A Study to Evaluate the Efficacy and Safety of Fenebrutinib Compared With Ocrelizumab in Adult Participants With Primary Progressive Multiple Sclerosis

A study to evaluate the efficacy and safety of fenebrutinib on disability progression in adult participants with Primary Progressive Multiple Sclerosis (PPMS). All eligible participants will be randomized 1:1 to either daily oral fenebrutinib (and placebo) or intravenous (IV) ocrelizumab (and placebo) in a blinded fashion through an interactive voice or web-based response system (IxRS). 985 participants were enrolled and recruited globally. Participants who discontinue study medication early or discontinue from the study will not be replaced. The Open-Label Extension (OLE) phase is contingent on a positive benefit-risk result in the Primary Analysis of the study.

Inclusion Criteria: * For sites in Germany and Italy only, enrollment is restricted to participants aged 46-65 years * A diagnosis of PPMS in accordance to the revised 2017 McDonald Criteria (Thompson et al. 2018). * Disability progression in the 12 months prior to screening. * Expanded Disability Status Scale (EDSS) score from 3.0 to 6.5 inclusive at screening. * Pyramidal functional subscore \>=2 at screening. * For participants currently receiving proton pump inhibitors (PPIs), H2-receptor antagonists (H2RAs), symptomatic treatment for MS (e.g. fampridine, cannabis) and/or physiotherapy: treatment at a stable dose during the screening period prior to the initiation of study treatment and plans to remain at a stable dose for the duration of study treatment. * Neurologically stable for at least 30 days prior to randomization and baseline assessments. * Ability to complete the 9-Hole Peg Test (9-HPT) for each hand in \1 year prior to screening. * Known presence of other neurological disorders, that could interfere with the diagnosis of MS or assessments of efficacy or safety during the study, clinically significant cardiovascular, psychiatric, pulmonary, renal, hepatic, endocrine, metabolic or gastrointestinal disease. * Presence of cirrhosis (Child-Pugh Class A, B, or C) * Chronic liver disease unless considered stable for \>6 months * Acute liver disease * Any concomitant disease that may require chronic treatment with systemic corticosteroids, immunosuppressants or specific medication that could impact the primary evaluation of the study. * History of alcohol or other drug abuse within 12 months prior to screening. * Female participants who are pregnant or breastfeeding or intending to become pregnant during the study or 6 or 12 months (as applicable from the local label for ocrelizumab) after final dose of study drug. * Male participants intending to father a child during the study or for 28 days after final dose of study drug. * Lack of peripheral venous access. * Any previous treatment with immunomodulatory or immunosuppressive medication without an appropriate washout period. * Receipt of a live or live-attenuated vaccine within 6 weeks prior to randomization. * Immunocompromised state, history of primary or secondary (non-drug related) immunodeficiency, or history of transplantation or antirejection therapy * Known bleeding diathesis, anemia, or history of hospitalization or transfusion for gastrointestinal (GI) bleed * Any previous treatment with cladribine, mitoxantrone, daclizumab, alemtuzumab, or cyclophosphamide OLE Exclusion Criteria: * Chronic liver disease unless considered stable for \> 6 months * Acute liver disease