Efficacy and Safety of Remibrutinib in Patients with Secondary Progressive Multiple Sclerosis: A Phase III, Randomized, Double-Blind, Placebo-Controlled Study

The primary objective of this study is to evaluate the efficacy of remibrutinib in delaying disability progression in patients with secondary progressive multiple sclerosis, as measured by the Expanded Disability Status Scale (EDSS). 5 The secondary objectives include:

• Assessment of superiority compared to placebo regarding the delay of disability progression via EDSS and other clinical and magnetic resonance imaging (MRI) measures.
• Evaluation of the safety and tolerability of the investigational product.

The study involves a total of 608 patients diagnosed with secondary progressive multiple sclerosis. The population includes both males and females within the age range of 18 to 65 years. Participants must meet the 2017 revised McDonald criteria for diagnosis and present with an expanded disability status scale score between 3.0 and 6.0. Inclusion requires documented evidence of disability progression during the 12 months preceding screening, alongside an absence of clinical relapses in the 24 months prior to randomization.

This Phase III, randomized, double-blind, placebo-controlled study is designed to evaluate the efficacy and safety of remibrutinib in patients diagnosed with secondary progressive multiple sclerosis. The primary objective is to demonstrate the ability of the investigational product to delay disability progression, measured by the Expanded Disability Status Scale (EDSS). The methodology involves the administration of either remibrutinib or a placebo in film-coated tablet form. The clinical trial includes a screening visit to confirm eligibility based on specific criteria, such as an EDSS score between 3.0 and 6.0 and documented disability progression within the preceding 12 months. Following screening and randomization, participants undergo scheduled follow-up visits to monitor secondary endpoints, including the Timed 25-Foot Walk, the 9-Hole Peg Test, and brain atrophy rates. Safety assessments include adverse events monitoring, laboratory data, electrocardiogram, and the Columbia Suicide Severity Rating Scale. The study is estimated to conclude by January 2034.

The experimental medication, remibrutinib, is administered as a film-coated tablet via the oral route. This agent is being evaluated for the treatment of secondary progressive multiple sclerosis.

The control group receives a placebo in the form of tablets matched to the remibrutinib film-coated tablets.

The primary efficacy endpoint is the time to 6-month confirmed disability progression (6mCDP) assessed using the Expanded Disability Status Scale (EDSS) in patients with secondary progressive multiple sclerosis.

Secondary efficacy parameters include:

• Time to 3-month confirmed disability progression (3mCDP) on EDSS.
• Time to 6-month confirmed disability improvement (6mCDI) on EDSS.
• Time to 3-month worsening by at least 20% in the Timed 25-Foot Walk (T25FW).
• Time to 3-month worsening by at least 20% in the 9-Hole Peg Test (9-HPT).
• Annualized rate of new or enlarging T2 lesions.
• Percentage of participants with annualized rate of brain atrophy.
• Time to 6-month worsening by at least 4 points in the Symbol Digit Modalities Test (SDMT).