Clinical trial NCT01578850: Study Conducted in Subjects With Rheumatoid Arthritis Who Have Moderate to Severe Disease Activity Despite Methotrexate Therapy With or Without Other Non Biologic Disease Modifying Antirheumatic Drugs (DMARDs)for at Least 12 Weeks Prior to Screening
Official title: A Randomized, Double-blind Placebo-controlled Study Of The Maintenance Of Efficacy Of Etanercept Plus Dmard(s) Compared With Dmard(s) Alone In Subjects With Rheumatoid Arthritis After Achieving An Adequate Response With Etanercept Plus Dmard(s)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Rheumatoid Arthritis
Keywords: rheumatoid arthritis
etanercept
methotrexate
DMARDs
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2012-04-17
Enrollment: 491
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To compare the maintenance of efficacy of the combination of etanercept 50 mg once weekly plus methotrexate with or without other disease modifying antirheumatic drugs therapy with that of methotrexate with or without other disease modifying antirheumatic drugs therapy at Week 52 in subjects with moderately to severely active rheumatoid arthritis who have achieved low disease activity after 24 weeks of therapy with open label etanercept 50 mg once weekly plus MTX with or without other disease modifying antirheumatic drugs therapy.


Eligibility criteria: Inclusion Criteria:

1. Subject has a minimum 1 year history/diagnosis of rheumatoid arthritis based on the 1987 American College of Rheumatology (ACR) Revised criteria for RA.
2. Subject must have active rheumatoid arthritis despite methotrexate (MTX) therapy of ≥10 mg/wk for at least 12 weeks. The MTX dose must be stable for at least 4 weeks immediately prior to screening.

Exclusion Criteria:

1. Subjects who used any of the following systemic treatments during the washout periods given below:

   1. Oral corticosteroid dose of prednisone \>7.5 mg/day (or equivalent) or a change in dose within 28 days of baseline.
   2. Treatment with more than 1 NSAID within 14 days at baseline.
   3. Methotrexate dose greater than 25 mg/week, or change in the dose of methotrexate within 28 days of baseline.
   4. Subjects will be allowed to continue the following non biologic DMARDs: sulfasalazine, hydroxychloroquine, and leflumomide. All other non-biologic DMARDs (including but not limited to gold, penicillamine, azathioprine, cyclophospamide), and biologic DMARDs must have been discontinued at least 2 months prior to Week 1.
   5. Any biologic B cell depleting agent (eg, rituximab) within 2 years of Week 1.
2. Receipt of any live (attenuated) vaccine within 4 weeks prior to baseline.
3. Receipt of any live (attenuated) vaccine within 4 weeks prior to baseline.

Primary outcomes:
measure: Percentage of Participants Who Remained in Low Disease Activity (LDA) (Disease Activity Score in 28 Joints-erythrocyte Sedimentation Rate [DAS28-ESR] <3.2) at Week 52.
timeFrame: Baseline and Week 52
Secondary outcomes:
measure: Percentage of Participants Who Remained in Remission at Week 52 (DAS28-ESR)
timeFrame: Baseline and Week 52
measure: Percentage of Participants Achieving LDA (DAS28-ESR and DAS28-C-reactive Protein [CRP]) at Each Visit During Period 1
timeFrame: Baseline, Weeks 4, 8, 16 and 24
measure: Percentage of Participants Achieving LDA (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2
timeFrame: Baseline, Weeks 24, 28, 36, 44 and 52
measure: Percentage of Participants Achieving Remission (DAS28-ESR and DAS28-CRP) at Each Visit During Period 1
timeFrame: Baseline, Weeks 4, 8, 16 and 24
measure: Percentage of Participants Achieving Remission (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2
timeFrame: Baseline, Weeks 24, 28, 36, 44 and 52
measure: Change From Baseline in DAS28-CRP and DAS28-ESR in Period 1
timeFrame: Baseline, Weeks 4, 8, 16 and 24
measure: Change From Baseline in DAS28-CRP and DAS28-ESR in Period 2
timeFrame: Baseline, Weeks 24, 28, 36, 44 and 52
measure: Percentage of Participants Who Had a Recurrence of Disease Symptoms During Period 2, Based on the Protocol Criteria
timeFrame: Baseline and Week 52
measure: Percentage of Participants Achieving European League Against Rheumatism (EULAR) Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 1.
timeFrame: Baseline, Weeks 4, 8, 16 and 24
measure: Percentage of Participants Achieving EULAR Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 2.
timeFrame: Baseline, Weeks 24, 28, 36, 44 and 52
measure: Percentage of Participants Achieving LDA or Remission Based on Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) at Each Visit During Period 1.
timeFrame: Baseline, Weeks 4, 8, 16 and 24
measure: Percentage of Participants Achieving LDA or Remission Based on CDAI and SDAI at Each Visit During Period 2.
timeFrame: Baseline, Weeks 24, 28, 36, 44 and 52
measure: Change of CDAI and SDAI at Each Visit During Period 1.
timeFrame: Baseline, Weeks 4, 8, 16 and 24
measure: Change of CDAI and SDAI at Each Visit During Period 2
timeFrame: Baseline, Weeks 24, 28, 36, 44 and 52
measure: Percentage of Participants Achieving American College of Rheumatology (ACR) ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 1 at Each Visit.
timeFrame: Baseline, Weeks 4, 8, 16 and 24
measure: Percentage of Participants Achieving ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 2 at Each Visit.
timeFrame: Baseline, Weeks 24, 28, 36, 44 and 52
measure: Change in the Tender and Swollen Joint Counts at Each Visit During Period 1 (Using 28 Joint Count as Well as 66/68 Joint Counts).
timeFrame: Baseline, Weeks 4, 8, 16 and 24
measure: Change in the Tender and Swollen Joint Counts at Each Visit During Period 2 (Using 28 Joint Count as Well as 66/68 Joint Counts).
timeFrame: Baseline, Weeks 24, 28, 36, 44 and 52
measure: Change in the Physician Global Assessment of Arthritis at Each Visit During Period 1
timeFrame: Baseline, Weeks 4, 8, 16 and 24
measure: Change in the Physician Global Assessment of Arthritis at Each Visit During Period 2
timeFrame: Baseline, Weeks 24, 28, 36, 44 and 52
measure: Change in the Subject Global Assessment of Arthritis in Period 1
timeFrame: Baseline, Weeks 4, 8, 16 and 24
measure: Change in the Subject Global Assessment of Arthritis in Period 2
timeFrame: Baseline, Weeks 24, 28, 36, 44 and 52
measure: Change in Morning Stiffness (Measured in Minutes) at Each Visit During Period 1
timeFrame: Baseline, Weeks 4, 8, 16 and 24
measure: Change in Morning Stiffness (Measured in Minutes) at Each Visit During Period 2
timeFrame: Baseline, Weeks 24, 28, 36, 44 and 52
measure: Change in the Subject General Health Visual Analog Scale (VAS) and Pain VAS at Each Visit During Period 1
timeFrame: Baseline, Weeks 4, 8, 16 and 24
measure: Change in the Subject General Health VAS and Pain VAS at Each Visit During Period 2
timeFrame: Baseline, Weeks 24, 28, 36, 44 and 52
measure: Change in CRP and ESR at Each Visit During Period 1
timeFrame: Baseline, Weeks 4, 8, 16 and 24
measure: Change in CRP and ESR at Each Visit During Period 2
timeFrame: Baseline, Weeks 24, 28, 36, 44 and 52
Other outcomes:
Locations:
city: Salvador
country: Brazil
facility: Hospital Santa Izabel - Santa Casa de Misericórdia da Bahia
state: Bahia
city: Goiania
country: Brazil
facility: CIP (Centro Internacional de Pesquisa)
state: Goiás
city: Sao Paulo
country: Brazil
facility: CEPIC - Centro Paulista de Investigacao Clinica e Servicos Medicos LTDA
state: SP
city: Juiz de Fora
country: Brazil
facility: Research Center
city: Guangzhou
country: China
facility: Guangdong General Hospital
state: Guangdong
city: Beijing
country: China
facility: Chinese Academy of Medical Sciences - Peking Union Medical C
city: Shanghai
country: China
facility: Shanghai Changning District Guanghua Hospital of Traditional Chinese and Western Medicine
city: Shanghai
country: China
facility: Shanghai Changhai Hospital[Rheumatology &Immunology]
city: Barranquilla
country: Colombia
facility: Centro Integral de reumatolo[Gerencia / Representante Legal]
state: Atlántico
city: Bogota DC
country: Colombia
facility: Fundacion Instituto de Reumatologia Fernando Chalem
state: Cundinamarca
city: Antioquia
country: Colombia
facility: Hospital Pablo Tobon Uribe (HPTU)
city: Olomouc
country: Czech Republic
facility: Revmatologicka poradna III. Interni nefrologicka, revmatologicka a endokrinologicka klinika
city: Praha 2
country: Czech Republic
facility: Revmatologicky ustav
city: Praha 5
country: Czech Republic
facility: Revmatologicka ambulance
city: Zlin
country: Czech Republic
facility: PV-Medical s.r.o.
city: Alexandria
country: Egypt
facility: New University Hospital, Alexandria Clinical Research Center
state: Al Iskandariyah
city: Cairo
country: Egypt
facility: Al Azhar University Hospital [Rheumatology]
state: Al Qahirah
city: Cairo
country: Egypt
facility: Ain Shams University/Al Demerdash Hospital/Diabetology Unit
city: Budapest
country: Hungary
facility: Budai Irgalmasrendi Korhaz
city: Budapest
country: Hungary
facility: Magyar Honvédség Egészségügyi Központ
city: Irbid
country: Jordan
facility: Pharmaceutical Research Center- PRC. Jordan University of Science and Technology
city: Beirut
country: Lebanon
facility: American University of Beirut Medical Center
city: Kota Kinabalu
country: Malaysia
facility: Queen Elizabeth Hospital
state: Sabah
city: Putrajaya
country: Malaysia
facility: Hopsital Putrajaya [Medicine]
state: Wilayah Persekutuan Putrajaya
city: Kuala Lumpur
country: Malaysia
facility: University Malaysia Medical Centre
city: Durango
country: Mexico
facility: Centro de Investigación y Atención Integral de Durango, SC
state: Durango / Mexico
city: San Luis de Potosi
country: Mexico
facility: Centro de Alta Especialidad en Reumatología e Investigación
state: San Luis Potosí / Mexico
city: Merida
country: Mexico
facility: Centro Medico Las Americas
state: Yucatan
city: San Luis Potosi
country: Mexico
facility: Hospital Central
city: Dasmarinas
country: Philippines
facility: De La Salle University Health Sciences Campus- Clinical Epidemiology Unit
state: Cavite
city: Quezon
country: Philippines
facility: St. Luke's Mecical Center
state: Manila
city: Angeles City
country: Philippines
facility: Angeles University Foundation Medical Center
state: Pampanga
city: Cebu City
country: Philippines
facility: Chong Hua Hospital, Medical Arts Center
city: Manila
country: Philippines
facility: UP-Philippine General Hospital, Medical Research Laboratory, Medicine Department,
city: Doha
country: Qatar
facility: Hamad Medical Corporation
city: Baia Mare
country: Romania
facility: Spitalul Judetean
state: Maramure
city: Brasov
country: Romania
facility: Spitalul Clinic Judetean de Urgenta Brasov
city: Iasi
country: Romania
facility: Spitalul Clinic de Recuperare
city: Tg Mures
country: Romania
facility: Spitalul Clinic Judetean de Urgenta Targu Mures
city: Kazan
country: Russian Federation
facility: LLC Research Medical Complex Your Health based on City Clinical Hospital Number 7(Legal address)
city: Kazan
country: Russian Federation
facility: LLC Research Medical Complex Your Health based on City Clinical Hospital Number 7 (Actual address)
city: Krasnoyarsk
country: Russian Federation
facility: Krasnoyarsk State Medical University named after Professor V.F. Voyno-Yasenetsky
city: Krasnoyarsk
country: Russian Federation
facility: Krasnoyarsk State Medical University named after Professor V.F. Voyno-Yasenetsky,
city: Moscow
country: Russian Federation
facility: FSBSI "Scientific Research Institute of Rheumatology n. a. V.A. Nasonova"
city: St. Petersburg
country: Russian Federation
facility: LLC Institute of Medical Trials (Actual address)
city: Bloemfontein
country: South Africa
facility: Universitas Hospital [Cardiololgy]
state: Free State
city: Cape Town
country: South Africa
facility: Vincent Pallotti Hospital
city: Stellenbosch
country: South Africa
facility: Winelands Medical Research Centre
city: Taiwan
country: Taiwan
facility: Cathay General Hospital
state: Taoyuan
city: Chia-Yi
country: Taiwan
facility: Buddhist Tzu Chi General Hospital - Dalin Branch
city: Taichung
country: Taiwan
facility: China Medical University Hospital, Division of Rheumatology, Allergy and Immunology
city: Taipei
country: Taiwan
facility: Taipei Medical University Hospital
city: Amphoe Mueang
country: Thailand
facility: Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine,
state: Chiang Mai
city: Bangkok
country: Thailand
facility: Siriraj Hospital [Rheumatology]
city: Khon Kaen
country: Thailand
facility: Khon Kaen University (KKU) - Faculty of Medicine
city: Songkla
country: Thailand
facility: Songklanagarind Hospital
city: Simferopol
country: Ukraine
facility: Republican Clinical Hospital, Department of Internal Medicine #2 of Crimean State Medical University
state: Crimea
city: Kyiv
country: Ukraine
facility: Komunalnyi zaklad Kyivskoi oblasnoi rady "Kyivska oblasna klinichna likarnia"
city: Odessa
country: Ukraine
facility: Odessa Regional Clinical Hospital, Outpatient Department
city: Ternopil
country: Ukraine
facility: Municipal Institution of Ternopil Regional Council Ternopil University Hospital
city: Vinnitsa
country: Ukraine
facility: Vinnitsa Regional Clinical Hospital n.a. Pirogov, Department of Faculty Therapy of Vinnitsa NMU
city: Dubai
country: United Arab Emirates
facility: Al Baraha Hospital
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Tanaka Y, Smolen JS, Jones H, Szumski A, Marshall L, Emery P. The effect of deep or sustained remission on maintenance of remission after dose reduction or withdrawal of etanercept in patients with rheumatoid arthritis. Arthritis Res Ther. 2019 Jul 5;21(1):164. doi: 10.1186/s13075-019-1937-4.
citation: Zerbini CAF, Abud-Mendoza C, Mendez-Patarroyo P, De Angelo Andrade M, Pedersen R, Vlahos B, Borlenghi CE. Maintenance of low disease activity and remission with etanercept-disease-modifying antirheumatic drug (DMARD) combination therapy compared with treatment with DMARDs alone in Latin American patients with active rheumatoid arthritis: Subset analysis of a randomized trial. Medicine (Baltimore). 2018 Sep;97(36):e11989. doi: 10.1097/MD.0000000000011989.
citation: Pavelka K, Akkoc N, Al-Maini M, Zerbini CAF, Karateev DE, Nasonov EL, Rahman MU, Pedersen R, Dinh A, Shen Q, Vasilescu R, Kotak S, Mahgoub E, Vlahos B. Maintenance of remission with combination etanercept-DMARD therapy versus DMARDs alone in active rheumatoid arthritis: results of an international treat-to-target study conducted in regions with limited biologic access. Rheumatol Int. 2017 Sep;37(9):1469-1479. doi: 10.1007/s00296-017-3749-7. Epub 2017 Jun 9.