Evaluation of LY3541860 Versus Placebo in Reducing New T1 Gadolinium-Enhancing Lesions in Adults with Relapsing Multiple Sclerosis

The primary objective of this study is to evaluate the **efficacy** of LY3541860 compared to placebo in reducing the number of new T1 gadolinium-enhancing (GdE) MRI brain lesions in participants with **Relapsing Multiple Sclerosis** (RMS). This is clinically relevant as the presence of new T1 GdE lesions is indicative of active inflammation and disease progression in RMS, and reducing these lesions could potentially slow disease progression and improve patient outcomes.

The clinical trial involves a total of **26 participants** diagnosed with **Relapsing Multiple Sclerosis**. The study population includes both male and female subjects, with an age range corresponding to category code 3, which typically includes adults. Participants were selected based on specific criteria, including a relapsing course of multiple sclerosis activity and an Expanded Disability Status Scale (EDSS) score of less than or equal to 5.5 at screening and randomization. The trial does not focus on a vulnerable population, and no specific lifestyle considerations such as diet or physical activity are highlighted. The selection criteria ensure that participants have experienced recent disease activity, as evidenced by documented relapses or active brain lesions on MRI scans.

The clinical trial is designed as an **adaptive Phase 2a/2b, randomized, double-blind, parallel-group study** to evaluate the safety and efficacy of LY3541860 compared to placebo in adult participants with **relapsing multiple sclerosis**. The primary objective is to assess the efficacy of LY3541860 in reducing the number of new T1 gadolinium-enhancing (GdE) MRI brain lesions. The trial is expected to commence recruitment on June 23, 2024, and conclude by March 20, 2026, with an estimated duration of approximately 21 months.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a relapsing course of multiple sclerosis and an Expanded Disability Status Scale (EDSS) score of ≤5.5. Following randomization, participants will receive either LY3541860 or placebo, administered as a **solution for injection/infusion**. The study will include regular follow-up visits to monitor safety and efficacy, with MRI scans conducted to measure the primary endpoint of cumulative new T1 GdE lesions. The end-of-study visit will finalize data collection and assess the overall outcomes of the trial.

Participant involvement is expected to last for the duration of the trial, with conditions for early termination including withdrawal of consent, adverse events, or non-compliance with study protocols. The trial will utilize a placebo-controlled design, with LY3541860 serving as the investigational product and 0.9% sodium chloride as an auxiliary product. The study aims to provide valuable insights into the potential benefits of LY3541860 in managing relapsing multiple sclerosis, contributing to the broader understanding of treatment options for this condition.

The clinical trial involves the administration of **LY3541860**, a solution for injection/infusion, as the experimental medication. LY3541860 is a protein-based substance developed by Eli Lilly and Company Limited. The pharmaceutical form is a solution for injection/infusion, and it is administered via injection. The dosing schedule allows for a maximum treatment period of 1 day, with the dosage measured in milligrams. The specific dosage and frequency of administration are determined by the study protocol, and participant compliance is monitored throughout the trial.

**Gadoteric acid**, also known as meglumine gadoterate, is used as a comparator treatment in the study. It is a radiology MRI contrast agent with the ATC code V08CA02. The pharmaceutical form is identified as PHF00231MIG, and it is administered via injection. The maximum treatment period for gadoteric acid is 72 hours. The dosage is measured in millimoles, and the administration schedule is aligned with the imaging requirements of the study. Compliance with the administration schedule is monitored to ensure accurate imaging results.

**0.9% sodium chloride** is utilized as an auxiliary treatment in the trial. It serves as a standard diluent or placebo, depending on the specific requirements of the study protocol. The pharmaceutical form and route of administration are not specified in the provided data. The use of 0.9% sodium chloride is consistent with standard clinical practices for maintaining participant hydration and ensuring the proper administration of other injectable medications. Compliance with the administration of 0.9% sodium chloride is monitored as part of the overall study protocol.

The efficacy of LY3541860 in the clinical trial will be assessed by evaluating its impact on the number of new T1 **Gadolinium-Enhancing** (GdE) lesions in participants with Relapsing Multiple Sclerosis (RMS). The primary endpoint for efficacy is the cumulative number of new T1 GdE lesions, which will be measured using magnetic resonance imaging (MRI) scans. This assessment will provide quantitative data on the progression of the disease and the potential therapeutic effect of LY3541860 compared to a placebo.