Clinical trial NCT00413660: Comparison Of 6 CP-690,550 Doses Vs.Placebo, Each Combined With Methotrexate, For The Treatment Of Rheumatoid Arthritis
Official title: A Phase 2B, Randomized, Double Blind, Placebo-Controlled, Multicenter Study To Compare 6 Dose Regimens Of CP-690,550 Vs. Placebo, Each Combined With Methotrexate, Administered For 6 Months In The Treatment Of Subjects With Active Rheumatoid Arthritis Who Have Had An Inadequate Response To Methotrexate Alone
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Arthritis, Rheumatoid
Keywords: DMARD therapy
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2006-12-20
Enrollment: 509
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the effectiveness and safety, over 6 months, of 6 dose regimens of CP-690,550, combined with methotrexate, for the treatment of adults with active rheumatoid arthritis.


Eligibility criteria: Inclusion Criteria:

* Active rheumatoid arthritis
* Inadequate response to stably dosed methotrexate

Exclusion Criteria:

* Current therapy with any DMARD or biologic other than methotrexate

Primary outcomes:
measure: Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Week 12
timeFrame: Week 12
Secondary outcomes:
measure: Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response
timeFrame: Week 2, 4, 6, 8, 16, 20, 24/Early Termination (ET)
measure: Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response
timeFrame: Week 2, 4, 6, 8, 12, 16, 20, 24/ET
measure: Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response
timeFrame: Week 2, 4, 6, 8, 12, 16, 20, 24/ET
measure: Area Under the Numeric Index of American College of Rheumatology Response (ACR-n) Curve
timeFrame: Baseline up to Week 2, 4, 6, 8, 12
measure: Tender Joints Count (TJC)
timeFrame: Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET
measure: Change From Baseline in Tender Joints Count (TJC) at Week 2, 4, 6, 8, 12, 16, 20 and 24/ET
timeFrame: Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET
measure: Swollen Joints Count (SJC)
timeFrame: Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET
measure: Change From Baseline in Swollen Joints Count (SJC) at Week 2, 4, 6, 8, 12, 16, 20 and 24/ET
timeFrame: Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET
measure: Patient Assessment of Arthritis Pain
timeFrame: Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET
measure: Change From Baseline in Patient Assessment of Arthritis Pain at Week 2, 4, 6, 8, 12, 16, 20 and 24/ET
timeFrame: Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET
measure: Patient Global Assessment (PtGA) of Arthritis
timeFrame: Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET
measure: Change From Baseline in Patient Global Assessment (PtGA) of Arthritis at Week 2, 4, 6, 8, 12, 16, 20 and 24/ET
timeFrame: Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET
measure: Physician Global Assessment of Arthritis
timeFrame: Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET
measure: Change From Baseline in Physician Global Assessment of Arthritis at Week 2, 4, 6, 8, 12, 16, 20 and 24/ET
timeFrame: Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET
measure: Health Assessment Questionnaire-Disability Index (HAQ-DI)
timeFrame: Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET
measure: Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 2, 4, 6, 8, 12, 16, 20 and 24/ET
timeFrame: Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET
measure: C-Reactive Protein (CRP)
timeFrame: Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET
measure: Change From Baseline in C-Reactive Protein (CRP) at Week 2, 4, 6, 8, 12, 16, 20 and 24/ET
timeFrame: Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET
measure: Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP])
timeFrame: Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET
measure: Change From Baseline in Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) at Week 2, 4, 6, 8, 12, 16, 20 and 24/ET
timeFrame: Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET
measure: Percentage of Participants With Categorization of Disease Improvement Based on DAS28-3 (CRP)
timeFrame: Week 2, 4, 6, 8, 12, 16, 20, 24/ET
measure: Percentage of Participants With Disease Remission Based on DAS28-3 (CRP)
timeFrame: Week 2, 4, 6, 8, 12, 16, 20, 24/ET
measure: 36-Item Short-Form Health Survey (SF-36)
timeFrame: Baseline, Week 12, 24/ET
measure: Change From Baseline in 36-Item Short-Form Health Survey (SF-36) at Week 12 and 24/ET
timeFrame: Baseline, Week 12, 24/ET
measure: Euro Quality of Life-5 Dimentions (EQ-5D) - Health State Profile Utility Score
timeFrame: Baseline, Week 12, 24/ET
measure: Change From Baseline in Euro Quality of Life-5 Dimentions (EQ-5D) - Health State Profile Utility at Week 12 and 24/ET
timeFrame: Baseline, Week 12, 24/ET
measure: Medical Outcome Study- Sleep Scale (MOS-SS)
timeFrame: Baseline, Week 2, 12, 24/ET
measure: Change From Baseline in Medical Outcome Study- Sleep Scale (MOS-SS) at Week 2, 12 and 24/ET
timeFrame: Baseline, Week 2, 12, 24/ET
measure: Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale
timeFrame: Baseline, Week 2, 12, 24/ET
measure: Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale at Week 2, 12 and 24/ET
timeFrame: Baseline, Week 2, 12, 24/ET
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Pfizer Investigational Site
state: Arizona
city: Hot Springs
country: United States
facility: Pfizer Investigational Site
state: Arkansas
city: Upland
country: United States
facility: Pfizer Investigational Site
state: California
city: Denver
country: United States
facility: Pfizer Investigational Site
state: Colorado
city: Newark
country: United States
facility: Pfizer Investigational Site
state: Delaware
city: Debary
country: United States
facility: Pfizer Investigational Site
state: Florida
city: Lake Mary
country: United States
facility: Pfizer Investigational Site
state: Florida
city: Ocala
country: United States
facility: Pfizer Investigational Site
state: Florida
city: Orlando
country: United States
facility: Pfizer Investigational Site
state: Florida
city: Tampa
country: United States
facility: Pfizer Investigational Site
state: Florida
city: Zephyrhills
country: United States
facility: Pfizer Investigational Site
state: Florida
city: Rockford
country: United States
facility: Pfizer Investigational Site
state: Illinois
city: Rockford
country: United States
facility: Pfizer Investigational Site
state: Illinois
city: Dubuque
country: United States
facility: Pfizer Investigational Site
state: Iowa
city: Frederick
country: United States
facility: Pfizer Investigational Site
state: Maryland
city: Boston
country: United States
facility: Pfizer Investigational Site
state: Massachusetts
city: Albany
country: United States
facility: Pfizer Investigational Site
state: New York
city: Binghamton
country: United States
facility: Pfizer Investigational Site
state: New York
city: Charlotte
country: United States
facility: Pfizer Investigational Site
state: North Carolina
city: Raleigh
country: United States
facility: Pfizer Investigational Site
state: North Carolina
city: Dayton
country: United States
facility: Pfizer Investigational Site
state: Ohio
city: Philladelphia
country: United States
facility: Pfizer Investigational Site
state: Pennsylvania
city: West Reading
country: United States
facility: Pfizer Investigational Site
state: Pennsylvania
city: Greenville
country: United States
facility: Pfizer Investigational Site
state: South Carolina
city: Austin
country: United States
facility: Pfizer Investigational Site
state: Texas
city: Dallas
country: United States
facility: Pfizer Investigational Site
state: Texas
city: Dallas
country: United States
facility: Pfizer Investigational Site
state: Texas
city: Mesquite
country: United States
facility: Pfizer Investigational Site
state: Texas
city: Seattle
country: United States
facility: Pfizer Investigational Site
state: Washington
city: Seattle
country: United States
facility: Pfizer Investigational Site
state: Washington
city: Tacoma
country: United States
facility: Pfizer Investigational Site
state: Washington
city: Tacoma
country: United States
facility: Pfizer Investigational Site
state: Washington
city: Onalaska
country: United States
facility: Pfizer Investigational Site
state: Wisconsin
city: Capital Federal
country: Argentina
facility: Pfizer Investigational Site
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Pfizer Investigational Site
city: Buenos Aires
country: Argentina
facility: Pfizer Investigational Site
city: Buenos Aires
country: Argentina
facility: Pfizer Investigational Site
city: Goiania
country: Brazil
facility: Pfizer Investigational Site
state: GO
city: Goiânia
country: Brazil
facility: Pfizer Investigational Site
state: GO
city: Curitiba
country: Brazil
facility: Pfizer Investigational Site
state: PR
city: Curitiba
country: Brazil
facility: Pfizer Investigational Site
state: PR
city: Sao Paulo
country: Brazil
facility: Pfizer Investigational Site
state: SP
city: São Paulo
country: Brazil
facility: Pfizer Investigational Site
state: SP
city: Sofia 1606
country: Bulgaria
facility: Pfizer Investigational Site
city: Sofia
country: Bulgaria
facility: Pfizer Investigational Site
city: Sofia
country: Bulgaria
facility: Pfizer Investigational Site
city: Providencia
country: Chile
facility: Pfizer Investigational Site
state: RM
city: Santiago
country: Chile
facility: Pfizer Investigational Site
state: RM
city: Viña Del Mar
country: Chile
facility: Pfizer Investigational Site
state: V Region
city: Santiago
country: Chile
facility: Pfizer Investigational Site
city: Brno
country: Czech Republic
facility: Pfizer Investigational Site
city: Ceske Budejovice
country: Czech Republic
facility: Pfizer Investigational Site
city: Praha 11 - Chodov
country: Czech Republic
facility: Pfizer Investigational Site
city: Praha 2
country: Czech Republic
facility: Pfizer Investigational Site
city: Praha 4
country: Czech Republic
facility: Pfizer Investigational Site
city: Zlin
country: Czech Republic
facility: Pfizer Investigational Site
city: Budapest
country: Hungary
facility: Pfizer Investigational Site
city: Komarom
country: Hungary
facility: Pfizer Investigational Site
city: Szolnok
country: Hungary
facility: Pfizer Investigational Site
city: Veszprem
country: Hungary
facility: Pfizer Investigational Site
city: Mexico
country: Mexico
facility: Pfizer Investigational Site
state: DF
city: Morelia
country: Mexico
facility: Pfizer Investigational Site
state: Michoacan
city: Bialystok
country: Poland
facility: Pfizer Investigational Site
city: Bialystok
country: Poland
facility: Pfizer Investigational Site
city: Grudziadz
country: Poland
facility: Pfizer Investigational Site
city: Poznan
country: Poland
facility: Pfizer Investigational Site
city: Sopot
country: Poland
facility: Pfizer Investigational Site
city: Warszawa
country: Poland
facility: Pfizer Investigational Site
city: Wroclaw
country: Poland
facility: Pfizer Investigational Site
city: Bratislava
country: Slovakia
facility: Pfizer Investigational Site
city: Piestany
country: Slovakia
facility: Pfizer Investigational Site
city: Zilina
country: Slovakia
facility: Pfizer Investigational Site
city: Santiago de Compostela
country: Spain
facility: Pfizer Investigational Site
state: A Coruña
city: Guadalajara
country: Spain
facility: Pfizer Investigational Site
city: Madrid
country: Spain
facility: Pfizer Investigational Site
city: Sevilla
country: Spain
facility: Pfizer Investigational Site
city: Jonkoping
country: Sweden
facility: Pfizer Investigational Site
city: Umea
country: Sweden
facility: Pfizer Investigational Site
city: Ankara
country: Turkey
facility: Pfizer Investigational Site
city: Istanbul
country: Turkey
facility: Pfizer Investigational Site
city: Izmir
country: Turkey
facility: Pfizer Investigational Site
city: Izmir
country: Turkey
facility: Pfizer Investigational Site
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Winthrop KL, Curtis JR, Yamaoka K, Lee EB, Hirose T, Rivas JL, Kwok K, Burmester GR. Clinical Management of Herpes Zoster in Patients With Rheumatoid Arthritis or Psoriatic Arthritis Receiving Tofacitinib Treatment. Rheumatol Ther. 2022 Feb;9(1):243-263. doi: 10.1007/s40744-021-00390-0. Epub 2021 Dec 6.
citation: Cohen SB, Tanaka Y, Mariette X, Curtis JR, Lee EB, Nash P, Winthrop KL, Charles-Schoeman C, Wang L, Chen C, Kwok K, Biswas P, Shapiro A, Madsen A, Wollenhaupt J. Long-term safety of tofacitinib up to 9.5 years: a comprehensive integrated analysis of the rheumatoid arthritis clinical development programme. RMD Open. 2020 Oct;6(3):e001395. doi: 10.1136/rmdopen-2020-001395.
citation: Panaccione R, Isaacs JD, Chen LA, Wang W, Marren A, Kwok K, Wang L, Chan G, Su C. Characterization of Creatine Kinase Levels in Tofacitinib-Treated Patients with Ulcerative Colitis: Results from Clinical Trials. Dig Dis Sci. 2021 Aug;66(8):2732-2743. doi: 10.1007/s10620-020-06560-4. Epub 2020 Aug 20.
citation: Mariette X, Chen C, Biswas P, Kwok K, Boy MG. Lymphoma in the Tofacitinib Rheumatoid Arthritis Clinical Development Program. Arthritis Care Res (Hoboken). 2018 May;70(5):685-694. doi: 10.1002/acr.23421. Epub 2018 Apr 2.
citation: Cohen SB, Tanaka Y, Mariette X, Curtis JR, Lee EB, Nash P, Winthrop KL, Charles-Schoeman C, Thirunavukkarasu K, DeMasi R, Geier J, Kwok K, Wang L, Riese R, Wollenhaupt J. Long-term safety of tofacitinib for the treatment of rheumatoid arthritis up to 8.5 years: integrated analysis of data from the global clinical trials. Ann Rheum Dis. 2017 Jul;76(7):1253-1262. doi: 10.1136/annrheumdis-2016-210457. Epub 2017 Jan 31.
citation: Wallenstein GV, Kanik KS, Wilkinson B, Cohen S, Cutolo M, Fleischmann RM, Genovese MC, Gomez Reino J, Gruben D, Kremer J, Krishnaswami S, Lee EB, Pascual-Ramos V, Strand V, Zwillich SH. Effects of the oral Janus kinase inhibitor tofacitinib on patient-reported outcomes in patients with active rheumatoid arthritis: results of two Phase 2 randomised controlled trials. Clin Exp Rheumatol. 2016 May-Jun;34(3):430-42. Epub 2016 Apr 28.
citation: Charles-Schoeman C, Burmester G, Nash P, Zerbini CA, Soma K, Kwok K, Hendrikx T, Bananis E, Fleischmann R. Efficacy and safety of tofacitinib following inadequate response to conventional synthetic or biological disease-modifying antirheumatic drugs. Ann Rheum Dis. 2016 Jul;75(7):1293-301. doi: 10.1136/annrheumdis-2014-207178. Epub 2015 Aug 14.
citation: Cohen S, Radominski SC, Gomez-Reino JJ, Wang L, Krishnaswami S, Wood SP, Soma K, Nduaka CI, Kwok K, Valdez H, Benda B, Riese R. Analysis of infections and all-cause mortality in phase II, phase III, and long-term extension studies of tofacitinib in patients with rheumatoid arthritis. Arthritis Rheumatol. 2014 Nov;66(11):2924-37. doi: 10.1002/art.38779.
citation: Kremer JM, Cohen S, Wilkinson BE, Connell CA, French JL, Gomez-Reino J, Gruben D, Kanik KS, Krishnaswami S, Pascual-Ramos V, Wallenstein G, Zwillich SH. A phase IIb dose-ranging study of the oral JAK inhibitor tofacitinib (CP-690,550) versus placebo in combination with background methotrexate in patients with active rheumatoid arthritis and an inadequate response to methotrexate alone. Arthritis Rheum. 2012 Apr;64(4):970-81. doi: 10.1002/art.33419. Epub 2011 Oct 17.