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: May 8, 2013
Last verified: May 2013
  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 (ACR 50) 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 Health Assessment Questionnaire (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 ]
    SF-36: 36-item questionnaire that measures general health-related quality of life in the following eight domains: physical function, role limitations due to physical health, bodily pain, general health perception, vitality, social functioning, role limitation due to emotional problems, and mental health. Scores for the 8 domains range from 0-100 where higher scores are better (100=highest level of functioning) and may be reported as 2 summary scores; Mental Component Score and Physical Component Score. Total score range for the summary scores = 0-100 where higher scores are better.

  • Van Der Heijde Modified Total Sharp Score (vdH mTSS) [ Time Frame: Baseline ] [ 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).

  • 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 JSN scores for 44 joints (16 per hand and 6 per foot). mTSS scores ranged from 0 (normal) to 448 (worst possible total score). Change = scores at observation minus score at Baseline. 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 52 and 104 of Phase 2 [ Time Frame: Baseline, Week 52 and 104 of Phase 2 ] [ Designated as safety issue: No ]
    DAS28 calculated from the number of swollen joints (SJC) and painful joints (PJC) using the 28 joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hour]) and patient's global assessment (PGA) of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28 ≤3.2 = low disease activity, DAS28 >3.2 to 5.1 = moderate to high disease activity.

  • Therapeutic Change Observed at Start of Phase 2 [ Time Frame: Week 52 of Phase 2 ] [ Designated as safety issue: No ]
    Therapeutic change observed at start of Phase 2 described the changes made by investigator to participant treatment based on efficacy of Phase 1 randomized therapy.


Enrollment: 429
Study Start Date: May 2009
Study Completion Date: April 2013
Primary Completion Date: March 2011 (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
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
Pfizer Investigational Site
Capital Federal, Buenos Aires, Argentina, C1425EKF
Pfizer Investigational Site
San Juan, Provinica de San Juan, Argentina, 5400
Pfizer Investigational Site
Buenos Aires, Argentina, 1114
Pfizer Investigational Site
Buenos Aires, Argentina, 1426
Pfizer Investigational Site
Buenos Aires, Argentina, 1015
Pfizer Investigational Site
Buenos Aires, Argentina, 1280
Pfizer Investigational Site
Buenos Aires, Argentina, 1055
Pfizer Investigational Site
Ciudad de Buenos Aires, Argentina, C1128AAF
Pfizer Investigational Site
Cordoba, Argentina, 5000
Pfizer Investigational Site
Corrientes, Argentina, 3400
Pfizer Investigational Site
San Miguel de Tucuman, Argentina, 4000
Pfizer Investigational Site
Santa Fe, Argentina, 2200
Pfizer Investigational Site
Tucuman, Argentina, 4000
Chile
Pfizer Investigational Site
Santiago, Region Metropolitana, Chile
Colombia
Pfizer Investigational Site
Medellin, Antioquia, Colombia
Pfizer Investigational Site
Barranquilla, Atlantico, Colombia, 0000
Pfizer Investigational Site
Barranquilla, Atlantico, Colombia
Pfizer Investigational Site
Bogota, Cundinamarca, Colombia, 0000
Pfizer Investigational Site
Bogota, Cundinamarca, Colombia
Pfizer Investigational Site
Chia, Cundinamarca, Colombia
Pfizer Investigational Site
Bucaramanga, Santander, Colombia
Mexico
Pfizer Investigational Site
Guadajara, Jalisco, Mexico, 45040
Pfizer Investigational Site
Merida, Yucatan, Mexico
Pfizer Investigational Site
Chihuahua, Mexico, 31000
Panama
Pfizer Investigational Site
Panama, Panama
Sponsors and Collaborators
Pfizer
Amgen
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

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: May 8, 2013
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
TNFR-Fc fusion protein
Antirheumatic Agents
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
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

ClinicalTrials.gov processed this record on October 02, 2014