Mirikizumab for Ulcerative Colitis

(LUCENT-URGE Trial)

Recruiting at 185 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

160 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a medication called mirikizumab, which aims to reduce bowel urgency in adults with severe ulcerative colitis. The medication works by calming the immune system to reduce inflammation in the intestines. The study will last for several months and include multiple phases.

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.

What data supports the effectiveness of the drug Mirikizumab for treating ulcerative colitis?

Mirikizumab has been shown to improve quality of life and reduce bowel urgency in patients with moderately to severely active ulcerative colitis, according to results from Phase 3 clinical trials. It is also approved in Japan and received a positive opinion in the EU for patients who did not respond well to other treatments. ^{1 2 3 4 5}

Is Mirikizumab safe for humans?

Mirikizumab has been tested in clinical trials for ulcerative colitis, and while these studies focused on its effectiveness, they also monitored safety. It was approved in Japan and received a positive opinion in the EU, suggesting it met safety standards for use in humans. ^{1 2 3 4 6}

What makes the drug Mirikizumab unique for treating ulcerative colitis?

Mirikizumab is unique because it is the first drug approved that specifically targets the IL-23p19 protein, which plays a role in inflammation, making it effective for patients with moderate to severe ulcerative colitis who haven't responded well to other treatments. ^{1 3 5 6 7}

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

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

Group I: Mirikizumab Experimental Treatment 1 Intervention

Participants will receive mirikizumab intravenously (IV) and mirikizumab subcutaneously (SC).

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

Findings from Research

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]

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 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 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]

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 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 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]

References

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

Mirikizumab: First Approval. [2023]

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

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

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. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

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

6. England pubmed.ncbi.nlm.nih.gov

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