A Study of Ocrelizumab in Patients With Primary Progressive Multiple Sclerosis

• Time to sustained disability progression, defined as an increase in EDSS score that is sustained for at least 24 weeks [ Time Frame: up to 5.5 years ] [ Designated as safety issue: No ]
• Change in timed 25-foot walk [ Time Frame: from baseline to Week 120 ] [ Designated as safety issue: No ]
• Change in total volume of T2 lesions on magnetic resonance imaging (MRI) scans of the brain [ Time Frame: from baseline to Week 180 ] [ Designated as safety issue: No ]
• Safety and tolerability: Incidence of adverse events [ Time Frame: up to 5.5 years ] [ Designated as safety issue: No ]

• Time to sustained disability progression, defined as an increase in EDSS score that is sustained for at least 24 weeks [ Time Frame: from baseline to sustained disability progression over a 3-year period ] [ Designated as safety issue: No ]
• Change in timed 25-foot walk [ Time Frame: from baseline to Week 120 ] [ Designated as safety issue: No ]
• Change in total volume of T2 lesions on magnetic resonance imaging (MRI) scans of the brain [ Time Frame: from baseline to Week 180 ] [ Designated as safety issue: No ]
• Safety and tolerability: Adverse events, laboratory parameters, vital signs, ECG, neurological examination, MRI [ Time Frame: up to 3 years ] [ Designated as safety issue: No ]

This randomized, parallel group, double-blind, placebo controlled study will evaluate the efficacy and safety of ocrelizumab in patients with primary progressive multiple sclerosis. Eligible patients will be randomized 2 : 1 to receive either ocrelizumab (300 mg intravenously, 2 infusions separated by 14 days in each treatment cycle) or placebo. The blinded treatment period will be at least 120 weeks, followed by open label treatment for patients in both groups who in the opinion of the investigator could benefit from further or newly initiated ocrelizumab treatment. Anticipated time on study treatment is up to 5.5 years.

• Drug: ocrelizumab
  2 intravenous infusions of 300 mg separated by 14 days in each treatment cycle
• Drug: Placebo
  Ocrelizumab placebo, 2 infusions separated by 14 days in each treatment cycle
• Drug: methylprednisolone
  100 mg iv 30 minutes prior to ocrelizumab or placebo infusion

• Experimental: A
  Interventions:

  • Drug: ocrelizumab
  • Drug: methylprednisolone
• Placebo Comparator: B
  Interventions:

  • Drug: Placebo
  • Drug: methylprednisolone

Inclusion Criteria:

• Adult patients, 18-55 years of age
• Primary Progressive Multiple Sclerosis (according to revised McDonald criteria)
• Expanded Disability Status Scale (EDSS) 3 to 6.5 points
• Disease duration from onset of MS symptoms < 15 years if EDSS > 5.0, < 10 years if EDSS >/= 5.0
• Sexually active male and female patients of reproductive potential must use two methods of contraception throughout the study treatment phase and for 48 weeks after the last dose

Exclusion Criteria:

• History of relapsing remitting multiple sclerosis, secondary progressive, or progressive relapsing multiple sclerosis at screening
• Contraindications for Magnetic Resonance Imaging (MRI)
• Known presence of other neurologic disorders
• Known active infection or history of or presence of recurrent or chronic infection
• History of cancer, including solid tumors and hematological malignancies (except for basal cell, in situ squamous cell carcinomas of the skin and in situ carcinoma of the cervix that have been excised and resolved)
• Previous treatment with B-cell targeted therapies (e.g. rituximab, ocrelizumab, atacicept, belimumab, or ofatumumab)
• Any previous treatment with lymphocyte trafficking blockers, with alemtuzumab, anti-CD4, cladribine, cyclophosphamide, mitoxantrone, azathioprine, mycophenolate mofetil, cyclosporine, methotrexate, total body irradiation, or bone marrow transplantation
• Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study