Long-Term Safety, Tolerability, and Efficacy of Zasocitinib in Adults With Active Psoriatic Arthritis: A Phase 3 Extension Study
- Trial ID
- 2025-522586-30-00
- Protocol
- TAK-279-PsA-3003
Trial statistics
Diseases & Conditions
Objectives
The primary objective is to evaluate the long-term safety and tolerability of zasocitinib in adults with active psoriatic arthritis, which is clinically relevant for assessing sustained treatment risk over extended use. The secondary objective is to evaluate long-term efficacy of zasocitinib in subjects with active psoriatic arthritis.
Participants
The trial population comprised 544 adult subjects with active psoriatic arthritis, including both female and male participants. The age range was adult, with inclusion of subjects aged 65 years or older. Participants were selected from individuals who had completed the 52-week treatment period in one of the parent studies and had not met criteria for permanent discontinuation of trial intervention. The population was required to be able to understand and comply with study procedures, and all subjects provided written informed consent. Relevant lifestyle considerations included smoking or chewing tobacco history, which required investigator benefit-risk assessment for continued inclusion. Concomitant treatment conditions also applied, including limits on conventional synthetic disease-modifying antirheumatic drugs, stable doses of certain concurrent therapies, and contraceptive requirements for individuals with potential for pregnancy.
Plans and Procedures
This is a Phase 3, multicenter, long-term extension study in adult subjects with active psoriatic arthritis. The trial is designed to evaluate the long-term safety, tolerability, and efficacy of oral zasocitinib and includes comparator placebo treatment. The overall study duration is planned from July 2026 to December 2029. Eligible subjects are those who completed the 52-week treatment period in a parent study and who are considered by the investigator to benefit from continued or newly initiated therapy. Study participation begins with a screening visit, during which eligibility, informed consent, prior study completion, and ongoing treatment requirements are confirmed. This is followed by treatment and follow-up assessments during the study period, with evaluations of adverse events, serious adverse events, adverse events of special interest, vital signs, laboratory parameters, and efficacy outcomes at prespecified time points, including Weeks 24, 48, and 104. An end-of-study visit is performed at study completion. Expected participant involvement extends through the long-term extension period, up to approximately 104 weeks of efficacy assessment within the overall study timeframe. Early termination may occur if permanent discontinuation criteria are met, if the subject no longer meets eligibility or continuation requirements, or if the investigator determines that continued participation is not justified based on benefit-risk considerations or protocol requirements.
Treatment
Zasocitinib was administered as a film-coated tablet by oral route. The study included two dose presentations, designated as Dose A and Dose B, although the specific milligram strength and dosing frequency were not provided in the source data. Administration was part of a long-term extension setting in adult subjects with active psoriatic arthritis, and treatment exposure was intended to support evaluation of long-term safety, tolerability, and efficacy.
Matching placebo tablets for TAK-279 Dose A and matching placebo tablets for TAK-279 Dose B were used as non-experimental treatments. These placebo products were formulated to match the corresponding active study medication presentations. No route, dose, or pharmaceutical form details beyond the matching placebo designation were provided in the source data.
Efficacy
Efficacy will be assessed by the proportion of subjects achieving American College of Rheumatology (ACR)20 response, ACR50 response, ACR70 response, Minimal disease activity (MDA), and Psoriasis Area and Severity Index (PASI)75. ACR20, ACR50, ACR70, and MDA will be assessed at Weeks 24, 48, and 104. PASI75 will be assessed in subjects with a baseline body surface area of at least 3% at Weeks 24, 48, and 104.
Inclusion and Exclusion Criteria
Inclusion Criteria
- The subject is willing and able to understand and fully comply with study procedures and requirements (including digital tools and applications, as necessary), in the opinion of the investigator.
- For subjects who elect to use hormonal contraception as a form of highly effective contraception, the investigator must perform a benefit-risk assessment to justify the subject’s continued inclusion in the LTE study.
- The subject has provided written informed consent (that is, in writing, documented via a signed and dated informed consent form [ICF]) and any required privacy authorization before the initiation of any study or eligibility-related procedures.
- The subject has completed the 52-week treatment period in one of the parent studies (TAK-279-PsA-3001 or TAK-279-PsA-3002) independent of treatment assignment, and without meeting the criteria for permanent discontinuation of trial intervention defined in the parent studies.
- The subject must be deemed by the investigator to benefit from continued or newly initiated (that is, for subjects randomized to comparator in parent study TAK-279-PsA-3001) zasocitinib therapy.
- The subject continues to meet the following birth control requirements from the parent studies: a) An individual with potential for pregnancy, who is now surgically sterile; OR b) A subject of nonchildbearing potential. Note: postmenopausal status from the parent study will be carried into the long-term extension (LTE) study; OR c) If sexually active with a nonsterilized individual who produces sperm, an individual with potential for pregnancy who agrees to use a highly effective method of contraception from the signing of the ICF for the LTE study throughout the duration of the study and for at least 10 days after the last dose of the trial intervention.
- If the subject is taking concomitant conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), they must be on ≤2 csDMARDs. The maximum allowed doses for csDMARDs are as follows: methotrexate (MTX; ≤25 mg/week; ≤16 mg/week at Japan sites), sulfasalazine (SSZ; ≤3000 mg/day), leflunomide (LEF; ≤20 mg/day), and hydroxychloroquine (HCQ; ≤400 mg/day). The combination of MTX and LEF is prohibited.
- If the subject is receiving other concurrent treatments, they must be at the following stable doses: oral corticosteroids (≤10 mg/day prednisone or equivalent), nonsteroidal anti-inflammatory drugs (NSAIDs) or cyclooxygenase-2 (COX-2) inhibitors or paracetamol/acetaminophen or low-potency opiates (only tramadol up to 300 mg/day or combination of acetaminophen and codeine or hydrocodone are permitted).
- subjects aged 65 years or older, the investigator must perform a benefit-risk assessment to justify the subject’s continued inclusion in the LTE study.
- For subjects currently smoking/chewing tobacco or with a history of long-term smoking (≥20 pack years)/chewing tobacco use, the investigator must perform a benefit-risk assessment to justify the subject’s continued inclusion in the LTE study.
Exclusion Criteria
- Any subject who is deemed by the investigator to be not benefiting from the trial intervention based upon lack of improvement or worsening of their symptoms in the respective parent study.
- Any subject who met the criteria for permanent discontinuation of trial intervention defined in the parent studies (TAK-279-PsA-3001 or TAK-279-PsA-3002).
- The subject has developed any disease(s) that might confound the evaluations of benefit of zasocitinib therapy since enrollment in the respective parent study, including but not limited to rheumatoid arthritis, axial spondyloarthritis (this does not include a primary diagnosis of PsA with spondylitis), systemic lupus erythematosus, Lyme disease, gout, or fibromyalgia (prior history of reactive arthritis or axial spondyloarthritis, including ankylosing spondylitis and nonradiographic axial spondyloarthritis, is permitted if there is documentation of change in diagnosis to PsA or additional diagnosis of PsA is made. Prior history of fibromyalgia is permitted if there is documentation of change in diagnosis to PsA or documentation that the diagnosis of fibromyalgia was made incorrectly).
- The subject has developed evidence of non-plaque psoriasis (erythrodermic, pustular, predominantly guttate psoriasis, predominantly inverse, or drug-induced psoriasis) since enrollment in the respective parent study.
- The subject is not willing to minimize natural and artificial sunlight exposure during the study period. Use of sunscreen products and protective apparel is recommended when sun exposure cannot be avoided.
- Tuberculosis (TB): The subject has newly developed signs or symptoms of active TB (including but not limited to chronic fever, chronic productive cough, night sweats, or weight loss) as judged by the investigator.
- Nonherpetic viral diseases (laboratory assessments at the most recent visit from the respective parent study [that is, the Week 44 visit]): a) The subject has developed the presence of hepatitis C virus (HCV) antibody and a positive confirmatory test result for HCV RNA (nucleic acid test or polymerase chain reaction [PCR]). b) The subject has developed the presence of positive hepatitis B virus surface antigen (HBsAg+), indeterminate hepatitis B surface antigen, positive anti-hepatitis B core antibody (HBcAb+), or elevated hepatitis B virus (HBV) DNA PCR at any time during the parent study. Note: In China and Japan, HBV DNA testing will continue to be performed for subjects with positive anti-hepatitis B surface antibody (HBsAb+) and/or positive anti-hepatitis B core antibody (HBcAb+) at the parent study screening visit. HBV DNA testing must remain non-detectable on periodic monitoring throughout the LTE study (Table 1.c). c) The subject has a positive result for HIV by serology, regardless of viral load. d) Additional monitoring guidelines for nonherpetic viral diseases may be applicable per local guidelines.
- The subject developed any of the following during the respective parent study: a) Serious herpetic infection including any episode of disseminated disease, multidermatomal herpes zoster, herpes encephalitis, ophthalmic herpes, or multiple episodes of herpes zoster. b) An opportunistic infection (for example, Pneumocystis jirovecii pneumonia, histoplasmosis, coccidiomycosis). c) Two occurrences of serious infection (infections meeting the definition of a serious adverse event). d) A single serious infection that, in the opinion of the investigator, precludes participation in the study.
- The subject developed any new clinically significant medical condition, evidence of an unstable clinical condition (for example, cardiovascular, renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, or immunologic), or vital signs/physical/laboratory/electrocardiogram (ECG) abnormality during the respective parent study that would, in the opinion of the investigator, put the subject at undue risk or interfere with interpretation of study results.
- The subject experienced a cardiovascular event (including but not limited to acute coronary syndrome, cerebrovascular event, myocardial infarction, deep vein thrombosis, or pulmonary embolism) or a cardiac hospitalization (coronary stenting or aortocoronary bypass surgery) during the respective parent study. If the subject experienced any other cardiovascular events (including but not limited to new atrial fibrillation or atrial fibrillation with rapid ventricular response or other dysrhythmia, pulmonary embolism, or deep venous thrombosis) during the respective parent study in the European Union (EU)/European Economic Area (EEA), a subject may enroll if under the condition that the investigator documents an updated favorable risk-benefit assessment to justify the subject’s inclusion in the study, taking into account any changes since initial assessment.
- The subject has a new diagnosis of cancer or lymphoproliferative disease. An exception is made for localized nonmelanoma skin cancer (NMSC) or carcinoma in situ of the cervix. Additionally, if the NMSC or carcinoma in situ of the cervix was diagnosed during the respective parent study, the investigator must continue to ascertain that there are no suitable treatment alternatives available for the subject, and that the subject has received appropriate treatment per local guideline, and that participation in the LTE study is appropriate in the investigator’s opinion.
- The subject has a major surgery planned during the study.
- The subject has developed significant/uncontrolled psychiatric illness during the respective parent study, in the opinion of the investigator.
- Per medical judgement, the subject has developed a history of clinically significant drug or alcohol abuse during the respective parent study, excluding stable medical or legal recreational marijuana (cannabis)/tetrahydrocannabinol/cannabidiol use.
- The subject has received a prohibited PsA or PsO treatment during the respective parent study, whether or not that treatment was documented as a concomitant medication, and is expected to continue that treatment.
- The subject has received any other prohibited concomitant medications, including but not limited to systemic strong or moderate cytochrome P450 3A4 (CYP3A4) inhibitors or systemic strong or moderate CYP3A4 inducers, any live-attenuated vaccine and marketed or investigational agents, during the respective parent study, whether or not that treatment was documented as a concomitant medication, and is expected to continue that treatment.
- The subject has any of the following laboratory values at the most recent visit from the respective parent study in which they are enrolled (that is, the Week 44 visit): a) Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) values ˃3 times the upper limit of the normal range (ULN). b) Total bilirubin (TBili) unconjugated and/or conjugated ˃1.5 times the ULN. c) Hemoglobin (Hgb) <9.0 g/dL (<90.0 g/L). d) Absolute white blood cell count <3.0 × 109/L (<3000/mm3). e) Absolute neutrophil count of <1.0 × 109/L (<1000/mm3). f) Absolute lymphocyte count of <0.5 × 109/L (<500/mm3). g) Platelet count <100 × 109/L (<100,000/mm3). h) Estimated creatinine clearance <45 mL/min based on the Cockcroft-Gault calculation. i) Creatine phosphokinase (CPK) >2.5 times the ULN. CPK may be repeated once; if repeat value is ≤2.5 times the ULN, subject remains eligible. Investigators should assess the subject for modulating factors including concomitant medications or vigorous exercise that may affect CPK levels. j) Subject has any other significant laboratory abnormalities that, in the opinion of the investigator, might place the subject at unacceptable risk for participation in this study.
- The subject does not tolerate venipuncture or inability to be venipunctured.
- The subject has developed a history of significant drug allergy (such as anaphylaxis).
- The subject has developed a known or suspected allergy to zasocitinib or any of its components.
- The subject has a positive pregnancy test result or plans to become pregnant during the study period, or subject is pregnant or lactating/nursing.
- Subjects who plan to donate blood during the course of the study.
- The subject is compulsorily detained for treatment of either a psychiatric or physical (for example, infectious disease) illness, or is committed to an institution (for example, prison) by virtue of an order issued either by judicial or administrative authorities.
- The subject is a study site employee, an immediate family member (for example, spouse, parent, child, sibling), or is in a dependent relationship with study site employee who is involved in the conduct of this study or may consent under duress.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Not Yet Recruiting | 22 Jul 2026 | 12 |
 Bulgaria | Not Yet Recruiting | 22 Jul 2026 | 61 |
 Croatia | Not Yet Recruiting | 22 Jul 2026 | 19 |
 Czechia | Recruiting | 22 Jul 2026 | 48 |
 Estonia | Recruiting | 22 Jul 2026 | 24 |
 France | Not Yet Recruiting | 22 Jul 2026 | 8 |
 Germany | Recruiting | 22 Jul 2026 | 56 |
 Hungary | Not Yet Recruiting | 22 Jul 2026 | 28 |
 Italy | Not Yet Recruiting | 22 Jul 2026 | 21 |
 Latvia | Recruiting | 22 Jul 2026 | 6 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Matching Placebo for TAK-279 Dose A | Placebo | N/A | — | — | — | N/A |
Matching Placebo for TAK-279 Dose B | Placebo | N/A | — | — | — | N/A |
ZASOCITINIB | Test | FILM-COATED TABLET | ORAL | 0 | 104 | PRD11872724 |
ZASOCITINIB | Test | FILM-COATED TABLET | ORAL | 0 | 104 | PRD10260454 |