• Area Under the Serum Concentration-Time Curve (AUC) of Ocrelizumab following subcutaneous (SC) administration [ Time Frame: At predefined intervals from baseline through end of study (approximately 5 years) ]
• Area Under the Serum Concentration-Time Curve (AUC) of Ocrelizumab following single IV (intravenous Infusion)administration [ Time Frame: At predefined intervals from baseline through end of study (approximately 5 years) ]
• Percentage of participants with adverse events [ Time Frame: Baseline to end of study (approximately 5 years) ]
• Percentage of participants with change from baseline in Marked Abnormality in Electrocardiogram (ECG) Parameters [ Time Frame: Baseline to end of study (approximately 5 years) ]
• Incidence of local pain at site of injection assessed using Visual Analog Scale (VAS [ Time Frame: Baseline to end of study (approximately 5 years) ]
• Incidence of local-injection reaction (ISR) assessed using Local Injection-Site Symptom Assessment (LISSA) [ Time Frame: Baseline to end of study (approximately 5 years) ]

• Percentage of Participants with Anti-Drug Antibodies (ADAs) to ocrelizumab [ Time Frame: Baseline to end of study (approximately 5 years) ]
• Percentage of Participants with Anti-Drug Antibodies (ADAs) to rHuPH20 [ Time Frame: Baseline to end of study (approximately 5 years) ]

• Drug: Ocrelizumab
  Administered by subcutaneous Injection
• Drug: Ocrelizumab
  Administered by Intravenous (IV) Injection
• Drug: rHuPH20
  Administered in a 2-mL glass vial as a sterile, single-use, injectable liquid to be manually mixed with SC ocrelizumab

• Experimental: Group A: Cohorts A1-A4

  Participants (participants pretreated with ocrelizumab) will receive a single injection of subcutaneous (SC) ocrelizumab co-mixed with rHuPH20 in the abdomen. For every new dose level, recruitment will be staggered by enrolling 1 participant in each cohort followed by a 48-hour waiting period to review safety and tolerability data by the Safety Monitoring Committee (SMC) prior to enrolling subsequent participants in the same cohort. Currently, the planned dose escalation steps for patients who enroll in Group A are as follows:

  • Cohort A1: 40 mg of SC ocrelizumab
  • Cohort A2: 200 mg of SC ocrelizumab
  • Cohort A3: 600 mg of SC ocrelizumab
  • Cohort A4: 1200 mg of SC ocrelizumab
  Interventions:

  • Drug: Ocrelizumab
  • Drug: rHuPH20
• Experimental: Group A: Cohort A5
  In the non-randomized subphase, participants will receive a single SC injection of ocrelizumab co-mixed with rHuPH20 in the abdomen.
  Interventions:

  • Drug: Ocrelizumab
  • Drug: rHuPH20
• Experimental: Group A: Cohort AA
  Participants will receive a single 600-mg dose ocrelizumab by intravenous (IV) infusion
  Intervention: Drug: Ocrelizumab
• Experimental: Group B: Cohorts B1-B4

  Ocrelizumab treatment- naive participants will receive a minimum of 3 patients in Cohort B will receive a single SC injection of ocrelizumab co-mixed with rHuPH20 in the abdomen.

  • Cohort B1: 40 mg of SC ocrelizumab
  • Cohort B2: 200 mg of SC ocrelizumab
  • Cohort B3: 600 mg of SC ocrelizumab
  • Cohort B4: 1200 mg of SC ocrelizumab
  Interventions:

  • Drug: Ocrelizumab
  • Drug: rHuPH20

Inclusion Criteria:

• Diagnosis of Primary Progressive Multiple Sclerosis (PPMS) or Relapsing Multiple Sclerosis (RMS) according to the revised McDonald 2017 criteria (Thompson et al. 2018)
• Expanded Disability Status Scale (EDSS) score, 0-6.5, inclusive, at screening
• Absence of relapses for 30 days prior to the screening visit
• For the dose escalation phase for participants pretreated with ocrelizumab (Group A):

treatment with IV ocrelizumab for at least 1 year prior to screening (i.e., at least two 600-mg doses of ocrelizumab separated by 24 weeks)

• For women of childbearing potential: agreement to remain abstinent or use acceptable contraceptive methods during the treatment period and for 6 months after the final dose of ocrelizumab.
• For female perticipants without reproductive potential:

Women may be enrolled if post-menopausal unless the participant is receiving a hormonal therapy for her menopause or if surgically sterile (i.e., hysterectomy, complete bilateral oophorectomy).

Exclusion Criteria:

• MS disease duration of more than 15 years for participants with an Expanded Disability Status Scale (EDSS) score <2.0 at screening.
• Known presence of other neurologic disorders that may mimic MS, including, but not limited to, the following:
• History of ischemic cerebrovascular disorders (e.g., stroke, transient ischemic attack) or ischemia of the spinal cord
• History or known presence of Central Nervous System (CNS) or spinal cord tumor (e.g., meningioma,glioma)
• History or known presence of potential metabolic causes of myelopathy (e.g., untreated vitamin B12 deficiency)
• History or known presence of infectious causes of myelopathy (e.g., syphilis, Lyme disease, human T-lymphotropic virus 1, herpes zoster and myelopathy.
• History of genetically inherited progressive CNS degenerative disorder (e.g., hereditary paraparesis and mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke syndrome)
• Neuromyelitis optica
• History or known presence of systemic autoimmune disorders potentially causing progressive neurologic disease (e.g., lupus, anti-phospholipid antibody syndrome, Sjögren syndrome, Behçet disease, sarcoidosis).
• History of severe, clinically significant brain or spinal cord trauma (e.g., cerebral contusion, spinal cord compression