A Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Efficacy of Fenebrutinib in Relapsing Multiple Sclerosis

The primary objective of this study is to evaluate the **efficacy** of fenebrutinib compared with placebo on the total number of new gadolinium-enhancing T1 magnetic resonance imaging (MRI) lesions in patients with **Relapsing Multiple Sclerosis**. This is clinically relevant as it aims to determine the potential of fenebrutinib to reduce the formation of new lesions, which are indicative of disease activity and progression in multiple sclerosis.

Secondary objectives include: - Evaluating the effect of fenebrutinib on MRI lesions, which may provide additional insights into its impact on disease pathology. - Assessing the safety of fenebrutinib compared with placebo, which is crucial for understanding the risk-benefit profile of the treatment. - Characterizing the pharmacokinetic (PK) profile of fenebrutinib, which will help in understanding the drug's absorption, distribution, metabolism, and excretion characteristics.

The clinical trial involves a total of **42 participants** diagnosed with **Relapsing Multiple Sclerosis**. The study population includes both male and female subjects, aged between 18 to 55 years, who meet specific diagnostic criteria in accordance with the revised 2017 McDonald Criteria. Participants were selected based on their documented clinical relapses and MRI evidence of T1 gadolinium-enhancing lesions. The general health status of participants is assessed using the Expanded Disability Status Scale, with scores ranging from 0 to 5.5. Lifestyle considerations include adherence to contraceptive measures for both men and women of childbearing potential during the treatment period and for 28 days after the final dose of fenebrutinib. The trial population includes a vulnerable group, ensuring comprehensive evaluation across diverse demographics.

The clinical trial is designed to evaluate the efficacy of **fenebrutinib** in individuals with **relapsing multiple sclerosis**. This study is structured as a randomized, double-blind, placebo-controlled trial, ensuring that neither the participants nor the investigators are aware of the treatment assignments, thereby minimizing bias. The trial is expected to span from February 2022 to December 2026, with participant involvement anticipated to last approximately 12 weeks. The primary objective is to assess the total number of new gadolinium-enhancing T1 lesions on MRI scans at weeks 4, 8, and 12. Secondary endpoints include the evaluation of new or enlarging T2-weighted lesions, adverse events, changes in vital signs and laboratory test results, and the plasma concentration of fenebrutinib.

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 **Expanded Disability Status Scale** (EDSS) score. Following randomization, participants will attend follow-up visits at weeks 4, 8, and 12, during which MRI scans and other assessments will be conducted to monitor the progression of the disease and the safety of the treatment. The end-of-study visit will occur at the conclusion of the 12-week treatment period, where final evaluations will be performed.

Involvement in the study may be terminated early if participants experience significant adverse events, fail to adhere to the study protocol, or withdraw consent. The trial is conducted in accordance with ethical guidelines, ensuring the safety and well-being of all participants throughout the study duration.

The clinical trial involves the administration of **fenebrutinib**, an experimental medication developed by Genentech, Inc. Fenebrutinib is a chemical substance with the sponsor product code RO 701-0939/F41-01. The pharmaceutical form, dosage, route, and frequency of administration are not specified in the provided data. The medication is not a pediatric formulation and is classified as a chemical medicinal product. The trial aims to evaluate the efficacy of fenebrutinib in patients with relapsing multiple sclerosis by comparing it to a placebo.

In addition to fenebrutinib, the study includes a placebo as a comparator treatment. The placebo is used to maintain the double-blind nature of the trial, ensuring that neither the participants nor the investigators know which treatment is being administered. The placebo is designed to match the experimental medication in appearance and administration method, although specific details regarding its formulation and administration are not provided.

Another product, with the sponsor product code RO 701-0939/F57, is also included in the trial. This product is chemically identical to fenebrutinib and is developed by Genentech, Inc. It is not a pediatric formulation and is classified as a chemical medicinal product. The specific role of this product in the trial is not detailed in the provided data, but it is likely used in a similar capacity to the primary experimental medication.

The efficacy of fenebrutinib in the treatment of **Relapsing Multiple Sclerosis** will be assessed through a randomized, double-blind, placebo-controlled study. The primary endpoint for evaluating efficacy is the total number of new gadolinium-enhancing T1 lesions observed on magnetic resonance imaging (MRI) scans of the brain at Weeks 4, 8, and 12. Secondary endpoints include the total number of new or enlarging T2-weighted lesions on brain MRI at the same timepoints, the proportion of participants free from any new gadolinium-enhancing T1 lesions and new or enlarging T2-weighted lesions, incidence and severity of adverse events, changes from baseline in vital signs and targeted clinical laboratory test results, the proportion of participants with suicidal ideation or behavior as assessed by the Columbia-Suicide Severity Rating Scale, and plasma concentration of fenebrutinib at specified timepoints.