A Study of the Efficacy and Safety of Ocrelizumab in Patients With Relapsing-Remitting Multiple Sclerosis

• Annualized protocol defined relapse rate [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
• Proportion of patients who remain relapse-free [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
• Change in total volume of T2 lesions on MRI scans of the brain [ Time Frame: Baseline to week 24 ] [ Designated as safety issue: No ]

• The annualized protocol defined relapse rate [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
• Proportion of patients who remain relapse-free [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
• Change in total volume of T2 lesions on MRI scans of the brain [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]

This is a phase II, multicenter, randomized, parallel-group, partially blinded, placebo and Avonex (interferon beta-1a) controlled dose finding study to evaluate the efficacy as measured by brain MRI lesions, and safety of 2 dose regimens of ocrelizumab in patients with RRMS.

• Drug: ocrelizumab
  IV repeating dose\n
• Drug: placebo
  Intravenous repeating dose
• Drug: methylprednisolone
  IV repeating dose\n
• Drug: interferon beta-1a
  Intramuscular repeating dose\n

• Experimental: 1
  Interventions:

  • Drug: ocrelizumab
  • Drug: methylprednisolone
• Experimental: 2
  Interventions:

  • Drug: ocrelizumab
  • Drug: methylprednisolone
• Placebo Comparator: 3
  Interventions:

  • Drug: placebo
  • Drug: methylprednisolone
• Active Comparator: 4
  Interventions:

  • Drug: methylprednisolone
  • Drug: interferon beta-1a

Inclusion Criteria:

• Ability to provide written informed consent and to be compliant with the schedule of protocol assessments
• Relapsing-remitting MS
• Ages 18-55 years inclusive
• For sexually active female and male patients of reproductive potential, use of reliable means of contraception

Exclusion Criteria:

• Secondary or primary progressive multiple sclerosis at screening
• Incompatibility with MRI
• Contra-indications to or intolerance of oral or i.v. corticosteroids
• Known presence of other neurologic disorders
• Pregnancy or lactation
• Lack of peripheral venous access
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
• Significant, uncontrolled disease, such as cardiovascular, pulmonary, renal, hepatic, endocrine or gastrointestinal
• Congestive heart failure
• Known active bacterial, viral, fungal, mycobacterial infection or other infection or any major episode of infection requiring hospitalization or treatment with i.v. antibiotics within 4 weeks prior to screening or oral antibiotics within 2 weeks prior to screening
• History or known presence of recurrent or chronic infection
• History of cancer, including solid tumors and hematological malignancies (except basal cell, in situ squamous cell carcinomas of the skin, and in situ carcinoma of the cervix of the uterus that have been excised and resolved)
• History of alcohol or drug abuse within 24 weeks prior to randomization
• History of or currently active primary or secondary immunodeficiency
• History of coagulation disorders
• Treatment with any investigational agent within 4 weeks of screening
• Receipt of a live vaccine within 6 weeks prior to randomization
• Incompatibility with Avonex use
• Previous treatment with rituximab
• Previous treatment with lymphocyte-depleting therapies except mitoxantrone
• Treatment with lymphocyte trafficking blockers within 24 weeks prior to randomization
• Treatment with beta interferons, glatiramer acetate, i.v. immunoglobulin, plasmapheresis, or immunosuppressive therapies within 12 weeks prior to randomization
• Systemic corticosteroid therapy within 4 weeks prior to randomization