Efficacy and Safety Evaluation of Obexelimab in Relapsing Multiple Sclerosis: A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study

The primary objective of this study is to evaluate the effect of weekly subcutaneous administration of **obexelimab** versus placebo in patients with **relapsing multiple sclerosis** (RMS) on the prevention of new gadolinium-enhancing T1 (GdE T1) hyperintense lesions detected using MRI. This is clinically relevant as the presence of GdE T1 lesions is indicative of active inflammation and disease progression in RMS, and their reduction could signify a potential therapeutic benefit.

Secondary objectives include:

• Evaluating the effect of weekly SC administration of obexelimab versus placebo on additional MRI endpoints and neurofilament light chain (NfL) levels, which are biomarkers of neuronal damage and disease activity.
• Assessing the safety and tolerability of weekly SC administration of obexelimab in patients with RMS, which is crucial for determining the feasibility of long-term treatment.

The clinical trial involves a total of **52 participants** diagnosed with **relapsing multiple sclerosis** (RMS), including both relapsing-remitting and secondary progressive forms with relapses. The study population comprises both male and female subjects, aged between 18 and 60 years. Participants were selected based on their ability to provide informed consent and meet specific diagnostic criteria, including an Expanded Disability Status Scale (EDSS) score of 5.5 or lower. The trial includes individuals who have experienced at least one relapse in the past year, two relapses in the past two years, or have at least one active gadolinium-enhancing brain lesion on an MRI scan within the past six months. The study population is not restricted by general health status but includes considerations for reproductive health, requiring female participants to not be pregnant or breastfeeding and to adhere to contraceptive guidelines. Male participants must agree to use contraception or be surgically sterile. The trial does not specify any particular lifestyle considerations such as diet or physical activity. The selection criteria ensure a focus on a vulnerable population, given the nature of the disease and the trial's objectives.

The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled** study to evaluate the efficacy and safety of **Obexelimab** in patients with **relapsing multiple sclerosis**. The primary objective is to assess the effect of weekly subcutaneous administration of Obexelimab versus placebo on the prevention of new Gd-enhancing T1 hyperintense lesions detected using MRI. The trial is expected to commence recruitment on October 18, 2024, and conclude by November 14, 2025, with an estimated duration of 24 weeks for each participant.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, diagnosis, and disease activity. The inclusion criteria require participants to be between 18 and 60 years of age, have a diagnosis of relapsing multiple sclerosis according to the 2017 McDonald criteria, and meet specific disease activity requirements. Following the screening, eligible participants will be randomized to receive either Obexelimab or placebo via subcutaneous injection.

Study visits will occur at regular intervals, including baseline, Week 4, Week 8, and Week 12, to monitor the cumulative number of new GdE T1 hyperintense lesions and other secondary endpoints such as the number of new and/or enlarging T2 weighted hyperintense lesions, changes in T2 lesion volume, and serum neurofilament light chain levels. Safety assessments will include monitoring for adverse events, serious adverse events, and adverse events of special interest.

The end-of-study visit will occur at Week 12, where final assessments will be conducted. Participants are expected to be involved in the study for approximately 24 weeks, including follow-up. Conditions that may lead to early termination from the study include non-compliance with study procedures, withdrawal of consent, or the occurrence of significant adverse events. The trial is conducted in accordance with regulatory guidelines to ensure the safety and well-being of participants.

The clinical trial involves the administration of **Obexelimab**, an investigational medicinal product, to evaluate its efficacy and safety in patients with relapsing multiple sclerosis. Obexelimab is formulated as an injection and is administered via **subcutaneous injection**. The active substance in Obexelimab is a protein of other origin, specifically designed for this study. The maximum daily dose of Obexelimab is 250 mg, with a total maximum dose of 6000 mg over the treatment period. The treatment is administered weekly for a maximum duration of 24 weeks. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the protocol.

In addition to the experimental treatment, a **placebo** is used as a comparator in this double-blind, placebo-controlled study. The placebo is a sterile solution intended for subcutaneous injection, mirroring the administration route of Obexelimab. The use of a placebo allows for the assessment of the true efficacy and safety profile of Obexelimab by providing a baseline for comparison. The placebo is administered with the same frequency and duration as the investigational product to maintain the study's integrity and blinding.

The efficacy of Obexelimab in patients with **Relapsing Multiple Sclerosis** (RMS) will be assessed through a series of primary and secondary endpoints. The primary endpoint is the cumulative number of new Gd-enhancing T1 (GdE T1) hyperintense lesions over Week 8 and Week 12, as measured by brain MRI. Secondary endpoints include the cumulative number of new and/or enlarging T2 weighted hyperintense lesions detected over Week 8 and Week 12, the number of new GdE T1 hyperintense lesions at Week 4, Week 8, and Week 12, and the change from baseline in the volume of T2 lesions at Week 12. Additionally, serum neurofilament light chain (NfL) levels will be measured at Week 12.

The efficacy parameters will be collected and analyzed at specified timepoints, including Week 4, Week 8, and Week 12. Brain MRI will be utilized to detect and quantify the lesions, providing a robust and objective measure of disease activity. The incidence of adverse events (AEs), serious adverse events (SAEs), and AEs of special interest will also be monitored and recorded, following the Common Terminology Criteria for Adverse Events Version 5.0, to ensure a comprehensive evaluation of the treatment's safety profile alongside its efficacy.