A Phase 3, Long-Term Extension Study to Evaluate the Long-Term Safety, Tolerability, and Efficacy of Zasocitinib in Subjects with Active Psoriatic Arthritis With or Without Prior Biologic DMARD Exposure

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Takeda Development Center Americas Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Decision date (initial)

2026-05-18

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Takeda Development Center Americas, Inc.

External identifiers

EU CT number

2025-522586-30-00

ClinicalTrials.gov

NCT07286058

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate the long-term safety and tolerability of zasocitinib in adult subjects with active psoriatic arthritis.

Secondary objectives 1

1. To evaluate the long-term efficacy of zasocitinib in subjects with active psoriatic arthritis.

Conditions and MedDRA coding

Psoriatic Arthritis

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. 1. 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.
2. 10. 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.
3. 2. 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.
4. 3. 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.
5. 4. 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.
6. 5. 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.
7. 6. 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.
8. 7. 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).
9. 8. 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.
10. 9. 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 24

1. 1. 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.
2. 2. 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).
3. 3. 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).
4. 4. 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.
5. 5. 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.
6. 6. 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.
7. 7. 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.
8. 8. 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.
9. 9. 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.
10. 10. 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.
11. 11. 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.
12. 12. The subject has a major surgery planned during the study.
13. 13. The subject has developed significant/uncontrolled psychiatric illness during the respective parent study, in the opinion of the investigator.
14. 14. 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.
15. 15. 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.
16. 16. 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.
17. 17. 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.
18. 18. The subject does not tolerate venipuncture or inability to be venipunctured.
19. 19. The subject has developed a history of significant drug allergy (such as anaphylaxis).
20. 20. The subject has developed a known or suspected allergy to zasocitinib or any of its components.
21. 21. The subject has a positive pregnancy test result or plans to become pregnant during the study period, or subject is pregnant or lactating/nursing.
22. 22. Subjects who plan to donate blood during the course of the study.
23. 23. 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.
24. 24. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Incidence of treatment-emergent adverse events, Incidence of serious adverse events, Incidence of adverse events of special interest, Changes in vital signs and clinical laboratory parameters.

Secondary endpoints 5

1. American College of Rheumatology (ACR)20 response: Assessed as proportion of subjects achieving ACR20 at Weeks 24, 48, and 104.
2. ACR50 response: Assessed as proportion of subjects achieving ACR50 at Weeks 24, 48, and 104.
3. ACR70 response: Assessed as proportion of subjects achieving ACR70 at Weeks 24, 48, and 104.
4. Minimal disease activity (MDA): Assessed as proportion of subjects achieving MDA status at Weeks 24, 48, and 104.
5. Psoriasis Area and Severity Index (PASI)75 (in subjects with a baseline ≥3% body surface area): Assessed as proportion of subjects achieving ≥75% improvement from baseline in PASI score at Weeks 24, 48, and 104.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Takeda Development Center Americas Inc.

Sponsor organisation

Takeda Development Center Americas Inc.

Address

500 Kendall Street

City

Cambridge

Postcode

02142-1108

Country

United States

Scientific contact point

Organisation

Takeda Development Center Americas Inc.

Contact name

Takeda

Public contact point

Organisation

Takeda Development Center Americas Inc.

Contact name

Takeda

Third parties 9

Locations

13 EU/EEA countries · 116 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 116 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications