Mirikizumab + Tirzepatide for Ulcerative Colitis

(COMMIT-UC Trial)

Recruiting at 172 trial locations

Overseen By There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or

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

Trial Summary

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.

What data supports the effectiveness of the drug 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 moderate-to-severe ulcerative colitis. It has been tested in several clinical trials and shown to improve quality of life for these patients. ^{1 2 3 4 5}

Is the combination of Mirikizumab and Tirzepatide safe for humans?

Mirikizumab has been shown to be well-tolerated in clinical trials for ulcerative colitis and Crohn's disease, with no major safety concerns reported in these studies. ^{1 4 6 7 8}

How is the drug combination of Mirikizumab and Tirzepatide unique for treating ulcerative colitis?

Mirikizumab is unique as it is the first drug approved that targets the IL-23p19 protein, which plays a role in inflammation, specifically for ulcerative colitis. This makes it different from other treatments that may target different proteins or pathways. Tirzepatide, while not detailed in the research, is known for its use in diabetes and weight management, suggesting a novel combination approach for ulcerative colitis. ^{1 5 6 7 9}

What is the purpose of this trial?

The main purpose of this study is to show whether in these individuals, treatment with both mirikizumab and tirzepatide, compared with treatment with mirikizumab and placebo, leads to decrease or disappearance of UC symptoms, and loss of at least one-tenth of the overall body weight. Participation in this study will last up to 61 weeks, including 52 weeks of treatment.

Research Team

Contact Lilly at 1-800-LillyRx (1-800-545-5979)

Principal Investigator

Eli Lilly and Company

Eligibility Criteria

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

I have had ulcerative colitis for 8+ years and a recent colonoscopy showed no signs of cancer or severe cell changes.

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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-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]

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 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]

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]

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]

References

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

Mirikizumab Regulates Genes Involved in Ulcerative Colitis Disease Activity and Anti-TNF Resistance: Results From a Phase 2 Study. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Impact of Bowel Urgency on Quality of Life and Clinical Outcomes in Patients With Ulcerative Colitis. [2023]

3. England 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. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Resolving Histological Inflammation in Ulcerative Colitis With Mirikizumab in the LUCENT Induction and Maintenance Trial Programmes. [2023]

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

Mirikizumab-Induced Transcriptome Changes in Ulcerative Colitis Patient Biopsies at Week 12 Are Maintained Through Week 52. [2023]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Mirikizumab: First Approval. [2023]

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

Efficacy and Safety of Continued Treatment With Mirikizumab in a Phase 2 Trial of Patients With Ulcerative Colitis. [2022]

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

Efficacy and Safety of Mirikizumab in a Randomized Phase 2 Study of Patients With Crohn's Disease. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Mirikizumab Pharmacokinetics in Patients with Moderately to Severely Active Ulcerative Colitis: Results from Phase III LUCENT Studies. [2023]