Infliximab Plus Methotrexate for the Treatment of Rheumatoid Arthritis

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the safety and effectiveness of infliximab (an anti-TNF chimeric monoclonal antibody [cA2]) in patients with active Rheumatoid Arthritis, despite methotrexate treatment.

Detailed Description
-----------------
This is a placebo-controlled, double-blinded, randomized clinical study to evaluate the safety and effectiveness of infliximab in patients with active Rheumatoid Arthritis, despite methotrexate treatment. Infliximab is an anti-TNF chimeric monoclonal antibody (cA2). The primary measures of effectiveness include the change from baseline in American College of Rheumatology (ACR20) response at week 30, and the change in the modified van der Heijde Sharp Score. The ACR20 Responder Index a composite of clinical, laboratory, and functional measures and the van der Heijde-Sharp (vdH-S) scoring method is a method of rating structural damage in patients.. Patients will be treated with either infliximab or matching placebo.

Official Title
-----------------
A Placebo-Controlled, Double-Blinded, Randomized Clinical Trial of Anti-TNF Chimeric Monoclonal Antibody (cA2) in Patients With Active Rheumatoid Arthritis Despite Methotrexate Treatment

Conditions
-----------------
Rheumatoid Arthritis

Intervention / Treatment
-----------------
* Drug: Placebo
* Drug: Infliximab 3 mg/kg
* Drug: Infliximab 10 mg/kg


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with active Rheumatoid Arthritis despite treatment with methotrexate Diagnosed with Rheumatoid Arthritis at least 6 months prior to screening Having active disease at the time of screening and pre-infusion as defined by having at least 6 or more swollen joints and 6 or more tender joints Using methotrexate for at least 3 months prior to study enrollment Exclusion Criteria: Patients having any systemic inflammatory condition Having Lyme disease or a rheumatic disease other than Rheumatoid Arthritis Who have used Disease-Modifying Antirheumatic Drugs (DMARDs) other than methotrexate within 4 weeks prior to screening Who have used corticosteroids within 4 weeks prior to screening Having received previous administration of infliximab

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Matching placebo will be adminstered at Week 0, 2, 6 and every 4 weeks up to Week 54. | Drug: Placebo<br>* Matching placebo will be adminstered at Week 0, 2, 6 and every 4 weeks up to Week 54.<br>|
| Experimental: Infliximab 3 mg/kg every 8 weeks<br>Infliximab 3 milligram per kilogram (mg/kg) will be administered as infusion at Week 0, 2, 6 and every 8 weeks up to Week 52. | Drug: Infliximab 3 mg/kg<br>* Infliximab (anti-TNF chimeric monoclonal antibody [cA2]) 3 milligram per kilogram (mg/kg) will be administered as infusion at Week 0, 2, 6 and every 8 weeks or every 4 weeks up to Week 52.<br>* Other names: anti-TNF chimeric monoclonal antibody (cA2);|
| Experimental: Infliximab 3 mg/kg every 4 weeks<br>Infliximab 3 mg/kg will be administered as infusion at Week 0, 2, 6 and every 4 weeks up to Week 52. | Drug: Infliximab 3 mg/kg<br>* Infliximab (anti-TNF chimeric monoclonal antibody [cA2]) 3 milligram per kilogram (mg/kg) will be administered as infusion at Week 0, 2, 6 and every 8 weeks or every 4 weeks up to Week 52.<br>* Other names: anti-TNF chimeric monoclonal antibody (cA2);|
| Experimental: Infliximab 10 mg/kg every 8 weeks<br>Infliximab 10 mg/kg will be administered as infusion at Week 0, 2, 6 and every 8 weeks up to Week 52. | Drug: Infliximab 10 mg/kg<br>* Infliximab (anti-TNF chimeric monoclonal antibody [cA2]) 3 milligram per kilogram (mg/kg) will be administered as infusion at Week 0, 2, 6 and every 8 weeks or every 4 weeks up to Week 52.<br>* Other names: anti-TNF chimeric monoclonal antibody (cA2);|
| Experimental: Infliximab 10 mg/kg every 4 weeks<br>Infliximab 3 mg/kg will be administered as infusion at Week 0, 2, 6 and every 4 weeks up to Week 52. | Drug: Infliximab 10 mg/kg<br>* Infliximab (anti-TNF chimeric monoclonal antibody [cA2]) 3 milligram per kilogram (mg/kg) will be administered as infusion at Week 0, 2, 6 and every 8 weeks or every 4 weeks up to Week 52.<br>* Other names: anti-TNF chimeric monoclonal antibody (cA2);|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in ACR20 response at week 30; Change in modified van der Heijde-Sharp Score |  | Baseline and Week 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety |  | up to Week 54 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Rheumatoid Arthritis, infliximab, methotrexate