TAK-279 for Crohn's Disease

Recruiting at 280 trial locations

Overseen By Takeda Contact

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Takeda

Disqualifiers: Ulcerative colitis, Ostomy, others

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

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

Compensation: Varies

Number of Visits: 15

Duration: 40 weeks

268 Participants Needed

Trial Summary

What is the purpose of this trial?

Crohn's disease (CD) is a long-lasting condition causing inflammation that can affect any part of the gut. The purpose of this study is to evaluate the efficacy and safety of TAK-279 versus placebo in participants with moderately to severely active Crohn's disease (CD). The main aim of this study is to learn if the 3 different doses of TAK-279 reduce bowel inflammation and ulcers in the bowel compared to the placebo after 12 weeks of treatment. Another aim is to compare any medical problems that participants have when they take TAK-279 or placebo and how well the participants tolerate medical problems. An endoscopy will be used to check the bowel for inflammation. The participants will be treated with TAK-279 for 52 weeks (1 year). During the study, participants will visit their study clinic 15 times.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking 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 Crohn's Disease?

Research shows that TYK2 inhibitors, like TAK-279, can help reduce inflammation in diseases similar to Crohn's Disease by blocking specific pathways that cause inflammation. Studies on similar drugs have shown promising results in treating inflammatory bowel diseases, suggesting TAK-279 might also be effective. ^{1 2 3 4 5}

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

Research on TYK2 inhibitors, like TAK-279, suggests they may have fewer side effects compared to other similar drugs, as they are more selective in their action. Studies have shown that these inhibitors can be safe for long-term use in animal models, but more human studies are needed to confirm this. ^{1 2 3 6 7}

How is the drug TAK-279 different from other treatments for Crohn's Disease?

TAK-279 is a unique treatment for Crohn's Disease because it is a selective TYK2 inhibitor, which means it specifically targets and blocks the TYK2 enzyme involved in inflammation, unlike broader JAK inhibitors that affect multiple enzymes. This selectivity may help reduce side effects while effectively managing inflammation. ^{1 2 3 8 9}

Research Team

Study Director

Principal Investigator

Takeda

Eligibility Criteria

This trial is for adults aged 18-75 with Crohn's Disease that's active and moderate to severe. They should have tried other treatments without success or couldn't tolerate them. Participants must follow specific contraception advice.

Inclusion Criteria

I have Crohn's disease and treatments so far haven't worked well for me.

Participants must meet the contraception recommendations

My Crohn's disease is moderate to severe, confirmed by tests.

Exclusion Criteria

I have a form of colitis or ulcerative colitis.

I currently have an ostomy.

I might need surgery for my Crohn's disease complications during the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Participants are randomly assigned to receive one of three doses of TAK-279 or placebo for 12 weeks to evaluate efficacy and safety

12 weeks

Approximately 6 visits (in-person)

Treatment

Participants continue to receive TAK-279 or placebo for an additional 40 weeks to assess long-term effects

40 weeks

Approximately 9 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• TAK-279

Trial Overview The study tests TAK-279, a potential new treatment for reducing bowel inflammation in Crohn's Disease, against a placebo over one year. It aims to see if different doses of TAK-279 are effective and safe after 12 weeks using endoscopy.

Participant Groups

Group I: TAK-279 Dose 3 Experimental Treatment 1 Intervention

Participants will be randomized to receive TAK-279 Dose 3 capsules orally.

Group II: TAK-279 Dose 2 Experimental Treatment 2 Interventions

Participants will be randomized to receive TAK-279 Dose 2 capsules with TAK-279 placebo-matching capsule orally.

Group III: TAK-279 Dose 1 Experimental Treatment 2 Interventions

Participants will be randomized to receive TAK-279 Dose 1 capsules with TAK-279 placebo-matching capsule orally.

Group IV: Placebo Experimental Treatment 1 Intervention

Participants will be randomized to receive TAK-279 placebo-matching capsules orally.

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]

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]

Selective inhibition of TYK2, a type of Janus kinase, offers a promising approach to treat inflammatory and autoimmune diseases while minimizing safety concerns associated with broader JAK inhibition.

Deucravacitinib, an FDA-approved allosteric TYK2 inhibitor, and ropsacitinib, currently in clinical trials, represent significant advancements in the development of targeted therapies that balance efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and Therapeutic Implications of Tyrosine Kinase 2 Inhibitors. Zhang, K., Ye, K., Tang, H., et al.[2023]

Compound 48 is a highly selective inhibitor of TYK2 and JAK1, showing strong potency with IC50 values of 6 nM and 37 nM, respectively, and over 23-fold selectivity for JAK2, indicating its potential for targeted therapy.

In models of acute ulcerative colitis, compound 48 demonstrated superior anti-inflammatory effects compared to tofacitinib, suggesting it could be a promising candidate for clinical development due to its ability to regulate key immune responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of a Novel 2,8-Diazaspiro[4.5]decan-1-one Derivative as a Potent and Selective Dual TYK2/JAK1 Inhibitor for the Treatment of Inflammatory Bowel Disease. Yang, T., Cui, X., Tang, M., et al.[2022]

Selective inhibition of TYK2 signaling may offer a safer alternative to conventional JAK inhibitors for treating inflammatory bowel disease (IBD), as it reduces the risk of toxicities associated with less selective therapies.

Deucravacitinib, a novel oral TYK2 inhibitor, shows promise in clinical development for IBD, potentially providing effective treatment with fewer side effects compared to traditional JAK1-3 inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selective Tyrosine Kinase 2 Inhibition for Treatment of Inflammatory Bowel Disease: New Hope on the Rise. Danese, S., Peyrin-Biroulet, L.[2023]

Tofacitinib, a pan-JAK inhibitor, was ineffective in treating Crohn's disease (CD), leading to the discontinuation of its clinical development for this condition, despite its success in ulcerative colitis.

In contrast, filgotinib, a selective JAK1 inhibitor, and upadacitinib have shown promising efficacy in CD patients in phase II trials, prompting ongoing phase III studies to further evaluate their effectiveness and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of JAK inhibitors in Crohn's Disease. Rogler, G.[2021]

Compound 14l is a selective TYK2 inhibitor with a strong inhibition potency (IC50 of 9 nM) and shows good selectivity over other JAK kinases, indicating its potential for targeted therapy in immune-mediated diseases.

In a colitis model, compound 14l effectively reduced pro-inflammatory cytokines and improved inflammation symptoms, suggesting it could be a promising treatment option for inflammatory conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Discovery of 3-(4-(2-((1H-Indol-5-yl)amino)-5-fluoropyrimidin-4-yl)-1H-pyrazol-1-yl)propanenitrile Derivatives as Selective TYK2 Inhibitors for the Treatment of Inflammatory Bowel Disease. Zhang, C., Qi, W., Li, Y., et al.[2021]

Compound 30, a novel TYK2 inhibitor, showed superior potency in inhibiting STAT3 phosphorylation compared to the positive control, deucravacitinib, indicating its potential effectiveness in treating autoimmune diseases.

In addition to its selectivity for JAK isoforms, compound 30 demonstrated favorable pharmacokinetic properties and was effective in animal models of IL-23-driven acanthosis and anti-CD40-induced colitis, supporting its therapeutic potential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel TYK2 Inhibitors with an N-(Methyl-d 3)pyridazine-3-carboxamide Skeleton for the Treatment of Autoimmune Diseases. Liu, F., Wang, B., Liu, Y., 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. Netherlands pubmed.ncbi.nlm.nih.gov

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

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

Development and Therapeutic Implications of Tyrosine Kinase 2 Inhibitors. [2023]

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

Identification of a Novel 2,8-Diazaspiro[4.5]decan-1-one Derivative as a Potent and Selective Dual TYK2/JAK1 Inhibitor for the Treatment of Inflammatory Bowel Disease. [2022]

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

Selective Tyrosine Kinase 2 Inhibition for Treatment of Inflammatory Bowel Disease: New Hope on the Rise. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Efficacy of JAK inhibitors in Crohn's Disease. [2021]

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

Discovery of 3-(4-(2-((1H-Indol-5-yl)amino)-5-fluoropyrimidin-4-yl)-1H-pyrazol-1-yl)propanenitrile Derivatives as Selective TYK2 Inhibitors for the Treatment of Inflammatory Bowel Disease. [2021]

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

Novel TYK2 Inhibitors with an N-(Methyl-d 3)pyridazine-3-carboxamide Skeleton for the Treatment of Autoimmune Diseases. [2023]