Mirikizumab + Tirzepatide for Ulcerative Colitis

(COMMIT-UC Trial)

Recruiting at 238 trial locations

Overseen By Physicians interested in becoming principal investigators please contact

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Eli Lilly and Company

Disqualifiers: Crohn's disease, Type 1 Diabetes, others

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

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

Duration: 52 weeks

350 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a combination of two drugs, mirikizumab (an antibody therapy) and tirzepatide (a medication for type 2 diabetes and weight management), can reduce symptoms of ulcerative colitis and aid in weight loss. It compares the effects of these two drugs together against mirikizumab with a placebo (a substance with no active drug). The study targets individuals who have had ulcerative colitis for at least three months, experience moderate to severe symptoms, and struggle with obesity or being overweight, along with other health issues like high blood pressure or type 2 diabetes. Participants should also have not responded well to previous treatments for ulcerative colitis. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that participants should have had an inadequate response or intolerance to certain medications for ulcerative colitis, which might imply that some changes to your medication regimen could be necessary. Please consult with the trial coordinators for specific guidance.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that mirikizumab is generally well-tolerated in clinical trials for ulcerative colitis and Crohn's disease, with no major safety concerns reported. This finding reassures potential participants, suggesting that mirikizumab is generally safe.

Less specific information is available about tirzepatide for ulcerative colitis. However, the study's advanced stage indicates that earlier trials found it safe enough to proceed, suggesting serious safety issues are unlikely.

Overall, both treatments in the study have been considered safe so far, with mirikizumab having a particularly strong safety record. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using Mirikizumab and Tirzepatide for ulcerative colitis because they offer a fresh approach compared to current treatments, which often include aminosalicylates, corticosteroids, and biologics targeting TNF or integrins. Mirikizumab is unique as it targets the IL-23 pathway, which plays a critical role in inflammation, potentially offering better control of symptoms. Tirzepatide, traditionally used for diabetes, is being explored for its anti-inflammatory effects and its ability to improve metabolic health, which might benefit patients with ulcerative colitis. The combination of these drugs could provide a more comprehensive approach to managing the disease by addressing both inflammation and overall health.

What evidence suggests that this trial's treatments could be effective for ulcerative colitis?

Research has shown that mirikizumab can reduce symptoms such as the urgent need to use the bathroom and inflammation in people with ulcerative colitis. Studies have found that ongoing treatment with mirikizumab can maintain symptom relief for many patients over several years. In this trial, one group of participants will receive a combination of mirikizumab and tirzepatide, which aids weight loss by affecting hormones that control blood sugar and appetite. This combination aims to ease symptoms of ulcerative colitis and assist with weight loss. Early findings suggest that using both drugs together might offer more benefits than using mirikizumab alone, which is being tested in another group with a placebo. ^{1 2 3 4 6}

Who Is on the Research Team?

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST)

Principal Investigator

Eli Lilly and Company

Are You a Good Fit for This Trial?

This trial is for adults with moderate to severe ulcerative colitis who are also overweight or obese. Participants will be involved in the study for up to 61 weeks, receiving treatments for 52 of those weeks.

Inclusion Criteria

I have been diagnosed with ulcerative colitis for over 3 months, confirmed by endoscopy and biopsy.

My BMI is 30 or higher.

My ulcerative colitis is moderate to severe, with a Mayo score of 5-9.

Exclusion Criteria

I have had or will need surgery on my intestines or abdomen.

Have a self-reported change in body weight greater than 5% (gain or reduction) within 3 months prior to screening

Have a current or recent acute, active infection

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive treatment with mirikizumab and tirzepatide or mirikizumab and placebo for ulcerative colitis and weight reduction

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-5 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Mirikizumab
• Tirzepatide

Trial Overview The study tests if using mirikizumab and tirzepatide together is more effective than mirikizumab with a placebo in reducing ulcerative colitis symptoms and helping participants lose at least 10% body weight.

How Is the Trial Designed?

Group I: Mirikizumab + Tirzepatide Experimental Treatment 2 Interventions

Mirikizumab administered intravenously (IV) then Mirikizumab administered subcutaneously (SC). Tirzepatide administered SC.

Group II: Mirikizumab + Placebo Experimental Treatment 2 Interventions

Mirikizumab administered IV then Mirikizumab administered SC. Placebo administered SC.

Who Is Running the Clinical Trial?

Eli Lilly and Company

Lead Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Published Research Related to This Trial

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]

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]

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 a Phase 2 clinical trial involving 249 patients with moderate-to-severe ulcerative colitis, mirikizumab significantly reduced bowel urgency, which is linked to improved quality of life and clinical outcomes.

Patients who experienced no bowel urgency after 12 weeks of treatment showed greater improvements in disease activity and inflammatory markers compared to those who still had urgency, indicating that managing urgency could be a key treatment goal in ulcerative colitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Bowel Urgency on Quality of Life and Clinical Outcomes in Patients With Ulcerative Colitis. Dubinsky, MC., Panaccione, R., Lewis, JD., et al.[2023]

Mirikizumab, an anti-interleukin-23 treatment, significantly improved histological and endoscopic outcomes in patients with moderately-to-severely active ulcerative colitis, showing better results compared to placebo in a study involving 1162 patients at Week 12 and 544 patients at Week 40.

Achieving early endoscopic and histological improvements with mirikizumab was linked to better long-term outcomes, including clinical remission and reduced symptoms, highlighting the importance of early intervention in managing ulcerative colitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Resolving Histological Inflammation in Ulcerative Colitis With Mirikizumab in the LUCENT Induction and Maintenance Trial Programmes. Magro, F., Pai, RK., Kobayashi, T., et al.[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]

Mirikizumab, an anti-interleukin-23 monoclonal antibody, demonstrated pharmacokinetic properties typical of monoclonal antibodies, with a half-life of approximately 9.5 days and a subcutaneous bioavailability of 48%, based on data from 1362 patients with ulcerative colitis.

The study found that while body weight and serum albumin levels influenced the drug's clearance and distribution, these effects were relatively small compared to individual variability, suggesting that no dose adjustments are necessary based on patient characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mirikizumab Pharmacokinetics in Patients with Moderately to Severely Active Ulcerative Colitis: Results from Phase III LUCENT Studies. Chua, L., Friedrich, S., Zhang, XC.[2023]

In a study of 191 patients with moderate-to-severe Crohn's disease, mirikizumab significantly improved endoscopic response at Week 12 compared to placebo, with the highest response rate observed in the 1000 mg group (43.8%).

Mirikizumab demonstrated durable efficacy, maintaining a high endoscopic response rate of around 58.5% at Week 52, while the safety profile was comparable to placebo, indicating it is a promising treatment option for Crohn's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Mirikizumab in a Randomized Phase 2 Study of Patients With Crohn's Disease. Sands, BE., Peyrin-Biroulet, L., Kierkus, J., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06937086

Study Details | NCT06937086 | Mirikizumab Administered ... The main purpose of this study is to show whether in these individuals, treatment with both mirikizumab and tirzepatide, compared with treatment with ...

2. withpower.com withpower.com/trial/phase-3-colitis-5-2025-1e698

Mirikizumab + Tirzepatide for Ulcerative Colitis Research shows that Mirikizumab, one of the drugs in the treatment, has been effective in reducing symptoms like bowel urgency and inflammation in patients with ...

3. trials.lilly.com trials.lilly.com/en-CA/trial/600155

Mirikizumab Administered at the Same Time as Tirzepatide in ... The main purpose of this study is to show whether in these individuals, treatment with both mirikizumab and tirzepatide, compared with treatment with ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39448057/

Results From the LUCENT-3 Open-Label Extension Study 3-year continuous treatment with mirikizumab maintained clinical remission in most induction clinical responders, regardless of previous biologic failure ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06937099

NCT06937099 | Mirikizumab and Tirzepatide Administered ... The main purpose of this study is to evaluate the efficacy and safety of mirikizumab and placebo compared with mirikizumab and concomitantly administered ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06937099

NCT06937099 | Mirikizumab and Tirzepatide Administered ... The main purpose of this study is to evaluate the efficacy and safety of mirikizumab and placebo compared with mirikizumab and concomitantly administered ...