A Study to Evaluate the Efficacy, Safety and Pharmacokinetics of a Higher Dose of Ocrelizumab in Adults With Primary Progressive Multiple Sclerosis (PPMS)

Inclusion Criteria:

Diagnosis of primary progressive multiple sclerosis (PPMS).
Expanded disability status scale (EDSS) score at screening and baseline, from 3 to 6.5 inclusive.
Average T25FWT score over two trials at screening and over two trials at baseline respectively, up to 150 (inclusive) seconds
Average 9HPT score over four trials (two trials with each hand) at screening and over four trials (two trials with each hand) at baseline respectively, up to 250 (inclusive) seconds
Score of >/= to 2.0 on the Functional Systems scale for the pyramidal system that was due to lower extremity findings at screening and baseline.
Documented MRI of brain with abnormalities consistent with MS
Participants requiring symptomatic treatment for MS and/or physiotherapy must be treated at a stable dose. No initiation of symptomatic treatment for MS or physiotherapy within 4 weeks of randomization.
Participants must be neurologically stable for at least 30 days prior to randomization and baseline.
Disease duration from the onset of MS symptoms; if EDSS score at screening is less or equal to 5, disease duration must be less than 10 years; If EDSS score at screening is more than 5, disease duration must be less than 15 years
Documented evidence of the presence of at least one cerebrospinal fluid-specific oligoclonal bands.
For females of childbearing potential, agreement to remain abstinent or use adequate contraceptive methods.
For female participants without reproductive potential, may be enrolled if post-menopausal unless receiving a hormonal therapy for her menopause or if surgically sterile.

Exclusion Criteria:

History of relapsing remitting or secondary progressive MS at screening.
Any known or suspected active infection at screening or baseline (except nailbed infections), or any major episode of infection requiring hospitalization or treatment with IV antimicrobials within 8 weeks or treatment with oral antimicrobials within 2 weeks, prior to and during screening.
History of confirmed or suspected progressive multifocal leukoencephalopathy.
History of cancer, including hematologic malignancy and solid tumors, within 10 years of screening.
Immunocompromised state.
Receipt of a live or live-attenuated vaccine within 6 weeks prior to randomization.
Inability to complete an MRI or contraindication to gadolinium administration.
Contraindications to mandatory pre-medications for IRRs.
Known presence of other neurologic disorders that could interfere with the diagnosis of MS or assessments of efficacy and/or safety during the study.
Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study.
Significant, uncontrolled disease that may preclude participant from participating in the study.
History of or currently active primary or secondary, non-drug-related, immunodeficiency.
Pregnant or breastfeeding or intending to become pregnant.
Lack of peripheral venous access.
History of alcohol or other drug abuse within 12 months prior to screening.
Treatment with any investigational agent or treatment with any experimental procedure for MS.
Previous use of anti-CD20s (including ocrelizumab), unless the last infusion was more than 2 years before screening, B-cell count is normal, and the stop of the treatment was not motivated by safety reasons or lack of efficacy.
Any previous treatment with mitoxantrone, cladribine, atacicept, alemtuzumab, and daclizumab
Previous treatment with fingolimod, siponimod, or ozanimod within 6 weeks of baseline
Previous treatment with natalizumab within 4.5 months of baseline
Previous treatment with interferons beta (1a or 1b), or glatiramer acetate within 2 weeks of baseline
Previous treatment with any other immunomodulatory or immunosuppressive medication not already listed above without appropriate washout as described in the applicable local label. If the washout requirements are not described in the applicable local label, then the wash out period must be five times the half-life of the medication.
Any previous treatment with bone marrow transplantation and hematopoietic stem cell transplantation.
Any previous history of transplantation or anti-rejection therapy.
Treatment with intravenous (IV) immunoglobulin (Ig) or plasmapheresis within 12 weeks prior to randomization.
Systemic corticosteroid therapy within 4 weeks prior to screening.
Positive screening tests for active, latent, or inadequately treated hepatitis B
Sensitivity or intolerance to any ingredient (including excipients) of ocrelizumab.
Any additional exclusionary criterion as per ocrelizumab local label, if more stringent than the above.