Efficacy, Safety, and Tolerability of BMS-986368, a FAAH/MAGL Inhibitor, in Treating Spasticity in Multiple Sclerosis: A Randomized, Double-Blind, Placebo-Controlled Study

The primary objective of this study is to evaluate the effect of **BMS-986368** compared with placebo on **spasticity** in patients with **Multiple Sclerosis** (MS). This is clinically relevant as spasticity is a common and debilitating symptom in MS, affecting patients' quality of life and functional abilities. Understanding the efficacy of BMS-986368 could lead to improved management of spasticity in this patient population.

Secondary objectives include:

• Assessing the impact of BMS-986368 compared with placebo on walking, overall functional ability, and patients' experiences living with spasticity in MS.
• Evaluating the safety profile of BMS-986368 and determining the pharmacokinetics, specifically the levels of the drug in the body after administration in patients with MS spasticity.

The clinical trial involves a total of **100 participants** diagnosed with **Multiple Sclerosis Spasticity**. The study population includes both male and female subjects, aged between **18 and 70 years**. Participants were selected based on specific criteria, including a confirmed diagnosis of multiple sclerosis and a history of spasticity for at least six months prior to the screening visit. The participants exhibit a modified Ashworth Scale score of 2 or higher in at least two muscle groups, with at least one group in the leg, and an Expanded Disability Status Scale score ranging from 3.0 to 6.5, indicating moderate to significant disability. The trial does not include a vulnerable population, and no specific lifestyle considerations such as diet or physical activity are highlighted in the selection process.

The clinical trial is a **Phase II**, randomized, double-blind, four-arm, placebo-controlled, multicenter study designed to assess the efficacy, safety, and tolerability of three doses of orally administered BMS-986368, a **FAAH/MAGL inhibitor**, for the treatment of spasticity in participants with **Multiple Sclerosis**. The trial is expected to commence recruitment on September 19, 2025, and conclude by January 27, 2027. Participants will be randomly assigned to one of four groups, receiving either one of the three doses of BMS-986368 or a placebo. The study will be conducted over a period of six weeks, with the primary endpoint being the change in stiffness in the most affected leg, measured using the Total Numeric-transformed Modified Ashworth Scale-Most Affected Lower Limb (TNmAS-MALL).

The sequence of study visits includes an initial screening visit, where eligibility criteria are assessed. Participants must be aged 18-70 years, have a diagnosis of multiple sclerosis with a history of spasticity for at least six months, and meet specific criteria on the modified Ashworth Scale and Expanded Disability Status Scale. Following the screening, participants will undergo baseline assessments before randomization. Subsequent visits will occur weekly to monitor safety, efficacy, and adherence to the study protocol. The end-of-study visit will involve final assessments and evaluations of the primary and secondary endpoints, including the Numeric Rating Scale-Spasticity (NRS-S), MS Spasticity Scale (MSSS-88), Timed 25-Foot Walk (T25FW) test, and Clinical Global Impression of Severity.

Participant involvement is expected to last approximately six weeks, with conditions for early termination including adverse events, non-compliance with the study protocol, or withdrawal of consent. The study aims to provide valuable insights into the potential benefits of BMS-986368 in managing spasticity associated with multiple sclerosis, contributing to the broader understanding of treatment options for this condition.

The clinical trial involves the administration of **BMS-986368**, a **FAAH/MAGL inhibitor**, for the treatment of spasticity in participants with **Multiple Sclerosis**. The experimental medication, BMS-986368, is provided in the form of a capsule. The active substance in BMS-986368 is **CC-97489**, which is chemically derived. The pharmaceutical form of the medication is a hard capsule, and it is administered orally. The trial includes three different dosages of BMS-986368: 1 mg, 3 mg, and an unspecified third dosage. The maximum daily dose and total dose are set at 9999 mg, with a maximum treatment period of 9999 days, although specific dosing schedules are not detailed. The medication is not formulated for pediatric use.

In addition to the experimental treatment, the study employs a placebo control. The placebo is a capsule with no active medicinal ingredient, designed to match the experimental medication in appearance and administration route. The placebo is administered orally, in a manner consistent with the experimental treatment, to maintain the double-blind nature of the trial. The use of a placebo allows for the assessment of the efficacy, safety, and tolerability of BMS-986368 by providing a baseline for comparison.

Participant compliance with the dosing regimen is monitored throughout the study, although specific methods for compliance monitoring are not detailed in the provided data. The trial is structured as a randomized, double-blind, four-arm, placebo-controlled, multicenter study, ensuring rigorous evaluation of the treatment's effects on spasticity in participants with Multiple Sclerosis.

The efficacy of the investigational drug BMS-986368, a **FAAH/MAGL inhibitor**, will be assessed in a Phase II, randomized, double-blind, placebo-controlled, multicenter study. The primary endpoint for evaluating efficacy is the change in stiffness in the most affected leg of participants with Multiple Sclerosis (MS) from the start of the study to the end of Week 6. This will be measured using the Total Numeric-transformed Modified Ashworth Scale-Most Affected Lower Limb (TNmAS-MALL).

Secondary endpoints include several measures to further assess the impact of the treatment on spasticity and overall function. These include the Numeric Rating Scale-Spasticity (NRS-S), which participants will complete daily using an eDiary, and the MS Spasticity Scale (MSSS-88), which evaluates spasticity in daily life. Additionally, the Timed 25-Foot Walk (T25FW) test will be used to measure mobility, and the Clinical Global Impression of Severity will be used by investigators to assess the severity of the participant's condition. These assessments will provide a comprehensive evaluation of the drug's efficacy in managing spasticity in MS patients.