Study Comparing Etanercept and Methotrexate vs. Methotrexate Alone in Rheumatoid Arthritis

Study Overview
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Brief Summary
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To compare the effects of the combination of ETN and MTX to MTX alone on radiographic change and clinical disease activity in subjects with early RA over 12 months.

Official Title
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A 24-Month,Randomized,Double-Blind,Two-Period Study to Evaluate the Efficacy and Safety of the Combination of Etanercept and Methotrexate and Methotrexate Alone in Subjects With Early Rheumatoid Arthritis

Conditions
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Rheumatoid Arthritis

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Satisfies the 1987 ACR Revised Criteria for Rheumatoid Arthritis Has RA greater than or equal to 3 months and less than or equal to 2 years Exclusion Criteria: Received any previous treatment with MTX Received any previous treatment with ETN or other tumour necrosis factor antagonist

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1a<br>Etanercept + Methorexate for Period 1 (first 12 months) and Period 2 (Second 12 months) | Drug: Etanercept<br>* Group 1a: Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 1 & 2 Group 1b: Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 1 then Etanercept 50 mg SC injections weekly + Placebo weekly for Period 2 Group 2a: Oral Methotrexate weekly + Placebo for Period 1, then Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 2<br>Drug: Methotrexate<br>* Group 1a: Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 1 & 2 Group 1b: Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 1 then Etanercept 50 mg SC injections weekly + Placebo weekly for Period 2 Group 2a: Oral Methotrexate weekly + Placebo for Period 1, then Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 2 Group 2b: Oral Methotrexate weekly for both Periods 1 and 2<br>|
| Active Comparator: 1b<br>Etanercept + Methotrexate for Period 1 (First 12 months) and Etanercept alone for Period 2 (Second 12 months) | Drug: Etanercept<br>* Group 1a: Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 1 & 2 Group 1b: Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 1 then Etanercept 50 mg SC injections weekly + Placebo weekly for Period 2 Group 2a: Oral Methotrexate weekly + Placebo for Period 1, then Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 2<br>Drug: Methotrexate<br>* Group 1a: Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 1 & 2 Group 1b: Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 1 then Etanercept 50 mg SC injections weekly + Placebo weekly for Period 2 Group 2a: Oral Methotrexate weekly + Placebo for Period 1, then Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 2 Group 2b: Oral Methotrexate weekly for both Periods 1 and 2<br>Drug: Placebo<br>* Group 1b: Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 1 then Etanercept 50 mg SC injections weekly + Placebo weekly for Period 2 Group 2a: Oral Methotrexate weekly + Placebo for Period 1, then Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 2<br>|
| Active Comparator: 2a<br>Methotrexate alone in Period 1 (First 12 months) and etanercept + Methotrexate in Period 2 (Second 12 months) | Drug: Etanercept<br>* Group 1a: Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 1 & 2 Group 1b: Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 1 then Etanercept 50 mg SC injections weekly + Placebo weekly for Period 2 Group 2a: Oral Methotrexate weekly + Placebo for Period 1, then Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 2<br>Drug: Methotrexate<br>* Group 1a: Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 1 & 2 Group 1b: Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 1 then Etanercept 50 mg SC injections weekly + Placebo weekly for Period 2 Group 2a: Oral Methotrexate weekly + Placebo for Period 1, then Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 2 Group 2b: Oral Methotrexate weekly for both Periods 1 and 2<br>Drug: Placebo<br>* Group 1b: Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 1 then Etanercept 50 mg SC injections weekly + Placebo weekly for Period 2 Group 2a: Oral Methotrexate weekly + Placebo for Period 1, then Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 2<br>|
| Active Comparator: 2b<br>Methotrexate alone in Period 1 (First 12 months) and Methotrexate alone in Period 2 (Second 12 months) | Drug: Methotrexate<br>* Group 1a: Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 1 & 2 Group 1b: Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 1 then Etanercept 50 mg SC injections weekly + Placebo weekly for Period 2 Group 2a: Oral Methotrexate weekly + Placebo for Period 1, then Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 2 Group 2b: Oral Methotrexate weekly for both Periods 1 and 2<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Participants Achieving Remission As Measured by a Disease Activity Score for 28 Joints (DAS 28) < 2.6. | Effects of the combination of etanercept and methotrexate to methotrexate alone on clinical disease activity. DAS28 scale 0 - 10, 3.2 or lower showing controlled disease while 5.1 implies active disease. | 12 months | 
| Year 1 Participants Having an Annualized Modified Total Sharp Score (mTSS) < 0.5. | The (van der Heijde) modified total Sharp score (mTSS) is the sum of scores for erosions (range 0-280) and joint space narrowings (range 0-168) and thus has a total range of (0 - 448 ), where zero is the best score , indicating no damage. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety Measured by Number of Participants Reporting a Serious Adverse Event That Led to Death | Safety report for entire trial where participants reported a serious adverse event that led to death. | 12 and 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rheumatoid Arthritis