Mirikizumab for Ulcerative Colitis

(LUCENT-URGE Trial)

Not currently recruiting at 204 trial locations

Overseen By Jonathan Siegel

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Eli Lilly and Company

Disqualifiers: Crohn's disease, Ulcerative proctitis, Cancer, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 36 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests mirikizumab, a new treatment for people with ulcerative colitis (UC) who have moderate to severe symptoms, including sudden bowel urgency. The study aims to evaluate how well this medication manages these symptoms over 36 weeks. Participants should have had UC for at least three months and not responded well to other treatments. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to the potential availability of a new treatment option.

Will I have to stop taking my current medications?

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

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

Research has shown that mirikizumab has been tested in people with ulcerative colitis. Common side effects include colds, injection site reactions, joint pain, and rash. These side effects are typical for many medications and are usually mild.

Studies indicate that mirikizumab can improve symptoms of ulcerative colitis, such as the urgent need to use the bathroom, and help maintain symptom relief for longer periods. This means it helps many people feel better over time.

Although no treatment is without risk, evidence suggests that most patients generally tolerate mirikizumab well. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for ulcerative colitis?

Mirikizumab is unique because it targets the p19 subunit of interleukin-23, a different mechanism of action compared to many current ulcerative colitis treatments that focus on tumor necrosis factor (TNF) inhibitors. This targeted approach may offer a more precise way to control inflammation. Additionally, mirikizumab is administered intravenously every four weeks, which could be more convenient for some patients compared to daily oral medications or more frequent injections. Researchers are excited about the potential for mirikizumab to provide effective relief with a less frequent dosing schedule and a novel mechanism of action.

What evidence suggests that mirikizumab might be an effective treatment for ulcerative colitis?

Research has shown that mirikizumab, which participants in this trial will receive, may help treat ulcerative colitis. In earlier studies, patients experienced quick and lasting relief from bowel urgency, a main symptom of this condition. By 12 weeks, 58% of patients showed noticeable healing of the colon lining. Additionally, those who responded to the treatment remained symptom-free for up to three years. Overall, mirikizumab offers long-term benefits, helping many patients manage their symptoms effectively. ^{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 9 AM - 5 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 moderately to severely active ulcerative colitis who have had it for at least 3 months. They should be experiencing bowel urgency and not responding well to conventional or certain advanced therapies. People with Crohn's disease, limited rectal disease, gastrointestinal cancer history, tuberculosis, HIV, or specific immunodeficiency syndromes cannot join.

Inclusion Criteria

I often feel a sudden need to use the bathroom.

I have been diagnosed with ulcerative colitis for over 3 months.

My ulcerative colitis is moderate to severe.

Exclusion Criteria

I have active tuberculosis.

I am HIV positive.

I have a type of inflammatory bowel disease that hasn't been specifically classified.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive mirikizumab intravenously (IV) and subcutaneously (SC) for the treatment of moderately to severely active ulcerative colitis

36 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Mirikizumab

Trial Overview The study tests Mirikizumab's effect on bowel urgency in people with moderate to severe ulcerative colitis. It spans over 36 weeks and includes four different periods of assessment to understand how well the treatment works.

How Is the Trial Designed?

Group I: 300 mg Mirikizumab Experimental Treatment 1 Intervention

Participants received 300 milligram (mg) mirikizumab every 4 weeks (Q4W) at week 0, 4, and 8 administered intravenously (IV).

Mirikizumab is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Omvoh for:

• Moderately to severely active ulcerative colitis

Approved in United States as Omvoh for:

• Moderately to severely active ulcerative colitis

Approved in Canada as Omvoh for:

• Moderately to severely active ulcerative colitis

Approved in Japan as Omvoh for:

• Moderately to severely active ulcerative colitis

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]

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 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 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 phase 3 studies (LUCENT-1 and LUCENT-2) involving 1162 patients with moderately-to-severely active ulcerative colitis, mirikizumab significantly improved quality of life outcomes, including scores on the Inflammatory Bowel Disease Questionnaire and the 36-Item Short Form Health Survey.

Mirikizumab-treated patients showed higher rates of achieving response and remission in quality of life measures compared to placebo, indicating its efficacy in enhancing overall well-being in patients with ulcerative colitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mirikizumab Improves Quality of Life in Patients With Moderately-to-Severely Active Ulcerative Colitis: Results From the Phase 3 LUCENT-1 Induction and LUCENT-2 Maintenance Studies. Sands, BE., Feagan, BG., Hunter Gibble, T., 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]

Citations

1. lilly.gcs-web.com lilly.gcs-web.com/news-releases/news-release-details/lillys-omvoh-mirikizumab-mrkz-demonstrated-early-and-sustained

Lilly's Omvoh (mirikizumab-mrkz) demonstrated early and ... Lilly's Omvoh (mirikizumab-mrkz) demonstrated early and sustained improvement in bowel urgency outcomes for patients with ulcerative colitis.

2. omvoh.lilly.com omvoh.lilly.com/ulcerative-colitis/clinical-results

UC Clinical Results & Safety Data | Omvoh® (mirikizumab-mrkz) Omvoh works within your gut to help repair your colon lining at 1 year. Among people that saw improvement at Week 12, 58% had visible healing of their colon ...

3. 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 ...

4. omvoh.lilly.com omvoh.lilly.com/hcp/ulcerative-colitis/clinical-studies

Clinical Studies, Trial Design & Data | UC - Omvoh - Eli Lilly Three-year efficacy and safety of mirikizumab following 152 weeks of continuous treatment for ulcerative colitis: results from the LUCENT-3 open-label extension ...

5. prnewswire.com prnewswire.com/news-releases/lillys-omvoh-mirikizumab-mrkz-is-the-first-and-only-il-23p19-antagonist-to-show-four-years-of-sustained-corticosteroid-free-comprehensive-patient-outcomes-in-ulcerative-colitis-302576255.html

Lilly's Omvoh (mirikizumab-mrkz) is the first and only IL ... Mirikizumab provides sustained long-term efficacy up to 4 years of treatment for ulcerative colitis: final results from the LUCENT-3 open-label ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05767021?term=mirikizumab&viewType=Table&rank=5

A Study of Mirikizumab (LY3074828) in Participants With ... A study to investigate bowel urgency in adults with moderately to severely active ulcerative colitis (UC) treated with mirikizumab . The study will have 4 ...