A Study to Assess the Effect of Tocilizumab + Methotrexate on Signs and Symptoms in Patients With Moderate to Severe Active Rheumatoid Arthritis Currently on Methotrexate Therapy

Study Overview
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Brief Summary
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This 3 arm study will compare the safety and efficacy, with regard to reduction of signs and symptoms, of tocilizumab versus placebo in combination with methotrexate (MTX) in patients with moderate to severe active rheumatoid arthritis (RA) currently on MTX therapy, and who have had an inadequate response to prior therapy with an anti-tumor necrosis factor (anti-TNF) agent. Patients will be randomized to receive tocilizumab 4mg/kg iv, tocilizumab 8mg/kg or placebo iv, every 4 weeks. All patients will also receive methotrexate 10-25mg/week. The anticipated time on study treatment is 3-12 months, and the target sample size is 500+ individuals.

Official Title
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A Randomized, Double-blind Study of Safety and Reduction in Signs and Symptoms During Treatment With Tocilizumab Versus Placebo, in Combination With Methotrexate, in Patients With Moderate to Severe Active Rheumatoid Arthritis and Inadequate Response to Anti-TNF Therapy

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: Methotrexate
* Drug: Placebo
* Drug: tocilizumab [RoActemra/Actemra]
* Drug: tocilizumab [RoActemra/Actemra]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients at least 18 years of age with moderate to severe active RA for at least 6 months; inadequate response to current anti-rheumatic therapies, including MTX; inadequate response or intolerance to treatment with 1 or more anti-TNF therapies within 1 year of entering study; on stable MTX for at least 8 weeks before entering study; patients of reproductive potential must be using reliable methods of contraception. Exclusion Criteria: major surgery (including joint surgery) within 8 weeks before screening, or planned major surgery within 6 months after entering study; women who are pregnant or breast-feeding.

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: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: Methotrexate<br>* 10-25mg weekly<br>Drug: tocilizumab [RoActemra/Actemra]<br>* 4mg/kg iv every 4 weeks<br>|
| Experimental: 2<br> | Drug: Methotrexate<br>* 10-25mg weekly<br>Drug: tocilizumab [RoActemra/Actemra]<br>* 8mg/kg iv every 4 weeks<br>|
| Placebo Comparator: 3<br> | Drug: Methotrexate<br>* 10-25mg weekly<br>Drug: Placebo<br>* iv every 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with ACR 20 response |  | Week 24 | 
| AEs, laboratory parameters, vital signs, ECGs. |  | Throughout study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with ACR 50 and ACR 70 responses |  | Week 24 | 
| Mean changes in parameters of ACR core set |  | Week 24 |