Mirikizumab + Tirzepatide for Crohn's Disease

(COMMIT-CD Trial)

Recruiting at 231 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: Ulcerative colitis, 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

290 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments to evaluate their effectiveness and safety for individuals with Crohn's disease and weight issues, such as obesity or being overweight. One group receives mirikizumab (an antibody therapy) and tirzepatide (a medication for weight management) together, while another group receives mirikizumab with a placebo. It targets those who have had Crohn's for at least three months and face related weight problems, such as high blood pressure or type 2 diabetes. Participants should have experienced moderate to severe Crohn's symptoms and not found success with other treatments. 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.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop your current medications. However, it mentions that participants should have had an inadequate response to or intolerance to certain conventional or advanced therapies for Crohn's Disease.

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

Research has shown that mirikizumab has been tested for safety in conditions like psoriasis, ulcerative colitis, and Crohn's disease. These studies indicate it is generally safe for people. In one study, more than half of the patients with Crohn's disease experienced clinical remission (their symptoms went away) after one year of using mirikizumab.

The FDA has already approved tirzepatide for treating type 2 diabetes, suggesting it is safe for people. However, since researchers are testing it for a new use in Crohn's disease, monitoring for any side effects is important.

Overall, both treatments have undergone safety studies, but each new trial provides a better understanding of their tolerance when used together. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for Crohn's disease, such as corticosteroids and TNF inhibitors, this new combination of Mirikizumab and Tirzepatide offers a fresh approach. Researchers are excited because Mirikizumab is an antibody that specifically targets the p19 subunit of IL-23, a protein involved in inflammation, which could lead to more precise control of the immune response. Meanwhile, Tirzepatide, a dual GIP and GLP-1 receptor agonist primarily used for diabetes, may enhance metabolic regulation and reduce inflammation in a novel way. This combination not only targets inflammation but also addresses metabolic aspects, offering a potentially more comprehensive treatment for Crohn's disease.

What evidence suggests that this trial's treatments could be effective for Crohn's Disease?

Research has shown that mirikizumab may effectively treat Crohn's Disease, with about 58.5% of patients experiencing significant improvements after a year of treatment. This indicates that more than half of the patients saw their condition improve. The safety profile of mirikizumab was similar to other treatments. In this trial, some participants will receive a combination of mirikizumab and tirzepatide, while others will receive mirikizumab with a placebo. Tirzepatide, another medication in this study, is already used to help manage weight and blood sugar, which could benefit people with Crohn's Disease who are also overweight. Using mirikizumab and tirzepatide together might offer extra benefits, potentially improving both Crohn's symptoms and weight-related issues. ^{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?

Adults with moderate to severe Crohn's Disease who are also overweight or obese can join this trial. Specific details about what makes someone eligible or not weren't provided, but typically participants must meet certain health standards and not have conditions that could interfere with the study.

Inclusion Criteria

I was diagnosed with Crohn's disease or perianal fistulizing CD over 3 months ago.

My Crohn's disease severity score is high enough for the study.

My Crohn's disease is moderate to severe.

Exclusion Criteria

I have more than 2 parts of my colon or rectum missing.

I might have an abscess.

I've had severe low blood sugar or didn't notice it happening in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive mirikizumab and placebo or mirikizumab with tirzepatide for Crohn's Disease and obesity or overweight

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Mirikizumab
• Tirzepatide

Trial Overview The trial is testing if Mirikizumab alone or combined with Tirzepatide is effective and safe for treating Crohn's Disease in adults who are overweight. Some will get a placebo instead of Tirzepatide to compare results. The study lasts up to 61 weeks.

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

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]

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]

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]

Azathioprine (AZA) and its metabolite 6-mercaptopurine (6-MP) are effective for treating active Crohn's disease and preventing relapses in patients in remission, but they require combination with other medications initially due to delayed onset of action.

While AZA/6-MP therapy is generally effective, about 15% of patients experience side effects such as skin rash and increased risk of infections, necessitating careful monitoring and potential dose adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Azathioprine: an update on clinical efficacy and safety in inflammatory bowel disease. Lamers, CB., Griffioen, G., van Hogezand, RA., et al.[2019]

A large-scale analysis of adverse events (AEs) reported for dupilumab, omalizumab, and mepolizumab revealed that omalizumab had the highest association with anaphylaxis, indicating a significant safety concern for this biologic (ROR = 20.80).

Dupilumab was linked to a higher incidence of ophthalmologic issues, such as blurry vision and visual impairment, as well as injection-site reactions, suggesting that while it is effective, it may have specific side effects that need monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterizing Adverse Events of Biologic Treatment of T2 Disease: A Disproportionality Analysis of the FDA Adverse Event Reporting System. Stack, TJ., Kim, S., Lamb, MM., et al.[2023]

In a study of 100 patients with moderate-to-severe Crohn's disease who had previously failed multiple treatments, risankizumab achieved a steroid-free clinical remission rate of 45.8% and a clinical response rate of 78.5% by week 12, indicating its effectiveness in a real-world setting.

The treatment was generally well-tolerated, with 20 adverse events reported, including 7 serious cases, but the majority of patients experienced significant improvements in their condition, highlighting risankizumab's potential as a viable option for refractory Crohn's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of risankizumab induction therapy for 100 patients with Crohn's disease: A GETAID multicentre cohort study. Fumery, M., Defrance, A., Roblin, X., et al.[2023]

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]

Vedolizumab, a gut-selective integrin blocker for Crohn's disease and ulcerative colitis, showed a similar rate of serious adverse events (35.9%) compared to anti-TNF drugs (32.1%) in a study analyzing 499 reports for vedolizumab and 119,620 for anti-TNFs.

The study identified 22 groups of adverse events associated with vedolizumab, including 9 with serious outcomes, suggesting potential cardiovascular risks; however, these findings are preliminary and require further investigation through long-term studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of the real-world safety profile of vedolizumab using the United States Food and Drug Administration adverse event reporting system. Cross, RK., Chiorean, M., Vekeman, F., et al.[2023]

Citations

1. 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 ...

2. withpower.com withpower.com/trial/phase-3-crohn-disease-5-2025-c1713

Mirikizumab + Tirzepatide for Crohn's Disease Mirikizumab demonstrated durable efficacy, maintaining a high endoscopic response rate of around 58.5% at Week 52, while the safety profile was comparable to ...

3. trials.lilly.com trials.lilly.com/en-CA/trial/600156

Mirikizumab and Tirzepatide Administered in Adult ... - Lilly Trials The main purpose of this study is to evaluate the efficacy and safety of mirikizumab and placebo compared with mirikizumab and concomitantly administered ...

4. theglobeandmail.com theglobeandmail.com/investing/markets/stocks/LLY/pressreleases/33670107/eli-lillys-new-study-on-mirikizumab-and-tirzepatide-a-potential-game-changer-for-crohns-disease/

Eli Lilly's New Study on Mirikizumab and Tirzepatide The purpose of these interventions is to assess their effectiveness in treating Crohn's Disease in conjunction with obesity or overweight ...

5. 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 ...

6. prnewswire.com prnewswire.com/news-releases/more-than-one-half-of-patients-with-crohns-disease-treated-with-lillys-mirikizumab-achieved-clinical-remission-at-one-year-including-patients-with-previous-biologic-failure-302150721.html

More than one-half of patients with Crohn's disease treated ... At one year, clinical remission and endoscopic response were achieved by 54.1% and 48.4% of patients on mirikizumab, respectively. Notably, of ...