A Study of Ocrelizumab in Combination With Methotrexate in Patients With Rheumatoid Arthritis Who Are Naive to Methotrexate (FILM)

• Health Assessments Questionnaire - Disability Index (HAQ-DI) score [ Time Frame: Week 104 ] [ Designated as safety issue: No ]
• Proportion of patients with a major clinical response [ Time Frame: Weeks 52 and 104 ] [ Designated as safety issue: No ]
• Proportion of patients achieving Disease Activity Score (DAS28) remission [ Time Frame: Weeks 24, 52, and 104 ] [ Designated as safety issue: No ]
• Change in DAS28 from baseline [ Time Frame: Weeks 24, 52, and 104 ] [ Designated as safety issue: No ]
• EULAR response rates [ Time Frame: Weeks 24, 52, and 104 ] [ Designated as safety issue: No ]
• Proportion of patients achieving an ACR20/ACR50/ACR70/ACR90 response [ Time Frame: Weeks 24, 52, and 104 ] [ Designated as safety issue: No ]
• Proportion of patients with a reduction of at least 0.25 units in the HAQ-DI score from baseline [ Time Frame: Weeks 24 and 52 ] [ Designated as safety issue: No ]

• Health Assessments Questionnaire - Disability Index (HAQ-DI) score
• SF-36 and FACIT Fatigue Scale scores
• Modified Brief Pain Inventory (BPI), disease status and activity limitation questions on the eCRF
• Percentage of patients with clinical response of 20%, 50%, and 70% according to ACR criteria (ACR20, ACR50, and ACR70) and the components of this outcome
• Disease activity scores (DAS28)
• European League Against Rheumatism (EULAR) response rates
• Incidence of adverse events graded according to the NCI CTC AE (Version 3.0)
• Incidence of clinical laboratory abnormalities
• Incidence of human anti-ocrelizumab antibodies (HAHA)

This study will evaluate the efficacy and safety of ocrelizumab, compared with placebo, in combination with methotrexate in patients with active rheumatoid arthritis who are naive to methotrexate. Patients will be randomized to receive placebo, ocrelizumab 200mg i.v. or ocrelizumab 500mg i.v. on Days 1 and 15. Repeat courses of i.v. treatment will be administered at weeks 24, 52 and 76. All patients will receive concomitant methotrexate (7.5 mg escalating to 20mg p.o. weekly). The anticipated time on study treatment is 2+ years, and the target sample size is 500+ individuals.

• Drug: methotrexate
  Oral repeating dose
• Drug: ocrelizumab
  Intravenous repeating dose
• Drug: placebo
  Intravenous repeating dose

• Experimental: 1
  Interventions:

  • Drug: methotrexate
  • Drug: ocrelizumab
• Placebo Comparator: 2
  Interventions:

  • Drug: methotrexate
  • Drug: placebo

Inclusion criteria:

• Age ≥ 18
• Rheumatoid arthritis for 3 months-5 years
• Naive to methotrexate
• If receiving steroids or NSAIDs, must be on a stable dose for 4 weeks prior to baseline

Exclusion criteria:

• Rheumatic autoimmune disease or inflammatory joint disease other than RA
• Prior receipt of any biologic therapy for RA
• Concurrent treatment with any DMARD