Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

Open-Label Study Comparing Etanercept to Conventional Disease Modifying Antirheumatic Drug (DMARD) Therapy

This study has been completed.
Sponsor:
Collaborator:
Amgen
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00848354
First received: February 18, 2009
Last updated: December 11, 2015
Last verified: December 2015
  Purpose
The purpose of this 2 phased, open-label study is to compare the safety and efficacy of etanercept with conventional Disease Modifying Antirheumatic Drug (DMARD) therapy in Latin American subjects with moderate to severe rheumatoid arthritis over 128 weeks. Phase 1 is a randomized 24 week treatment period; Phase 2 is an optional open-label 104 week period that allows the investigator to choose continuation with the phase I treatment or the addition, discontinuation or titration of other DMARD therapy already being utilized for the study.

Condition Intervention Phase
Rheumatoid Arthritis
Biological: Phase 1: Etanercept
Drug: Phase 1: Methotrexate
Drug: Phase 2: Optional ETN, SSZ, HCQ, MTX
Drug: Phase 1: Conventiaonal DMARD
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Open-label Study In The Latin America Region Comparing The Safety And Efficacy Of Etanercept With Conventional Dmard Therapy In Subjects With Rheumatoid Arthritis.

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Percentage of Participants Achieving American College of Rheumatology 50 (ACR50) Response at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    ACR50 response: greater than or equal to 50 percent improvement from Baseline in tender joint count and swollen joint count; and greater than or equal to 50 percent improvement from Baseline in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; participant's self-assessed disability (disability index of the Health Assessment Questionnaire; HAQ); and C-Reactive Protein (CRP).


Secondary Outcome Measures:
  • Change From Baseline in HAQ Score at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    HAQ: self-reported, valid assessment of functional disability in rheumatoid arthritis. Assessed based on ability of participants to perform daily activities in 8 categories: dressing, arising, eating, walking, reaching, gripping, hygiene, and carrying out daily activities. HAQ score range: 0-3: without any difficulty: 0, with some difficulty: 1, with much difficulty: 2, unable to do: 3. HAQ total scores expressed as overall mean score with range 0-3: 0-0.25: normal functioning; 0.25-0.5: mild functional limitation; 0.5-1: moderate functional limitation; more than 1: significant functional limitation.

  • Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Score at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    The SF-36 is standardized 36-item survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health perception, vitality, and mental health. Domain scores range from 0-100, with greater scores reflecting better health status. Two additional overall summary scores - physical and mental component scores - were also obtained. Summary scores are standardized where the general population mean is 50 with a standard deviation of 10. Greater scores again indicate better health status.

  • Change From Baseline in Van Der Heijde Modified Total Sharp Score (vdH mTSS), Annualized, at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    mTSS: sum of erosion and joint space narrowing (JSN) scores for 44 joints (16 per hand and 6 per foot). mTSS scores ranged from 0 (normal) to 448 (worst possible total score). Each x-ray visit included 4 films, each of which were read by 2 readers. The mTSS was calculated by the images scored for erosions and JSN. An increase in mTSS from Baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.

  • Change From Baseline in Disease Activity Score Based on a 28-joint Count (DAS28) at Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24 [ Time Frame: Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24 ] [ Designated as safety issue: No ]
    DAS28 calculated from the number of swollen joints and painful joints using the 28 joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour; mm/hour) and the participant`s general health using a 100 mm-visual analog scale (VAS). DAS28<3.2 indicates low disease activity and DAS28<2.6 remission.

  • Change From Baseline in DAS28 at Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128 [ Time Frame: Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128 ] [ Designated as safety issue: No ]
    DAS28 calculated from the number of swollen joints and painful joints using the 28 joints count, the ESR (mm/hour) and the participant`s general health using a 100 mm-VAS. DAS28<3.2 indicates low disease activity and DAS28<2.6 remission.

  • Summary of Changes in Therapy at the Beginning of Phase 2 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    The investigators were allowed to alter each participant`s therapy at the beginning of Phase 2. Continuations, discontinuations and additions made to Phase 1 treatment regimen were summarized.

  • Percentage of Participants Achieving ACR50 Response at Week 2, Week 4, Week 8, Week 12, Week 16, and Week 20 [ Time Frame: Week 2, Week 4, Week 8, Week 12, Week 16, and Week 20 ] [ Designated as safety issue: No ]
    ACR50 response: greater than or equal to 50 percent improvement from Baseline in tender joint count and swollen joint count; and greater than or equal to 50 percent improvement from Baseline in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; participant's self-assessed disability (disability index of HAQ); and CRP.

  • Percentage of Participants Achieving ACR50 Response at Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128 [ Time Frame: Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128 ] [ Designated as safety issue: No ]
    ACR50 response: greater than or equal to 50 percent improvement from Baseline in tender joint count and swollen joint count; and greater than or equal to 50 percent improvement from Baseline in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; participant's self-assessed disability (disability index of HAQ); and ESR.

  • Percentage of Participants Achieving ACR20 Response at Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24 [ Time Frame: Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24 ] [ Designated as safety issue: No ]
    ACR20 response: greater than or equal to 20 percent improvement from Baseline in tender joint count and swollen joint count; and greater than or equal to 20 percent improvement from Baseline in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; participant's self-assessed disability (disability index of HAQ); and CRP.

  • Percentage of Participants Achieving ACR20 Response at Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128 [ Time Frame: Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128 ] [ Designated as safety issue: No ]
    ACR20 response: greater than or equal to 20 percent improvement from Baseline in tender joint count and swollen joint count; and greater than or equal to 20 percent improvement from Baseline in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; participant's self-assessed disability (disability index of HAQ); and ESR.

  • Percentage of Participants Achieving ACR70 Response at Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24 [ Time Frame: Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24 ] [ Designated as safety issue: No ]
    ACR70 response: greater than or equal to 50 percent improvement from Baseline in tender joint count and swollen joint count; and greater than or equal to 70 percent improvement from Baseline in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; participant's self-assessed disability (disability index of HAQ); and CRP.

  • Percentage of Participants Achieving ACR70 Response at Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128 [ Time Frame: Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128 ] [ Designated as safety issue: No ]
    ACR70 response: greater than or equal to 70 percent improvement from Baseline in tender joint count and swollen joint count; and greater than or equal to 70 percent improvement from Baseline in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; participant's self-assessed disability (disability index of HAQ); and ESR.

  • Change From Baseline in Disease Activity Score (DAS) at Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24 [ Time Frame: Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24 ] [ Designated as safety issue: No ]
    DAS calculated from number of painful joints using the ritchie articular index (RAI), number of swollen joints using the same 44 joints as in RAI, ESR (mm/hour) and participant`s general health using a 100 mm-VAS. DAS≤2.4 indicates low disease activity and DAS<1.6 remission.

  • Change From Baseline in DAS at Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128 [ Time Frame: Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128 ] [ Designated as safety issue: No ]
    DAS calculated from number of painful joints using RAI, number of swollen joints using the same 44 joints as in RAI, ESR (mm/hour) and participant`s general health using a 100 mm-VAS. DAS≤2.4 indicates low disease activity and DAS<1.6 remission.

  • Percentage of Participants Achieving DAS<2.4 (Low Disease Activity) Response at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    DAS calculated from number of painful joints using RAI, number of swollen joints using the same 44 joints as in RAI, ESR (mm/hour) and participant`s general health using a 100 mm-VAS. DAS<2.4: low disease activity, DAS<1.6: remission.

  • Percentage of Participants Achieving DAS<1.6 (Remission) Response at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    DAS calculated from number of painful joints using RAI, number of swollen joints using the same 44 joints as in RAI, ESR (mm/hour) and participant`s general health using a 100 mm-VAS. DAS<2.4: low disease activity, DAS<1.6: remission.

  • Percentage of Participants Achieving DAS Improvement of ≥0.6 From Baseline at Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24 [ Time Frame: Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24 ] [ Designated as safety issue: No ]
    DAS calculated from number of painful joints using RAI, number of swollen joints using the same 44 joints as in RAI, ESR (mm/hour) and participant`s general health using a 100 mm-VAS. DAS<2.4: low disease activity, DAS<1.6: remission.

  • Percentage of Participants Achieving DAS Improvement of ≥0.6 From Baseline at Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128 [ Time Frame: Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128 ] [ Designated as safety issue: No ]
    DAS calculated from number of painful joints using RAI, number of swollen joints using the same 44 joints as in RAI, ESR (mm/hour) and participant`s general health using a 100 mm-VAS. DAS<2.4: low disease activity, DAS<1.6: remission.

  • Percentage of Participants Achieving DAS Improvement of ≥1.2 From Baseline at Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24 [ Time Frame: Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24 ] [ Designated as safety issue: No ]
    DAS calculated from number of painful joints using RAI, number of swollen joints using the same 44 joints as in RAI, ESR (mm/hour) and participant`s general health using a 100 mm-VAS. DAS<2.4: low disease activity, DAS<1.6: remission.

  • Percentage of Participants Achieving DAS Improvement of ≥1.2 From Baseline at Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128 [ Time Frame: Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128 ] [ Designated as safety issue: No ]
    DAS calculated from number of painful joints using RAI, number of swollen joints using the same 44 joints as in RAI, ESR (mm/hour) and participant`s general health using a 100 mm-VAS. DAS<2.4: low disease activity, DAS<1.6: remission.

  • Percentage of Participants Achieving Moderate/Good DAS-Based European League Against Rheumatism (EULAR) Response at Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24 [ Time Frame: Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24 ] [ Designated as safety issue: No ]

    DAS-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from Baseline and the level of disease activity reached. Moderate or good DAS-based EULAR response was defined as:

    • DAS-value ≤3.7 and DAS-improvement from Baseline >0.6
    • DAS-value >3.7 and DAS-improvement from Baseline >1.2

  • Percentage of Participants Achieving Moderate/Good Disease DAS-Based EULAR Response at Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128 [ Time Frame: Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128 ] [ Designated as safety issue: No ]

    DAS-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from Baseline and the level of disease activity reached. Moderate or good DAS-based EULAR response was defined as:

    • DAS-value ≤3.7 and DAS-improvement from Baseline >0.6
    • DAS-value >3.7 and DAS-improvement from Baseline >1.2

  • Percentage of Participants Achieving Good DAS-Based EULAR Response at Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24 [ Time Frame: Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24 ] [ Designated as safety issue: No ]
    DAS-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from Baseline and the level of disease activity reached. Good DAS-based EULAR response was defined as: DAS-value ≤2.4 and DAS-improvement from Baseline >1.2.

  • Percentage of Participants Achieving Good DAS-Based EULAR Response at Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128 [ Time Frame: Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128 ] [ Designated as safety issue: No ]
    DAS-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from Baseline and the level of disease activity reached. Good DAS-based EULAR response was defined as: DAS-value ≤2.4 and DAS-improvement from Baseline >1.2.

  • Percentage of Participants Achieving Moderate/Good DAS28-Based EULAR Response at Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24 [ Time Frame: Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24 ] [ Designated as safety issue: No ]

    DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from Baseline and the level of disease activity reached. Moderate or good DAS28-based EULAR response was defined as:

    • DAS28-value ≤5.1 and DAS28-improvement from Baseline >0.6
    • DAS28-value >5.1 and DAS28-improvement from Baseline >1.2

  • Percentage of Participants Achieving Moderate/Good DAS28-Based EULAR Response at Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128 [ Time Frame: Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128 ] [ Designated as safety issue: No ]

    DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from Baseline and the level of disease activity reached. Moderate or good DAS28-based EULAR response was defined as:

    • DAS28-value ≤5.1 and DAS28-improvement from Baseline >0.6
    • DAS28-value >5.1 and DAS28-improvement from Baseline >1.2

  • Percentage of Participants Achieving Good DAS28-Based EULAR Response at Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24 [ Time Frame: Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24 ] [ Designated as safety issue: No ]
    DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from Baseline and the level of disease activity reached. Good DAS28-based EULAR response was defined as: DAS28-value ≤3.2 and DAS28-improvement from Baseline >1.2.

  • Percentage of Participants Achieving Good DAS28-Based EULAR Response at Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128 [ Time Frame: Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128 ] [ Designated as safety issue: No ]
    DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from Baseline and the level of disease activity reached. Good DAS28-based EULAR response was defined as: DAS28-value ≤3.2 and DAS28-improvement from Baseline >1.2.

  • Percentage of Participants Achieving DAS28<2.6 (Remission) Response at Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24 [ Time Frame: Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24 ] [ Designated as safety issue: No ]
    DAS28 calculated from number of swollen joints and painful joints using the 28 joints count, ESR (mm/hour) and participant`s general health using a 100 mm-VAS. DAS28<3.2: low disease activity, DAS28<2.6: remission.

  • Percentage of Participants Achieving DAS28<2.6 (Remission) Response at Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128 [ Time Frame: Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128 ] [ Designated as safety issue: No ]
    DAS28 calculated from number of swollen joints and painful joints using the 28 joints count, ESR (mm/hour) and participant`s general health using a 100 mm-VAS. DAS28<3.2: low disease activity, DAS28<2.6: remission.

  • Percentage of Participants Achieving DAS28<3.2 (Low Disease Activity) Response at Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24 [ Time Frame: Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24 ] [ Designated as safety issue: No ]
    DAS28 calculated from number of swollen joints and painful joints using the 28 joints count, ESR (mm/hour) and participant`s general health using a 100 mm-VAS. DAS28<3.2: low disease activity, DAS28<2.6: remission.

  • Percentage of Participants Achieving DAS28<3.2 (Low Disease Activity) Response at Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128 [ Time Frame: Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128 ] [ Designated as safety issue: No ]
    DAS28 calculated from number of swollen joints and painful joints using the 28 joints count, ESR (mm/hour) and participant`s general health using a 100 mm-VAS. DAS28<3.2: low disease activity, DAS28<2.6: remission.

  • Percentage of Participants Achieving DAS28 Improvement of ≥0.6 From Baseline at Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24 [ Time Frame: Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24 ] [ Designated as safety issue: No ]
    DAS28 calculated from number of swollen joints and painful joints using the 28 joints count, ESR (mm/hour) and participant`s general health using a 100 mm-VAS. DAS28<3.2: low disease activity, DAS28<2.6: remission.

  • Percentage of Participants Achieving DAS28 Improvement of ≥0.6 From Baseline at Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128 [ Time Frame: Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128 ] [ Designated as safety issue: No ]
    DAS28 calculated from number of swollen joints and painful joints using the 28 joints count, ESR (mm/hour) and participant`s general health using a 100 mm-VAS. DAS28<3.2: low disease activity, DAS28<2.6: remission.

  • Percentage of Participants Achieving DAS28 Improvement of ≥1.2 From Baseline at Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24 [ Time Frame: Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24 ] [ Designated as safety issue: No ]
    DAS28 calculated from number of swollen joints and painful joints using the 28 joints count, ESR (mm/hour) and participant`s general health using a 100 mm-VAS. DAS28<3.2: low disease activity, DAS28<2.6: remission.

  • Percentage of Participants Achieving DAS28 Improvement of ≥1.2 From Baseline at Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128 [ Time Frame: Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128 ] [ Designated as safety issue: No ]
    DAS28 calculated from number of swollen joints and painful joints using the 28 joints count, ESR (mm/hour) and participant`s general health using a 100 mm-VAS. DAS28<3.2: low disease activity, DAS28<2.6: remission.

  • Change From Baseline in Painful Joint Counts at Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24 [ Time Frame: Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24 ] [ Designated as safety issue: No ]
    Painful joint count is a physical assessment of the ACR-specified 68 joint set for tenderness/pain. Each joint is rated as either painful or not painful with the total number of painful joints reported as the score. Score range is from 0-68 with lower scores indicating the better outcome.

  • Change From Baseline in Painful Joint Counts at Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128 [ Time Frame: Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128 ] [ Designated as safety issue: No ]
    Painful joint count is a physical assessment of the ACR-specified 68 joint set for tenderness/pain. Each joint is rated as either painful or not painful with the total number of painful joints reported as the score. Score range is from 0-68 with lower scores indicating the better outcome.

  • Change From Baseline in Swollen Joint Counts at Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24 [ Time Frame: Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24 ] [ Designated as safety issue: No ]
    Swollen joint count is a physical assessment of the ACR-specified 66 joint set for swelling. Each joint is rated as either swollen or not swollen with the total number of swollen joints reported as the score. Score range is from 0-66 with lower scores indicating the better outcome.

  • Change From Baseline in Swollen Joint Counts at Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128 [ Time Frame: Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128 ] [ Designated as safety issue: No ]
    Swollen joint count is a physical assessment of the ACR-specified 66 joint set for swelling. Each joint is rated as either swollen or not swollen with the total number of swollen joints reported as the score. Score range is from 0-66 with lower scores indicating the better outcome.

  • Change From Baseline in Physician Global Assessment Score at Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24 [ Time Frame: Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24 ] [ Designated as safety issue: No ]
    The participant`s global disease activity was estimated over the preceding 2-3 days on a scale from 0 (no disease activity) to 10 (extreme disease activity) by the physician.

  • Change From Baseline in Physician Global Assessment Score at Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128 [ Time Frame: Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128 ] [ Designated as safety issue: No ]
    The participant`s global disease activity was estimated over the preceding 2-3 days on a scale from 0 (no disease activity) to 10 (extreme disease activity) by the physician.

  • Change From Baseline in Subject Global Assessment Score at Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 [ Time Frame: Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24 ] [ Designated as safety issue: No ]
    The participant assessed overall arthritis activity on a scale from 0 (no disease activity) to 10 (extreme disease activity).

  • Change From Baseline in Subject Global Assessment Score at Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128 [ Time Frame: Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128 ] [ Designated as safety issue: No ]
    The participant assessed overall arthritis activity on a scale from 0 (no disease activity) to 10 (extreme disease activity).

  • Change From Baseline in Duration of Morning Stiffness at Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24 [ Time Frame: Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24 ] [ Designated as safety issue: No ]
    The duration of morning stiffness was determined over the preceding 2 days using a 2-question worksheet.

  • Change From Baseline in Duration of Morning Stiffness at Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128 [ Time Frame: Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128 ] [ Designated as safety issue: No ]
    The duration of morning stiffness was determined over the preceding 2 days using a 2-question worksheet.

  • Change From Baseline in General Health VAS at Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24 [ Time Frame: Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24 ] [ Designated as safety issue: No ]
    The participants had to indicate on a 100 mm-VAS (0 mm: very well, 100 mm: extremely bad) in general how they rated their health over the preceding 2-3 weeks.

  • Change From Baseline in General Health VAS at Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128 [ Time Frame: Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128 ] [ Designated as safety issue: No ]
    The participants had to indicate on a 100 mm-VAS (0 mm: very well, 100 mm: extremely bad) in general how they rated their health over the preceding 2-3 weeks.

  • Change From Baseline in Pain VAS at Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24 [ Time Frame: Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24 ] [ Designated as safety issue: No ]
    The participants had to indicate on a 100 mm-VAS (0 mm: no pain, 100 mm: pain as bad as it could be) the amount of pain they experienced over the preceding 2-3 days.

  • Change From Baseline in Pain VAS at Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128 [ Time Frame: Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128 ] [ Designated as safety issue: No ]
    The participants had to indicate on a 100 mm-VAS (0 mm: no pain, 100 mm: pain as bad as it could be) the amount of pain they experienced over the preceding 2-3 days.

  • Change From Baseline in Fatigue VAS at Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24 [ Time Frame: Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24 ] [ Designated as safety issue: No ]
    The participants had to indicate on a 100 mm-VAS (0 mm: no fatigue, 100 mm: a great deal of fatigue) how much of a problem had fatigue or tiredness been for them in the preceding week.

  • Change From Baseline in Fatigue VAS at Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128 [ Time Frame: Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128 ] [ Designated as safety issue: No ]
    The participants had to indicate on a 100 mm-VAS (0 mm: no fatigue, 100 mm: a great deal of fatigue) how much of a problem had fatigue or tiredness been for them in the preceding week.

  • Change From Baseline in Joint Space Narrowing Score Using vdH mTSS at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    mTSS: sum of erosion and JSN scores for 44 joints (16 per hand and 6 per foot). mTSS scores ranged from 0 (normal) to 448 (worst possible total score). Each x-ray visit included 4 films, each of which were read by 2 readers. The mTSS was calculated by the images scored for erosions and JSN. An increase in mTSS from Baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.

  • Change From Baseline in Erosion Score Using vdH mTSS at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    mTSS: sum of erosion and JSN scores for 44 joints (16 per hand and 6 per foot). mTSS scores ranged from 0 (normal) to 448 (worst possible total score). Each x-ray visit included 4 films, each of which were read by 2 readers. The mTSS was calculated by the images scored for erosions and JSN. An increase in mTSS from Baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.

  • Change From Baseline in Westergren ESR at Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24 [ Time Frame: Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24 ] [ Designated as safety issue: No ]
    ESR is a laboratory test that provides a non-specific measure of inflammation. The test assesses the rate at which red blood cells fall in a test tube. Normal range is 0-30 mm/hour. A higher rate is consistent with inflammation. ESR was performed at the investigative site using an ESR kit supplied by the centralized laboratory.

  • Change From Baseline in Westergren ESR at Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128 [ Time Frame: Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128 ] [ Designated as safety issue: No ]
    ESR is a laboratory test that provides a non-specific measure of inflammation. The test assesses the rate at which red blood cells fall in a test tube. Normal range is 0-30 mm/hour. A higher rate is consistent with inflammation. ESR was performed at the investigative site using an ESR kit supplied by the centralized laboratory.

  • Change From Baseline in CRP at Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24 [ Time Frame: Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24 ] [ Designated as safety issue: No ]
    The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement. CRP was analysed at a central laboratory.

  • Change From Baseline in SF-36 Health Survey Vitality Domain Score at Week 8, Week 16, and Week 24 [ Time Frame: Week 8, Week 16, and Week 24 ] [ Designated as safety issue: No ]
    The SF-36 is standardized 36-item survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health perception, vitality, and mental health. Domain scores range from 0-100, with greater scores reflecting better health status. Two additional overall summary scores - physical and mental component scores - were also obtained. Summary scores are standardized where the general population mean is 50 with a standard deviation of 10. Greater scores again indicate better health status.

  • Change From Baseline in SF-36 Health Survey Vitality Domain Score at Week 50, Week 76, Week 102, and Week 128 [ Time Frame: Week 50, Week 76, Week 102, and Week 128 ] [ Designated as safety issue: No ]
    The SF-36 is standardized 36-item survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health perception, vitality, and mental health. Domain scores range from 0-100, with greater scores reflecting better health status. Two additional overall summary scores - physical and mental component scores - were also obtained. Summary scores are standardized where the general population mean is 50 with a standard deviation of 10. Greater scores again indicate better health status.

  • Change From Baseline in SF-36 Health Survey Mental Component Score at Week 8, Week 16, and Week 24 [ Time Frame: Week 8, Week 16, and Week 24 ] [ Designated as safety issue: No ]
    The SF-36 is standardized 36-item survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health perception, vitality, and mental health. Domain scores range from 0-100, with greater scores reflecting better health status. Two additional overall summary scores - physical and mental component scores - were also obtained. Summary scores are standardized where the general population mean is 50 with a standard deviation of 10. Greater scores again indicate better health status.

  • Change From Baseline in SF-36 Health Survey Mental Component Score at Week 50, Week 76, Week 102, and Week 128 [ Time Frame: Week 50, Week 76, Week 102, and Week 128 ] [ Designated as safety issue: No ]
    The SF-36 is standardized 36-item survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health perception, vitality, and mental health. Domain scores range from 0-100, with greater scores reflecting better health status. Two additional overall summary scores - physical and mental component scores - were also obtained. Summary scores are standardized where the general population mean is 50 with a standard deviation of 10. Greater scores again indicate better health status.

  • Change From Baseline in SF-36 Health Survey Physical Component Score at Week 8, Week 16, and Week 24 [ Time Frame: Week 8, Week 16, and Week 24 ] [ Designated as safety issue: No ]
    The SF-36 is standardized 36-item survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health perception, vitality, and mental health. Domain scores range from 0-100, with greater scores reflecting better health status. Two additional overall summary scores - physical and mental component scores - were also obtained. Summary scores are standardized where the general population mean is 50 with a standard deviation of 10. Greater scores again indicate better health status.

  • Change From Baseline in SF-36 Health Survey Physical Component Score at Week 50, Week 76, Week 102, and Week 128 [ Time Frame: Week 50, Week 76, Week 102, and Week 128 ] [ Designated as safety issue: No ]
    The SF-36 is standardized 36-item survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health perception, vitality, and mental health. Domain scores range from 0-100, with greater scores reflecting better health status. Two additional overall summary scores - physical and mental component scores - were also obtained. Summary scores are standardized where the general population mean is 50 with a standard deviation of 10. Greater scores again indicate better health status.

  • Change From Baseline in SF-36 Health Survey Bodily Pain Domain Score at Week 8, Week 16, and Week 24 [ Time Frame: Week 8, Week 16, and Week 24 ] [ Designated as safety issue: No ]
    The SF-36 is standardized 36-item survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health perception, vitality, and mental health. Domain scores range from 0-100, with greater scores reflecting better health status. Two additional overall summary scores - physical and mental component scores - were also obtained. Summary scores are standardized where the general population mean is 50 with a standard deviation of 10. Greater scores again indicate better health status.

  • Change From Baseline in SF-36 Health Survey Role Limitations Due to Emotional Problems Domain Score at Week 8, Week 16, and Week 24 [ Time Frame: Week 8, Week 16, and Week 24 ] [ Designated as safety issue: No ]
    The SF-36 is standardized 36-item survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health perception, vitality, and mental health. Domain scores range from 0-100, with greater scores reflecting better health status. Two additional overall summary scores - physical and mental component scores - were also obtained. Summary scores are standardized where the general population mean is 50 with a standard deviation of 10. Greater scores again indicate better health status.

  • Change From Baseline in SF-36 Health Survey General Health Perceptions Domain Score at Week 8, Week 16, and Week 24 [ Time Frame: Week 8, Week 16, and Week 24 ] [ Designated as safety issue: No ]
    The SF-36 is standardized 36-item survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health perception, vitality, and mental health. Domain scores range from 0-100, with greater scores reflecting better health status. Two additional overall summary scores - physical and mental component scores - were also obtained. Summary scores are standardized where the general population mean is 50 with a standard deviation of 10. Greater scores again indicate better health status.

  • Change From Baseline in SF-36 Health Survey Mental Health Domain Score at Week 8, Week 16, and Week 24 [ Time Frame: Week 8, Week 16, and Week 24 ] [ Designated as safety issue: No ]
    The SF-36 is standardized 36-item survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health perception, vitality, and mental health. Domain scores range from 0-100, with greater scores reflecting better health status. Two additional overall summary scores - physical and mental component scores - were also obtained. Summary scores are standardized where the general population mean is 50 with a standard deviation of 10. Greater scores again indicate better health status.

  • Change From Baseline in SF-36 Health Survey Physical Functioning Domain Score at Week 8, Week 16, and Week 24 [ Time Frame: Week 8, Week 16, and Week 24 ] [ Designated as safety issue: No ]
    The SF-36 is standardized 36-item survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health perception, vitality, and mental health. Domain scores range from 0-100, with greater scores reflecting better health status. Two additional overall summary scores - physical and mental component scores - were also obtained. Summary scores are standardized where the general population mean is 50 with a standard deviation of 10. Greater scores again indicate better health status.

  • Change From Baseline in SF-36 Health Survey Role Limitations Due to Physical Health Domain Score at Week 8, Week 16, and Week 24 [ Time Frame: Week 8, Week 16, and Week 24 ] [ Designated as safety issue: No ]
    The SF-36 is standardized 36-item survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health perception, vitality, and mental health. Domain scores range from 0-100, with greater scores reflecting better health status. Two additional overall summary scores - physical and mental component scores - were also obtained. Summary scores are standardized where the general population mean is 50 with a standard deviation of 10. Greater scores again indicate better health status.

  • Change From Baseline in SF-36 Health Survey Social Functioning Domain Score at Week 8, Week 16, and Week 24 [ Time Frame: Week 8, Week 16, and Week 24 ] [ Designated as safety issue: No ]
    The SF-36 is standardized 36-item survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health perception, vitality, and mental health. Domain scores range from 0-100, with greater scores reflecting better health status. Two additional overall summary scores - physical and mental component scores - were also obtained. Summary scores are standardized where the general population mean is 50 with a standard deviation of 10. Greater scores again indicate better health status.


Enrollment: 429
Study Start Date: June 2009
Study Completion Date: April 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase 1 Etanercept + methotrexate
Phase 1: Etanercept + methotrexate
Biological: Phase 1: Etanercept
Phase 1: prefilled syringe 50mg/ml, administered once weekly for study weeks 0 - 24
Other Name: Enbrel
Drug: Phase 1: Methotrexate
Phase 1: oral tablet, 2.5mg, dose variable from 7.5mg to 25mg, once weekly for study weeks 0 - 24.
Drug: Phase 2: Optional ETN, SSZ, HCQ, MTX

Phase 2: All therapies are optional and may include any combination of the following: ETN, SSZ, HCQ, MTX Phase 2: Optional ETN: prefilled syringe 50mg/ml, dose variable after study week 24 to week 128.

Phase 2: Optional SSZ: oral tablet, 0.5gm, dose variable per approved local label recommendations after study week 24 to week 128.

Phase 2: HCQ: oral tablet, 200mg, dose variable per approved local label recommendations after study week 24 to week 128.

Phase 2: MTX: oral tablet, 2.5mg dose variable after week 24 to week 128.

Active Comparator: Phase 1 Conventional DMARD (SSZ or HCQ) + MTX
Phase 1: Sulfasalazine (SSZ) + methotrexate (MTX) OR Phase 1: Hydrocholoquine (HCQ) + methotrexate
Drug: Phase 1: Methotrexate
Phase 1: oral tablet, 2.5mg dose variable from 7.5mg to 25mg, once weekly for study weeks 0 - 24.
Drug: Phase 1: Conventiaonal DMARD
Phase 1: SSZ: oral tablet, 0.5gm, dose variable per approved local label recommendations. OR Phase 1: HCQ: oral tablet, 200mg, dose variable per approved local label recommendations.

  Eligibility

Ages Eligible for Study:   18 Years to 69 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of Rheumatoid Arthritis (RA)
  • Currently receiving a suboptimal response to a stable dose of methotrexate for treatment of Rheumatoid Arthritis (RA)
  • Active Rheumatoid Arthritis (RA) at time of screening and baseline

Exclusion Criteria:

  • Previous or current treatment with etanercept, other tumor necrosis factor-alpha inhibitors, or other biologic agents
  • Concurrent treatment with a Disease Modifying Antirheumatic Drug (DMARD), other than methotrexate, at screening
  • Receipt of any Disease Modifying Antirheumatic Drug (DMARD), other than methotrexate, within 3 months before screening
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00848354

Locations
Argentina
Consultorios Especializados en Investigaciones Medicas
Capital Federal, Buenos Aires, Argentina, C1425EKF
CER San Juan
San Juan, Provinica de San Juan, Argentina, 5400
Instituto CAICI
Rosario, Santa Fe, Argentina, S2000PBJ
OMI
Buenos Aires, Argentina, 1015
Centro de Investigaciones en Enfermedades Reumaticas
Buenos Aires, Argentina, 1055
Hospital Britanico
Buenos Aires, Argentina, 1280
Atencion Integral en Reumatologia
Buenos Aires, Argentina, 1426
Investigaciones Reumatológicas y Osteológicas
Ciudad Autónoma de Buenos Aires, Argentina, C1114AAH
Centro de Osteopatías Médicas
Ciudad Autónoma de Buenos Aires, Argentina, C1128AAF
Sanatorio Mayo
Cordoba, Argentina, 5000
Hospital Escuela Gral. San Martin
Corrientes, Argentina, 3400
Centro Medico Privado de Reumatologia
San Miguel de Tucuman, Argentina, 4000
Centro de Investigaciones Reumatologicas
Tucuman, Argentina, 4000
Chile
Dr Miranda Private Practice
Santiago, Region Metropolitana, Chile
Hospital del Salvador
Santiago, Region Metropolitana, Chile
Colombia
Reumalab
Medellin, Antioquia, Colombia
Centro de Reumatologia y Ortopedia
Barranquilla, Atlantico, Colombia
IPS Centro Integral de Rematología del Caribe S.A.S CIRCARIBE S.A.S Sede 1
Barranquilla, Atlantico, Colombia
IPS Centro Integral de Rematología del Caribe S.A.S CIRCARIBE S.A.S Sede 2
Barranquilla, Atlantico, Colombia
Centro Integral de Reumatologia e Inmunologia LTDA
Bogota, Cundinamarca, Colombia, 0000
Foqus Ips Ltda
Bogota, Cundinamarca, Colombia
Fundacion Instituto de Reumatologia Fernando Chalem
Bogota, Cundinamarca, Colombia
Riesgo de fractura S.A. Clinica de Artritis y Rehabilitacion
Bogota, Cundinamarca, Colombia
Preventive Care Ltda
Chia, Cundinamarca, Colombia
Centro Medico Carlos Ardila Lulle
Bucaramanga, Santander, Colombia
Servimed EU
Bucaramanga, Santander, Colombia
Mexico
Hospital Angeles Chapalita
Guadajara, Jalisco, Mexico, 45040
Centro de Especialidades Medicas del Sureste SA de CV
Merida, Yucatan, Mexico
Centro de Investigación y Biomedicina de Chihuahua
Chihuahua, Mexico, 31000
Hospital Christus Mugerza
Chihuahua, Mexico, 31000
Hospital Christus Muguerza del Parque
Chihuahua, Mexico, 31000
Panama
Centro de Infusion Marbella
Panama, Panama
Centro de Investigacion Marbella
Panama, Panama
Sponsors and Collaborators
Pfizer
Amgen
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00848354     History of Changes
Other Study ID Numbers: 0881A1-4532  B1801004 
Study First Received: February 18, 2009
Results First Received: February 2, 2012
Last Updated: December 11, 2015
Health Authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica

Keywords provided by Pfizer:
enbrel
moderate arthritis
severe arthritis
rheumatoid arthritis

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
Etanercept
Antirheumatic Agents
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Nucleic Acid Synthesis Inhibitors
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on December 06, 2016