A Study to Evaluate Ocrelizumab in Combination With Methotrexate Compared With Infliximab Plus Methotrexate in Patients With Active Rheumatoid Arthritis Currently Responding Inadequately to Etanercept or Adalimumab

Study Overview
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Brief Summary
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This is a Phase II, randomized, active-controlled, double-blind, double-dummy, parallel-group, multicenter study in the United States enrolling patients with active RA. The study will enroll approximately 290 patients at approximately 130 sites.

Official Title
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A PHASE II RANDOMIZED, DOUBLE-BLIND, PARALLEL GROUP STUDY TO EVALUATE THE EFFICACY AND SAFETY OF OCRELIZUMAB IN COMBINATION WITH METHOTREXATE, COMPARED TO INFLIXIMAB PLUS METHOTREXATE IN PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS CURRENTLY RESPONDING INADEQUATELY TO ETANERCEPT OR ADALIMUMAB

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: Infliximab
* Drug: Methotrexate
* Drug: Methylprednisolone
* Drug: Ocrelizumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >= 18 years Current treatment for RA on an outpatient basis Active disease Currently receiving 50 mg etanercept subcutaneously (SC) every week or 40 mg adalimumab SC every other week. Considered by Investigator to be a primary non-responder to their first anti-TNFÎ± treatment for efficacy reasons Exclusion Criteria: Rheumatic autoimmune disease other than RA, or significant systemic involvement secondary to RA History of, or current, inflammatory joint disease other than RA (e.g., gout, reactive arthritis, psoriatic arthritis, seronegative spondyloarthropathy, Lyme disease) or other systemic autoimmune disorder (e.g., systemic lupus erythematosus, inflammatory bowel disease, scleroderma, inflammatory myopathy, mixed connective tissue disease or other overlap syndrome) Previous treatment with a any biologic therapy for RA (including investigational products with the exception of etanercept or adalimumab Treatment with more than one prior anti-TNFÎ± therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ocrelizumab 200mg<br>Participants received two intravenous (IV) infusions of 200 mg ocrelizumab administered on Day 1 and Day 15 and placebo IV infliximab infusions administered on Day 1, Day 15, Week 6, and Week 14. In addition to the study medication, all patients were to receive methotrexate at a stable dose of 7.5-25 mg/week and folic acid or equivalent at a dose of 5 mg/week to minimize methotrexate toxicity. | Drug: Methotrexate<br>* Oral or parenteral repeating dose<br>Drug: Methylprednisolone<br>* Intravenous repeating dose<br>Drug: Ocrelizumab<br>* Intravenous repeating dose<br>Drug: Placebo<br>* Intravenous repeating dose<br>|
| Active Comparator: Infliximab 5mg/kg<br>Participants received four IV infusions of 5 mg/kg infliximab administered on Day 1, Day 15, Week 6, and Week 14 and placebo ocrelizumab infusions administered on Day 1 and Day 15. In addition to the study medication, all patients were to receive methotrexate at a stable dose of 7.5-25 mg/week and folic acid or equivalent at a dose of 5 mg/week to minimize methotrexate toxicity. | Drug: Infliximab<br>* Intravenous repeating dose<br>Drug: Methotrexate<br>* Oral or parenteral repeating dose<br>Drug: Methylprednisolone<br>* Intravenous repeating dose<br>Drug: Placebo<br>* Intravenous repeating dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in DAS28(ESR) at Week 20 |  | Week 20 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Clinical Response of 20% According to ACR Criteria |  | Baseline up to 30 months | 
| Percentage of Participants With Clinical Response of 50% According to ACR Criteria |  | Baseline up to 30 months | 
| Percentage of Participants With Clinical Response of 70% According to ACR Criteria |  | Baseline up to 30 months | 
| European League Against Rheumatism (EULAR) Response Rates |  | Baseline up to 30 months | 
| Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score |  | Baseline up to 30 months | 
| Change in Fatigue Visual Analog Scale Score (VAS) |  | Baseline up to 30 months | 
| Percentage of Participants With Adverse Events (AEs) |  | Baseline up to 30 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RA, Arthritis