A Study to Evaluate the Efficacy, Safety and Pharmacokinetics/Pharmacodynamics (PK/PD) of Ocrelizumab in Patients With Rheumatoid Arthritis

Study Overview
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Brief Summary
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This study will evaluate the efficacy, safety and PK/PD of ocrelizumab at each dose in combination with methotrexate（MTX）in patients with active rheumatoid arthritis (RA). The data from this study will also be compared with those from a clinical study of ocrelizumab in patients with active RA that was conducted in the U.S.

Detailed Description
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This study will evaluate the efficacy, safety and PK/PD of ocrelizumab at each dose in combination with MTX in patients with active RA. The data from this study will also be compared with those from a clinical study of ocrelizumab in patients with active RA that was conducted in the U.S.

Official Title
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A Randomized, Double-blind, Parallel-group, Study to Evaluate the Efficacy, Safety and PK/PD of Ocrelizumab in Patients With Active Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate Therapy

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: placebo
* Drug: methotrexate
* Drug: ocrelizumabu 50mg
* Drug: ocrelizumabu 200mg
* Drug: ocrelizumab 500mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of RA for ≧6 months according to the revised 1987 ACR criteria for the classification of RA. Adult patients, ≧20 years of age. Receiving methotrexate at a dose of 6 to 8mg/week（oral）for ≧12 weeks, with a stable dose for the last 4 weeks before treatment. Positive serum RF. Exclusion Criteria: Rheumatic autoimmune disease other than RA, or Significant systemic involvement secondary to RA (including but not limited to vasculitis, pulmonary fibrosis, or Felty's syndrome).Patients with secondary Sjögren's syndrome or secondary limited cutaneous vasculitis with RA are eligible. Functional Class Ⅳ as defined by the ACR Classification of Functional Status in 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). Any surgical procedure (except for minor surgeries requiring local or no anaesthesia and without any complications or sequelae) within 12 weeks prior to or planned within 24 weeks after baseline.

Ages Eligible for Study
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Minimum Age: 20 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 1<br> | Drug: placebo<br>* Intravenous repeating dose<br>Drug: methotrexate<br>* Oral repeating dose<br>|
| Experimental: 2<br> | Drug: methotrexate<br>* Oral repeating dose<br>Drug: ocrelizumabu 50mg<br>* Intravenous repeating dose (50mg)<br>|
| Experimental: 3<br> | Drug: methotrexate<br>* Oral repeating dose<br>Drug: ocrelizumabu 200mg<br>* Intravenous repeating dose (200mg)<br>|
| Experimental: 4:<br> | Drug: methotrexate<br>* Oral repeating dose<br>Drug: ocrelizumab 500mg<br>* Intravenous repeating dose (500mg)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with ACR20 response. |  | week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with ACR20, 50, and 70 response, and the components of this outcome. |  | very 4 Weeks, from Week 4 to Week 24 | 
| EULAR response rate. |  | Every 4 Weeks, from Week 4 to Week 24 | 
| DAS 28, HAQ-DI score. |  | Every 4 Weeks, from Week 4 to Week 24 | 
| FACIT Fatigue Scale score |  | Weeks 4,12,and 24 | 
| Weeks 4,12,and 24 |  | Length of study | 
| Incidence of human anti-human(ocrelizumab) antibodies (HAHA) |  | Length of study | 
| Pharmacokinetics and Pharmacodynamics of ocrelizumab. |  | Length of study |