A Study of Ocrelizumab in Comparison With Interferon Beta-1a (Rebif) in Patients With Relapsing Multiple Sclerosis

• Time to onset of sustained disability progression for at least 12 weeks [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
• Time to onset of sustained disability progression for at least 24 weeks [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
• Proportion of relapse-free patients [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
• Change in total T2 lesion volume as detected by brain MRI [ Time Frame: from baseline to Week 96 ] [ Designated as safety issue: No ]
• Total number of new, and/or enlarging T2 hyperintense lesions as detected by brain MRI [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
• Change in Multiple Sclerosis Functional Composite Scale (MSFCS) score [ Time Frame: from baseline to Week 96 ] [ Designated as safety issue: No ]
• Change in brain volume as detected by brain MRI [ Time Frame: from Week 24 to Week 96 ] [ Designated as safety issue: No ]
• Safety: Incidence of adverse events [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
• Pharmacokinetics: Exposure to ocrelizumab (area under the concentration - time curve) [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
• Immunogenicity: Human anti-human antibodies (HAHA) levels [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]

• Time to onset of sustained disability progression for at least 12 weeks [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
• Time to onset of sustained disability progression for at least 24 weeks [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
• Proportion of relapse-free patients [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
• Change in total T2 lesion volume as detected by brain MRI [ Time Frame: from baseline to Week 96 ] [ Designated as safety issue: No ]
• Total number of new, and/or enlarging T2 hyperintense lesions as detected by brain MRI [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
• Change in Multiple Sclerosis Functional Composite Scale (MSFCS) score [ Time Frame: from baseline to Week 96 ] [ Designated as safety issue: No ]
• Change in brain volume as detected by brain MRI [ Time Frame: from Week 24 to Week 96 ] [ Designated as safety issue: No ]
• Safety: Incidence of adverse events [ Time Frame: 120 weeks ] [ Designated as safety issue: No ]
• Pharmacokinetics: Exposure to ocrelizumab (area under the concentration - time curve) [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
• Immunogenicity: Human anti-human antibodies (HAHA) levels [ Time Frame: 120 weeks ] [ Designated as safety issue: No ]

This randomized, double-blind, double-dummy, parallel-group study will evaluate the efficacy and safety of ocrelizumab in comparison with Rebif (interferon beta-1a) in patients with relapsing multiple sclerosis. Patients will be randomized to receive either in group A, ocrelizumab 600 mg intravenously (iv) every 24 weeks plus Rebif placebo subcutaneously (sc) three times weekly, or, in group B, Rebif 8.8 mcg (Weeks 1+2)/22 mcg (Weeks 3+4)/44 mcg (Week 5 and following) sc three times weekly plus ocrelizumab placebo iv every 24 weeks. Anticipated time on study treatment is 96 weeks.

• Drug: ocrelizumab
  600 mg iv every 24 weeks (dual infusions of 300 mg on Day 1 and 15 of Cycle 1, single infusion of 600 mg on Day 1 of each following cycle), 96 weeks
• Drug: Rebif
  8.8 mcg (Weeks 1+2) / 22 mcg (Weeks 3+4) / 44mcg (Week 5 and following) subcutaneously 3 times weekly, 96 weeks
  Other Name: Rebif
• Drug: ocrelizumab placebo
  Ocrelizumab dummy placebo iv according to schedule in ocrelizumab active group A
• Drug: Rebif placebo
  Rebif dummy placebo sc according to schedule in Rebif active group B

• Experimental: A
  Interventions:

  • Drug: ocrelizumab
  • Drug: Rebif placebo
• Active Comparator: B
  Interventions:

  • Drug: Rebif
  • Drug: ocrelizumab placebo

Inclusion Criteria:

• Adult patients, 18-55 years of age inclusive
• Diagnosis of multiple sclerosis, in accordance with the revised McDonald criteria (2010)
• At least 2 documented clinical attacks within the last 2 years prior to screening or one clinical attack in the years prior to screening (but not within 30 days prior to screening)
• Neurologic stability for >/= 30 days prior to both screening and baseline
• Expanded Disability Status Scale (EDSS) score 0 to 5.5 inclusive

Exclusion Criteria:

• Primary progressive multiple sclerosis
• Disease duration of more than 10 years in patients with EDSS </= 2.0 at screening
• Contraindications for MRI
• Known presence of other neurological disorders which may mimic multiple sclerosis
• Pregnancy or lactation
• Requirement for chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study
• History of or currently active primary or secondary immunodeficiency
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
• Active infection, or history of or known presence of recurrent or chronic infection (e.g. hepatitis B or C, HIV, syphilis, tuberculosis)
• History of progressive multifocal leukoencephalopathy
• Contraindications to or intolerance of oral or iv corticosteroids
• Contraindications to Rebif or incompatibility with Rebif use