digits. Tenderness is scored on a binary scale (0 = non-tender, 1 = tender). Only digits with a circumference ratio exceeding 10% are considered to have dactylitis. A higher score indicates worse dactylitis. Percentage of participants achieving LDI =0 (in participants with a baseline LDI \>=1) at Week 16 for zasocitinib Dose A and B compared to placebo will be reported.
Percentage of Participants Achieving PASI-75 Response (in Participants With a Baseline >=3% BSA) at Week 8 for Zasocitinib Dose A and B Compared to Placebo	Baseline, at Week 8	A PASI-75 response is defined as \>=75% improvement in the PASI score from baseline. It is a ClinRO used to measure psoriasis severity, combining the percent of affected skin surface area with the severity of erythema, induration, and desquamation across four body regions: head, upper extremities, trunk, and lower extremities. Severity is scored on a 0-4 scale, with 0 indicating no involvement and 4 indicating very marked involvement. PASI scores range from 0 to 72, with \<=3 representing mild disease, \>=3 to 15 representing moderate disease, and \>=15 indicating severe disease. Percentage of participants achieving PASI-75 response (in participants with a baseline \>=3% BSA) at Week 8 for zasocitinib Dose A and B compared to placebo will be reported.
Percentage of Participants Achieving PASI-100 Response (in Participants With a Baseline >=3% BSA) at Week 16 for Zasocitinib Dose A and B Compared to Placebo	Baseline, at Week 16	A PASI-100 response is defined as \>=100% improvement in the PASI score from baseline. It is a ClinRO used to measure psoriasis severity, combining the percent of affected skin surface area with the severity of erythema, induration, and desquamation across four body regions: head, upper extremities, trunk, and lower extremities. Severity is scored on a 0-4 scale, with 0 indicating no involvement and 4 indicating very marked involvement. PASI scores range from 0 to 72, with \<=3 representing mild disease, \>=3 to 15 representing moderate disease, and \>=15 indicating severe disease. Percentage of participants achieving PASI-100 response (in participants with a baseline \>=3% BSA) at Week 16 for zasocitinib Dose A and B compared to placebo will be reported.
Percentage of Participants Achieving ACR50 and PASI-100 Response (in Participants With a Baseline >=3% BSA) Simultaneously at Week 16 for Zasocitinib Dose A and B Compared to Placebo	Baseline, at Week 16	ACR responses measure improvement in multiple criteria, a composite COA with ClinROs and PROs. An ACR50 response is \>=50% improvement in SJC66 and TJC68, and 3 of 5 assessments: PtGA of PsA pain; PtGA of PsA; PGA of PsA, HAQ-DI, hsCRP. A PASI-100 response is \>=100% improvement in the PASI score from baseline. It's a ClinRO measuring psoriasis severity, combining the percent of affected skin surface area with the severity of erythema, induration, and desquamation across four body regions: head, upper extremities, trunk, and lower extremities. Severity is scored from 0 (no involvement) to 4 (very marked involvement). PASI scores range from 0 to 72, with \<=3 as mild, \>=3 to 15 as moderate, and \>=15 as severe disease. Percentage of participants achieving ACR50 and PASI-100 response (in participants with a baseline \>=3% BSA) simultaneously at Week 16 for zasocitinib Dose A and B compared to placebo will be reported.
Percentage of Participants Achieving sPGA Response of Clear (0) or Almost Clear (1) With >=2-Point Decrease From Baseline (in Participants With a Baseline sPGA >=2) at Week 16 for Zasocitinib Dose A and B Compared to Placebo	Baseline, at Week 16	Static physician's global assessment (sPGA) is defined as a 5-point ClinRO measure used to assess the current state of psoriasis based on severity of erythema, induration, and scaling. The total sPGA score ranges from 0 to 4, where 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate, and 4 = severe, with higher scores indicating greater disease severity. Each lesion characteristic (erythema, induration, and scaling) is graded separately on a 5-point scale: erythema (0 = no evidence to 4 = bright red coloration), induration (0 = no evidence to 4 = severe plaque elevation), and scaling (0 = no evidence to 4 = thick scaling). Lesion scores for erythema, induration, and scaling are averaged and rounded to nearest whole number to compute total score. Percentage of participants achieving sPGA response of clear (0) or almost clear (1) with \>=2-point decrease from baseline (in participants with a baseline sPGA \>=2) at Week 16 for zasocitinib Dose A and B compared to placebo will be reported.
Percentage of Responders Achieving Minimal Clinically Important Differences (Reduction of >=0.35 From Baseline) in HAQ-DI Score From Baseline at Week 16 for Zasocitinib Dose A and B Compared to Placebo	Baseline, at Week 16	The HAQ-DI is defined as a 20-item PRO measure used to assess functional ability over the past week across 8 categories: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and common daily activities. Each category includes 2-3 activities rated on a 4-point scale (0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty, 3 = unable to do). Assistive devices and personal assistance are also noted. The HAQ-DI score is calculated as the mean of the category scores (0 = no disability, 3 = completely disabled), with scores of 0-1 indicating mild-to-moderate disability, 1-2 moderate-to-severe, and 2-3 severe-to-very severe disability. Participants must have scores for at least 6 categories for the HAQ-DI to be computed. Percentage of responders achieving minimal clinically important differences (reduction of \>=0.35 from baseline) in HAQ-DI score from baseline at Week 16 for zasocitinib Dose A and B compared to placebo will be reported.
Change From Baseline in the SF-36 v2.0 Mental Component Summary (MCS) Score at Week 16 for Zasocitinib Dose A and B Compared to Placebo	Baseline, at Week 16	The SF-36 v2.0 is defined as a self-administered, validated questionnaire designed to measure general health-related quality of life (QoL). This 36-item questionnaire measures 8 domains over the past 4 weeks, including physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health, physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. Summary score MCS, will be calculated ranging from 0 (worst) to 100 (best). Higher scores indicate better QoL. Change from baseline in the SF-36 v2.0 MCS score at Week 16 for zasocitinib Dose A and B compared to placebo will be reported.
Change From Baseline in Psoriatic Arthritis Impact of Disease-12 Items (PsAID-12) Total Score at Week 16 for Zasocitinib Dose A and B Compared to Placebo	Baseline, at Week 16	The PsAID-12 is defined as a 12-item PRO measure that assesses symptoms such as pain, fatigue, and skin problems and the impact of PsA on the participant's life over the past week. It covers areas including work and/or leisure activities, physical activities, sleep, anxiety, embarrassment or shame, social participation, and depression. The response options are rated on a numerical rating scale (NRS) from 0 (none/no difficulty) to 10 (extreme difficulty), with higher scores indicating a greater impact of the disease. Change from baseline in PsAID-12 total score at Week 16 for zasocitinib Dose A and B compared to placebo will be reported.
Change From Baseline in Disease Activity Index for Psoriatic Arthritis (DAPSA) Score at Week 16 for Zasocitinib Dose A and B Compared to Placebo	Baseline, at Week 16	The DAPSA is defined as a composite measure of peripheral joint disease activity that includes ClinROs, PROs, and a laboratory test. DAPSA is calculated as the sum of the following components: tender joint count (0-68), swollen joint count (0-66), hsCRP level (milligrams per deciliter \[mg/dL\]), PtGA of PsA pain (0-100 VAS), and PtGA of PsA (0-100 VAS). DAPSA cutoffs for disease activity are: remission (\<=4), low disease activity (\>4 to \<=14), moderate disease activity (\>14 to \<=28), and high disease activity (\>28). Change from baseline in DAPSA score at Week 16 for zasocitinib Dose A and B compared to placebo will be reported.
Change From Baseline in Disease Activity Score-28 (DAS28) (C-Reactive Protein) Score at Week 16 for Zasocitinib Dose A and B Compared to Placebo	Baseline, at Week 16	The DAS28 with high-sensitivity C-reactive protein is defined as a derived index combining the tender joint count (28 joints), swollen joint count (28 joints), hsCRP, and PtGA of PsA. The 28-joint count includes the shoulder, elbow, wrist, metacarpophalangeal (MCP) 1-5, proximal interphalangeal (PIP) 1-5 of both upper extremities, and the knee joints of both lower extremities. The DAS28 score ranges from 0 to 10, with higher scores indicating greater disease activity. Change from baseline in DAS28 C-reactive protein score at Week 16 for zasocitinib Dose A and B compared to placebo will be reported.
Change From Baseline in Physician's Global Assessment of Fingernail Psoriasis (PGA-F) Score in Participants With Psoriatic Nail Involvement (PGA-F Greater than [>] 0) From Baseline at Week 16 for Zasocitinib Dose A and B Compared to Placebo	Baseline, at Week 16	The PGA-F is defined as a ClinRO measure assessing the severity of fingernail PsO. It evaluates nail bed signs (onycholysis, hyperkeratosis, erythema, splinter hemorrhages) and nail matrix signs (pitting, ridging, discoloration). Clinicians rate the severity using categories: clear (0), minimal (1), mild (2), moderate (3), and severe (4). The total score is based on the area with the most involvement (nail bed or matrix), ranging from 0 (clear) to 4 (very severe), with higher scores indicating more severe fingernail PsO. Change from baseline in PGA-F score in participants with PGA-F \>0 from baseline at Week 16 for zasocitinib Dose A and B compared to placebo will be reported.
Change From Baseline in the SF-36 v2.0 PCS Score at Week 16 for Zasocitinib Dose B Compared to Placebo	Baseline, at Week 16	The SF-36 v2.0 is defined as a self-administered, validated questionnaire designed to measure general health-related quality of life (QoL). This 36-item questionnaire measures 8 domains over the past 4 weeks, including physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health, physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. Summary score PCS, will be calculated ranging from 0 (worst) to 100 (best). Higher scores indicate better QoL. Change from baseline in the SF-36 v2.0 PCS score at Week 16 for zasocitinib Dose B compared to placebo will be reported.
Change From Baseline in the FACIT- Fatigue Score at Week 16 for Zasocitinib Dose B Compared to Placebo	Baseline, at Week 16	The FACIT-fatigue score is defined as a 13-item PRO measure that assesses the severity of self-reported fatigue and its impact on daily functioning over the past 7 days. It includes items measuring tiredness, weakness, listlessness, lack of energy, and the effects on activities such as sleep and social interactions. Each item is rated on a 5-point scale (0 = not at all; 1 = a little bit; 2 = somewhat; 3 = quite a bit; 4 = very much). The total score ranges from 0 to 52, with higher scores indicating less fatigue. Change from baseline in the FACIT- fatigue score at Week 16 for zasocitinib Dose B compared to placebo will be reported.