TAK-279 for Ulcerative Colitis

Recruiting in Palo Alto (17 mi)

+176 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Takeda

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

Prior Safety Data

Trial Summary

What is the purpose of this trial?

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 problems that participants have when they take TAK-279 or placebo and how well the participants tolerate any problems. The participants will take capsules of either TAK-279 or placebo for up to 3 months (12 weeks). Then all the participants will receive TAK-279 for the rest of the treatment part of the study (1 year or 52 weeks). During the study, participants will visit their study clinic several times.

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.

What data supports the effectiveness of the drug TAK-279 for ulcerative colitis?

Research shows that tyrosine kinase 2 (TYK2) inhibitors, like TAK-279, can help reduce inflammation in conditions like ulcerative colitis by blocking specific signals in the body that cause inflammation. Similar drugs, such as tofacitinib, have been effective in treating ulcerative colitis, suggesting that TAK-279 might also be beneficial. ^{1 2 3 4 5}

Is TAK-279 (a TYK2 inhibitor) generally safe for humans?

Research on similar TYK2 inhibitors suggests they can be effective for inflammatory bowel diseases like ulcerative colitis, with some studies showing low toxicity and a high safety profile in long-term use. However, serious side effects have been reported with other similar drugs, so it's important to weigh the benefits and risks. ^{1 2 3 5 6}

What makes the drug TAK-279 unique for treating ulcerative colitis?

TAK-279 is a small molecule drug that selectively inhibits TYK2, a protein involved in the inflammation process of ulcerative colitis, offering a targeted approach compared to broader treatments like tofacitinib, which affects multiple proteins and may have more side effects. ^{1 2 6 7 8}

Research Team

Study Director

Principal Investigator

Takeda

Eligibility Criteria

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 am between 18 and 75 years old and was diagnosed with ulcerative colitis over 30 days ago.

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

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.

Trial Timeline

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

Treatment Details

Interventions

• TAK-279 (Corticosteroid)

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.

Participant Groups

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

Findings from Research

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]

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 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]

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]

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]

References

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

Tyrosine Kinase 2 Signalling Drives Pathogenic T cells in Colitis. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Selective tyrosine kinase 2 inhibitors in inflammatory bowel disease. [2022]

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

Oral Ritlecitinib and Brepocitinib for Moderate-to-Severe Ulcerative Colitis: Results From a Randomized, Phase 2b Study. [2023]

4. United Arab Emirates pubmed.ncbi.nlm.nih.gov

JAK Inhibition: The Most Promising Agents in the IBD Pipeline? [2020]

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

Development of Gut-Selective Pan-Janus Kinase Inhibitor TD-1473 for Ulcerative Colitis: A Translational Medicine Programme. [2021]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Therapeutic potential of a synthetic dual JAK1/TYK2 inhibitor in inflammatory bowel disease. [2023]

7. England 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. [2023]

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

1-Year Comparative Effectiveness of Tofacitinib vs Ustekinumab for Patients With Ulcerative Colitis and Prior Antitumor Necrosis Factor Failure. [2023]