efficacy, safety and pharmacokinetics of a higher dose of ocrelizumab per intravenous (IV)
infusion every 24 weeks in participants with PPMS, in comparison to the approved 600 mg dose
– Diagnosis of primary progressive multiple sclerosis (PPMS).
– Expanded disability status scale (EDSS) score at screening and baseline, from 3 to 6.5
– Score of >/= to 2.0 on the Functional Systems scale for the pyramidal system that was
due to lower extremity findings.
– 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
– Disease duration from the onset of MS symptoms, less than 15 years in participants
with an EDSS score at screening >5.0, less than 10 years in participants with an EDSS
score at screening =5.0. - Documented evidence of the presence of 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. - 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. - 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 if in the last 2 years before screening, or if B-cell count is not normal, or if treatment was stopped due to safety reasons or lack of efficacy. - Previous use of mitoxantrone, cladribine, atacicept, and alemtuzumab. - 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 of ocrelizumab. - Any additional exclusionary criterion as per ocrelizumab local label, if more stringent than the above.
- University of California Irvine, Irvine, California, United States, 92697
- University of California Davis Medical Center, Sacramento, California, United States, 95817
- University of California San Francisco, San Francisco, California, United States, 94117
- Stanford University Medical Center; Stanford Neuroscience Health Center, Stanford, California, United States, 94305
- Los Angeles Biomedical Research Institute at Harbor-UCLA, Torrance, California, United States, 90502