Clinical trial NCT00565409: Study Comparing Etanercept in Combination With Methotrexate in Subjects With Rheumatoid Arthritis
Official title: A Randomized, Double-Blind Study Comparing the Safety & Efficacy of Once-Weekly Etanercept 50 mg, Etanercept 25 mg, & Placebo in Combination With Methotrexate in Subjects With Active Rheumatoid Arthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Arthritis, Rheumatoid
Keywords: Active Rheumatoid Arthritis
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2007-11-30
Enrollment: 834
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 efficacy of the combination of etanercept 50 mg once weekly plus methotrexate with that of methotrexate monotherapy in the treatment of rheumatoid arthritis over 88 weeks.


Eligibility criteria: Inclusion Criteria:

* Diagnosis of rheumatoid arthritis.
* Currently receiving an optimal dose of oral Methotrexate (MTX)(at least 15 mg/week but no more than 25 mg/week) for the treatment of rheumatoid arthritis.
* Active rheumatoid arthritis at the time of screening.

Exclusion Criteria:

* Previous or current treatment with etanercept, other tumor necrosis factor-alpha (TNF) inhibitors, or other biologic agents.
* Concurrent treatment with any disease-modifying anti-rheumatoid drugs (DMARD), other than MTX within 28 days before baseline.
* Concurrent treatment with more than 1 non-steroid anti-inflammatory drug (NSAID) at baseline.

Primary outcomes:
measure: Percentage of Participants Achieving 28 Joint Disease Activity Score (DAS28) Less Than or Equal to (≤) 3.2 at Week 88
timeFrame: Week 88
Secondary outcomes:
measure: Percentage of Participants Achieving DAS28 Low Disease Activity or Remission at Baseline, Weeks 4, 8, 12, 20, 28 and 36
timeFrame: Baseline, Weeks 4, 8, 12, 20, 28, 36
measure: Percentage of Participants Achieving DAS28 Low Disease Activity or Remission
timeFrame: Weeks 36, 40, 48, 56, 64, 72, 80 and 88
measure: Change From Baseline in DAS28 at Weeks 4, 8, 12, 20, 28 and 36
timeFrame: Baseline, Weeks 4, 8, 12, 20, 28 and 36
measure: Change From Week 36 in DAS28 at Weeks 40, 48, 56, 64, 72, 80 and 88
timeFrame: Weeks 36, 40, 48, 56, 64, 72, 80 and 88
measure: Time to Loss of Low Disease Activity DAS28 and a Change of ≥ 0.6 Units in the DAS28
timeFrame: Week 36 up to Week 88
measure: Time to Loss of Low Disease Activity DAS28
timeFrame: Week 36 up to Week 88
measure: Proportion of Time Participants Had Low Disease Activity DAS28 Week 36 to Week 88
timeFrame: Week 36 up to Week 88
measure: Change From Baseline in Prorated Swollen Joint Count at Weeks 4, 8, 12, 20, 28 and 36
timeFrame: Baseline, Weeks 4, 8, 12, 20, 28 and 36
measure: Prorated Swollen Joint Count at Week 36
timeFrame: Week 36
measure: Change From Week 36 in Prorated Swollen Joint Count at Weeks 40, 48, 56, 64, 72, 80 and 88
timeFrame: Week 36, Weeks 40, 48, 56, 64, 72, 80 and 88
measure: Change From Baseline in the Painful Joint Count at Weeks 4, 8, 12, 20, 28 and 36
timeFrame: Baseline, Weeks 4, 8, 12, 20, 28 and 36
measure: Painful Joint Count at Week 36
timeFrame: Week 36
measure: Change From Week 36 in Painful Joint Count at Weeks 40, 48, 56, 64, 72, 80 and 88
timeFrame: Weeks 36 40, 48, 56, 64, 72, 80 and 88
measure: Change From Baseline in the Physician Global Assessment (PGA) at Weeks 4, 8, 12, 20, 28 and 36
timeFrame: Baseline, Weeks 4, 8, 12, 20, 28 and 36
measure: PGA Score at Week 36
timeFrame: Week 36
measure: Change From Week 36 in the PGA Score at Weeks 40, 48, 56, 64, 72, 80 and 88
timeFrame: Weeks 36, 40, 48, 56, 64, 72, 80 and 88
measure: Change From Baseline in Patient's Global Assessment (PtGA) of Arthritis Pain at Weeks 4, 8, 12, 20, 28 and 36
timeFrame: Baseline, Weeks 4, 8, 12, 20, 28 and 36
measure: PtGA of Arthritis Pain at Week 36
timeFrame: Week 36
measure: Change From Week 36 in PtGA of Arthritis Pain at Weeks 40, 48, 56, 64, 72, 80, 88
timeFrame: Weeks 36, 40, 48, 56, 64, 72, 80, 88
measure: Change From Baseline in Duration of Morning Stiffness at Weeks 4, 8, 12, 20, 28 and 36
timeFrame: Baseline, Weeks 4, 8, 12, 20, 28 and 36
measure: Duration of Morning Stiffness at Week 36
timeFrame: Week 36
measure: Change From Week 36 in Duration of Morning Stiffness at Weeks 40, 48, 56, 64, 72, 80, 88
timeFrame: Weeks 36, 40, 48, 56, 64, 72, 80, 88
measure: Change From Baseline in General Health at Weeks 4, 8, 12, 20, 28 and 36
timeFrame: Baseline, Weeks 4, 8, 12, 20, 28 and 36
measure: General Health at Week 36
timeFrame: Week 36
measure: Change From Week 36 in General Health at Weeks 40, 48, 56, 64, 72, 80, 88
timeFrame: Weeks 36, 40, 48, 56, 64, 72, 80, 88
measure: Change From Baseline in Pain at Weeks 4, 8, 12, 20, 28 and 36
timeFrame: Baseline, Weeks 4, 8, 12, 20, 28 and 36
measure: Pain at Week 36
timeFrame: Week 36
measure: Change From Week 36 in Pain at Weeks 40, 48, 56, 64, 72, 80 and 88
timeFrame: Weeks 36, 40, 48, 56, 64, 72, 80 and 88
measure: Percentage of Participants Achieving an Acceptable State on the Patient Acceptable Symptom State (PASS) at Baseline and Week 36
timeFrame: Baseline, Week 36
measure: Percentage of Participants Achieving an Acceptable State on the PASS at Week 36 and Weeks 64 and 88
timeFrame: Weeks 36, 64 and 88
measure: Percentage of Participants Achieving European League Against Rheumatism (EULAR) Good or Moderate Response at Weeks 4, 8, 12, 20, 28 and 36
timeFrame: Weeks 4, 8, 12, 20, 28 and 36
measure: Percentage of Participants Achieving EULAR Good or Moderate Response at Week 36, 40, 48, 56, 64, 72, 80 and 88
timeFrame: Week 36, 40, 48, 56, 64, 72, 80 and 88
measure: Percentage of Participants With an American College of Rheumatology 20 Percent (%) (ACR20) Response at Weeks 4, 8, 12, 20, 28 and 36
timeFrame: Weeks 4, 8, 12, 20, 28 and 36
measure: Percentage of Participants With an ACR20 Response at Weeks 36, 40, 48, 56, 64, 72, 80 and 88
timeFrame: Weeks 36, 40, 48, 56, 64, 72, 80 and 88
measure: Percentage of Participants With an ACR50 Response at Weeks 4, 8, 12, 20, 28 and 36
timeFrame: Weeks 4, 8, 12, 20, 28 and 36
measure: Percentage of Participants With an ACR50 Response at Weeks 36, 40, 48, 56, 64, 72, 80 and 88
timeFrame: Weeks 36, 40, 48, 56, 64, 72, 80 and 88
measure: Percentage of Participants With an ACR70 Response at Weeks 4, 8, 12, 20, 28 and 36
timeFrame: Weeks 4, 8, 12, 20, 28 and 36
measure: Percentage of Participants With an ACR70 Response at Weeks 36, 40, 48, 56, 64, 72, 80 and 88
timeFrame: Weeks 36, 40, 48, 56, 64, 72, 80 and 88
measure: Percentage of Participants With an ACR90 Response at Weeks 4, 8, 12, 20, 28 and 36
timeFrame: Weeks 4, 8, 12, 20, 28 and 36
measure: Percentage of Participants With an ACR90 Response at Weeks 36, 40, 48, 56, 64, 72, 80 and 88
timeFrame: Weeks 36, 40, 48, 56, 64, 72, 80 and 88
measure: DAS28 at Week 36
timeFrame: Week 36
Other outcomes:
Locations:
city: Campsie
country: Australia
facility: Pfizer Investigational Site
state: New South Wales
city: Kogarah
country: Australia
facility: Pfizer Investigational Site
state: New South Wales
city: Maroochydore
country: Australia
facility: Pfizer Investigational Site
state: Queensland
city: Daw Park
country: Australia
facility: Pfizer Investigational Site
state: South Australia
city: Heidelberg West
country: Australia
facility: Pfizer Investigational Site
state: Victoria
city: Malvern
country: Australia
facility: Pfizer Investigational Site
state: Victoria
city: Victoria Park
country: Australia
facility: Pfizer Investigational Site
city: Wien
country: Austria
facility: Pfizer Investigational Site
city: Bruxelles
country: Belgium
facility: Pfizer Investigational Site
city: Liege
country: Belgium
facility: Pfizer Investigational Site
city: Yvoir
country: Belgium
facility: Pfizer Investigational Site
city: Santiago
country: Chile
facility: Pfizer Investigational Site
state: Region Metropolitana
city: Barranquilla
country: Colombia
facility: Pfizer Investigational Site
state: Atlantico
city: Bogota
country: Colombia
facility: Pfizer Investigational Site
state: Cundinamarca
city: Brno
country: Czech Republic
facility: Pfizer Investigational Site
city: Bruntal
country: Czech Republic
facility: Pfizer Investigational Site
city: Bruntal
country: Czech Republic
facility: Pfizer Investigational Site
city: Praha 2
country: Czech Republic
facility: Pfizer Investigational Site
city: Praha 5
country: Czech Republic
facility: Pfizer Investigational Site
city: Zlin
country: Czech Republic
facility: Pfizer Investigational Site
city: Belgrade
country: Former Serbia and Montenegro
facility: Pfizer Investigational Site
city: Niska Banja
country: Former Serbia and Montenegro
facility: Pfizer Investigational Site
city: Corbeil-Essonnes
country: France
facility: Pfizer Investigational Site
city: Le Kremlin Bicetre
country: France
facility: Pfizer Investigational Site
city: Le Mans
country: France
facility: Pfizer Investigational Site
city: Montpellier
country: France
facility: Pfizer Investigational Site
city: Nice
country: France
facility: Pfizer Investigational Site
city: Paris
country: France
facility: Pfizer Investigational Site
city: Strasbourg
country: France
facility: Pfizer Investigational Site
city: Toulouse
country: France
facility: Pfizer Investigational Site
city: Berlin
country: Germany
facility: Pfizer Investigational Site
city: Hamburg-Eilbek
country: Germany
facility: Pfizer Investigational Site
city: Koeln
country: Germany
facility: Pfizer Investigational Site
city: Leipzig
country: Germany
facility: Pfizer Investigational Site
city: Leipzig
country: Germany
facility: Pfizer Investigational Site
city: Wuerzburg
country: Germany
facility: Pfizer Investigational Site
city: Budapest
country: Hungary
facility: Pfizer Investigational Site
city: Debrecen
country: Hungary
facility: Pfizer Investigational Site
city: Debrecen
country: Hungary
facility: Pfizer Investigational Site
city: Szombathely
country: Hungary
facility: Pfizer Investigational Site
city: Catania
country: Italy
facility: Pfizer Investigational Site
state: CT
city: Orbassano
country: Italy
facility: Pfizer Investigational Site
state: TO
city: Roma
country: Italy
facility: Pfizer Investigational Site
city: Seo-gu
country: Korea, Republic of
facility: Pfizer Investigational Site
state: Daejeon
city: Namdong-gu
country: Korea, Republic of
facility: Pfizer Investigational Site
state: Incheon
city: Seoul
country: Korea, Republic of
facility: Pfizer Investigational Site
state: Korea
city: Seongdong-gu
country: Korea, Republic of
facility: Pfizer Investigational Site
state: Seoul
city: Anyang-si Gyeonggi-do
country: Korea, Republic of
facility: Pfizer Investigational Site
city: Seoul
country: Korea, Republic of
facility: Pfizer Investigational Site
city: Seoul
country: Korea, Republic of
facility: Pfizer Investigational Site
city: Merida
country: Mexico
facility: Pfizer Investigational Site
state: Yucatan
city: Guadalajara
country: Mexico
facility: Pfizer Investigational Site
city: Mexico City
country: Mexico
facility: Pfizer Investigational Site
city: Mexico DF
country: Mexico
facility: Pfizer Investigational Site
city: Monterrey
country: Mexico
facility: Pfizer Investigational Site
city: Queretaro
country: Mexico
facility: Pfizer Investigational Site
city: Heerlen
country: Netherlands
facility: Pfizer Investigational Site
city: Bydgoszcz
country: Poland
facility: Pfizer Investigational Site
city: Lodz
country: Poland
facility: Pfizer Investigational Site
city: Lublin
country: Poland
facility: Pfizer Investigational Site
city: Szczecin
country: Poland
facility: Pfizer Investigational Site
city: Warszawa
country: Poland
facility: Pfizer Investigational Site
city: Moscow
country: Russian Federation
facility: Pfizer Investigational Site
city: Moscow
country: Russian Federation
facility: Pfizer Investigational Site
city: Moscow
country: Russian Federation
facility: Pfizer Investigational Site
city: Moscow
country: Russian Federation
facility: Pfizer Investigational Site
city: St Petersburg
country: Russian Federation
facility: Pfizer Investigational Site
city: St. Petersburg
country: Russian Federation
facility: Pfizer Investigational Site
city: Santiago de Compostela
country: Spain
facility: Pfizer Investigational Site
state: A Coruña
city: Sabadell
country: Spain
facility: Pfizer Investigational Site
state: Barcelona
city: Barcelona
country: Spain
facility: Pfizer Investigational Site
city: La Coruña
country: Spain
facility: Pfizer Investigational Site
city: Malaga
country: Spain
facility: Pfizer Investigational Site
city: Sevilla
country: Spain
facility: Pfizer Investigational Site
city: Falun
country: Sweden
facility: Pfizer Investigational Site
city: Oskarström
country: Sweden
facility: Pfizer Investigational Site
city: Tapei City
country: Taiwan
facility: Pfizer Investigational Site
state: ROC
city: Kaohsiung City
country: Taiwan
facility: Pfizer Investigational Site
city: Wigan
country: United Kingdom
facility: Pfizer Investigational Site
state: Lancashire
city: Dudley
country: United Kingdom
facility: Pfizer Investigational Site
state: West Midlands
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: Smolen JS, Pedersen R, Jones H, Mahgoub E, Marshall L. Impact of flare on radiographic progression after etanercept continuation, tapering or withdrawal in patients with rheumatoid arthritis. Rheumatology (Oxford). 2020 Jan 1;59(1):153-164. doi: 10.1093/rheumatology/kez224.
citation: Smolen JS, Szumski A, Koenig AS, Jones TV, Marshall L. Predictors of remission with etanercept-methotrexate induction therapy and loss of remission with etanercept maintenance, reduction, or withdrawal in moderately active rheumatoid arthritis: results of the PRESERVE trial. Arthritis Res Ther. 2018 Jan 16;20(1):8. doi: 10.1186/s13075-017-1484-9.
citation: Smolen JS, Strand V, Koenig AS, Szumski A, Kotak S, Jones TV. Discordance between patient and physician assessments of global disease activity in rheumatoid arthritis and association with work productivity. Arthritis Res Ther. 2016 May 21;18(1):114. doi: 10.1186/s13075-016-1004-3.
citation: Smolen JS, Nash P, Durez P, Hall S, Ilivanova E, Irazoque-Palazuelos F, Miranda P, Park MC, Pavelka K, Pedersen R, Szumski A, Hammond C, Koenig AS, Vlahos B. Maintenance, reduction, or withdrawal of etanercept after treatment with etanercept and methotrexate in patients with moderate rheumatoid arthritis (PRESERVE): a randomised controlled trial. Lancet. 2013 Mar 16;381(9870):918-29. doi: 10.1016/S0140-6736(12)61811-X. Epub 2013 Jan 17.