Phase 2 Adaptive Dose-Ranging Study of Eltrekibart and Mirikizumab in Adults with Moderately to Severely Active Ulcerative Colitis

The primary objective of this study is to evaluate whether **eltrekibart** alone is superior to placebo in inducing clinical remission in participants with moderately to severely active **ulcerative colitis**. This is clinically relevant as achieving clinical remission is a critical goal in the management of ulcerative colitis, potentially improving patient outcomes and quality of life.

The clinical trial involves a total of **43 participants** diagnosed with **Ulcerative Colitis**. The study population includes both male and female subjects, with an age range corresponding to categories 3 and 4, which typically represent adults. Participants were selected based on their diagnosis of moderately to severely active Ulcerative Colitis, with a history of inadequate response, loss of response, or intolerance to at least one conventional medication or advanced therapy. The trial includes individuals who are on a stable dose of certain oral UC medications. The study population is characterized by a diverse group, including vulnerable populations, and adheres to specific contraception requirements. Lifestyle factors such as diet and physical activity were not specified by the sponsor.

The clinical trial is designed to evaluate the efficacy of **Eltrekibart** alone or in combination with **Mirikizumab** in inducing clinical remission in adult patients with moderately to severely active **ulcerative colitis**. This is a Phase II, adaptive, dose-ranging study that employs a randomized, double-blind, placebo-controlled design. The trial is expected to commence recruitment on May 19, 2025, and conclude by September 16, 2028. Participants will be randomly assigned to receive either Eltrekibart, Mirikizumab, a combination of both, or a placebo. The primary endpoint is the proportion of participants achieving clinical remission at Week 12.

The study involves several key visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a diagnosis of ulcerative colitis for at least three months, moderate to severe disease activity, and an inadequate response to conventional or advanced therapies. Participants must also adhere to specific contraception requirements. Following the screening, participants will attend regular follow-up visits to monitor their response to treatment and any adverse events. The end-of-study visit will assess the overall outcomes and safety of the interventions.

Participant involvement is expected to last for the duration of the treatment period, with the possibility of early termination if significant adverse effects occur or if the participant withdraws consent. The trial's methodology ensures rigorous assessment of the investigational products' safety and efficacy, contributing valuable data to the understanding of treatment options for ulcerative colitis.

The clinical trial involves the administration of **Mirikizumab**, a **solution for injection** provided in a pre-filled syringe. The active substance, **mirikizumab**, is a protein of other origin, specifically a monoclonal antibody. The pharmaceutical form is a solution for injection, and it is administered via subcutaneous injection. The dosing schedule and frequency of administration are determined by the study protocol, with compliance monitored through standard clinical trial procedures. The maximum treatment period is set at one unit of time, as defined by the trial's parameters.

**Eltrekibart** is another investigational product used in this study. It is a **solution for infusion** containing a humanised IgG4 kappa monoclonal antibody targeting CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, CXCL7, and CXCL8. The administration route is intravenous infusion. The dosing regimen is outlined in the study protocol, with a maximum treatment period of one unit of time. Participant compliance is monitored according to the trial's compliance procedures.

The study also includes a **placebo** for LY3074828 SC Injection, provided in a 1mL prefilled syringe. The placebo is used to maintain blinding and assess the efficacy of the investigational products. The administration route and frequency are consistent with the active treatment arms, ensuring comparability across study groups.

Additionally, **0.9% sodium chloride** is utilized as a non-experimental treatment. It serves as a standard diluent or control in the study, with no specific pharmaceutical form or administration route detailed in the trial documentation. Its role is primarily supportive, ensuring the integrity of the study's blinding and control measures.

Efficacy in this clinical trial will be assessed by evaluating the primary endpoint, which is the proportion of participants who achieve **clinical remission** at Week 12. The trial is designed to determine whether Eltrekibart alone is superior to placebo in inducing clinical remission in participants with moderately to severely active **ulcerative colitis**. The assessment of clinical remission will be conducted using the UC disease activity score, a validated scale for measuring disease activity in ulcerative colitis. Data collection will occur at specified timepoints, with the primary focus on the 12-week mark to determine the efficacy of the treatment. The trial will involve adult patients who have had an established diagnosis of ulcerative colitis for at least three months and have shown an inadequate response to, loss of response to, or intolerance to at least one conventional medication or advanced therapy. The trial will follow a structured schedule for measuring and analyzing the efficacy parameters to ensure accurate and reliable results.