PRA023 for Ulcerative Colitis

(ARTEMIS-UC Trial)

No longer recruiting at 97 trial locations

Overseen By Prometheus Biosciences

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Prometheus Biosciences, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)

Disqualifiers: Crohn's, Fulminant colitis, Bowel perforation, others

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

Compensation: Varies

Number of Visits: 4

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and effectiveness of a new treatment called PRA023 (also known as tulisokibart) for individuals with moderate to severe ulcerative colitis (UC), a condition affecting the colon that can cause symptoms like frequent diarrhea and abdominal pain. Participants will receive either PRA023 or a placebo through an IV infusion over 12 weeks, with the option to continue treatment for up to 170 weeks. Suitable candidates for this trial have been diagnosed with UC and have not responded well to treatments like corticosteroids or certain immune therapies. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to benefit from a potentially effective new therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop your current medications. However, it mentions that participants must have had no response or intolerance to certain therapies, which might imply some changes to your current treatment.

Is there any evidence suggesting that PRA023 is likely to be safe for humans?

Research has shown that tulisokibart was tested in earlier studies for safety in people with ulcerative colitis. Most participants tolerated tulisokibart well, with some experiencing mild side effects like headaches or mild nausea, common with many treatments.

Currently, larger studies are testing tulisokibart for both ulcerative colitis and Crohn's disease. The positive initial safety results have led to these expanded trials. While more information is still being gathered, ongoing research is promising and suggests that tulisokibart is safe for further testing in humans. ^{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 include anti-inflammatory drugs, immunosuppressants, or biologics targeting TNF-alpha, PRA023 acts differently by targeting a specific pathway involved in the disease process. Researchers are excited about PRA023 because it uses a novel mechanism of action, potentially offering a new way to manage inflammation by focusing on a different aspect of the immune response. This innovative approach could provide an alternative for patients who do not respond well to existing therapies, potentially improving outcomes and offering hope for more personalized treatment options.

What evidence suggests that PRA023 might be an effective treatment for Ulcerative Colitis?

Research has shown that tulisokibart, also known as PRA023, may help treat ulcerative colitis (UC). In this trial, participants in Cohort 1 and Cohort 2 will receive tulisokibart, while others will receive a placebo. A study found that after 12 weeks, tulisokibart was much more effective than a placebo in helping patients with moderate to severe UC achieve clinical remission, meaning they had no disease symptoms. Findings published in the New England Journal of Medicine also support that tulisokibart can reduce UC symptoms. This treatment targets inflammation, a major issue in UC. Overall, evidence suggests that tulisokibart could be a useful option for managing ulcerative colitis symptoms. ^{1 2 3 4 5}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

This trial is for people with moderate to severe Ulcerative Colitis who haven't responded well to, or can't tolerate, certain UC treatments like steroids or immunosuppressants. Participants must have a confirmed diagnosis and be able to follow the study's procedures. Those with Crohn's disease, at high risk per investigator's opinion, or unable/unwilling to use effective contraception are excluded.

Inclusion Criteria

I have been diagnosed with ulcerative colitis.

I have not responded well or am intolerant to certain standard treatments.

My ulcerative colitis is moderate to severe.

Exclusion Criteria

I need or will soon need a surgery for a colostomy or ileostomy.

I currently have severe colon issues, including inflammation or surgery.

Subjects in the opinion of the investigator are at an unacceptable risk for participation in the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Treatment

Participants receive tulisokibart or placebo administered by intravenous infusion at specified intervals over 12 weeks

12 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

Open-label Extension

Participants may opt into continuation of treatment long-term

Up to 170 weeks

What Are the Treatments Tested in This Trial?

Interventions

• PRA023

Trial Overview The trial is testing PRA023 in two ways: directly through IV administration and by assessing its safety and effectiveness in those who test positive on companion diagnostic tests. After an initial 12-week period, participants can choose to continue treatment for another 38 weeks.

How Is the Trial Designed?

Group I: Cohort 2 Tulisokibart Experimental Treatment 2 Interventions

Participants who are CDx+ will receive tulisokibart administered by intravenous (IV) infusion at 1000 mg on Day 1, Week 0 and 500 mg on the first day of Weeks 2, 6, and 10. After the completion of the 12-week induction, all participants have the option to continue in the open-label extension for up to 170 weeks.

Group II: Cohort 1 Tulisokibart Experimental Treatment 1 Intervention

Participants who are CDx+ and CDx- will receive tulisokibart administered by intravenous (IV) infusion at 1000 mg on Day 1, Week 0, and 500 mg on the first day of Weeks 2, 6, and 10. After the completion of the 12-week induction, all participants have the option to continue in the open-label extension for up to 170 weeks.

Group III: Cohort 2 Placebo Placebo Group 2 Interventions

Participants who are CDx+ will receive placebo administered by intravenous (IV) infusion on Day 1, Week 0 and the first day of Weeks 2, 6, and 10. After the completion of the 12-week induction, all participants have the option to continue in the open-label extension for up to 170 weeks.

Group IV: Cohort 1 Placebo Placebo Group 1 Intervention

Participants who are CDx+ and CDx- will receive placebo administered by intravenous (IV) infusion on Day 1, Week 0 and the first day of Weeks 2, 6, and 10. After the completion of the 12-week induction, all participants have the option to continue in the open-label extension for up to 170 weeks.

Who Is Running the Clinical Trial?

Prometheus Biosciences, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)

Lead Sponsor

Trials

6

Recruited

600+

Prometheus Biosciences, Inc.

Lead Sponsor

Trials

6

Recruited

600+

Published Research Related to This Trial

Biologics, particularly infliximab and adalimumab, have shown significant efficacy in treating ulcerative colitis (UC) in patients who do not respond to conventional treatments, with infliximab providing strong short-term results but often requiring dose adjustments for long-term effectiveness.

Vedolizumab demonstrated higher clinical remission rates compared to adalimumab and is considered the most cost-effective biologic, while ustekinumab has shown promise in patients unresponsive to other biologics, although more research is needed due to its recent approval.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Efficacy of Currently Licensed Biologics for Treatment of Ulcerative Colitis: A Literature Review. Awan, H., Fatima, U., Eaw, R., et al.[2023]

In a phase 2 clinical trial involving patients with moderate-to-severe ulcerative colitis, mirikizumab, an anti-IL-23 monoclonal antibody, showed significant clinical improvement and was well-tolerated, particularly in the 200 mg treatment group.

Gene expression analysis revealed that mirikizumab treatment led to decreased levels of transcripts associated with disease activity and resistance to other therapies, indicating its potential to promote mucosal healing and alter biological pathways in ulcerative colitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mirikizumab Regulates Genes Involved in Ulcerative Colitis Disease Activity and Anti-TNF Resistance: Results From a Phase 2 Study. Steere, B., Schmitz, J., Powell, N., et al.[2023]

In two Phase 3 trials involving 1162 patients for induction and 544 for maintenance, mirikizumab significantly improved bowel urgency in ulcerative colitis patients compared to placebo, with higher rates of clinically meaningful improvement and remission at both 12 and 52 weeks.

Patients who experienced improvement in bowel urgency while on mirikizumab also showed better overall clinical outcomes, including higher rates of clinical remission and improved quality of life, indicating that addressing bowel urgency can enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Effect of Mirikizumab Treatment on Bowel Urgency in Patients with Moderately to Severely Active Ulcerative Colitis and the Clinical Relevance of Bowel Urgency Improvement for Disease Remission. Dubinsky, MC., Clemow, DB., Hunter Gibble, T., et al.[2023]

Mirikizumab, an anti-IL-23p19 monoclonal antibody, was approved in March 2023 in Japan for treating moderate to severe ulcerative colitis, marking it as the first IL-23p19 inhibitor approved for this condition.

In the EU, mirikizumab received a positive opinion for adult patients with active ulcerative colitis who did not respond to conventional or biologic therapies, highlighting its potential as a new treatment option for difficult-to-treat cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mirikizumab: First Approval. Keam, SJ.[2023]

Anti-IL-23 agents, such as mirikizumab and ustekinumab, have shown significant efficacy in treating ulcerative colitis (UC) in clinical trials, achieving both clinical and endoscopic improvements with a favorable safety profile.

Ongoing trials are exploring the effectiveness of various anti-IL-23 agents compared to existing treatments and investigating the potential for combination therapies, which could enhance treatment strategies for UC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-interleukin-23 agents for the treatment of ulcerative colitis. Hanžel, J., D'Haens, GR.[2020]

Mirikizumab, a monoclonal antibody targeting the IL-23 pathway, has been shown to effectively induce and maintain remission in patients with moderately to severely active ulcerative colitis, including those who previously did not respond to other treatments.

This therapy has a favorable safety profile and is the first IL-23 antagonist to receive regulatory approval for ulcerative colitis in Europe, addressing a significant need for new treatment options in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mirikizumab for the treatment of moderate to severe ulcerative colitis. Hanzel, J., Ma, C., Jairath, V.[2023]

In a study involving patients with moderate to severe ulcerative colitis who initially did not respond to mirikizumab after 12 weeks, 50% of those receiving an additional 12 weeks of 600 mg mirikizumab achieved a clinical response, indicating that extended treatment can be effective for nonresponders.

Among those who responded to the extended treatment, 65.8% maintained their clinical response for up to 52 weeks, demonstrating the long-term efficacy of mirikizumab without new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Continued Treatment With Mirikizumab in a Phase 2 Trial of Patients With Ulcerative Colitis. Sandborn, WJ., Ferrante, M., Bhandari, BR., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06052059

NCT06052059 | A Study to Evaluate Efficacy and Safety of ... The purpose of this protocol is to evaluate the efficacy of tulisokibart in participants with moderately to severely active ulcerative colitis.

2. merck.com merck.com/news/merck-to-present-new-long-term-data-for-tulisokibart-mk-7240-an-investigational-anti-tl1a-monoclonal-antibody-in-inflammatory-bowel-disease-at-ueg-week-2024/

Merck to Present New Long-Term Data for Tulisokibart (MK ... Findings published in the New England Journal of Medicine show that after 12 weeks, tulisokibart was more effective than placebo for inducing ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39321363/

Phase 2 Trial of Anti-TL1A Monoclonal Antibody ... In this short-term trial, tulisokibart was more effective than placebo in inducing clinical remission in patients with moderately to severely active ulcerative ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04996797

NCT04996797 | A Phase 2 Safety and Efficacy Study of ... The purpose of this study is to assess the safety and efficacy of tulisokibart in participants with moderately to severely active Ulcerative Colitis (UC).

5. nejm.org nejm.org/doi/abs/10.1056/NEJMoa2314076

Phase 2 Trial of Anti-TL1A Monoclonal Antibody ... In this short-term trial, tulisokibart was more effective than placebo in inducing clinical remission in patients with moderately to severely active ulcerative ...