TAK-279 for Ulcerative Colitis

Recruiting at 221 trial locations

Overseen By Takeda Contact

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Takeda

Disqualifiers: Crohn's disease, Ileostomy, J-pouch, others

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

Compensation: Varies

Number of Visits: Unknown

207 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called TAK-279, a small molecule TYK2 inhibitor, for individuals with ulcerative colitis (UC), a condition causing inflammation and ulcers in the colon. The goal is to determine if TAK-279 can reduce symptoms and inflammation more effectively than a placebo, which contains no active medication. Participants will take either TAK-279 or a placebo for the first 12 weeks, after which everyone will receive TAK-279 for the remainder of the year-long study. The trial seeks individuals with moderately to severely active UC who have not found success with other treatments. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop your current medications. It's best to discuss this with the study team or your doctor.

Is there any evidence suggesting that TAK-279 is likely to be safe for humans?

Research shows that TAK-279, also known as zasocitinib, has been explored as a possible treatment for various immune-related diseases. In earlier studies, patients taking TAK-279 experienced significant improvements in their conditions compared to those who took a placebo. These studies also examined the drug's safety and tolerability.

Evidence suggests that TAK-279 has been well-tolerated by patients. In a recent study, few adverse events occurred, indicating that most patients did not experience severe side effects. This suggests that TAK-279 might be a safe option for treating conditions like ulcerative colitis.

Additionally, TAK-279 has undergone long-term safety studies to ensure it remains safe over time. While all medications can have side effects, the available data suggests that TAK-279 generally has a favorable safety profile. This means it could be a good option for those considering joining a clinical trial for ulcerative colitis. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for ulcerative colitis?

Unlike the standard treatments for ulcerative colitis, which often involve anti-inflammatory drugs, immunosuppressants, or biologics like TNF inhibitors, TAK-279 offers a novel approach. Researchers are excited about TAK-279 because it utilizes a new mechanism, targeting specific pathways involved in the disease process, potentially leading to more effective symptom control. Additionally, TAK-279 is administered orally, making it a convenient option compared to some current treatments that require injections or infusions. This could enhance patient adherence and overall quality of life.

What evidence suggests that TAK-279 might be an effective treatment for ulcerative colitis?

Research has shown that TAK-279, also known as zasocitinib, is a promising treatment for immune-related diseases. TAK-279 blocks TYK2, a protein involved in inflammation. In earlier studies, TAK-279 effectively treated psoriasis, with up to 46% of patients achieving clear skin, while none in the placebo group did. Although ulcerative colitis differs from psoriasis, both involve immune system issues. This trial will evaluate TAK-279 at different dosages to determine its effectiveness in reducing bowel inflammation and symptoms in ulcerative colitis. Early results suggest TAK-279 might help in a similar way. ^{1 2 3 5 6}

Who Is on the Research Team?

Study Director

Principal Investigator

Takeda

Are You a Good Fit for This Trial?

This trial is for adults aged 18-75 with moderately to severely active ulcerative colitis (UC) who haven't responded well to other UC treatments. They must have been diagnosed at least 30 days prior and meet specific medical criteria for disease activity. Participants are also required to follow contraception guidelines.

Inclusion Criteria

Participants must meet the contraception recommendations

I have tried at least one UC treatment without success or could not tolerate it.

My ulcerative colitis is moderate to severe, confirmed by tests.

Exclusion Criteria

I have a current ileostomy or colostomy.

I have UC complications that might need surgery during the study.

I have tried and not responded to 3 different types of advanced cancer treatments.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Treatment

Participants receive a 12-week double-blinded induction treatment with either TAK-279 or placebo

12 weeks

Several visits (in-person)

Open-label Treatment

All participants receive TAK-279 for an additional 40 weeks

40 weeks

Several visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• TAK-279

Trial Overview The study tests if TAK-279 can reduce bowel inflammation in UC patients compared to a placebo. Initially, participants will be randomly assigned to receive either TAK-279 or a placebo for 12 weeks, after which all participants will take TAK-279 for up to one year.

How Is the Trial Designed?

Group I: TAK-279 Dose 2 Experimental Treatment 1 Intervention

TAK-279, capsules, orally at Dose 2 up to Week 12 followed by either Dose 1 or Dose 2 up to week 52 based on the response.

Group II: TAK-279 Dose 1 Experimental Treatment 1 Intervention

TAK-279, capsules, orally at Dose 1 up to Week 12 followed by either Dose 1 or Dose 2 up to week 52 based on the response.

Group III: Placebo Placebo Group 2 Interventions

TAK-279 matching placebo capsules, orally, for 12 weeks followed by TAK-279 capsules, orally either Dose 1 or Dose 2 up to Week 52 based on the response.

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

TD-1473 is a gut-selective pan-JAK inhibitor that showed potent activity in preclinical studies and was well tolerated in a Phase 1b clinical trial involving patients with moderately to severely active ulcerative colitis (UC).

The treatment resulted in high concentrations of the drug in colonic tissue with low plasma exposure, leading to trends of reduced disease activity in UC patients, indicating its potential efficacy while minimizing systemic side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of Gut-Selective Pan-Janus Kinase Inhibitor TD-1473 for Ulcerative Colitis: A Translational Medicine Programme. Sandborn, WJ., Nguyen, DD., Beattie, DT., et al.[2021]

A new small molecule, referred to as 18, selectively inhibits JAK1 and TYK2 with high potency (IC50 of 39 nM for JAK1 and 21 nM for TYK2) and shows a promising oral bioavailability of 59.82%, making it a strong candidate for treating inflammatory bowel disease (IBD).

In mouse models of acute ulcerative colitis, compound 18 demonstrated superior therapeutic effects compared to the established drug tofacitinib, while also exhibiting low toxicity and a high safety profile after 32 days of administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic potential of a synthetic dual JAK1/TYK2 inhibitor in inflammatory bowel disease. Cui, X., Teng, Y., Hu, Y., et al.[2023]

Upadacitinib and risankizumab effectively modify immune response mechanisms in patients with inflammatory bowel disease (IBD) who do not respond to anti-TNF-α therapies, as shown by significant decreases in upregulated immune modules and cell types associated with inflammation.

In a study involving tissue transcriptomic data from IBD patients, upadacitinib treatment led to a notable reduction in the expression of inflammatory markers and immune cell types in responders, indicating its potential to improve clinical outcomes in TNF-IR patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Clinical Response of Upadacitinib and Risankizumab Is Associated With Reduced Inflammatory Bowel Disease Anti-TNF-α Inadequate Response Mechanisms. Wang, J., Macoritto, M., Guay, H., et al.[2023]

Janus kinase inhibitors (JAKis) represent a promising new class of oral medications that can effectively target and modulate inflammation in chronic inflammatory diseases, including inflammatory bowel disease (IBD).

Selective TYK2 inhibitors (TYK2is) may offer a safer alternative to pan-JAK inhibitors like tofacitinib, which have been associated with serious adverse effects, by specifically targeting the TYK2 signaling pathway involved in IBD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selective tyrosine kinase 2 inhibitors in inflammatory bowel disease. Nielsen, OH., Boye, TL., Chakravarti, D., et al.[2022]

In a study of 166 patients with ulcerative colitis who had previously failed anti-TNF therapy, tofacitinib and ustekinumab showed similar effectiveness in achieving steroid-free clinical remission at both 12 and 52 weeks.

The safety profiles of both medications were consistent with known data, with tofacitinib reporting 17 adverse events (most commonly shingles) and ustekinumab reporting 10 adverse events (most commonly arthralgia and rash).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

1-Year Comparative Effectiveness of Tofacitinib vs Ustekinumab for Patients With Ulcerative Colitis and Prior Antitumor Necrosis Factor Failure. Dalal, RS., Sharma, PP., Bains, K., et al.[2023]

The novel selective TYK2 inhibitor (TYK2i) effectively prevented weight loss and reduced disease activity in a mouse model of T cell transfer colitis, indicating its potential efficacy in treating inflammatory bowel disease (IBD).

Transfer of T cells lacking TYK2 activity also showed reduced colitis symptoms, suggesting that targeting TYK2 could be a promising strategy for IBD treatment by modulating T cell differentiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tyrosine Kinase 2 Signalling Drives Pathogenic T cells in Colitis. De Vries, LCS., Ghiboub, M., van Hamersveld, PHP., et al.[2021]

In a study of 319 patients with moderate-to-severe ulcerative colitis, both ritlecitinib and brepocitinib showed significant improvement in total Mayo Score compared to placebo after 8 weeks, indicating their efficacy as induction therapies.

The safety profile of both medications was acceptable, with mostly mild adverse events reported; however, there were some infections associated with brepocitinib and one death linked to ritlecitinib, though both were deemed unrelated to the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral Ritlecitinib and Brepocitinib for Moderate-to-Severe Ulcerative Colitis: Results From a Randomized, Phase 2b Study. Sandborn, WJ., Danese, S., Leszczyszyn, J., et al.[2023]

Many patients with moderate to severe ulcerative colitis or Crohn's disease do not achieve sustained remission with current treatments, highlighting the need for new therapies.

Janus kinase (JAK) inhibitors, particularly tofacitinib, have shown promising efficacy and a favorable safety profile in clinical trials, making them a potential new option for treating inflammatory bowel diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

JAK Inhibition: The Most Promising Agents in the IBD Pipeline? Fernández-Clotet, A., Castro-Poceiro, J., Panés, J.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06254950

NCT06254950 | A Study on the Safety of TAK-279 and ... The main aim of this study is to learn if TAK-279 reduces bowel inflammation and symptoms compared to placebo. Another aim is to compare any medical ...

2. takeda.com takeda.com/newsroom/newsreleases/2023/takeda-announces-positive-results-in-phase-2b-study-of-investigational-tak-279/

Takeda Announces Positive Results in Phase 2b Study ... A significantly greater proportion of TAK-279 patients achieved PASI 90 (21%, 45%, 46%; 5mg, 15mg, 30mg, respectively) versus placebo (0%; p< ...

3. drugtargetreview.com drugtargetreview.com/article/187029/inside-zasocitinib-a-new-model-for-tyk2-inhibition-in-immune-mediated-diseases/

Inside Zasocitinib: a new model for TYK2 inhibition in ... Zasocitinib, a selective TYK2 inhibitor by Takeda, shows promise as a targeted oral therapy for immune-mediated inflammatory diseases.

4. sciencedirect.com sciencedirect.com/science/article/pii/S0022202X25005317

An Oral, Highly Selective, and Potent Allosteric TYK2 Inhibitor Zasocitinib (TAK-279) is an investigational, oral, highly selective, and potent allosteric TYK2 inhibitor. This study assessed the TYK2 ...

5. drugdiscoverytrends.com drugdiscoverytrends.com/tak-279-an-oral-small-molecule-tyk2-inhibitor-offering-the-convenience-of-a-once-daily-pill-and-biologic-like-clinical-responses/

Takeda's oral TYK2 inhibitor matches biologic efficacy TAK-279 TYK2 inhibitor psoriasis treatment shows significant skin clearance in trials. We catch up with a Takeda exec to learn more.

6. clinicaltrials.eu clinicaltrials.eu/trial/study-on-long-term-safety-of-zasocitinib-for-adults-with-moderate-to-severe-ulcerative-colitis-and-crohns-disease/

Study on Long-term Safety of Zasocitinib for Adults with ... This clinical trial is focused on studying the long-term safety and tolerability of a medication called zasocitinib, also known by its code name TAK-279.