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

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 etal. 2018).

• Disability progression in the 12 months prior to screening.

• Expanded Disability Status Scale (EDSS) score from 3.0 to 6.5 inclusive atscreening.

• Pyramidal functional subscore >=2 at screening.

• For participants currently receiving proton pump inhibitors (PPIs), H2-receptorantagonists (H2RAs), symptomatic treatment for MS (e.g. fampridine, cannabis) and/orphysiotherapy: treatment at a stable dose during the screening period prior to theinitiation of study treatment and plans to remain at a stable dose for the durationof study treatment.

• Neurologically stable for at least 30 days prior to randomization and baselineassessments.

• Ability to complete the 9-Hole Peg Test (9-HPT) for each hand in <240 seconds.

• Ability to perform Timed 25-Foot Walk Test (T25FWT) in <150 seconds.

• For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and refrainfrom donating eggs.

• For male participants: agreement to remain abstinent (refrain from heterosexualintercourse) or use contraceptive measures, and refrain from donating sperm.

OLE Inclusion Criteria:

• Completed the Double-Blind Treatment (DBT) phase of the study (remaining on studytreatment; no other Disease-Modifying Therapy (DMT) administered) and who, in theopinion of the investigator, may benefit from treatment with fenebrutinib.

• For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and refrainfrom donating eggs.

• For male participants: agreement to remain abstinent (refrain from heterosexualintercourse) or use contraceptive measures, and refrain from donating sperm.

Exclusion Criteria:

• For participants enrolled in Germany and in Italy only: Presence ofgadolinium-enhancing lesions on T1-weighted MRI (T1Gd +) lesion on the screening MRI

• Any known or suspected active infection (excluding onychomycosis) at screening,including but not limited to a positive screening test for Hepatitis B and C, anactive or latent or inadequately treated infection with tuberculosis (TB), aconfirmed or suspected progressive multifocal leukoencephalopathy (PML).

• Participants with a previous history of a serious Infusion-Related Reaction (IRR) (Common Terminology Criteria for Adverse Events [CTCAE] Grade >= 4) and/or anyhypersensitivity reaction to ocrelizumab.

• History of cancer including hematologic malignancy and solid tumors within 10 yearsof screening. Exceptions: Basal/squamous cell carcinoma of skin cured by excision.In situ carcinoma of the cervix successfully treated by curative therapy >1 yearprior to screening.

• Known presence of other neurological disorders, that could interfere with thediagnosis of MS or assessments of efficacy or safety during the study, clinicallysignificant 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 systemiccorticosteroids, immunosuppressants or specific medication that could impact theprimary 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 becomepregnant during the study or 6 or 12 months (as applicable from the local label forocrelizumab) after final dose of study drug.

• Male participants intending to father a child during the study or for 28 days afterfinal dose of study drug.

• Lack of peripheral venous access.

• Any previous treatment with immunomodulatory or immunosuppressive medication withoutan 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 forgastrointestinal (GI) bleed

• Any previous treatment with cladribine, mitoxantrone, daclizumab, alemtuzumab, orcyclophosphamide

OLE Exclusion Criteria:

• Chronic liver disease unless considered stable for > 6 months

• Acute liver disease