OPERA I

Treatment tested

• Ocrelizumab

  B-lymphocyte antigen CD20 binding agent

Compared with

• Interferon beta-1a

  Interferon alpha/beta receptor agonist

Placebo or sham

• Ocrelizumab-matching placebo
• Interferon beta-1a-matching placebo

Other measures (14)

Inclusion Criteria: * 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 greater than or equal to (>=) 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 participants with EDSS less than or equal to (\<=) 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, human immunodeficiency virus [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

This randomized, double-blind, double-dummy, parallel-group study will evaluate the efficacy and safety of ocrelizumab in comparison with interferon beta-1a (Rebif) in participants with relapsing multiple sclerosis. Participants will be randomized to receive either ocrelizumab 600 mg or matching placebo intravenous (IV) as 300 mg infusions on Days 1 and 15 for the first dose and as a single infusion of 600 mg for all subsequent infusions every 24 weeks, with placebo injections matching interferon beta-1a SC three times per week; or interferon beta-1a 44 mcg SC injections three times per week (with placebo infusions matching ocrelizumab infusions every 24 weeks). Planned duration of double-blind treatment is 96 weeks. Participants who complete the 96-week double-blind treatment will have an option to enter a single-group, active-treatment, open-label extension period, providing they fulfill the eligibility criteria.