I6T-MC-AMBA - A Multicenter, Phase 3, Open-Label Study to Investigate the Efficacy, Pharmacokinetics, and Safety of Mirikizumab in Participants 2 Years to Less Than 18 Years of Age with Moderately to Severely Active Ulcerative Colitis

The primary objective of this multicenter, Phase 3, open-label study is to demonstrate the **superiority** of **mirikizumab** treatment compared to adult placebo in achieving Modified Mayo Score (MMS) clinical remission among pediatric participants aged 2 to less than 18 years with moderately to severely active **ulcerative colitis** who were clinical responders at Week 12. This objective is clinically relevant as achieving clinical remission is a critical goal in the management of ulcerative colitis, aiming to improve patient outcomes and quality of life by reducing disease activity and associated symptoms.

The clinical trial involves a total of **30 participants** diagnosed with **moderately to severely active ulcerative colitis**. The study population includes both male and female subjects, aged between **2 and 18 years**, who weigh more than 10 kg. Participants were selected based on their failure to respond to previous treatments, including corticosteroids, biologics, anti-TNF antibodies, anti-integrin antibodies, or Janus Kinase (JAK)-Inhibitor treatment. All participants have had ulcerative colitis for at least three months prior to the baseline, with endoscopic evidence corroborated by a histopathology report. The trial includes a vulnerable population, given the age range of the participants. Lifestyle considerations such as diet and physical activity were not specified by the sponsor.

The clinical trial is designed to evaluate the **efficacy**, pharmacokinetics, and safety of **mirikizumab** in participants aged 2 to less than 18 years with moderately to severely active **ulcerative colitis**. This is a multicenter, Phase 3, open-label study. The trial will involve a randomized, controlled design to ensure the reliability of the results. The estimated duration of the trial is from December 15, 2023, to July 20, 2026, with the primary endpoint being the percentage of participants achieving Modified Mayo Score (MMS) clinical remission at Week 52 among those who were clinical responders at Week 12.

Participants will undergo a sequence of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age, weight, and previous treatment failures. The inclusion criteria require participants to have a history of ulcerative colitis for at least three months, confirmed by endoscopic evidence and a histopathology report. Follow-up visits will be scheduled to monitor the participants' response to treatment and any adverse effects. The end-of-study visit will conclude the trial, assessing the long-term outcomes of the treatment.

The expected length of participant involvement is approximately 52 weeks, with conditions for early termination including significant adverse events or withdrawal of consent. The trial will utilize two formulations of mirikizumab: a 100 mg solution for injection in a pre-filled syringe administered subcutaneously, and a 300 mg concentrate for solution for infusion administered intravenously. The trial aims to demonstrate the superiority of mirikizumab treatment compared to adult placebo in achieving clinical remission, thereby providing valuable insights into its potential as a therapeutic option for pediatric patients with ulcerative colitis.

The clinical trial involves the administration of **mirikizumab**, an investigational medication, in two distinct pharmaceutical forms. The first form is "Omvoh 100 mg solution for injection in pre-filled syringe," which is a **solution for injection**. This formulation is administered via **subcutaneous injection**. The dosage is 100 mg per administration, and the frequency of administration is determined by the study protocol. The product is manufactured by ELI LILLY NEDERLAND B.V. and is not a pediatric formulation. The active substance, mirikizumab, is a protein of non-specific origin, and its administration is monitored for compliance throughout the study.

The second form of the investigational medication is "Omvoh 300 mg concentrate for solution for infusion," which is a **solution for infusion**. This formulation is administered intravenously. The dosage is 300 mg per administration, with the frequency and schedule of administration specified in the study protocol. Similar to the first form, this product is also manufactured by ELI LILLY NEDERLAND B.V. and is not a pediatric formulation. The active substance, mirikizumab, is consistent across both formulations, and participant compliance is closely monitored to ensure adherence to the dosing schedule.

In this clinical trial, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The trial aims to evaluate the efficacy, pharmacokinetics, and safety of mirikizumab in participants aged 2 to less than 18 years with moderately to severely active **ulcerative colitis**. The study is designed to demonstrate the superiority of mirikizumab treatment compared to adult placebo in achieving clinical remission among participants who were clinical responders at Week 12. Compliance with the dosing schedule is critical, and adherence is monitored through established clinical trial procedures.

Efficacy in this clinical trial will be assessed by evaluating the primary endpoint, which is the percentage of participants achieving **Modified Mayo Score (MMS) Clinical Remission** at Week 52 among those who were clinical responders at Week 12. The trial is designed to demonstrate the superiority of **mirikizumab** treatment compared to an adult placebo in achieving this endpoint. The MMS is a validated scale used to measure disease activity in patients with **ulcerative colitis**. Participants will be monitored and assessed at specified timepoints, including Week 12 and Week 52, to determine their clinical response and remission status. The trial will involve participants aged 2 to less than 18 years with moderately to severely active ulcerative colitis who have previously failed treatments such as corticosteroids, biologics, anti-TNF antibodies, anti-integrin antibodies, or Janus Kinase (JAK)-Inhibitors. The efficacy assessments will be conducted in a multicenter, open-label study format, ensuring comprehensive data collection and analysis to evaluate the treatment's impact on the target population.