Mirikizumab for Pediatric Ulcerative Colitis

(SHINE-2 Trial)

Recruiting at 82 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, 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: 52 weeks

60 Participants Needed

Trial Summary

What is the purpose of this trial?

The main purpose of this study is to investigate efficacy, pharmacokinetics and safety of the drug in pediatric participants with moderately to severely active ulcerative colitis (UC).

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, since it mentions participants who have failed certain treatments, it's possible that some medication changes might be required. Please consult with the trial coordinators for specific guidance.

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

Mirikizumab has been shown to be effective in treating moderate to severe ulcerative colitis in adults, including those who did not respond to other treatments. It works by targeting a specific part of the immune system (IL-23) that is involved in inflammation, and it has been approved for use in several countries for this condition. ^{1 2 3 4 5}

Is Mirikizumab safe for humans?

Mirikizumab, also known as Omvoh, has been approved in Japan and received a positive opinion in the EU for treating ulcerative colitis, indicating it has been evaluated for safety in humans. While specific safety data is not detailed in the provided articles, its approval suggests that it has met safety standards for use in humans with ulcerative colitis. ^{1 2 3 6 7}

How is the drug Mirikizumab unique for treating pediatric 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 different from other treatments that may target different proteins or pathways. It is used for patients who do not respond well to conventional therapies, offering a new option for those with moderate to severe ulcerative colitis. ^{1 3 6 8 9}

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 children and teens aged 2 to less than 18, weighing over 10 kg, with moderate to severe ulcerative colitis (UC) that's lasted at least 3 months. They should have tried other treatments like corticosteroids or biologics without success. It's not for those with Crohn's disease, certain other bowel conditions, a history of significant bowel surgery, toxic megacolon, or gastrointestinal cancer.

Inclusion Criteria

My ulcerative colitis is moderate to severe.

I have tried steroids, biologics, or other specific medications without success.

I have had ulcerative colitis for at least 3 months, confirmed by a colonoscopy and biopsy.

Exclusion Criteria

Evidence of toxic megacolon

Have immune deficiency syndrome

I have had surgery on my intestines before.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive mirikizumab weight-based dosing intravenously (IV) or subcutaneously (SC)

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term extension

Participants have the option to enter the long-term extension Study I6T-MC-AMAZ (AMAZ)

Treatment Details

Interventions

• Mirikizumab

Trial Overview The study tests Mirikizumab given by IV (intravenous) or SC (subcutaneous injection) in young patients with UC. The goal is to see how well it works (efficacy), how the body processes it (pharmacokinetics), and its safety profile.

Participant Groups

Group I: Mirikizumab Weight-Based Group 3 Experimental Treatment 2 Interventions

Experimental: Mirikizumab Participants will receive mirikizumab weight-based dosing IV or SC.

Group II: Mirikizumab Weight-Based Group 2 Experimental Treatment 2 Interventions

Experimental: Participants will receive mirikizumab weight-based dosing IV or SC.

Group III: Mirikizumab Weight-Based Group 1 Experimental Treatment 2 Interventions

Experimental: Participants will receive mirikizumab weight-based dosing intravenously (IV) or 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]

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 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]

Mirikizumab, a monoclonal antibody targeting the IL-23 pathway, has been shown to effectively induce and maintain remission in patients with moderately to severely active ulcerative colitis, including those who previously did not respond to other treatments.

This therapy has a favorable safety profile and is the first IL-23 antagonist to receive regulatory approval for ulcerative colitis in Europe, addressing a significant need for new treatment options in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mirikizumab for the treatment of moderate to severe ulcerative colitis. Hanzel, J., Ma, C., Jairath, V.[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]

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]

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. Switzerland pubmed.ncbi.nlm.nih.gov

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

4. 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]

5. England pubmed.ncbi.nlm.nih.gov

Mirikizumab for the treatment of moderate to severe ulcerative colitis. [2023]

6. 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]

7. 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]

8. 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]

9. 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]