Effects of Tofacitinib (CP-690,550) on Magnetic Resonance Imaging (MRI)- Assessed Joint Structure In Early Rheumatoid Arthritis (RA)

NCT01164579 | Completed Phase 2 Results DMC

• 2 other identifiers: A39210682010-020890-18
• Study Type: interventional
• Target: 109
• Locations: 9 countries
• Sites: 40

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.

Conditions

Rheumatoid Arthritis

Keywords

Early Rheumatoid Arthritis; Joint Structure; Magnetic Resonance Imaging; Janus Kinase (JAK) Inhibitor; Tasocitinib; Tofacitinib

Outcome Measures

Primary Outcomes (2)

• 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

  Synovitis is defined as an area in the synovial compartment that shows above normal postgadolinium enhancement of a thickness greater than the width of the normal synovium. T1-weighted images were acquired before and after the administration of intravenous contrast agent containing gadolinium. Intravenous contrast was required to demonstrate enhancing synovitis. Synovitis was scored 0 to 3 in 3 wrist regions and in each of the first through fifth MCP joints. A score of 0 is normal, with no enhancement or enhancement up to the thickness of normal synovium, while scores of 1 to 3 (mild, moderate, severe) refer to increments of one-third of the presumed maximum volume of enhancing tissue in the synovial compartment. Total synovitis score ranges from a minimum of 0 to a maximum of 24. A negative value in synovitis change from Baseline score indicates an improvement.

  Month 3

• Change From Baseline to Month 6 in OMERACT RAMRIS Wrist and MCP Bone Marrow Edema

  Bone edema was assessed at 25 anatomic locations: 15 in 1 wrist and 10 in attached hand. Bone edema was defined as a lesion within the trabecular bone, with ill-defined margins and signal characteristics consistent with increased water content. Each bone was scored separately; the scale was 0-3 based on the proportion of bone with edema, as follows 0: no edema; 1: 1-33% of bone edematous; 2: 34-66% of bone edematous; 3: 67-100%. OMERACT RAMRIS total bone edema score for hands/wrists was sum of the individual scores for each location. Thus the maximum score per hand/wrist was 75 (range 0-75). Increasing score=greater severity.

  Month 6

Secondary Outcomes (22)

• Change From Baseline to Months 1, 6, and 12 in OMERACT RAMRIS Wrist and MCP Synovitis

  Months 1, 6, and 12

• Change From Baseline to Months 1, 3, and 12 in OMERACT RAMRIS Bone Marrow Edema in Wrist and MCP

  Months 1, 3, and 12

• Change From Baseline to Months 1, 3, 6, and 12 in OMERACT RAMRIS Wrist and MCP Erosions

  Months 1, 3, 6, and 12

• Modified Total Sharp Score (mTSS) at Months 6 and 12

  Months 6 and 12

• Change From Baseline to Months 6 and 12 in mTSS

  Months 6 and 12

Study Arms (3)

Tofacitinib (CP 690,550) 10 mg BID plus MTX

EXPERIMENTAL

Drug: Tasocitinib plus Methotrexate

Tofacitinib (CP-690,550) 10 mg BID, tablet plus placebo MTX

EXPERIMENTAL

Drug: Tofacitinib plus placebo methotrexate

Placebo tofacitinib (CP-690,55) plus MTX 10 mg/wk to 20 mg/wk

ACTIVE COMPARATOR

Drug: Placebo tofacitinib plus Methotrexate

Interventions

Tasocitinib plus Methotrexate DRUG

Tofacitinib (CP 690,550) 10 mg BID, tablets + methotrexate (MTX) 10 mg/wk to 20 mg/wk, titrated over 2 months

Tofacitinib (CP 690,550) 10 mg BID plus MTX

Tofacitinib plus placebo methotrexate DRUG

Tofacitinib (CP-90,550) 10 mg BID, tablets. Placebo to match methotrexate (MTX) capsules titrated as in Treatment Arm 1.

Tofacitinib (CP-690,550) 10 mg BID, tablet plus placebo MTX

Placebo tofacitinib plus Methotrexate DRUG

Methotrexate (MTX) 10 mg/wk to 20 mg/wk, capsules, titrated over 2 months. Placebo in tablets to match tofacitinib

Placebo tofacitinib (CP-690,55) plus MTX 10 mg/wk to 20 mg/wk

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (40)

ArthroCare, Arthritis Care & Research, PC

Gilbert, Arizona, 85234, United States

Location

Talbert Medical Group

Huntington Beach, California, 92646, United States

Location

Inland Rheumatology Clinical Trials, Inc.

Upland, California, 91786, United States

Location

Millennium Research

Ormond Beach, Florida, 32174, United States

Location

DMI Research, Inc.

Pinellas Park, Florida, 33782, United States

Location

St. Petersburg Arthritis Center

St. Petersburg, Florida, 33710, United States

Location

Oklahoma Medical Research Foundation

Oklahoma City, Oklahoma, 73104 5005, United States

Location

Office of John P. Lavery, MD, PA

Allen, Texas, 75013, United States

Location

OMI - Organización Médica de Investigación

Buenos Aires, C1015ABO, Argentina

Location

Saint Dennis Medical Group S.A.

Buenos Aires, C1034ACO, Argentina

Location

Consultorios Reumatologicos Pampa

Buenos Aires, C1428DZF, Argentina

Location

Consulta Privada Dr. Juan Ignacio Vargas

Osorno, Los Lagos Region, 5311089, Chile

Location

Hospital Base Valdivia

Valdivia, Region XIV, 5090145, Chile

Location

University Hospital Centre Split,Department for Internal Medicine, Division of Clinical Rheumatology

Split, 21000, Croatia

Location

General Hospital Sveti Duh

Zagreb, 10000, Croatia

Location

ARTMEDI UPD s r.o.

Hostivice, 253 01, Czechia

Location

Nemocnice na Frantisku s poliklinikou

Prague, 110 00, Czechia

Location

Nemocnice na Frantisku

Prague, 110 00, Czechia

Location

Revmatologicky ustav

Prague, 128 50, Czechia

Location

DC Mediscan

Praha 11 - Chodov, 148 00, Czechia

Location

Uherskohradistska nemocnice, a.s.

Uherské Hradiště, 686 68, Czechia

Location

Nemocnice Atlas, a.s.

Zlín, 760 01, Czechia

Location

PV-Medical s.r.o.

Zlín, 760 01, Czechia

Location

Drug Research Center Kft.

Balatonfüred, 8230, Hungary

Location

Orszagos Reumatologiai es Fizioterapias Intezet

Budapest, 1023, Hungary

Location

Synexus Magyarorszag Kft.

Budapest, 1036, Hungary

Location

Debreceni Egyetem Orvos- es Egeszsegtudomanyi Centrum, Reumatologiai Tanszek

Debrecen, 4032, Hungary

Location

Petz Aladar Megyei Oktato Korhaz/Reumatologiai es Mozgasszervi Rehabilitacios Centrum

Győr, 9027, Hungary

Location

Centro de Investigacion y Tratamiento Reumatologico S.C.

México, D. F., 11850, Mexico

Location

Hospital Angeles Mocel

México, D.f., 11850, Mexico

Location

Centro de Investigacion y Tratamiento Reumatologico SC

Mexico City, Mexico City, 11850, Mexico

Location

Hospital Angeles Mocel

Mexico City, Mexico City, 11850, Mexico

Location

Centro de Alta Especialidad en Reumatologia e Investigacion del Potosi S.C.

San Luis Potosí City, San Luis Potosí, 78200, Mexico

Location

Hospital Angeles Mocel

Chapultepec, 11850, Mexico

Location

Investigacion y Biomedicina de Chihuahua S.C

Chihuahua City, 31000, Mexico

Location

Niepubliczny Zaklad Opieki Zdrowotnej Centrum Osteoporozy i Chorob Kostno-Stawowych J.

Bialystok, 15-879, Poland

Location

Prywatna Praktyka Lekarska Prof. UM dr hab. med. Pawel Hrycaj

Poznan, 61-397, Poland

Location

Nzoz "Nasz Lekarz"

Torun, 87-100, Poland

Location

Mindful Medical Research

San Juan, PR, 00918, Puerto Rico

Location

San Juan Arthritis & Research Center

San Juan, 00918, Puerto Rico

Location

Related Publications (14)

• Hetland ML, Strangfeld A, Bonfanti G, Soudis D, Deuring JJ, Edwards RA. Machine learning prediction and explanatory models of serious infections in patients with rheumatoid arthritis treated with tofacitinib. Arthritis Res Ther. 2024 Aug 27;26(1):153. doi: 10.1186/s13075-024-03376-9.

  PMID: 39192350 DERIVED

• Wright GC, Mysler E, Kwok K, Cadatal MJ, Germino R, Yndestad A, Kinch CD, Ogdie A. Impact of Race on the Efficacy and Safety of Tofacitinib in Rheumatoid Arthritis: Post Hoc Analysis of Pooled Clinical Trials. Rheumatol Ther. 2024 Oct;11(5):1135-1164. doi: 10.1007/s40744-024-00677-y. Epub 2024 Jul 3.

  PMID: 38958913 DERIVED

• Kristensen LE, Danese S, Yndestad A, Wang C, Nagy E, Modesto I, Rivas J, Benda B. Identification of two tofacitinib subpopulations with different relative risk versus TNF inhibitors: an analysis of the open label, randomised controlled study ORAL Surveillance. Ann Rheum Dis. 2023 Jul;82(7):901-910. doi: 10.1136/ard-2022-223715. Epub 2023 Mar 17.

  PMID: 36931693 DERIVED

• Hansen KE, Mortezavi M, Nagy E, Wang C, Connell CA, Radi Z, Litman HJ, Adami G, Rossini M. Fracture in clinical studies of tofacitinib in rheumatoid arthritis. Ther Adv Musculoskelet Dis. 2022 Dec 27;14:1759720X221142346. doi: 10.1177/1759720X221142346. eCollection 2022.

  PMID: 36601090 DERIVED

• Curtis JR, Yamaoka K, Chen YH, Bhatt DL, Gunay LM, Sugiyama N, Connell CA, Wang C, Wu J, Menon S, Vranic I, Gomez-Reino JJ. Malignancy risk with tofacitinib versus TNF inhibitors in rheumatoid arthritis: results from the open-label, randomised controlled ORAL Surveillance trial. Ann Rheum Dis. 2023 Mar;82(3):331-343. doi: 10.1136/ard-2022-222543. Epub 2022 Dec 5.

  PMID: 36600185 DERIVED

• Winthrop KL, Yndestad A, Henrohn D, Danese S, Marsal S, Galindo M, Woolcott JC, Jo H, Kwok K, Shapiro AB, Jones TV, Diehl A, Su C, Panes J, Cohen SB. Influenza Adverse Events in Patients with Rheumatoid Arthritis, Ulcerative Colitis, or Psoriatic Arthritis in the Tofacitinib Clinical Development Programs. Rheumatol Ther. 2023 Apr;10(2):357-373. doi: 10.1007/s40744-022-00507-z. Epub 2022 Dec 17.

  PMID: 36526796 DERIVED

• 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.

  PMID: 34870800 DERIVED

• 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.

  PMID: 33127856 DERIVED

• 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.

  PMID: 33057725 DERIVED

• 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.

  PMID: 32816215 DERIVED

• 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.

  PMID: 31639034 DERIVED

• 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.

  PMID: 28143815 DERIVED

• 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.

  PMID: 27002108 DERIVED

• 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.

  PMID: 25047021 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

tofacitinib; Methotrexate

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2010
• First Posted: July 16, 2010
• Study Start: October 1, 2010
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2013
• Last Updated: April 22, 2015
• Results First Posted: April 22, 2015

Record last verified: 2015-04

Locations

US (8); PR (2); ME (7); CZ (8); AR (3); CL (2); PL (3); CR (2); HU (5)