A Study of The Effect of RoActemra/Actemra (Tocilizumab) in Combination With Methotrexate on Articular Damage in The Hand in Patients With Moderate to Severe Rheumatoid Arthritis Who Have an Inadequate Response to Non-Biological DMARDs

Study Overview
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Brief Summary
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This open-label, single arm study will evaluate the effect of RoActemra/Actemra in combination with methotrexate on articular damage in the hand (synovitis/osteitis and erosions) in patients with moderate to severe rheumatoid arthritis who have an inadequate response to non-biological disease-modifying ante-rheumatic drugs (DMARDs). Patients will receive RoActemra/Actemra 8 mg/kg intravenously every 4 weeks for 24 weeks.

Official Title
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Open Label Study to Describe the Effect of Tocilizumab in Combination With MTX in the Evolution of Articular Damage (Synovitis/Osteitis and Erosions) Evaluated by MRI in the Hand of Patients With Moderate to Severe Rheumatoid Arthritis (RA) and Inadequate Response to Non-biological DMARDs

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: methotrexate
* Drug: tocilizumab [RoActemra/Actemra]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients, >/= 18 years of age Diagnosis of rheumatoid arthritis according to ACR/EULAR classification (2010) of >/= 6 months duration Active moderate to severe rheumatoid arthritis (DAS >/= 3.2) Swollen joint count (SJC) >/= 6, tender joint count >/= 8 Synovitis in the dominant hand Inadequate response to stable dose of a non-biological DMARD for at least 3 months Oral corticosteroids must have been on stable dose for at least 25 out of 28 days before first dose of study drug Patient on outpatient treatment Exclusion Criteria: Major surgery (including joint surgery) in the 8 weeks prior to screening, or planned major surgery within 6 months of randomization Rheumatic autoimmune disease other than rheumatoid arthritis American College of Rheumatology (ACR) functional class IV History of or current inflammatory joint disease other than rheumatoid arthritis Previous inadequate response to a biologic DMARD; prior biologic therapy for no longer than 1 month is allowed if discontinued for reasons of tolerability at least 6 months prior to study recruitment Intra-articular or parenteral corticosteroids within 6 weeks prior to study start Inadequate hematologic, renal or liver function Positive for hepatitis B, hepatitis C or HIV infection Pregnant or lactating women History of severe allergic reactions or anaphylaxis to human, humanized or mural monoclonal antibodies Current infections or history of recurrent infections History of or currently active primary or acquired immunodeficiency Active tuberculosis requiring treatment in the previous 3 years Body weight > 150 kg

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: RoActemra/Actemra<br> | Drug: methotrexate<br>* stable dose<br>Drug: tocilizumab [RoActemra/Actemra]<br>* 8 mg/kg intravenously every 4 weeks, 24 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in extent and degree of synovitis in the hand assessed by MRI according to the OMERACT RAMRIS scale |  | from baseline to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiological changes in the hand according to the modified Sharp scale |  | from baseline to Week 24 | 
| Change in Ritchie articular index |  | from baseline to Week 24 | 
| Proportion of patients with American College of Rheumatology (ACR 20/50/70) response at Weeks 12 and 24 |  | Weeks 12 and 24 | 
| Change in pain: Visual analogue scale (VAS) |  | from baseline to Week 24 | 
| Change in disability: Stanford Health Assessment Questionnaire |  | from baseline to Week 24 | 
| Change in FACIT-fatigue questionnaire |  | from baseline to Week 24 | 
| Change in disease activity: Disease activity score 28 - erythrocyte sedimentation rate (DAS28-ESR) |  | from baseline to Week 28 | 
| Change in C-reactive protein |  | from baseline to Week 24 | 
| Change in immunologic parameters: Rheumatic factor/anti-CCP |  | from baseline to Week 24 | 
| Safety: Incidence of adverse events |  | approximately 2 years |