Mirikizumab for Ulcerative Colitis

(SHINE-ON Trial)

Recruiting at 87 trial locations

Overseen By Physicians interested in becoming principal investigators please contact

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Eli Lilly and Company

Disqualifiers: Unstable illness, Adenomatous polyps, 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: 44

Duration: 52 weeks

150 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the long-term effectiveness of mirikizumab for children with ulcerative colitis or Crohn's disease. The study administers different doses of mirikizumab based on the child's weight and spans approximately 172 weeks with multiple check-ins. It includes a special dosing option if the initial response to treatment diminishes. Children who participated in earlier studies of mirikizumab and found it beneficial might be suitable candidates for this trial. As a Phase 3 trial, it represents the final step before FDA approval, offering a chance to contribute to the approval of a potentially effective treatment.

Will I have to stop taking my current medications?

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

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

Research has shown that mirikizumab, a treatment for ulcerative colitis (UC), can cause some common side effects, such as colds, injection site reactions, joint pain, and skin rash. Studies have found that its safety profile in adults with UC is generally similar to that in adults with Crohn's disease (CD).

The FDA has already approved mirikizumab for adults with moderately to severely active ulcerative colitis, indicating confidence in its safety for this condition. However, individual experiences may vary, so discussing any concerns with a healthcare provider is advisable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Mirikizumab for ulcerative colitis because it targets the p19 subunit of interleukin-23 (IL-23), a cytokine involved in inflammation, which is different from many existing treatments that often target TNF-alpha. Unlike standard options such as mesalamine or corticosteroids, Mirikizumab offers a novel approach by specifically blocking this pathway, potentially leading to better control of inflammation. Additionally, Mirikizumab is administered subcutaneously, which could offer more convenient dosing compared to intravenous options. This unique mechanism and delivery method have the potential to provide more effective and convenient treatment for patients with ulcerative colitis.

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

Research shows that mirikizumab may help treat ulcerative colitis. In earlier studies, patients experienced quick and lasting relief from the urgent need to use the bathroom. Among those who improved after 12 weeks, 58% showed visible healing of their colon lining after a year. Another study found that ongoing treatment with mirikizumab helped many patients remain symptom-free for three years. This treatment remains effective for a long time without requiring corticosteroids for up to four years. The trial will evaluate different doses of mirikizumab to determine its effectiveness in managing ulcerative colitis symptoms over the long term. ^{1 4 6 7 8}

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 pediatric patients who have ulcerative colitis or Crohn's disease and were part of previous mirikizumab studies. They should have completed the last study without serious side effects and could benefit from continued treatment. Girls must agree to use birth control, and participants can't join if they've had severe reactions before, stopped the drug due to risks, have unstable illnesses, untreated polyps, or are pregnant/breastfeeding.

Inclusion Criteria

Participants from originating studies (I6T-MC-AMBU [NCT04004611], I6T-MC-AMAM [NCT03926130]) , I6T-MC-AMAY [NCT05509777]) who would, in the opinion of the investigator, derive clinical benefit from further treatment with mirikizumab

I completed all required steps in a previous study and am still on the study medication.

I agree to follow the study's birth control requirements.

Exclusion Criteria

Participants must not be pregnant or breastfeeding.

I haven't had severe side effects from previous treatments that would make continuing treatment risky.

I have never stopped taking the study drug in a way that restarting it would be unsafe.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive various doses of Mirikizumab based on their condition and weight, with potential intravenous rescue dosing if response is lost

52 weeks

Up to 44 visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Long-term evaluation of the efficacy and safety of Mirikizumab in pediatric participants

116 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Mirikizumab

Trial Overview The trial tests the long-term effectiveness of a medication called mirikizumab in young patients with two types of inflammatory bowel diseases: ulcerative colitis and Crohn's disease. It spans roughly 172 weeks with up to 44 clinic visits to monitor how well the drug works over time.

How Is the Trial Designed?

Group I: Mirikizumab Dose 7 for UC or CD Experimental Treatment 1 Intervention

Intravenous (IV) rescue dosing, if response is lost.

Group II: Mirikizumab Dose 6 for CD Experimental Treatment 1 Intervention

Dose 6 of Mirikizumab is administered SC Dosing is based on the participant's weight.

Group III: Mirikizumab Dose 5 for CD Experimental Treatment 1 Intervention

Dose 5 of Mirikizumab is administered SC Dosing is based on the participant's weight.

Group IV: Mirikizumab Dose 4 for CD Experimental Treatment 1 Intervention

Dose 4 of Mirikizumab is administered SC Dosing is based on the participant's weight.

Group V: Mirikizumab Dose 3 for UC Experimental Treatment 1 Intervention

Dose 3 of Mirikizumab is administered SC Dosing is based on the participant's weight.

Group VI: Mirikizumab Dose 2 for UC Experimental Treatment 1 Intervention

Dose 2 of Mirikizumab is administered SC Dosing is based on the participant's weight.

Group VII: Mirikizumab Dose 1 for UC Experimental Treatment 1 Intervention

Dose 1 of Mirikizumab is administered subcutaneously (SC) Dosing is based on the participant's weight.

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]

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-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 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 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 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]

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. 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 ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06696014

Study Details | NCT06696014 | Mirikizumab Real World ... The goal of this observational study is to learn about how effective mirikizumab (Omvoh) is when treating patients with ulcerative colitis (UC).

6. omvoh.lilly.com omvoh.lilly.com/hcp/safety-profile

Safety Profile & Adverse Events | Omvoh® (mirikizumab-mrkz) Overall, the safety profiles in adult patients with CD and in adult patients with UC treated with Omvoh are generally consistent.

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2023/761279s000lbl.pdf

Omvoh - accessdata.fda.gov OMVOH is a prescription medicine used in adults with moderately to severely active ulcerative colitis. It is not known if OMVOH is safe and effective in ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT07059130

Evaluating the Efficacy and Safety of Mirikizumab in Adults ... This research study looks at how safe and effective a medicine called Mirikizumab is for treating older adults (aged 60 and above) who have moderate to severe ...