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

Primary Purpose

Rheumatoid Arthritis

Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Etanercept , Methotrexate
Methotrexate; sulfasalazine; hydroxychloroquine;leflunomide
Sponsored by
Wyeth is now a wholly owned subsidiary of Pfizer
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rheumatoid Arthritis

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

1

2

Arm Description

Etanercept + Methotrexate

DMARD therapy Methotrexate + Sulfasalazine/Hydroxychloroquine/Leflunomide

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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).
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).
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.
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).
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.
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.
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.
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.

Full Information

First Posted
January 11, 2007
Last Updated
July 28, 2010
Sponsor
Wyeth is now a wholly owned subsidiary of Pfizer
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1. Study Identification

Unique Protocol Identification Number
NCT00422227
Brief Title
Study Comparing Etanercept With Usual DMARD Therapy in Subjects With Rheumatoid Arthritis in the Asia Pacific Region
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2010
Overall Recruitment Status
Completed
Study Start Date
June 2007 (undefined)
Primary Completion Date
March 2009 (Actual)
Study Completion Date
March 2009 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Wyeth is now a wholly owned subsidiary of Pfizer

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
300 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Active Comparator
Arm Description
Etanercept + Methotrexate
Arm Title
2
Arm Type
Active Comparator
Arm Description
DMARD therapy Methotrexate + Sulfasalazine/Hydroxychloroquine/Leflunomide
Intervention Type
Drug
Intervention Name(s)
Etanercept , Methotrexate
Intervention Description
Etanercept: 25 mg twice weekly over 16 weeks, SC Methotrexate: > 7.5 mg/week and no more than 25 mg/week, PO
Intervention Type
Drug
Intervention Name(s)
Methotrexate; sulfasalazine; hydroxychloroquine;leflunomide
Intervention Description
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
Primary Outcome Measure Information:
Title
Change From Baseline in Adjusted Mean of American College of Rheumatology Response (ACR-N) Area Under Curve (AUC) Over 16 Weeks
Description
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.
Time Frame
16 weeks
Secondary Outcome Measure Information:
Title
Percentage of Participants Achieving ACR 20, 50, and 70 Responses
Description
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.
Time Frame
Week 16
Title
Percentage of Participants Achieving DAS28 <3.2 (Low Disease Activity) and <2.6 (Remission)
Description
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).
Time Frame
Week 16
Title
Percent Change From Baseline in DAS28 at Week 16
Description
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).
Time Frame
Week 16
Title
Percentage of Participants Achieving European League Against Rheumatism (EULAR) Moderate or Good Response
Description
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.
Time Frame
Week 16
Title
Percentage of Participants With DAS28 Improvement of ≥0.6 and ≥1.2
Description
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).
Time Frame
Week 16
Title
Percent Change From Baseline in Painful and Swollen Joint Counts
Description
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.
Time Frame
Week 2, 4, 8, 12, 16
Title
Percent Change From Baseline in Physician And Subject Global Assessments
Description
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.
Time Frame
Week 2, 4, 8, 12, 16
Title
Percent Change From Baseline in Duration (Minutes) of Morning Stiffness
Description
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.
Time Frame
Week 2, 4, 8, 12, 16
Title
Percent Change From Baseline in General Health, Pain, and Fatigue, Visual Analog Scales
Description
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.
Time Frame
Week 2, 4, 8, 12, 16

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Monitor
Organizational Affiliation
Wyeth is now a wholly owned subsidiary of Pfizer
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Trial Manager
Organizational Affiliation
For Hong Kong: medinfo@wyeth.com
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Trial Manager
Organizational Affiliation
For Taiwan: medinfo@wyeth.com
Official's Role
Principal Investigator
Facility Information:
City
Hong Kong
Country
Hong Kong
City
Bangalore
ZIP/Postal Code
560017
Country
India
City
Bangalore
ZIP/Postal Code
560034
Country
India
City
Hyderabaad
ZIP/Postal Code
500082
Country
India
City
New Delhi
ZIP/Postal Code
110029
Country
India
City
In Cheon
State/Province
Korea
ZIP/Postal Code
400-711
Country
Korea, Republic of
City
Seoul
State/Province
Korea
ZIP/Postal Code
110-744
Country
Korea, Republic of
City
Seoul
State/Province
Korea
ZIP/Postal Code
120-752
Country
Korea, Republic of
City
Seoul
State/Province
Korea
ZIP/Postal Code
133-792
Country
Korea, Republic of
City
Seoul
State/Province
Korea
ZIP/Postal Code
137-701
Country
Korea, Republic of
City
Seoul
State/Province
Korea
ZIP/Postal Code
138-736
Country
Korea, Republic of
City
Ipoh, Perak
ZIP/Postal Code
30450
Country
Malaysia
City
Kuala Lumpur
ZIP/Postal Code
68100
Country
Malaysia
City
Pulau Pinang
ZIP/Postal Code
10450
Country
Malaysia
City
Putrajaya
ZIP/Postal Code
62250
Country
Malaysia
City
Seremban
ZIP/Postal Code
70300
Country
Malaysia
City
Cebu
ZIP/Postal Code
6000
Country
Philippines
City
Makati City
ZIP/Postal Code
1200
Country
Philippines
City
Manila
ZIP/Postal Code
1000
Country
Philippines
City
Manila
ZIP/Postal Code
1004
Country
Philippines
City
Manila
ZIP/Postal Code
1500
Country
Philippines
City
Quezon City
ZIP/Postal Code
1102
Country
Philippines
City
Singapore
ZIP/Postal Code
308433
Country
Singapore
City
Kaohsiung City
ZIP/Postal Code
807
Country
Taiwan
City
Taipei
ZIP/Postal Code
100
Country
Taiwan
City
Taipei
ZIP/Postal Code
112
Country
Taiwan
City
Bangkok
ZIP/Postal Code
10400
Country
Thailand

12. IPD Sharing Statement

Citations:
PubMed Identifier
24907147
Citation
Fleischmann R, Koenig AS, Szumski A, Nab HW, Marshall L, Bananis E. Short-term efficacy of etanercept plus methotrexate vs combinations of disease-modifying anti-rheumatic drugs with methotrexate in established rheumatoid arthritis. Rheumatology (Oxford). 2014 Nov;53(11):1984-93. doi: 10.1093/rheumatology/keu235. Epub 2014 Jun 6.
Results Reference
derived
PubMed Identifier
23294908
Citation
Bae SC, Gun SC, Mok CC, Khandker R, Nab HW, Koenig AS, Vlahos B, Pedersen R, Singh A. Improved health outcomes with etanercept versus usual DMARD therapy in an Asian population with established rheumatoid arthritis. BMC Musculoskelet Disord. 2013 Jan 8;14:13. doi: 10.1186/1471-2474-14-13.
Results Reference
derived

Learn more about this trial

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

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