Study Comparing Etanercept With Usual DMARD Therapy in Subjects With Rheumatoid Arthritis in the Asia Pacific Region

Study Overview
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Brief Summary
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The purpose of this study is to compare the efficacy of etanercept with usual disease-modifying anti-rheumatic drug (DMARD) therapy in the treatment of moderate to severe rheumatoid arthritis (RA) over 16 weeks in the Asia Pacific region.

Official Title
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A Randomized, Open-Label Study in the Asia-Pacific Region Comparing the Safety and Efficacy of Etanercept With Usual DMARD Therapy in Subjects With Rheumatoid Arthritis

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: Etanercept , Methotrexate
* Drug: Methotrexate; sulfasalazine; hydroxychloroquine;leflunomide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of RA Currently receiving an adequate dose of methotrexate (MTX) for treatment of RA Active RA at time of screening and baseline Exclusion Criteria: Previous or current treatment with etanercept (ETN), other tumor necrosis factor-alpha inhibitors, or other biologic agents Concurrent treatment with a DMARD, other than MTX, at screening Receipt of any DMARD, other than MTX, within 3 months before screening

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Etanercept + Methotrexate | Drug: Etanercept , Methotrexate<br>* Etanercept: 25 mg twice weekly over 16 weeks, SC Methotrexate: > 7.5 mg/week and no more than 25 mg/week, PO<br>|
| Active Comparator: 2<br>DMARD therapy Methotrexate + Sulfasalazine/Hydroxychloroquine/Leflunomide | Drug: Methotrexate; sulfasalazine; hydroxychloroquine;leflunomide<br>* Methotrexate: at least 7.5 mg/wk and not more than 25 mg/wk.;PO Sulfasalazine: Start treatment w/500 mg daily for 1 wk, thereafter increase dose by 1 tab each wk to a max of 3 g/day;PO Hydroxychloroquine:400 mg daily in divided dose, may be reduced to 200 mg. Max: 6.5 mg/kg/day Leflunomide: Initially, loading dose 100 mg daily for 3 days. Maintenance: 20 mg daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Adjusted Mean of American College of Rheumatology Response (ACR-N) Area Under Curve (AUC) Over 16 Weeks | ACR-N = the lowest of 3 values (percent change in the number of swollen joints, percent change in the number of tender joints, and median of the other 5 measures in the ACR core data set). Negative numbers indicate worsening. The ACR-N AUC was calculated using the trapezoidal rule as the ACR-N multiplied by the duration of the assessment period (in weeks) and was presented as %-weeks. | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving ACR 20, 50, and 70 Responses | Response includes improvement in tender or swollen joints as well as 20 percent improvement in three of the other five criteria. Required: ≥ 20%, 50% or 70% improvement in tender joint count ≥ 20% , 50% or 70% improvement in swollen joint count and at least 20%, 50%, 70% improvement in 3 of the following 5:Patient pain assessment , Patient global assessment ,Physician global assessment, Patient self-assessed disability. | Week 16 | 
| Percentage of Participants Achieving DAS28 <3.2 (Low Disease Activity) and <2.6 (Remission) | Disease Activity Score 28 based on 28 Joints (DAS28) is the calculation of DAS28: DAS28 = 0.56 sqrt (28 painful joint count) + 0.28 sqrt (28 swollen joint count) + 0.70 (ln erythrocyte sedimentation rate (ESR)) + 0.014 (General Health) (GH). GH = Subject general health visual analog scale (0-10 mm). | Week 16 | 
| Percent Change From Baseline in DAS28 at Week 16 | Disease Activity Score 28 based on 28 Joints (DAS28) is the calculation of DAS28: DAS28 = 0.56 sqrt (28 painful joint count) + 0.28 sqrt (28 swollen joint count) + 0.70 (ln erythrocyte sedimentation rate (ESR)) + 0.014 (General Health) (GH). GH = Subject general health visual analog scale (0-10 mm). | Week 16 | 
| Percentage of Participants Achieving European League Against Rheumatism (EULAR) Moderate or Good Response | EULAR Response Criteria DAS28) improvement at week 16. Good response was defined as >1.2 improvement in DAS from Baseline and DAS attained during follow-up of ≤2.4. Non-responders were participants with improvement of ≤0.6 or participants with improvement of >0.6 but ≤1.2 and DAS attained during follow-up of >3.7. Remaining participants were classified as moderate. Scores of good and moderate were considered to have therapeutic response. | Week 16 | 
| Percentage of Participants With DAS28 Improvement of ≥0.6 and ≥1.2 | Disease Activity Score 28 based on 28 Joints (DAS28) is the calculation of DAS28: DAS28 = 0.56 sqrt (28 painful joint count) + 0.28 sqrt (28 swollen joint count) + 0.70 (ln erythrocyte sedimentation rate (ESR) + 0.014 (General Health) (GH). GH = Subject general health visual analog scale (0-10 mm). | Week 16 | 
| Percent Change From Baseline in Painful and Swollen Joint Counts | Participant's assessment of pain - A horizontal pain visual analog scale (VAS) (0-100 mm) is used to assess the participants current level of pain; 0 = no pain and 100 = worst pain. Swollen joint count - ACR swollen joint count, an assessment of 28 joints. Joints are classified as either swollen or not swollen. | Week 2, 4, 8, 12, 16 | 
| Percent Change From Baseline in Physician And Subject Global Assessments | The Physician Global Assessment of Disease Activity: The participant's disease activity is estimated over the last two - three days by the physician; A zero (0) means no disease activity and a ten (10) means extreme disease activity. The Subject Global Assessment of Disease Activity: The participant assesses overall arthritis activity. A zero (0) means no disease activity and a ten (10) means extreme disease activity. | Week 2, 4, 8, 12, 16 | 
| Percent Change From Baseline in Duration (Minutes) of Morning Stiffness | The duration of morning stiffness on the day of examination should be determined by asking the following two questions: When did you awaken this morning? When were you able to resume your normal activities without stiffness? Duration of morning stiffness is equal to the time elapsed between the above two times in minutes; If none is present enter 0, If morning stiffness is still continuing, please indicate average of duration of stiffness over the past 3 days. If stiffness persists the entire day 1440 minutes (24h x 60 minutes) should be recorded. | Week 2, 4, 8, 12, 16 | 
| Percent Change From Baseline in General Health, Pain, and Fatigue, Visual Analog Scales | VAS, participant indicates by marking a vertical line at an appropriate position through a horizontal line. The length of the line measures from left (in mm) and the value (in mm) is recorded. General Health VAS, in general how would you rate your heath over the last 2-3 weeks, 0mm equals very well and 100mm equals extremely bad. Pain VAS: indicate the amount of pain experienced during the last 2-3 days, 0 mm equals no pain and 100 mm equals pain as bad as it can be. Fatigue VAS: how fatigued or tired have you been over the last week, range =No Fatigue - Extremely Fatigued. | Week 2, 4, 8, 12, 16 |