A Study of Imatinib 400 mg Once Daily in Combination With Methotrexate in the Treatment of Rheumatoid Arthritis.

Study Overview
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Brief Summary
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Imatinib is a member of a new class of drugs known as signal transduction inhibitors. The purpose of this study is to evaluate the efficacy, safety and tolerability of imatinib in the treatment of rheumatoid arthritis in combination with methotrexate in patients who do not respond satisfactorily to standard treatment, e.g. methotrexate.

Official Title
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3-Month, Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Efficacy, Safety & Tolerability of Imatinib 400 mg Daily in Combination With Methotrexate (MTX)Compared to MTX Alone in the Treatment of Rheumatoid Arthritis (RA).

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: Imatinib
* Drug: Methotrexate
* Drug: Imatinib Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: With a diagnosis of RA classified by ACR 1987 revised criteria with symptoms for at least 6 months Functional status class I, II, III according to the ACR 1991 revised classification criteria Patients have to have been treated with MTX at the maximum tolerated dose for at least 3 months, and be on a stable dose and route of administration for at least 2 months prior to study entry Disease activity criteria of minimum 6 out of 28 tender and swollen joints at baseline Exclusion Criteria: With current use of DMARDs other than MTX. DMARDs include but are not limited to: biologic agents, thiolates (D-penicillamine, thiopronine), sulfasalazine, gold compounds, antimalarials, cyclosporine A, azathioprine, leflunomide and alkylating agents such as cyclophosphamide With any DMRAD treatment used in combination with methotrexate within 1 month prior to study entry. In case of infliximab and leflunomide, a washout period of 2 months is required With any therapy by intra-articular injection, including intra-articular corticosteroid use within 1 month prior to study entry Other protocol-defined inclusion/exclusion criteria may apply.

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

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Imatinib 400mmg OD +MTX<br> | Drug: Imatinib<br> <br> Drug: Methotrexate<br> <br> |
| Placebo Comparator: Imatinib Placebo + MTX<br> | Drug: Methotrexate<br> <br> Drug: Imatinib Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of imatinib in combination with MTX in pts with active RA by assessing response to treatment(ACR20) after 3 mos compared to MTX alone |  |  | 
| Overall safety and tolerability of imatinib in combination with MTX in pts with active RA over 3 mos compared to MTX alone. |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of imatinib in combination with MTX by assessing the response to treatment (ACR50 and ACR70 criteria; DAS28/EULAR28) after 3 mos compared to MTX alone |  |  | 
| Effect of imatinib in combination with MTX on ACR components after 3 mos compared to MTX alone |  |  | 
| Effect of imatinib in combination with MTX on rheumatoid factor concentrations |  |  | 
| Determine time of onset of clinical response to imatinib in combination with MTX |  |  | 
| Determine retention on treatment of imatinib in combination with MTX over 3 mos |  |  | 
| Assess pt's quality of life by means of the Euro QoL 50 Health Questionnaire |  |  | 
| Assess in a subset of pts pharmacokinetics of imatinib and MTX and their potential interactions when co-administered |  |  | 
| Assess pharmacodynamic effect of imatinib in combination with MTX on liver enzymes, hematology and kidney function |  |  | 
| Explore potential for RA and drug-specific biomarkers |  |  | 
| Explore decrease in synovitis by means of ultrasound in a sub-set of patients. |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rheumatoid arthritis, imatinib, methotrexate