Official Title: “A Randomized, Double-Blind, Parallel Group, International Study to Evaluate the Safety and Efficacy of Ocrelizumab Compared to Placebo in Patients With Active Rheumatoid Arthritis Who Have an Inadequate Response to at Least One Anti-TNF-α Therapy”

This study will evaluate the efficacy and safety of ocrelizumab, compared with placebo, in patients with active rheumatoid arthritis who have an inadequate response to at least one anti-TNF-alpha therapy. Patients will be randomized to receive placebo, 200mg of intravenous ocrelizumab, or 500mg of i.v. ocrelizumab on days 1 and 15. A repeat course of i.v. treatment will be administered at weeks 24 and 26. All patients will receive stable doses of either concomitant methotrexate (7.5-25mg/week) or leflunomide (10-20mg po daily) and may receive additional DMARDs. The anticipated time on study treatment is 1-2 years. Target sample size is 1000.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment

Intervention(s) in this Clinical Trial

• Drug: ocrelizumab
  • Intravenous repeating dose (200mg)
• Drug: ocrelizumab
  • Intravenous repeating dose (500mg)
• Drug: placebo
  • Intravenous repeating dose
• Drug: methotrexate
  • Oral or parenteral repeating dose
• Drug: leflunomide
  • Oral repeating dose

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
• Experimental: 2
• Placebo Comparator: 3

Primary Measures

• Percentage of patients with ACR20 responses
  • Time Frame: Weeks 24 and 48
    Safety Issue?: No

Secondary Measures

• Proportion of patients with a major clinical response
  • Time Frame: Week 48
    Safety Issue?: No
• Proportion of patients achieving Disease Activity Score (DAS28) remission
  • Time Frame: Weeks 24 and 48
    Safety Issue?: No
• Change in DAS28 from baseline
  • Time Frame: Weeks 24 and 48
    Safety Issue?: No
• EULAR response rates
  • Time Frame: Weeks 24 and 48
    Safety Issue?: No
• Proportion of patients achieving an ACR50 response
  • Time Frame: Weeks 24 and 48
    Safety Issue?: No
• Proportion of patients achieving an ACR70 response
  • Time Frame: Weeks 24 and 48
    Safety Issue?: No
• Proportion of patients with a reduction in the HAQ-DI score
  • Time Frame: Weeks 24 and 48
    Safety Issue?: No

Inclusion Criteria:

• Adult patients, ≥ 18 years of age
• Rheumatoid arthritis for ≥ 3 months
• Inadequate response to previous or current treatment with at least one anti-TNF-alpha agent
• Receiving either leflunomide or methotrexate for ≥ 12 weeks, with a stable dose for the last 4 weeks

Exclusion Criteria:

• Rheumatic autoimmune disease or inflammatory joint disease, other than RA
• Any surgical procedure in past 12 weeks,or planned within 48 weeks of baseline

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Genentech

Overall Clinical Trial Officials and Contacts

Wolfgang Dummer, M.D. Study Director Genentech  

Overall Contact: Genentech Trial Information Support Line 888-662-6728 

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00476996

Study ID Number: ACT3986g

ClinicalTrials.gov Identifier: NCT00476996

Health Authority: United States: Food and Drug Administration

Ex-U.S. Study Information (Ex-US this trial is sponsored/managed by Hoffmann-La Roche)