Zasocitinib for Psoriatic Arthritis

Recruiting at 197 trial locations

Overseen By Takeda Contact

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

Trial Summary

What is the purpose of this trial?

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 who have not previously been treated with biologic disease-modifying antirheumatic drugs. The participants will be treated with either zasocitinib, active comparator, or placebo. Participants will be in the study for up to 60 weeks.

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.

What data supports the effectiveness of the drug Zasocitinib for treating psoriatic arthritis?

Tofacitinib, a similar drug to Zasocitinib, has been shown to effectively manage psoriatic arthritis by improving symptoms like joint pain and skin issues, and it works well for patients who haven't responded to other treatments. This suggests that Zasocitinib might also be effective for psoriatic arthritis. ^{1 2 3 4 5}

What safety data exists for Zasocitinib in humans?

There is no specific safety data available for Zasocitinib, but similar drugs like tofacitinib, which are also Janus kinase inhibitors, have been studied for safety in conditions like psoriatic arthritis and rheumatoid arthritis. These studies have shown some safety concerns, especially in older patients with additional heart risk factors, but generally indicate an acceptable safety profile for these types of medications. ^{6 7 8 9 10}

Research Team

Study Director

Principal Investigator

Takeda

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of generic tofacitinib in spondyloarthritis: A real-world retrospective analysis from India. [2023]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Tofacitinib in the management of active psoriatic arthritis: patient selection and perspectives. [2023]

3. United States 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. [2023]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Tofacitinib: A Review in Psoriatic Arthritis. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Efficacy of tofacitinib in reducing pain in patients with rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Post-Marketing Safety Surveillance of Tofacitinib over 9 Years in Patients with Psoriatic Arthritis and Rheumatoid Arthritis. [2023]

7. Canada pubmed.ncbi.nlm.nih.gov

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

8. England pubmed.ncbi.nlm.nih.gov

Small molecule therapy for managing moderate to severe psoriatic arthritis. [2018]

9. England 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. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Comparative Risk of Harm Associated With the Use of Targeted Immunomodulators: A Systematic Review. [2022]