Tulisokibart for Crohn's Disease

Recruiting at 398 trial locations

Overseen By Toll Free Number

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme LLC

Disqualifiers: Ulcerative colitis, Short bowel, Cancer, others

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

1200 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It might be best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Tulisokibart for Crohn's Disease?

The research mentions that drugs like ustekinumab, which blocks certain proteins involved in inflammation, have been effective in treating Crohn's disease, especially for patients who did not respond to other treatments. This suggests that targeting similar pathways could be beneficial for Crohn's disease. ^{1 2 3 4 5}

What is the purpose of this trial?

The purpose of this protocol is to evaluate the efficacy and safety of tulisokibart in participants with moderately to severely active Crohn's disease. Study 1's primary hypotheses are that at least 1 tulisokibart dose level is superior to placebo in the proportion of participants achieving clinical remission per Crohn's Disease Activity Index score (\<150, US/FDA) or per stool frequency and abdominal pain score (EU/EMA) and in the proportion of participants achieving endoscopic response at Week 52 (US/FDA and EU/EMA), and that at least 1 tulisokibart dose level is superior to placebo in the proportion of participants achieving clinical remission per Crohn's Disease Activity Index score (\<150, US/FDA) or per stool frequency and abdominal pain score (EU/EMA) and in the proportion of participants achieving endoscopic response at Week 12 (US/FDA and EU/EMA). Study 2's primary hypothesis is that at least 1 tulisokibart dose level is superior to placebo in the proportion of participants achieving clinical remission per Crohn's Disease Activity Index score (\<150, US/FDA) or stool frequency and abdominal pain score (EU/EMA) and in the proportion of participants achieving endoscopic response at Week 12 (US/FDA and EU/EMA).

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

This trial is for people with moderate to severe Crohn's Disease. Participants should have active symptoms and be willing to receive either an IV or SC injection of the study drug or placebo. Specific details on who can join are not provided, but typically participants must meet certain health criteria.

Inclusion Criteria

I was diagnosed with Crohn's disease over 3 months ago.

I have not responded well to steroids, immunomodulators, or advanced therapies.

My Crohn's disease is moderate to severe.

Exclusion Criteria

I have been diagnosed with ulcerative colitis or indeterminate colitis.

I have or might have COVID-19.

I have previously been treated with tulisokibart or a similar medication.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Treatment

Participants receive high or low dose IV tulisokibart or placebo for induction treatment

12 weeks

Maintenance Treatment

Participants receive high or low dose SC tulisokibart or placebo for maintenance treatment

40 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Extension

Participants may continue in a high or low dose SC tulisokibart regimen if they meet protocol-specific prerequisites

Treatment Details

Interventions

• Tulisokibart

Trial Overview The trial is testing Tulisokibart, given through IV or SC injections, against a placebo to see if it helps achieve clinical remission and endoscopic response in Crohn's Disease patients at weeks 12 and 52.

Participant Groups

Group I: Study 2: Low Dose Induction Experimental Treatment 3 Interventions

Participants receive low dose IV tulisokibart.

Group II: Study 2: Low Dose Extension Experimental Treatment 1 Intervention

Participants receive a low dose SC tulisokibart regimen. Participants may continue in this arm only after completing participation in their original arm, if they meet protocol-specific prerequisites.

Group III: Study 2: High Dose Induction Experimental Treatment 2 Interventions

Participants receive high dose IV tulisokibart.

Group IV: Study 2: High Dose Extension Experimental Treatment 1 Intervention

Participants receive a high dose SC tulisokibart regimen. Participants may continue in this arm only after completing participation in their original arm, if they meet protocol-specific prerequisites.

Group V: Study 1: Low Dose Induction, Low Dose Maintenance Experimental Treatment 3 Interventions

Participants receive low dose IV tulisokibart, followed by a low dose SC tulisokibart regimen.

Group VI: Study 1: Low Dose Extension Experimental Treatment 2 Interventions

Participants receive a low dose SC tulisokibart and placebo regimen. Participants may continue in this arm after completing participation in their original arm, if they meet protocol-specific prerequisites.

Group VII: Study 1: High Dose Induction, Low Dose Maintenance Experimental Treatment 3 Interventions

Participants receive high dose IV tulisokibart, followed by a low dose SC tulisokibart regimen.

Group VIII: Study 1: High Dose Induction, High Dose Maintenance Experimental Treatment 2 Interventions

Participants receive high dose intravenous (IV) tulisokibart, followed by a high dose subcutaneous (SC) tulisokibart regimen.

Group IX: Study 1: High Dose Extension Experimental Treatment 1 Intervention

Participants receive a high dose SC tulisokibart regimen. Participants may continue in this arm after completing participation in their original arm, if they meet protocol-specific prerequisites.

Group X: Study 2: Placebo Placebo Group 3 Interventions

Participants receive IV placebo.

Group XI: Study 1: Placebo Placebo Group 3 Interventions

Participants receive IV placebo, followed by an SC placebo regimen.

Who Is Running the Clinical Trial?

Merck Sharp & Dohme LLC

Lead Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

In a comparison of risankizumab (RZB) and ustekinumab (UST) for treating Crohn's disease, RZB showed significantly higher rates of clinical and endoscopic improvement during the induction phase, with 15% more patients achieving CDAI remission and 26% more showing endoscopic response.

After the maintenance phase, the rates of CDAI remission were similar between RZB and UST, but RZB still demonstrated better endoscopic response and remission rates, indicating that while both treatments are effective, RZB may offer advantages during initial treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Matching-Adjusted Indirect Comparison Between Risankizumab and Ustekinumab for Induction and Maintenance Treatment of Moderately to Severely Active Crohn's Disease. Dubinsky, M., Ma, C., Griffith, J., et al.[2023]

In a long-term study of 107 patients with Crohn's disease, upadacitinib demonstrated sustained clinical remission rates of around 54-61% over 30 months, indicating its efficacy as a treatment.

While upadacitinib showed long-term benefits, the safety profile revealed that higher doses (30 mg) were associated with increased rates of adverse events compared to lower doses (15 mg), consistent with its known safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upadacitinib Was Efficacious and Well-tolerated Over 30 Months in Patients With Crohn's Disease in the CELEST Extension Study. D'Haens, G., Panés, J., Louis, E., et al.[2022]

Recent advancements in treating Crohn's disease and ulcerative colitis include new drugs that target specific immune pathways, such as natalizumab and vedolizumab, which disrupt lymphocyte movement to the gut.

Ustekinumab and tofacitinib represent innovative therapies that block key cytokines involved in inflammation, showing promise in clinical trials for improving outcomes in patients with inflammatory bowel disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent developments in the treatment of inflammatory bowel disease. Rietdijk, ST., D'Haens, GR.[2018]

Vedolizumab is a safe and effective gut-specific biological agent for long-term treatment of Crohn's disease and ulcerative colitis, particularly in patients who have not responded to anti-TNF therapies.

Tofacitinib, an oral JAK inhibitor, shows promise for achieving remission in moderately to severely active ulcerative colitis, although its effectiveness in Crohn's disease is less certain, highlighting the need for careful monitoring of safety risks like infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Emerging Therapies: What Are Promising in the Near Future?] Seo, GS., Lee, SH.[2018]

Risankizumab, an IL-23 p19 inhibitor, demonstrated significant efficacy in inducing clinical remission and endoscopic response in patients with moderately to severely active Crohn's disease, with remission rates of up to 45% compared to 25% in the placebo group in the ADVANCE trial.

The treatment was well tolerated, with a similar incidence of adverse events across all groups, and the one death in the risankizumab group was determined to be unrelated to the drug, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risankizumab as induction therapy for Crohn's disease: results from the phase 3 ADVANCE and MOTIVATE induction trials. D'Haens, G., Panaccione, R., Baert, F., et al.[2022]

References

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

Matching-Adjusted Indirect Comparison Between Risankizumab and Ustekinumab for Induction and Maintenance Treatment of Moderately to Severely Active Crohn's Disease. [2023]

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

Upadacitinib Was Efficacious and Well-tolerated Over 30 Months in Patients With Crohn's Disease in the CELEST Extension Study. [2022]

3. Australia pubmed.ncbi.nlm.nih.gov

Recent developments in the treatment of inflammatory bowel disease. [2018]

4. Korea (South) pubmed.ncbi.nlm.nih.gov

[Emerging Therapies: What Are Promising in the Near Future?] [2018]

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

Risankizumab as induction therapy for Crohn's disease: results from the phase 3 ADVANCE and MOTIVATE induction trials. [2022]