A Study of Zasocitinib in Adults With Psoriatic Arthritis (LATITUDE PsA NeXt)

1. The participant is willing and able to understand and fully comply with trial procedures and requirements (including digital tools and applications, as necessary), in the opinion of the investigator.
2. The participant 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 trial or eligibility-related procedures.
3. The participant is aged 18 years or older (or the legal age of consent in the jurisdiction in which the trial is taking place) at the time of signing the ICF.

4. The participant meets the following birth control requirements:

   1. An individual with potential for pregnancy, who is now surgically sterile; OR
   2. A participant of nonchildbearing potential; OR
   3. 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 throughout the duration of the trial and for at least 10 days after the last dose of the trial intervention.

   The use of contraception is not required for participants assigned male sex at birth during the duration of the trial.

5. The participant has:

   1. A diagnosis of PsA. AND
   2. Signs and symptoms of PsA for at least 3 months prior to screening.
6. The participant meets the classification criteria for psoriatic arthritis (CASPAR) criteria.
7. The participant has active arthritis as shown by a minimum of >=3 tender joints in TJC68 and >=3 swollen joints in SJC66 at screening and baseline (Day 1) visit.
8. The participant has >=2 joints with erosions on radiographs of the hands and/or feet as determined by central read.
9. 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 at screening visit.
10. hs-CRP >=3 milligram per liter (mg/L) (eligibility assessment at screening only).

11. The participant has active PsA despite previous treatment with at least one of the following:

    1. Nonsteroidal anti-inflammatory drug (NSAID) therapy after a minimum of 4 weeks of scheduled therapy, OR
    2. Conventional synthetic disease-modifying antirheumatic drug (csDMARD) therapy (methotrexate [MTX], leflunomide [LEF], sulfasalazine [SSZ], or hydroxychloroquine [HCQ]) after a minimum of 12 weeks of therapy, or intolerance.

12. If the participant is on concomitant csDMARDs at trial entry, the participant must be on less than or equal to (\<=) 2 csDMARDs for >=12 weeks prior to the Day 1 visit. The doses must be stable for >=4 weeks prior to the Day 1 visit as follows: MTX (\<=25 mg/week; \<=16 mg/week for Japan sites), SSZ (\<=3000 mg/day), LEF (\<=20 mg/day), and HCQ (\<=400 mg/day). The combination of MTX and LEF is not allowed.

    Participants who need to discontinue csDMARDs prior to the Day 1 visit to comply with this inclusion criterion must follow the procedure specified below or at least 5 times the mean terminal elimination half-life of a drug:

    • >=8 weeks for LEF if no elimination procedure was followed, or adhere to an elimination procedure (that is, 11 days with cholestyramine, or 30 days washout with activated charcoal or per local label).
    • >=4 weeks for all others.
13. If the participant is receiving other concurrent treatments, they must be at the following stable doses: oral corticosteroids (\<=10 mg/day of prednisone equivalent), NSAIDs or paracetamol/acetaminophen or low-potency opiates (only tramadol up to 300 mg/day or combination of acetaminophen and codeine or hydrocodone are permitted) at stable dose for >=1 week prior to the Day 1 visit. Initiation of these treatments between screening and Day 1 is not permitted.

Exclusion Criteria:

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 (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 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.
2. The participant has a concomitant comorbid skin condition that, in the opinion of the investigator, would interfere with the trial assessments, such as evidence of non-plaque PsO (erythrodermic, pustular, predominately guttate PsO, inverse, or drug-induced PsO).

3. The participant has received any of the following treatments:

   1. A biologic that is used for treatment of PsA or PsO (for example, TNFi [eg. etanercept, adalimumab, infliximab, certolizumab pegol, golimumab]; IL-12/23, IL-17, or IL-23 inhibitors [eg, ustekinumab, secukinumab, bimekizumab, brodalumab, ixekizumab, guselkumab, tildrakizumab, icotrokinra, risankizumab]).
   2. Has received any TYK2 inhibitors (for example, zasocitinib, deucravacitinib, brepocitinib, envudeucinitib, VTX958, or GLPG3367) or oral JAK inhibitor (for example, upadacitinib, baricitinib, or tofacitinib).
   3. Rituximab or other immune cell-depleting agents within 6 months prior to Day 1.
   4. Agents that modulate integrin pathways to impact lymphocyte trafficking (for example, natalizumab) or agents that modulate B cells or T cells (for example, alemtuzumab, visilizumab, or abatacept) within 3 months prior to Day 1.
4. The participant is receiving current treatment with csDMARDs other than MTX, SSZ, LEF, and HCQ.
5. The participant has used medicated shampoo and/or body wash that includes but is not limited to salicylic acid, corticosteroids, coal tar, or vitamin D3 analogues within 2 weeks prior to Day 1.
6. The participant has used any topical medication that could affect PsA or PsO presentation, including but not limited to: corticosteroids, salicylic acid, roflumilast, urea, alpha- or beta-hydroxy acids, anthralin, retinoids, vitamin D analogues (such as calcipotriol), tazarotene, methoxsalen, trimethylpsoralen, pimecrolimus, tacrolimus, tapinarof, or tar within 2 weeks prior to Day 1; with the exception of low-potency topical steroids (World Health Organization [WHO] Class VI and VII) on the palms, soles, face, intertriginous areas, and/or genitals and/or bland emollients on all body regions.

7. The participant has used any other nonbiologic treatment that could affect PsA or PsO presentation (including intravenous, intramuscular, intra-articular, intrathecal, epidural, or intralesional corticosteroids; oral retinoids; immunosuppressive/immunomodulating medication; 6-thioguanidine; mercaptopurine; mycophenolate mofetil; hydroxyurea; cyclosporine; roflumilast; psoralens; fumaric acid derivatives) within 4 weeks prior to Day 1, or 5 half-lives, whichever is longer.

   Note: Intranasal corticosteroids, inhaled corticosteroids, and eye and ear drops containing corticosteroids are permitted.

8. The participant has received phototherapy (including ultraviolet [UV] B, psoralen and UV A, tanning beds, therapeutic sunbathing) or excimer laser to treat skin conditions within 4 weeks prior to Day 1.
9. The participant has used botanical preparations (for example, herbal or homeopathic supplements or traditional medicines, including traditional Chinese medicines derived from plants, minerals, or animals) intended to treat PsA, PsO, or other immunological diseases within 4 weeks prior to Day 1.
10. The participant has a history of active infection or febrile illness with or without symptoms (including but not limited to coryza and pharyngitis) within 10 days prior to Day 1, as assessed by the investigator.

11. Tuberculosis (TB):

    1. The participant has a history of active TB infection, regardless of treatment status.
    2. The participant has 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.

    3. The participant has evidence of a latent TB infection as evidenced by a positive QuantiFERON (QFT)-TB Gold result OR 2 indeterminate QFT interferon-gamma release assay (IGRA) results. The participant may remain eligible if: (1) there are no signs/symptoms of active TB and documentation of no prior history of active TB and (2) participant can provide documentation of prior completed treatment for latent tuberculosis infection (LTBI) (appropriate in duration and type per current local country guidelines) OR is willing to initiate LTBI prophylaxis (appropriate in duration and type per current local guidelines) a minimum of 2 weeks prior to Day 1.

       Note: TB prophylaxis regimens should be administered according to local guidelines; however, because of potential interactions with zasocitinib, rifampin should not be used.

       TB testing should be conducted using QFT submitted to the central laboratory unless alternate or additional tests are required per local guidelines.

    4. The participant has had any chest imaging trial during or 6 months prior to screening, suggesting evidence of currently active TB or a history of active TB. A chest x-ray is required for all participants regardless of QFT-TB Gold results unless the participant has had normal chest imaging in the 6 months prior to Day 1.

12. Herpes infections:

    1. The participant has active herpes virus infection, including herpes zoster or herpes simplex 1 and 2 (demonstrated on physical examination and/or medical history), at screening or Day 1.
    2. The participant has a history of serious herpetic infection that includes any episode of disseminated disease, multidermatomal herpes zoster, herpes encephalitis, ophthalmic herpes, or recurrent herpes zoster (defined as 2 episodes within 2 years).

13. Nonherpetic viral diseases:

    1. The participant has presence of hepatitis C virus (HCV) antibody and a positive confirmatory test result for HCV ribonucleic acid (RNA) (nucleic acid test or polymerase chain reaction).
    2. The participant tests positive for hepatitis B virus (HBV) infection.
    3. The participant has a history of positive results for human immunodeficiency virus (HIV) by serology, regardless of viral load.
    4. Additional monitoring guidelines for nonherpetic viral diseases may be applicable per local guidelines.

14. Other infectious diseases:

    1. The participant has a history of symptoms suggestive of systemic or invasive infection within 30 days prior to Day 1.
    2. The participant has a history of bacterial, viral, or fungal infection that required hospitalization, treatment with intravenous antimicrobial therapy within 8 weeks prior to Day 1, or oral antimicrobial therapy within 30 days prior to Day 1.
    3. The participant has a history of chronic or recurrent bacterial disease, including but not limited to chronic pyelonephritis or cystitis, chronic bronchitis/pneumonitis, osteomyelitis, or chronic skin ulcerations/infections or fungal infections (except superficial onychomycosis).
    4. The participant has a history of an infected joint prosthesis or has received antibiotics for a suspected infection of a joint prosthesis, unless that prosthesis has been removed or replaced at least 60 days prior to Day 1.
    5. The participant has a history of opportunistic infections (for example, Pneumocystis jirovecii pneumonia, histoplasmosis, coccidiomycosis).
    6. The participant had a bacterial infection within 60 days prior to Day 1 for which they did not receive treatment.
15. The participant has any 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 that would, in the opinion of the investigator, put the participant at undue risk or interfere with interpretation of trial results.
16. The participant has a history of known or suspected condition/illness that is consistent with compromised immunity, including but not limited to any identified congenital or acquired immunodeficiency; splenectomy.
17. The participant had a major surgery within 60 days prior to Day 1 or has a major surgery planned during the trial.
18. The participant has moderate or severe hepatic impairment per Child-Pugh classification (Class B and C).
19. The participant has uncontrolled hypertension characterized by systolic blood pressure greater than (>)160 millimiters of mercury (mm Hg) or diastolic blood pressure >100 mm Hg at screening or baseline, confirmed by 2 repeat assessments at that visit.
20. The participant has a history of Class III or IV congestive heart failure as defined by New York Heart Association criteria.
21. The participant has a history of cancer or lymphoproliferative disease within 5 years of screening. Participants with a lifetime history of treated nonmetastatic cutaneous squamous cell or basal cell carcinoma and/or localized carcinoma in situ of the cervix may remain eligible under the condition that the investigator performs a benefit-risk assessment.
22. For participants with asthma, chronic obstructive pulmonary disease, or other pulmonary illnesses, the participant has been hospitalized within the 3 months prior to Day 1, has ever required intubation for treatment, currently requires oral corticosteroids treatment, or has required more than 1 course of oral corticosteroids within 6 months prior to Day 1.

23. The participant has any of the following cardiovascular disease history:

    1. A new diagnosis of atrial fibrillation or an episode of atrial fibrillation with rapid ventricular response or other dysrhythmia, non acute cardiac hospitalization (for example, pacemaker implantation), pulmonary embolism, or deep venous thrombosis within the past 6 months prior to Day 1.
    2. Cerebrovascular event, myocardial infarction, coronary stenting, or aorto-coronary bypass surgery within the last 6 months prior to Day 1. A participant may enroll if it has been at least 6 months since the occurrence of any such event and the participant is considered clinically stable by the investigator; in the European Union/ European Economic Area (EU/EEA), the investigators should perform a benefit-risk assessment.
24. The participant has ECG abnormalities that are considered clinically significant and would pose an unacceptable risk to the participant if they participated in the trial, in the opinion of the investigator.
25. The participant has any lifetime history of suicide attempts, suicidal behavior, or active suicidal ideation with the intent and plan based on medical history, a YES response Columbia-Suicide Severity Rating Scale (C-SSRS) Question 5 or to any C-SSRS suicidal behavior questions; or is clinically deemed a suicide risk by the investigator.
26. Per medical judgement, the participant has a known history of clinically significant drug or alcohol abuse, excluding stable medical or legal recreational marijuana/tetrahydrocannabinol/cannabidiol use, within 12 months of Day 1.
27. The participant has received lithium or intramuscular gold therapy within 4 weeks prior to Day 1.
28. The participant is currently being treated with systemic strong or moderate CYP3A4 inhibitors (such as itraconazole or clarithromycin) or systemic strong or moderate CYP3A4 inducers (such as rifampin, carbamazepine, or phenytoin), or has received systemic strong or moderate CYP3A4 inhibitors or systemic strong or moderate CYP3A4 inducers within 4 weeks or 5 half-lives of the inducer or inhibitor, whichever is longer, prior to Day 1, or is expected to require treatment with systemic strong or moderate CYP3A4 inducers or inhibitors during the trial period.

29. The participant has received any live-attenuated vaccine within 60 days prior to Day 1 orplans to receive a live-attenuated vaccine during the trial and up to 4 weeks after the last trial intervention administration.

    Note: Non-live-attenuated vaccines or boosters for COVID-19 (for example, RNA-based vaccines, inactivated adenovirus-based vaccines, influenza vaccines, protein-based vaccines) are permitted during the trial.

30. The participant received a marketed or investigational immunosuppressive biological agent, other than those for the treatment of PsA or PsO, that could affect PsA or PsO within 12 weeks or 5 half-lives (whichever is longer) prior to Day 1.
31. The participant is currently enrolled in a clinical trial or anticipates enrollment in a clinical trial during the course of the trial.

32. The participant has any of the following laboratory values at the screening visit:

    1. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) values ˃3 × upper limit of normal (ULN).
    2. TBili (unconjugated and/or conjugated) ˃1.5 × ULN.
    3. Hemoglobin \<9.0 g/dL (\<90.0 g/L).
    4. Absolute white blood cell count \<3.0 × 10\^9/L (\<3000/mm\^3).
    5. Absolute neutrophil count of \<1.0 × 10\^9/L (\<1000/mm\^3).
    6. Absolute lymphocyte count of \<0.5 × 10\^9/L (\<500/mm\^3).
    7. Platelet count \<100 × 109/L (\<100,000/mm\^3).
    8. eGFR \< 30 mL/min/1.73m\^3.

    9. Creatine phosphokinase (CPK) > 2.5 x ULN. CPK may be repeated once; if repeat value is CTCAE Grade 1 or lower (\<=2.5 x ULN) and no higher than the initial value, the participant remains eligible.

       Investigators should assess the participant for modulating factors, including concomitant medications or vigorous exercise, that may affect CPK level.

    10. The participant has any other significant laboratory abnormalities that, in the opinion of the investigator, might place the participant at unacceptable risk for participation in this trial. Retesting of abnormal clinical laboratory tests (hematology, chemistry, urinalysis, follicle-stimulating hormone [FSH]) that may lead to exclusion will be allowed once with the exception of AST and ALT. Retesting can occur at an unscheduled visit during the specified screening phase.
33. The participant does not tolerate venipuncture or inability to be venipunctured.
34. The participant has a history of significant drug allergy (such as anaphylaxis).
35. The participant has a known or suspected allergy, hypersensitivity or intolerance to zasocitinib or any of its components.
36. The participant has a positive pregnancy test result or plans to become pregnant during the trial period, or the participant is pregnant or lactating/nursing.
37. The participant has given greater than 500 mL of blood or plasma within 30 days of screening (during a clinical trial or at a blood bank donation) or plans to donate blood during the course of the trial.
38. The participant 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.
39. The participant is a trial site employee, an immediate family member (for example, spouse, parent, child, sibling), or is in a dependent relationship with trial site employee who is involved in the conduct of the trial or may consent under duress.