TAK-279 for Crohn's Disease

Recruiting at 328 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness and safety of a new treatment called TAK-279, a small molecule TYK2 inhibitor, for individuals with Crohn's disease, a chronic condition causing inflammation in the digestive tract. The study compares three different doses of TAK-279 to a placebo to determine if it reduces bowel inflammation and ulcers over 12 weeks. Researchers will monitor participants for any side effects and their ability to manage them throughout the year-long study. The trial seeks individuals with moderately to severely active Crohn's disease for at least 30 days who have not responded well to 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 taking 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 has shown that TAK-279, also known as zasocitinib, is under study for its safety in treating immune-related conditions. In earlier studies, TAK-279 was tested on individuals with other inflammatory diseases, and these studies found that the drug was generally well-tolerated, with most participants not experiencing serious side effects.

Although specific side effects were not detailed in the sources, ongoing research in similar conditions provides some insights. The treatment aims to precisely target specific inflammation pathways, potentially lowering the risk of side effects compared to less targeted treatments.

Since TAK-279 is in a Phase 2 trial, researchers continue to collect important safety information. This phase examines how well participants tolerate the drug and monitors for possible side effects. Its progression to this stage suggests that initial safety findings support further testing, but more data is needed to fully understand its safety profile. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Crohn's disease?

Researchers are excited about TAK-279 for Crohn's disease because it offers a novel approach compared to the existing treatments like biologics or immunosuppressants. TAK-279 works by targeting specific pathways in the immune system more precisely, aiming to reduce inflammation directly at the source. This targeted action could potentially lead to fewer side effects and improved efficacy. Moreover, TAK-279 is taken orally, which may be more convenient for patients compared to some current treatments that require injections or infusions.

What evidence suggests that TAK-279 might be an effective treatment for Crohn's disease?

Research has shown that TAK-279, also known as zasocitinib, could be a promising treatment because it blocks TYK2, a protein involved in inflammation. This blocking action might help reduce the gut inflammation seen in Crohn's disease. In this trial, participants will receive different doses of TAK-279 or a placebo. Other studies have demonstrated positive results for TAK-279 in treating psoriasis, another inflammation-related condition, with significant improvements compared to a placebo. Specifically, patients with psoriasis who took TAK-279 experienced better skin clearance, indicating its potential to control inflammation. These findings suggest that TAK-279 could effectively treat conditions like Crohn's disease that involve inflammation. ^{1 3 4 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 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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 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]

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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06233461

NCT06233461 | A Study on the Safety of TAK-279 and ... 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 ( ...

2. 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 ... In simple terms, this in vitro data suggests that zasocitinib may maintain more consistent and effective blockade of key inflammatory pathways ...

3. 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< ...

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

An Oral, Highly Selective, and Potent Allosteric TYK2 Inhibitor These data are consistent with the high and sustained level of selectivity and potency demonstrated in this study and underscore the potential ...

5. 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 ...

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.