Clinical trial NCT00848354: Open-Label Study Comparing Etanercept to Conventional Disease Modifying Antirheumatic Drug (DMARD) Therapy
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Rheumatoid Arthritis
Keywords: enbrel
moderate arthritis
severe arthritis
rheumatoid arthritis
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
Collaborators: name: Amgen
First posted: 2009-02-20
Enrollment: 429
Sex: ALL
Minimum age (years): 18
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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

Primary outcomes:
measure: Percentage of Participants Achieving American College of Rheumatology 50 (ACR50) Response at Week 24
timeFrame: Week 24
Secondary outcomes:
measure: Change From Baseline in HAQ Score at Week 24
timeFrame: Baseline and Week 24
measure: Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Score at Week 24
timeFrame: Baseline and Week 24
measure: Change From Baseline in Van Der Heijde Modified Total Sharp Score (vdH mTSS), Annualized, at Week 24
timeFrame: Baseline and Week 24
measure: 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
timeFrame: Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
measure: Change From Baseline in DAS28 at Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
timeFrame: Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
measure: Summary of Changes in Therapy at the Beginning of Phase 2
timeFrame: Week 24
measure: Percentage of Participants Achieving ACR50 Response at Week 2, Week 4, Week 8, Week 12, Week 16, and Week 20
timeFrame: Week 2, Week 4, Week 8, Week 12, Week 16, and Week 20
measure: Percentage of Participants Achieving ACR50 Response at Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
timeFrame: Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
measure: Percentage of Participants Achieving ACR20 Response at Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
timeFrame: Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
measure: Percentage of Participants Achieving ACR20 Response at Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
timeFrame: Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
measure: Percentage of Participants Achieving ACR70 Response at Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
timeFrame: Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
measure: Percentage of Participants Achieving ACR70 Response at Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
timeFrame: Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
measure: Change From Baseline in Disease Activity Score (DAS) at Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
timeFrame: Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
measure: Change From Baseline in DAS at Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
timeFrame: Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
measure: Percentage of Participants Achieving DAS<2.4 (Low Disease Activity) Response at Week 24
timeFrame: Week 24
measure: Percentage of Participants Achieving DAS<1.6 (Remission) Response at Week 24
timeFrame: Week 24
measure: 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
timeFrame: Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
measure: 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
timeFrame: Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
measure: 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
timeFrame: Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
measure: 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
timeFrame: Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
measure: 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
timeFrame: Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
measure: 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
timeFrame: Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
measure: 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
timeFrame: Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
measure: 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
timeFrame: Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
measure: 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
timeFrame: Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
measure: 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
timeFrame: Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
measure: 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
timeFrame: Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
measure: 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
timeFrame: Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
measure: 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
timeFrame: Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
measure: 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
timeFrame: Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
measure: 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
timeFrame: Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
measure: 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
timeFrame: Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
measure: 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
timeFrame: Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
measure: 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
timeFrame: Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
measure: 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
timeFrame: Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
measure: 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
timeFrame: Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
measure: Change From Baseline in Painful Joint Counts at Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
timeFrame: Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
measure: 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
timeFrame: Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
measure: Change From Baseline in Swollen Joint Counts at Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
timeFrame: Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
measure: 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
timeFrame: Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
measure: Change From Baseline in Physician Global Assessment Score at Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
timeFrame: Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
measure: 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
timeFrame: Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
measure: Change From Baseline in Subject Global Assessment Score at Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24
timeFrame: Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
measure: 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
timeFrame: Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
measure: Change From Baseline in Duration of Morning Stiffness at Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
timeFrame: Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
measure: 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
timeFrame: Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
measure: Change From Baseline in General Health VAS at Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
timeFrame: Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
measure: 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
timeFrame: Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
measure: Change From Baseline in Pain VAS at Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
timeFrame: Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
measure: Change From Baseline in Pain VAS at Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
timeFrame: Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
measure: Change From Baseline in Fatigue VAS at Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
timeFrame: Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
measure: Change From Baseline in Fatigue VAS at Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
timeFrame: Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
measure: Change From Baseline in Joint Space Narrowing Score Using vdH mTSS at Week 24
timeFrame: Week 24
measure: Change From Baseline in Erosion Score Using vdH mTSS at Week 24
timeFrame: Week 24
measure: Change From Baseline in Westergren ESR at Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
timeFrame: Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
measure: Change From Baseline in Westergren ESR at Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
timeFrame: Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
measure: Change From Baseline in CRP at Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
timeFrame: Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
measure: Change From Baseline in SF-36 Health Survey Vitality Domain Score at Week 8, Week 16, and Week 24
timeFrame: Week 8, Week 16, and Week 24
measure: Change From Baseline in SF-36 Health Survey Vitality Domain Score at Week 50, Week 76, Week 102, and Week 128
timeFrame: Week 50, Week 76, Week 102, and Week 128
measure: Change From Baseline in SF-36 Health Survey Mental Component Score at Week 8, Week 16, and Week 24
timeFrame: Week 8, Week 16, and Week 24
measure: Change From Baseline in SF-36 Health Survey Mental Component Score at Week 50, Week 76, Week 102, and Week 128
timeFrame: Week 50, Week 76, Week 102, and Week 128
measure: Change From Baseline in SF-36 Health Survey Physical Component Score at Week 8, Week 16, and Week 24
timeFrame: Week 8, Week 16, and Week 24
measure: Change From Baseline in SF-36 Health Survey Physical Component Score at Week 50, Week 76, Week 102, and Week 128
timeFrame: Week 50, Week 76, Week 102, and Week 128
measure: Change From Baseline in SF-36 Health Survey Bodily Pain Domain Score at Week 8, Week 16, and Week 24
timeFrame: Week 8, Week 16, and Week 24
measure: Change From Baseline in SF-36 Health Survey Role Limitations Due to Emotional Problems Domain Score at Week 8, Week 16, and Week 24
timeFrame: Week 8, Week 16, and Week 24
measure: Change From Baseline in SF-36 Health Survey General Health Perceptions Domain Score at Week 8, Week 16, and Week 24
timeFrame: Week 8, Week 16, and Week 24
measure: Change From Baseline in SF-36 Health Survey Mental Health Domain Score at Week 8, Week 16, and Week 24
timeFrame: Week 8, Week 16, and Week 24
measure: Change From Baseline in SF-36 Health Survey Physical Functioning Domain Score at Week 8, Week 16, and Week 24
timeFrame: Week 8, Week 16, and Week 24
measure: Change From Baseline in SF-36 Health Survey Role Limitations Due to Physical Health Domain Score at Week 8, Week 16, and Week 24
timeFrame: Week 8, Week 16, and Week 24
measure: Change From Baseline in SF-36 Health Survey Social Functioning Domain Score at Week 8, Week 16, and Week 24
timeFrame: Week 8, Week 16, and Week 24
Other outcomes:
Locations:
city: Capital Federal
country: Argentina
facility: Consultorios Especializados en Investigaciones Medicas
state: Buenos Aires
city: San Juan
country: Argentina
facility: CER San Juan
state: Provinica de San Juan
city: Rosario
country: Argentina
facility: Instituto CAICI
state: Santa Fe
city: Buenos Aires
country: Argentina
facility: OMI
city: Buenos Aires
country: Argentina
facility: Centro de Investigaciones en Enfermedades Reumaticas
city: Buenos Aires
country: Argentina
facility: Hospital Britanico
city: Buenos Aires
country: Argentina
facility: Atencion Integral en Reumatologia
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: Investigaciones Reumatológicas y Osteológicas
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: Centro de Osteopatías Médicas
city: Cordoba
country: Argentina
facility: Sanatorio Mayo
city: Corrientes
country: Argentina
facility: Hospital Escuela Gral. San Martin
city: San Miguel de Tucuman
country: Argentina
facility: Centro Medico Privado de Reumatologia
city: Tucuman
country: Argentina
facility: Centro de Investigaciones Reumatologicas
city: Santiago
country: Chile
facility: Dr Miranda Private Practice
state: Region Metropolitana
city: Santiago
country: Chile
facility: Hospital del Salvador
state: Region Metropolitana
city: Medellin
country: Colombia
facility: Reumalab
state: Antioquia
city: Barranquilla
country: Colombia
facility: Centro de Reumatologia y Ortopedia
state: Atlantico
city: Barranquilla
country: Colombia
facility: IPS Centro Integral de Rematología del Caribe S.A.S CIRCARIBE S.A.S Sede 1
state: Atlantico
city: Barranquilla
country: Colombia
facility: IPS Centro Integral de Rematología del Caribe S.A.S CIRCARIBE S.A.S Sede 2
state: Atlantico
city: Bogota
country: Colombia
facility: Centro Integral de Reumatologia e Inmunologia LTDA
state: Cundinamarca
city: Bogota
country: Colombia
facility: Foqus Ips Ltda
state: Cundinamarca
city: Bogota
country: Colombia
facility: Fundacion Instituto de Reumatologia Fernando Chalem
state: Cundinamarca
city: Bogota
country: Colombia
facility: Riesgo de fractura S.A. Clinica de Artritis y Rehabilitacion
state: Cundinamarca
city: Chia
country: Colombia
facility: Preventive Care Ltda
state: Cundinamarca
city: Bucaramanga
country: Colombia
facility: Centro Medico Carlos Ardila Lulle
state: Santander
city: Bucaramanga
country: Colombia
facility: Servimed EU
state: Santander
city: Guadajara
country: Mexico
facility: Hospital Angeles Chapalita
state: Jalisco
city: Merida
country: Mexico
facility: Centro de Especialidades Medicas del Sureste SA de CV
state: Yucatan
city: Chihuahua
country: Mexico
facility: Centro de Investigación y Biomedicina de Chihuahua
city: Chihuahua
country: Mexico
facility: Hospital Christus Mugerza
city: Chihuahua
country: Mexico
facility: Hospital Christus Muguerza del Parque
city: Panama
country: Panama
facility: Centro de Infusion Marbella
city: Panama
country: Panama
facility: Centro de Investigacion Marbella
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: de la Vega M, Guerra Bautista G, Xavier RM, Pacheco-Tena C, Solano G, Pedersen RD, Szumski AE, Borlenghi C, Santana K, Vlahos B. Predictors of response to etanercept-methotrexate treatment: a post hoc logistic regression analysis of a randomized, open-label study in Latin American patients with rheumatoid arthritis. Adv Rheumatol. 2021 Sep 8;61(1):56. doi: 10.1186/s42358-021-00213-4.
citation: Guerra Bautista G, Xavier RM, de la Vega M, Simon-Campos JA, Solano G, Pedersen RD, Vlahos B, Borlenghi C. Clinical Improvements as Predictors of Improvements in Patient-Reported Outcomes: Post Hoc Analysis of a Randomized, Open-Label Study of Etanercept in Latin American Patients with Rheumatoid Arthritis. Open Access Rheumatol. 2019 Dec 12;11:275-281. doi: 10.2147/OARRR.S228866. eCollection 2019.
citation: Machado DA, Guzman R, Xavier RM, Simon JA, Mele L, Shen Q, Pedersen R, Kotak S, Vlahos B. Two-Year Safety and Efficacy Experience in Patients with Methotrexate-Resistant Active Rheumatoid Arthritis Treated with Etanercept and Conventional Disease-Modifying Anti-rheumatic Drugs in the Latin American Region. Open Rheumatol J. 2016 Feb 29;10:13-25. doi: 10.2174/1874312901610010013. eCollection 2016.
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.
citation: Machado DA, Guzman RM, Xavier RM, Simon JA, Mele L, Pedersen R, Ferdousi T, Koenig AS, Kotak S, Vlahos B. Open-label observation of addition of etanercept versus a conventional disease-modifying antirheumatic drug in subjects with active rheumatoid arthritis despite methotrexate therapy in the Latin American region. J Clin Rheumatol. 2014 Jan;20(1):25-33. doi: 10.1097/RHU.0000000000000055.