Clinical trial NCT00550446: A Phase 2 Study For Patients With A Physician's Diagnosis Of Rheumatoid Arthritis
Official title: A Phase 2b, Randomized, Double Blind, Placebo Controlled Active Comparator, Multicenter Study To Compare 5 Dose Regimens Of CP- 690,550 And Adalimumab Versus Placebo, Administered For 6 Months In The Treatment Of Subjects With Active Rheumatoid Arthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Arthritis, Rheumatoid
Keywords: Janus Kinase 3 Clinical Trial
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2007-10-29
Enrollment: 386
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 5 doses of CP-690,550 for the treatment of adults with active rheumatoid arthritis. Five out of seven subjects will receive CP-690,550. One out of seven will receive adalimumab (Humira®) and one out of seven will only receive inactive substances (placebo.)


Eligibility criteria: Inclusion Criteria:

* Subjects must have active rheumatoid arthritis
* Subjects must have failed at least 1 disease modifying anti-rheumatic drug (DMARD)
* Subjects must not be currently taking any DMARD other than an antimalarial

Exclusion Criteria:

* Subjects who discontinued any previous TNF inhibitor therapy for either lack of benefit or safety.
* Subjects who previously received adalimumab (Humira®) therapy for any reason.
* Subjects with evidence of blood disorders, chronic infections or untreated tuberculosis

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, 10, 16, 20 and 24/Early Termination (ET)
measure: Percentage of Participants Achieving American College of Rheumatology 50%(ACR50) Response
timeFrame: Week 2, 4, 6, 8, 10, 12, 16, 20 and 24/ET
measure: Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response
timeFrame: Week 2, 4, 6, 8, 10, 12, 16, 20 and 24/ET
measure: Percentage of Participants Achieving American College of Rheumatology 90% (ACR90) Response
timeFrame: Week 2, 4, 6, 8, 10, 12, 16, 20 and 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, 10, 12
measure: Tender Joint Count (TJC)
timeFrame: Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20 and 24/ET
measure: Change From Baseline in Tender Joint Count at Week 2, 4, 6, 8, 10, 12, 16, 20 and 24 or ET
timeFrame: Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20 and 24/ET
measure: Swollen Joint Counts (SJC)
timeFrame: Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20 and 24/ET
measure: Change From Baseline in Swollen Joint Count at Week 2, 4, 6, 8, 10, 12, 16, 20 and 24
timeFrame: Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20 and 24/ET
measure: Patient Assessment of Arthritis Pain
timeFrame: Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20, 24/ET
measure: Change From Baseline in Patient Assessment of Arthritis Pain at Week 2, 4, 6, 8, 10, 12, 16, 20 and 24/ET
timeFrame: Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20 and 24/ET
measure: Patient Global Assessment (PtGA) of Arthritis Pain
timeFrame: Baseline, 2, 4, 6, 8, 10, 12, 16, 20, 24/ET
measure: Change From Baseline in Patient Global Assessment (PtGA) of Arthritis at Week 2, 4, 6, 8, 10, 12, 16, 20 and 24/ET
timeFrame: Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20, 24/ET
measure: Physician Global Assessment (PGA) of Arthritis
timeFrame: Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20, 24/ET
measure: Change From Baseline in Physician's Global Assessment (PGA) of Arthritis Pain at Week 2, 4, 6, 8, 10, 12, 16, 20 and 24/ET
timeFrame: Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20, 24/ET
measure: C-Reactive Protein (CRP)
timeFrame: Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20, 24/ET
measure: Change From Baseline in C-reactive Protein (CRP) at Week 2, 4, 6, 8, 10, 12, 16, 20 and 24/ET
timeFrame: Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20, 24/ET
measure: Health Assessment Questionnaire-Disability Index (HAQ-DI)
timeFrame: Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20, 24/ET
measure: Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 2, 4, 6, 8, 10, 12, 16, 20 and 24/ET
timeFrame: Baseline, Week 2, 4, 6, 8, 10, 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, 10, 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, 10, 12, 16, 20 and 24/ET
timeFrame: Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20, 24/ ET
measure: Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR])
timeFrame: Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20, 24/ ET
measure: Change From Baseline in Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) at Week 2, 4, 6, 8, 12, 16, 20 and 24/ET
timeFrame: Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20, 24/ET
measure: Percentage of Participants With Disease Improvement Based on DAS28-4 (ESR)
timeFrame: Week 2, 4, 6, 8, 10, 12, 16, 20, 24/ET
measure: Percentage of Participants With Disease Remission Based on Normal C-reactive Protein (CRP)
timeFrame: Week 2, 4, 6, 8, 10, 12, 16, 20, 24/ ET
measure: Percentage of Participants With Disease Remission Based on DAS28-3 (CRP)
timeFrame: Week 2, 4, 6, 8, 10, 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 Dimension (EQ-5D)-Health State Profile Utility Score
timeFrame: Baseline, Week 12, 24/ ET
measure: Change From Baseline in Euro Quality of Life 5 Dimension (EQ-5D)- Health State Profile Utility Score at Week 12 and 24/ET
timeFrame: Baseline, Week 12, 24/ ET
Other outcomes:
measure: Serum Immunoglobulin G (IgG), Immunoglobulin M (IgM) and Immunoglobulin A (IgA) Levels
timeFrame: Baseline, Week 24/ ET
measure: Change From Baseline in Serum Immunoglobulin G (IgG), Immunoglobulin M (IgM) and Immunoglobulin A (IgA) Levels at Week 24
timeFrame: Baseline, Week 24/ ET
measure: Fluorescence Activated Cell Sorting (FACS) Lymphocyte Biomarkers
timeFrame: Baseline, Week 24/ ET
measure: Change From Baseline in Fluorescence Activated Cell Sorting (FACS) Lymphocyte Biomarkers at Week 24
timeFrame: Baseline, Week 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
Locations:
city: Mesa
country: United States
facility: Pfizer Investigational Site
state: Arizona
city: Little Rock
country: United States
facility: Pfizer Investigational Site
state: Arkansas
city: Northridge
country: United States
facility: Pfizer Investigational Site
state: California
city: Palo Alto
country: United States
facility: Pfizer Investigational Site
state: California
city: Stanford
country: United States
facility: Pfizer Investigational Site
state: California
city: Tarzana
country: United States
facility: Pfizer Investigational Site
state: California
city: Upland
country: United States
facility: Pfizer Investigational Site
state: California
city: Orlando
country: United States
facility: Pfizer Investigational Site
state: Florida
city: Tampa
country: United States
facility: Pfizer Investigational Site
state: Florida
city: Morton Grove
country: United States
facility: Pfizer Investigational Site
state: Illinois
city: Rockford
country: United States
facility: Pfizer Investigational Site
state: Illinois
city: Cedar Rapids
country: United States
facility: Pfizer Investigational Site
state: Iowa
city: Wichita
country: United States
facility: Pfizer Investigational Site
state: Kansas
city: Wichita
country: United States
facility: Pfizer Investigational Site
state: Kansas
city: New Orleans
country: United States
facility: Pfizer Investigational Site
state: Louisiana
city: Hickory
country: United States
facility: Pfizer Investigational Site
state: North Carolina
city: Hickory
country: United States
facility: Pfizer Investigational Site
state: North Carolina
city: Dayton
country: United States
facility: Pfizer Investigational Site
state: Ohio
city: Duncansville
country: United States
facility: Pfizer Investigational Site
state: Pennsylvania
city: Knoxville
country: United States
facility: Pfizer Investigational Site
state: Tennessee
city: Dallas
country: United States
facility: Pfizer Investigational Site
state: Texas
city: Mesquite
country: United States
facility: Pfizer Investigational Site
state: Texas
city: Porto Alegre
country: Brazil
facility: Pfizer Investigational Site
state: RS
city: Sao Paulo
country: Brazil
facility: Pfizer Investigational Site
state: SP
city: Pleven
country: Bulgaria
facility: Pfizer Investigational Site
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: Santiago
country: Chile
facility: Pfizer Investigational Site
state: RM
city: Santiago
country: Chile
facility: Pfizer Investigational Site
state: RM
city: Providencia
country: Chile
facility: Pfizer Investigational Site
state: Santiago, RM
city: Split
country: Croatia
facility: Pfizer Investigational Site
city: Zagreb
country: Croatia
facility: Pfizer Investigational Site
city: Brno
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: Dresden
country: Germany
facility: Pfizer Investigational Site
city: Hamburg
country: Germany
facility: Pfizer Investigational Site
city: Hildesheim
country: Germany
facility: Pfizer Investigational Site
city: Leipzig
country: Germany
facility: Pfizer Investigational Site
city: Goudi
country: Greece
facility: Pfizer Investigational Site
state: Athens
city: Thessaloniki
country: Greece
facility: Pfizer Investigational Site
city: Szolnok
country: Hungary
facility: Pfizer Investigational Site
city: Firenze
country: Italy
facility: Pfizer Investigational Site
city: Genova
country: Italy
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: Mexico
country: Mexico
facility: Pfizer Investigational Site
state: D.f.
city: Metepec
country: Mexico
facility: Pfizer Investigational Site
state: Estado de Mexico
city: Guadalajara
country: Mexico
facility: Pfizer Investigational Site
state: Jalisco
city: Cuernavaca
country: Mexico
facility: Pfizer Investigational Site
state: Morelos
city: Bucuresti
country: Romania
facility: Pfizer Investigational Site
city: Constanta
country: Romania
facility: Pfizer Investigational Site
city: Iasi
country: Romania
facility: Pfizer Investigational Site
city: Piestany
country: Slovakia
facility: Pfizer Investigational Site
city: Zilina
country: Slovakia
facility: Pfizer Investigational Site
city: Kharkiv
country: Ukraine
facility: Pfizer Investigational Site
city: Kyiv
country: Ukraine
facility: Pfizer Investigational Site
city: Lviv
country: Ukraine
facility: Pfizer Investigational Site
city: Vinnitsa
country: Ukraine
facility: Pfizer Investigational Site
city: Zaporizhzhia
country: Ukraine
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: Suzuki M, Shoji S, Miyoshi S, Krishnaswami S. Model-Based Comparison of Dose-Response Profiles of Tofacitinib in Japanese Versus Western Rheumatoid Arthritis Patients. J Clin Pharmacol. 2020 Feb;60(2):198-208. doi: 10.1002/jcph.1514. Epub 2019 Sep 12.
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: Fleischmann R, Cutolo M, Genovese MC, Lee EB, Kanik KS, Sadis S, Connell CA, Gruben D, Krishnaswami S, Wallenstein G, Wilkinson BE, Zwillich SH. Phase IIb dose-ranging study of the oral JAK inhibitor tofacitinib (CP-690,550) or adalimumab monotherapy versus placebo in patients with active rheumatoid arthritis with an inadequate response to disease-modifying antirheumatic drugs. Arthritis Rheum. 2012 Mar;64(3):617-29. doi: 10.1002/art.33383.