A Study of MabThera (Rituximab) in Patients With Rheumatoid Arthritis Who Have Had an Inadequate Response to Methotrexate

Study Overview
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Brief Summary
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This study will evaluate the safety and efficacy of MabThera in patients with active rheumatoid arthritis who have had an inadequate response or were intolerant to treatment with methotrexate. Eligible patients will receive MabThera (1000mg by intravenous infusion) on days 1 and 15, and background methotrexate (oral or subcutaneous dose of 10-25mg weekly). After the initial study period of 24 weeks, eligible patients may receive up to 3 re-treatments with MabThera. The anticipated time on study treatment is 1-2 years, and the target sample size is <100 individuals.

Official Title
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An Open Label Study to Evaluate the Safety and Efficacy of Rituximab in Patients With Active Rheumatoid Arthritis Who Have Had an Inadequate Response to Prior Treatment With Methotrexate

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: rituximab [MabThera/Rituxan]
* Drug: methotrexate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients, >=18 years of age; receiving out-patient treatment; experienced an inadequate response to previous or current treatment with methotrexate. 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; previous treatment with any cell-depleting therapies.

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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: rituximab [MabThera/Rituxan]<br>* 1000mg iv on days 1 and 15<br>Drug: methotrexate<br>* 10-25mg weekly<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With an Adverse Event (AE) |  | Week 104 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Activity Score Based on 28-Joint Count (DAS28) | DAS28 was calculated from the number of swollen joints and tender joints using the 28 joint count; the erythrocyte sedimentation rate (ESR) measured in millimeters per hour [mm/hr]); and the Patient's Global Assessment of disease activity (participant-rated visual analog assessment [VAS]) with transformed scores with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity. Overall, a DAS28 score of less than or equal to (≤) 3.2 equals (=) low disease activity, and a DAS28 score of greater than (>) 3.2 to 5.1 = moderate to high disease activity. | Day 1 and Week 24 | 
| Percentage of Participants With a DAS28 Response by European League Against Rheumatism (EULAR) Category | DAS28-based EULAR response criteria were used to measure individual response as no response, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders: change from baseline greater than (>)1.2 with DAS28 less than or equal to (≤)3.2; moderate responders: change from baseline >1.2 with DAS28 >3.2 to ≤5.1 or change from baseline >0.6 to ≤1.2 with DAS28 ≤5.1; non-responders: change from baseline ≤0.6 or change from baseline >0.6 and ≤1.2 with DAS28 >5.1. | Screening, Day 1, and Weeks 24 and 104 | 
| Percentage of Participants With Changes in Bone Density | Change in bone density in participants untreated with bisphosphonates was classified as percentage of participants with osteoporosis, osteopenia, or normal. In some participants, no determinations were available. | Screening, Weeks 48 and 104 |