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

Study Overview
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Brief Summary
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In this open-label single arm study the safety and efficacy of Mabthera will be evaluated in patients with active rheumatoid arthritis who have had an inadequate response to methotrexate. Patients will receive MabThera (1000mg iv infusion) on days 1 and 15, and background methotrexate (10-25mg po or sc 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 target sample size is <50

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
* Drug: methylprednisolone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients >/= 18 years of age rheumatoid arthritis DAS28 >/= 3.2 receiving treatment on an outpatient basis 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: single arm<br> | Drug: rituximab [MabThera/Rituxan]<br>* 1000 mg iv infusion on days 1 and 15<br>Drug: methotrexate<br>* 10-25 mg weekly (oral or parenteral)<br>Drug: methylprednisolone<br>* 100 mg iv prior to each rituximab infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Reporting Adverse Events (AEs) |  | Days 1 and 15, every 8 weeks up to Week 24 and and then every 3 months up to 18 months for a total of 104 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change in Disease Activity Score 28 (DAS28) From Baseline to Week 24 | The DAS28 score is a measure of the participant's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], participant's global assessment of disease activity [visual analog scale: [VAS] 0 equals (=) no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to 10. Scores less than (<) 2.6 indicate best disease control and scores greater than or equal to (≥) 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score < 2.6. The average improvement at each visit to the group score is equal to the formula (Previous DAS28 minus [-] current DAS 28)/ Previous DAS 28 x 100. Negative percentages indicate that the participant has worsened in comparison to last evaluation, and positive percentages indicate improvement of its DAS28 score and correlated with a bettering of clinical situation. | Baseline and Week 24 | 
| Percentage of Participants Whose DAS28 Improved by >1.2 at Week 24 | The DAS28 score is a measure of the participant's disease activity calculated using the TJC [28 joints], SJC [28 joints], participant's global assessment of disease activity [VAS: 0 = no disease activity to 100 = maximum disease activity] and the ESR for a total possible score of 0 to 10. Scores < 2.6 indicate best disease control and scores ≥ 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score < 2.6. An improvement of >1.2 was considered to be clinically significant improvement. | Baseline and Week 24 | 
| Change in Bone Density (in Participants Untreated With Bisphosphonates) | Bone mineral density test was performed using x-ray radiation and the values of bone density were provided directly by the apparatus as grams per square centimeter (g/cm^2) . T-score is the number of standard deviations above or below the mean for a healthy 30 year old adult of the same sex and ethnicity as the participant. A T-score with above -1 is normal bone density level. A T-score between -1 and -2.5 means that the bone density is below normal and it might be a sign of an osteopenia and may also lead into osteoporosis. A T-score below -2.5 indicates osteoporosis. | Screening and Week 84 |