A Study of Efficacy of Rituximab [Mabthera/Rituxan] in Patients With Rheumatoid Arthritis Using Magnetic Resonance Imaging of the Hand (RESONAR)

Study Overview
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Brief Summary
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This randomized, double-blind, placebo controlled, parallel group study will assess the efficacy and safety of rituximab [MabThera/Rituxan] in patients with severe active rheumatoid arthritis refractory to at least one anti-TNF treatment, using magnetic resonance imaging (MRI) of the hand for efficacy measurement. Patients will be randomized to receive 2 intravenous infusions 14 days apart of either 1000mg MabThera (group A) or placebo (group B). All patients will receive methotrexate 10-25mg weekly. Patients in group A demonstrating clinical response at week 24 may receive further cycles of MabThera, patients in group B without clinical response will also be treated with active MabThera. Anticipated time on study treatment is up to 2 years. Target sample size is <50 patients.

Official Title
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Efficacy of MabThera in Patients With Rheumatoid Arthritis, by Measurement of Disease Parameters Through Magnetic Resonance of the Hand (RESONAR Study)

Conditions
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Rheumatoid Arthritis

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients, 18-75 years of age active rheumatoid arthritis (DAS28-CRP>3.2) refractory to one or more anti-TNF on stable treatment for RA for >/=4 weeks evidence of erosive disease and/or synovitis in wrist and/or knuckles Exclusion Criteria: active systemic or local infection previous or current history of any demyelinization process in central nervous system, pancytopenia or aplasic anaemia signs of immunodeficiency, HIV infection or tuberculosis contraindications to MRI, such as metal devices, claustrophobia, moderate or severe renal insufficiency, or allergy to contrast agent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br> | Drug: rituximab [MabThera/Rituxan]<br>* 1000 mg by i.v. infusion on day 1 and 15<br>Drug: methotrexate<br>* 10-25 mg weekly<br>Drug: rituximab [Mabthera/Rituxan]<br>* 1000 mg by i.v. infusion on day 1 and 15, 2nd and further cycles in patients with (group A) or without (group B) clinical response in cycle 1<br>|
| Placebo Comparator: B<br> | Drug: placebo<br>* i.v. infusion on day 1 and 15<br>Drug: methotrexate<br>* 10-25 mg weekly<br>Drug: rituximab [Mabthera/Rituxan]<br>* 1000 mg by i.v. infusion on day 1 and 15, 2nd and further cycles in patients with (group A) or without (group B) clinical response in cycle 1<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone erosion score on magnetic resonance imaging (MRI) using the rheumatoid arthritis magnetic resonance imaging scoring system (RAMRIS) |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Synovitis score on MRI using RAMRIS |  | months 6, 12 and 24 | 
| Bone edema score on MRI using RAMRIS |  | months 6, 12 and 24 | 
| Bone erosion score on MRI using RAMRIS |  | months 12 and 24 | 
| Disease activity according to DAS28-CRP |  | months 12 and 24 | 
| Tender or swollen joint count (ACR criteria) |  | months 12 and 24 | 
| Health assessment questionnaire (HAQ) |  | months 12 and 24 |