Zasocitinib for Psoriatic Arthritis

Recruiting at 254 trial locations

Overseen By Norman Gaylis

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Takeda

Disqualifiers: Rheumatoid arthritis, Lupus, Fibromyalgia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

1088 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called zasocitinib for individuals with psoriatic arthritis, a condition causing joint pain and skin issues in those with psoriasis. The study aims to determine the effectiveness of zasocitinib compared to other treatments or a placebo (a pill with no active medicine). Participants will join one of several groups: taking zasocitinib, another active treatment, or a placebo initially followed by zasocitinib. Ideal participants have experienced active psoriatic arthritis symptoms for at least three months and have not previously received biologic drugs. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to the potential availability of a new treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that participants should have had an inadequate response to certain medications, which might imply that some current treatments could be continued. Please consult with the trial coordinators for specific guidance.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that zasocitinib is generally safe for humans. In past studies with individuals who have psoriatic arthritis, no new safety issues emerged, indicating the treatment did not cause unexpected side effects.

In another study involving individuals with psoriasis, about 53% to 62% of those taking zasocitinib experienced some side effects. However, 44% of those taking a placebo reported similar side effects. This suggests that many side effects could be mild and common in clinical trials. Overall, zasocitinib appears to be well-tolerated by most individuals who take it. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Zasocitinib is unique because it targets specific pathways in the immune system, potentially offering a more precise approach to treating psoriatic arthritis compared to traditional options like NSAIDs, methotrexate, or TNF inhibitors. Researchers are particularly excited about its distinct mechanism of action, which differs from most current treatments that primarily focus on broadly suppressing inflammation. Additionally, the different dosing regimens, including a potential switch from placebo to active treatment, provide flexibility in managing the condition, which could lead to more tailored and effective therapy.

What evidence suggests that this trial's treatments could be effective for psoriatic arthritis?

Research has shown that zasocitinib effectively treats psoriatic arthritis (PsA). This trial will administer different doses of zasocitinib, including Dose A and Dose B, to assess their effectiveness. One study found that 30 mg or 15 mg doses of zasocitinib improved symptoms in people with active PsA. By week 12, another study reported that 26.1% of patients with skin issues had completely clear skin with a 30 mg dose, and 32.8% had skin that was clear or almost clear. These findings suggest that zasocitinib can reduce joint pain and improve skin conditions in people with PsA. ^{1 2 3 4 5}

Who Is on the Research Team?

Study Director

Principal Investigator

Takeda

Are You a Good Fit for This Trial?

Adults with active psoriatic arthritis who haven't used biologic medicines can join this trial. They must have symptoms for at least 3 months, meet specific arthritis criteria, and show signs of active joint inflammation. Those who didn't respond well to NSAIDs or conventional drugs are eligible.

Inclusion Criteria

I didn't improve after taking NSAIDs or csDMARDs.

I have been diagnosed with Psoriatic Arthritis according to CASPAR criteria.

I have had symptoms of Psoriatic Arthritis for at least 3 months.

Exclusion Criteria

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).

I do not have conditions like rheumatoid arthritis or lupus that could affect the treatment's evaluation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either zasocitinib, active comparator, or placebo for up to 52 weeks

52 weeks

Initial Evaluation

Evaluation of primary and secondary outcomes, including ACR20, ACR50, and PASI responses at Week 16

16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Zasocitinib

Trial Overview The study tests Zasocitinib's effectiveness in treating psoriatic arthritis compared to an active comparator or placebo over a period of up to 60 weeks. Participants will be randomly assigned to receive one of the treatments.

How Is the Trial Designed?

Group I: Zasocitinib Dose B Experimental Treatment 1 Intervention

Participants will receive zasocitinib Dose B, tablets, orally, QD for up to Week 52.

Group II: Zasocitinib Dose A Experimental Treatment 1 Intervention

Participants will receive zasocitinib Dose A, tablets, orally, once daily (QD) for up to Week 52.

Group III: Placebo + Zasoctinib Experimental Treatment 2 Interventions

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.

Group IV: Active Comparator Dose C Active Control 1 Intervention

Participants will receive active comparator Dose C, capsules, orally, twice daily (BID) for up to Week 52.

Who Is Running the Clinical Trial?

Takeda

Lead Sponsor

Trials

1,255

Recruited

4,219,000+

Dr. Naoyoshi Hirota

Takeda

Chief Medical Officer since 2020

MD from University of Tokyo

Christophe Weber

Takeda

Chief Executive Officer since 2015

PhD in Molecular Biology from Université de Montpellier

Published Research Related to This Trial

Tofacitinib demonstrated rapid and sustained pain relief in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS), based on a post-hoc analysis of data from 3330 patients across seven clinical trials.

Patients treated with tofacitinib showed significant pain improvements compared to placebo as early as 3 months for RA and PsA, and at 12 weeks for AS, indicating its efficacy in managing pain associated with these inflammatory conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of tofacitinib in reducing pain in patients with rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis. Ogdie, A., de Vlam, K., McInnes, IB., et al.[2021]

Apremilast, a small molecule for treating psoriatic arthritis (PsA), shows promising efficacy and an acceptable safety profile based on recent studies, making it a viable option for patients who may not respond to conventional therapies.

Data on tofacitinib in PsA is limited, and while other small molecules like baricitinib and CF101 are being studied, their effectiveness and safety in PsA specifically require further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Small molecule therapy for managing moderate to severe psoriatic arthritis. Costa, L., Del Puente, A., Peluso, R., et al.[2018]

Janus kinase inhibitors (JAKi) are commonly used for treating immune-mediated inflammatory diseases like psoriatic arthritis, but recent studies have raised safety concerns, particularly in patients over 50 with cardiac risk factors.

This review summarizes the latest safety data for various JAKi, including tofacitinib and upadacitinib, and discusses findings from an oral surveillance study to provide context for these safety issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Janus Kinase Inhibitors: Safety in Patients With Psoriatic Arthritis. Nash, P.[2022]

Tofacitinib (5 mg twice daily) significantly improves key symptoms of active psoriatic arthritis (PsA) and related conditions after 3 months of treatment, with benefits maintained for up to 30 months in ongoing studies.

The drug has an acceptable safety profile, showing low rates of serious infections, malignancies, and other adverse events over 36 months, indicating it is a viable option for patients who have not responded to previous therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tofacitinib: A Review in Psoriatic Arthritis. Paik, J., Deeks, ED.[2020]

Tofacitinib has a consistent safety profile in psoriatic arthritis (PsA) similar to that observed in rheumatoid arthritis (RA), based on a review of 73,525 adverse event reports, with 5,394 cases related to PsA.

The analysis showed that the reporting rates for adverse events were higher for the modified release formulation compared to the immediate release, indicating potential differences in safety profiles based on the formulation used.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-Marketing Safety Surveillance of Tofacitinib over 9 Years in Patients with Psoriatic Arthritis and Rheumatoid Arthritis. Burmester, GR., Coates, LC., Cohen, SB., et al.[2023]

Upadacitinib, an oral Janus kinase inhibitor, demonstrated a safety profile similar to adalimumab in patients with active psoriatic arthritis over a treatment period of up to 3 years, with no new safety risks identified during long-term exposure.

While the overall rates of serious adverse events like malignancies and major cardiovascular events were comparable between upadacitinib and adalimumab, upadacitinib was associated with higher rates of herpes zoster and opportunistic infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Profile of Upadacitinib up to 3 Years in Psoriatic Arthritis: An Integrated Analysis of Two Pivotal Phase 3 Trials. Burmester, GR., Winthrop, K., Blanco, R., et al.[2022]

In a systematic review of 10 RCTs and 51 observational studies, infliximab was associated with a higher risk of treatment discontinuation and serious infections compared to abatacept, adalimumab, and etanercept in patients with rheumatoid arthritis (RA).

The safety profile of targeted immunomodulators generally favored abatacept, adalimumab, and etanercept over infliximab, although there was insufficient evidence to compare other TIMs or assess safety outcomes in non-RA populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Risk of Harm Associated With the Use of Targeted Immunomodulators: A Systematic Review. Desai, RJ., Thaler, KJ., Mahlknecht, P., et al.[2022]

In a study of 100 patients with spondyloarthritis in India, generic tofacitinib demonstrated significant effectiveness in reducing disease activity, as measured by the Ankylosing Spondylitis Disease Activity Score C-Reactive Protein (ASDAS-CRP), particularly in those with active peripheral arthritis.

The treatment was well-tolerated with no serious adverse events reported, although 10 patients experienced treatment failure; importantly, no baseline characteristics were found to predict this failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of generic tofacitinib in spondyloarthritis: A real-world retrospective analysis from India. Phatak, S., Khenat, A., Malandkar, M., et al.[2023]

Tofacitinib is an effective oral treatment for psoriatic arthritis (PsA), showing comparable efficacy to biologic therapies and helping manage treatment-resistant cases, including improvements in symptoms like enthesitis and dactylitis.

While tofacitinib offers significant benefits, it also carries risks such as serious infections and malignancies, making careful patient selection and assessment of individual health factors essential before starting treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tofacitinib in the management of active psoriatic arthritis: patient selection and perspectives. Ly, K., Beck, KM., Smith, MP., et al.[2023]

In a post hoc analysis of two phase 3 studies involving tofacitinib-treated patients with psoriatic arthritis, there was moderate agreement between the Disease Activity Index in Psoriatic Arthritis (DAPSA) and very low/minimal disease activity (VLDA/MDA) targets, indicating that achieving DAPSA-REM and DAPSA-LDA may not always align with VLDA and MDA outcomes.

Patients achieving DAPSA-REM or DAPSA-LDA showed significant improvements in health-related quality of life measures (HAQ-DI and SF-36 PCS scores) and reduced radiographic progression, suggesting that DAPSA is a valuable tool for assessing treatment response in psoriatic arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of disease activity index for psoriatic arthritis (DAPSA) and minimal disease activity (MDA) targets for patients with psoriatic arthritis: A post hoc analysis of data from phase 3 tofacitinib studies. Schneeberger, EE., Citera, G., Nash, P., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40615297/

Highly selective tyrosine kinase 2 inhibition with zasocitinib ... Conclusions: Here, 30 mg and 15 mg zasocitinib demonstrated efficacy across core domains in patients with active PsA with no new safety signals.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06671483

NCT06671483 | A Study of Zasocitinib in Adults With ... The main aim of the study is to know how well zasocitinib (TAK-279) works in participants with active PsA who have not previously been treated with biologic ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0003496725010416

Highly selective tyrosine kinase 2 inhibition with zasocitinib ... At week 12, 26.1% of patients with skin involvement treated with 30 mg of zasocitinib experienced complete skin clearance (PASI 100), and 32.8% achieved clear ...

4. jamanetwork.com jamanetwork.com/journals/jamadermatology/fullarticle/2822710

Tyrosine Kinase 2 Inhibition With Zasocitinib in Psoriasis Treatment-emergent adverse events were reported for 53% to 62% of zasocitinib-treated and 44% of placebo-treated patients, with no dose ...

5. psoriasis-hub.com psoriasis-hub.com/medical-information/zasocitinib-tak-279-in-psoriasis-results-from-a-phase-iib-trial

Zasocitinib (TAK-279) in psoriasis: Results from a phase IIb ... At 12 weeks, 67% of patients on 30 mg zasocitinib, 68% on 15 mg, 44% on 5 mg, and 18% on 2 mg achieved the primary endpoint of a ≥75% ...