Clinical trial NCT01164579: Effects of Tofacitinib (CP-690,550) on Magnetic Resonance Imaging (MRI)- Assessed Joint Structure In Early Rheumatoid Arthritis (RA)
Official title: An Exploratory Phase 2, Randomized, Double-blind, Multicenter Study To Assess The Effects Of Tofacitinib (Cp-690,550) On Magnetic Resonance Imaging Endpoints, In Methotrexate Naive Subjects With Early Active Rheumatoid Arthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Keywords: Early Rheumatoid Arthritis
Joint Structure
Magnetic Resonance Imaging
Janus Kinase (JAK) Inhibitor
Tasocitinib
Tofacitinib
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2010-07-16
Enrollment: 109
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: Evaluation of efficacy and safety of tofacitinib (CP-690,550) for the treatment of early rheumatoid arthritis in adult patients with moderate to severe disease who are methotrexate naïve. The efficacy will be evaluated by exploring the effects on joint structure assessed by magnetic resonance imaging, x-rays and by standard clinical assessment.


Eligibility criteria: Inclusion Criteria:

* Adult patients with moderate to severe early rheumatoid arthritis (\< 2 years) who are methotrexate and biologic disease modifying antirheumatic drug naive.

Exclusion Criteria:

* Pregnant or lactating patients;
* Patients with renal or hepatic impairment or other severe or progressing disease;
* Patients with contraindication to magnetic resonance imaging with gadolinium contrast.

Primary outcomes:
measure: Change From Baseline to Month 3 in Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) Wrist and Metacarpophalangeal (MCP) Synovitis
timeFrame: Month 3
measure: Change From Baseline to Month 6 in OMERACT RAMRIS Wrist and MCP Bone Marrow Edema
timeFrame: Month 6
Secondary outcomes:
measure: Change From Baseline to Months 1, 6, and 12 in OMERACT RAMRIS Wrist and MCP Synovitis
timeFrame: Months 1, 6, and 12
measure: Change From Baseline to Months 1, 3, and 12 in OMERACT RAMRIS Bone Marrow Edema in Wrist and MCP
timeFrame: Months 1, 3, and 12
measure: Change From Baseline to Months 1, 3, 6, and 12 in OMERACT RAMRIS Wrist and MCP Erosions
timeFrame: Months 1, 3, 6, and 12
measure: Modified Total Sharp Score (mTSS) at Months 6 and 12
timeFrame: Months 6 and 12
measure: Change From Baseline to Months 6 and 12 in mTSS
timeFrame: Months 6 and 12
measure: Joint Space Narrowing (JSN) Scores at Months 6 and 12
timeFrame: Months 6 and 12
measure: Change From Baseline to Months 6 and 12 in JSN Scores
timeFrame: Months 6 and 12
measure: Erosion Scores at Months 6 and 12
timeFrame: Months 6 and 12
measure: Change From Baseline to Months 6 and 12 in Erosion Score
timeFrame: Months 6 and 12
measure: Percentage of Participants With an American College of Rheumatology (ACR) 20 Percent (%) Improvement (ACR20) Response
timeFrame: Months 1, 2, 3, 6, 9, and 12
measure: Percentage of Participants With an ACR 50% Improvement (ACR50) Response
timeFrame: Months 1, 2, 3, 6, 9, and 12
measure: Percentage of Participants With an ACR 70% Improvement (ACR70) Response
timeFrame: Months 1, 2, 3, 6, 9, and 12
measure: Disease Activity Score Based on 28-Joint Count and CRP (DAS28-3 [CRP])
timeFrame: Baseline and Months 1, 2, 3, 6, 9, and 12
measure: Change From Baseline in DAS28-3 (CRP)
timeFrame: Months 1, 2, 3, 6, 9, and 12
measure: Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (DAS28-4 [ESR])
timeFrame: Baseline and Months 1, 2, 3, 6, 9, and 12
measure: Change From Baseline in DAS28-4 (ESR)
timeFrame: Months 1, 2, 3, 6, 9, and 12
measure: Percentage of Participants With DAS28-3 (CRP) Response (Good or Moderate Improvement)
timeFrame: Months 1, 2, 3, 6, 9, and 12
measure: Percentage of Participants With DAS28-3 (CRP) Score â‰¤3.2
timeFrame: Months 1, 2, 3, 6, 9, and 12
measure: Percentage of Participants With DAS28-3 (CRP) Score <2.6
timeFrame: Months 1, 2, 3, 6, 9, and 12
measure: Percentage of Participants With DAS28-4 (ESR) Response (Good or Moderate Improvement)
timeFrame: Months 1, 2, 3, 6, 9, and 12
measure: Percentage of Participants With DAS28-4 (ESR) â‰¤3.2
timeFrame: Months 1, 2, 3, 6, 9, and 12
measure: Percentage of Participants With DAS28-4 (ESR) <2.6
timeFrame: Months 1, 2, 3, 6, 9, and 12
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: ArthroCare, Arthritis Care & Research, PC
state: Arizona
city: Huntington Beach
country: United States
facility: Talbert Medical Group
state: California
city: Upland
country: United States
facility: Inland Rheumatology Clinical Trials, Inc.
state: California
city: Ormond Beach
country: United States
facility: Millennium Research
state: Florida
city: Pinellas Park
country: United States
facility: DMI Research, Inc.
state: Florida
city: St. Petersburg
country: United States
facility: St. Petersburg Arthritis Center
state: Florida
city: Oklahoma City
country: United States
facility: Oklahoma Medical Research Foundation
state: Oklahoma
city: Allen
country: United States
facility: Office of John P. Lavery, MD, PA
state: Texas
city: Buenos Aires
country: Argentina
facility: OMI - Organización Médica de Investigación
city: Buenos Aires
country: Argentina
facility: Saint Dennis Medical Group S.A.
city: Buenos Aires
country: Argentina
facility: Consultorios Reumatologicos Pampa
city: Valdivia
country: Chile
facility: Hospital Base Valdivia
state: Region XIV
city: Osorno
country: Chile
facility: Consulta Privada Dr. Juan Ignacio Vargas
state: X Region
city: Split
country: Croatia
facility: University Hospital Centre Split,Department for Internal Medicine, Division of Clinical Rheumatology
city: Zagreb
country: Croatia
facility: General Hospital Sveti Duh
city: Hostivice
country: Czech Republic
facility: ARTMEDI UPD s r.o.
city: Praha 11 - Chodov
country: Czech Republic
facility: DC Mediscan
city: Praha 1
country: Czech Republic
facility: Nemocnice na Frantisku s poliklinikou
city: Praha 1
country: Czech Republic
facility: Nemocnice na Frantisku
city: Praha 2
country: Czech Republic
facility: Revmatologicky ustav
city: Uherske Hradiste
country: Czech Republic
facility: Uherskohradistska nemocnice, a.s.
city: Zlin
country: Czech Republic
facility: Nemocnice Atlas, a.s.
city: Zlin
country: Czech Republic
facility: PV-Medical s.r.o.
city: Balatonfured
country: Hungary
facility: Drug Research Center Kft.
city: Budapest
country: Hungary
facility: Orszagos Reumatologiai es Fizioterapias Intezet
city: Budapest
country: Hungary
facility: Synexus Magyarorszag Kft.
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Orvos- es Egeszsegtudomanyi Centrum, Reumatologiai Tanszek
city: Gyor
country: Hungary
facility: Petz Aladar Megyei Oktato Korhaz/Reumatologiai es Mozgasszervi Rehabilitacios Centrum
city: Mexico
country: Mexico
facility: Centro de Investigacion y Tratamiento Reumatologico S.C.
state: D. F.
city: Mexico
country: Mexico
facility: Hospital Angeles Mocel
state: D.f.
city: Mexico
country: Mexico
facility: Centro de Investigacion y Tratamiento Reumatologico SC
state: Distrito Federal
city: Chapultepec
country: Mexico
facility: Hospital Angeles Mocel
city: Chihuahua
country: Mexico
facility: Investigacion y Biomedicina de Chihuahua S.C
city: Mexico D.F.
country: Mexico
facility: Hospital Angeles Mocel
city: San Luis Potosi
country: Mexico
facility: Centro de Alta Especialidad en Reumatologia e Investigacion del Potosi S.C.
city: Bialystok
country: Poland
facility: Niepubliczny Zaklad Opieki Zdrowotnej Centrum Osteoporozy i Chorob Kostno-Stawowych J.
city: Poznan
country: Poland
facility: Prywatna Praktyka Lekarska Prof. UM dr hab. med. Pawel Hrycaj
city: Torun
country: Poland
facility: Nzoz "Nasz Lekarz"
city: San Juan
country: Puerto Rico
facility: Mindful Medical Research
city: San Juan
country: Puerto Rico
facility: San Juan Arthritis & Research Center
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: van der Heijde D, Landewe RBM, Wollenhaupt J, Strengholt S, Terry K, Kwok K, Wang L, Cohen S. Assessment of radiographic progression in patients with rheumatoid arthritis treated with tofacitinib in long-term studies. Rheumatology (Oxford). 2021 Apr 6;60(4):1708-1716. doi: 10.1093/rheumatology/keaa476.
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: Conaghan PG, Ostergaard M, Troum O, Bowes MA, Guillard G, Wilkinson B, Xie Z, Andrews J, Stein A, Chapman D, Koenig A. Very early MRI responses to therapy as a predictor of later radiographic progression in early rheumatoid arthritis. Arthritis Res Ther. 2019 Oct 21;21(1):214. doi: 10.1186/s13075-019-2000-1.
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: Conaghan PG, Ostergaard M, Bowes MA, Wu C, Fuerst T, van der Heijde D, Irazoque-Palazuelos F, Soto-Raices O, Hrycaj P, Xie Z, Zhang R, Wyman BT, Bradley JD, Soma K, Wilkinson B. Comparing the effects of tofacitinib, methotrexate and the combination, on bone marrow oedema, synovitis and bone erosion in methotrexate-naive, early active rheumatoid arthritis: results of an exploratory randomised MRI study incorporating semiquantitative and quantitative techniques. Ann Rheum Dis. 2016 Jun;75(6):1024-33. doi: 10.1136/annrheumdis-2015-208267. Epub 2016 Jan 25.
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.