Mirikizumab for Pediatric Ulcerative Colitis

(SHINE-2 Trial)

Recruiting at 91 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: 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called mirikizumab to determine its effectiveness and safety for children with moderate to severe ulcerative colitis, a chronic condition causing inflammation and sores in the colon. The study involves different groups, each receiving varying doses of the drug either through an IV or an injection under the skin. Eligible children have had ulcerative colitis for at least three months and have tried other treatments, such as steroids or biologics, without success. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

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.

Is there any evidence suggesting that mirikizumab is likely to be safe for pediatric patients with ulcerative colitis?

Research shows that mirikizumab is generally well-tolerated by people with ulcerative colitis (UC). One study found that mirikizumab was more effective than a placebo in helping patients achieve remission, significantly improving their symptoms. Importantly, it maintained a good safety record, with serious side effects being rare.

Another study examined children and found results similar to those in adults, indicating that children also tolerated the treatment well. Early symptom improvements were observed, and side effects mirrored those seen in adults. This suggests that mirikizumab could be a safe option for children with UC. Prospective participants should consult a healthcare provider to determine if joining a trial is appropriate. ^{1 2 3 4 5}

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

Unlike the standard ulcerative colitis treatments that typically rely on broad immunosuppressants like corticosteroids or TNF inhibitors, Mirikizumab offers a targeted approach. It works by specifically inhibiting the activity of interleukin-23 (IL-23), a protein involved in inflammatory processes, which could potentially lead to better outcomes with fewer side effects. Researchers are excited because this targeted mechanism may provide a more effective and safer option for children suffering from ulcerative colitis, potentially transforming the management of this challenging condition.

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

Research shows that mirikizumab can help treat ulcerative colitis (UC). Studies have found that this medication can quickly and effectively reduce symptoms like the urgent need to use the bathroom. One study found that 24% of people taking mirikizumab experienced a significant reduction or disappearance of symptoms after 12 weeks. Among those who improved by week 12, 51% continued to have reduced symptoms after one year. Mirikizumab proved more effective than a placebo in easing several symptoms and was generally well-tolerated by patients. Overall, the results are promising for people with moderate to severe UC. Participants in this trial will receive mirikizumab in different weight-based dosing groups to further evaluate its effectiveness and safety in pediatric patients. ^{1 2 3 4 5}

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 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

I have had surgery on my intestines before.

Have immune deficiency syndrome

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

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 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, 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]

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]

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, 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 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]

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10910362/

PK, Efficacy, and Safety of Mirikizumab as Induction ... Outcomes in pediatric patients in the SHINE-1 study were comparable with or better than outcomes in adults in the LUCENT-1 trial, including clinical response by ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04844606

Study Details | NCT04844606 | A Master Protocol (AMAZ) ... The main purpose of this study is to evaluate the long-term efficacy of mirikizumab in pediatric participants with ulcerative colitis (UC) or Crohn's ...

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

UC Clinical Results & Safety Data | Omvoh® (mirikizumab-mrkz) At 12 weeks, 24% of people taking Omvoh achieved clinical remission. Among people who saw improvement at Week 12, 51% achieved clinical remission at 1 year.

5. ddw.digitellinc.com ddw.digitellinc.com/p/s/pk-efficacy-and-safety-of-mirikizumab-as-induction-therapy-in-pediatric-patients-with-moderately-to-severely-active-ulcerative-colitis-results-from-the-phase-2-shine-1-study-3117

PK, EFFICACY AND SAFETY OF MIRIKIZUMAB AS ... Mirikizumab was superior to placebo in inducing clinical remission as well as other symptomatic, clinical, and endoscopic endpoints and had an acceptable safety ...