Methotrexate Withdrawal Study of Tofacitinib Modified Release Formulation in Subjects With Rheumatoid Arthritis
A PHASE 3B/4 RANDOMIZED DOUBLE BLIND PLACEBO CONTROLLED STUDY OF METHOTREXATE (MTX) WITHDRAWAL IN SUBJECTS WITH RHEUMATOID ARTHRITIS (RA) TREATED WITH TOFACITINIB 11MG MODIFIED RELEASE (MR) FORMULATION
2 other identifiers
interventional
694
16 countries
136
Brief Summary
This study is designed to evaluate the efficacy and safety of tofacitinib modified release formulation (11mg QD) versus tofacitinib modified release formulation plus continued methotrexate treatment in subjects with moderate to severe rheumatoid arthritis who are insufficiently responding to their stable dose of methotrexate treatment.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_4 rheumatoid-arthritis
Started Sep 2016
136 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 11, 2016
CompletedFirst Posted
Study publicly available on registry
July 13, 2016
CompletedStudy Start
First participant enrolled
September 1, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 19, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
December 17, 2018
CompletedResults Posted
Study results publicly available
December 4, 2019
CompletedDecember 4, 2019
November 1, 2019
2.2 years
July 11, 2016
November 13, 2019
November 13, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Double Blind Phase: Change From Randomization in Disease Activity Score in 28 Joints Using 4 Variables (DAS28-4) (Erythrocyte Sedimentation Rate [ESR]) at Week 48
DAS28 is a measure of disease activity in participants with rheumatoid arthritis. DAS28-4 (ESR) was calculated from swollen joint count (SJC) and tender/painful joint count (TJC) using 28 joints count, ESR (millimeters per hour \[mm/hr\]) and participant global assessment of arthritis (PtGA) on a 100 millimeter (mm) visual analog scale (VAS: scores ranging from 0 mm \[very well\] to 100 mm \[worst\], higher scores indicate worse health condition). Total DAS28-4 (ESR) score range: 0 (none) to 9.4 (extreme disease activity), higher score indicated more disease activity. DAS28-4 (ESR) less than or equal to (\<=) 3.2 implied low disease activity and greater than (\>) 3.2 to \<=5.1 implied moderate disease activity, \>5.1 implied high disease activity, and DAS28-4 (ESR) less than (\<) 2.6 implied remission. DAS28-4 (ESR) = 0.56\*sqrt(TJC28) + 0.28\*sqrt(SJC28) + 0.70\*In(ESR in mm/hour) + 0.014\*PtGA in mm; ln = natural logarithm, sqrt = square root of.
Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Week 48
Secondary Outcomes (23)
Double Blind Phase: Change From Randomization in DAS28-4 ESR at Week 36
Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Week 36
Double Blind Phase: Change From Randomization in DAS28-4 (C-reactive Protein [CRP]) at Weeks 36 and 48
Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48
Double Blind Phase: Change From Randomization in Clinical Disease Activity Index (CDAI) at Weeks 36 and 48
Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48
Double Blind Phase: Change From Randomization in Simplified Disease Activity Index (SDAI) at Weeks 36 and 48
Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48
Double Blind Phase: Percentage of Participants With Low Disease Activity (LDA) Assessed by DAS28-4 (ESR) Less Than or Equal to (<=) 3.2 at Weeks 36 and 48
Weeks 36 and 48
- +18 more secondary outcomes
Other Outcomes (2)
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs
For OL Phase: Baseline up to Week 24; For DB Phase: Week 24 up to Week 52 (up to 28 days after last dose)
Number of Participants With Abnormal Laboratory Parameters
For OL Phase: Baseline up to Week 24; For DB Phase: Week 24 up to Week 48
Study Arms (2)
CP-690,550 and methotrexate
EXPERIMENTALOpen-label tofacitinib tablet and blinded methotrexate capsule
CP-690,550 and placebo
PLACEBO COMPARATORopen-label tofacitinib tablet and blinded matching placebo for methotrexate capsule
Interventions
During the open-label run-in phase (Day 1 to Week 24), all subjects will receive one tablet open-label tofacitinib MR 11mg orally QD and open-label methotrexate capsule(s) orally every week at prior stabilized dose. During the double-blind phase, subjects who are randomized to the treatment arm will receive the same dosage of tofacitinib and methotrexate as describe above.
During the open-label run-in phase (Day 1 to Week 24), all subjects will receive one tablet open-label tofacitinib MR 11mg orally QD and open-label methotrexate capsule(s) orally every week at prior stabilized dose. During the double-blind phase, subjects who are randomized to the treatment arm will receive the same dosage of tofacitinib and methotrexate as describe above.
During the double-blind phase, subjects who are randomized to the comparison arm will receive 11mg QD tofacitinib and the placebo capsules matching for methotrexate.
Eligibility Criteria
You may qualify if:
- \- Must be 18 years of age or older.
- Have a score of 6 or greater on the 2010 American College of Rheumatology/European League Against Rheumatism Classification Criteria for Rheumatoid Arthritis at and/or prior to Screening Visit.
- Have ≥4 tender/painful joints on motion and ≥4 swollen joints (28 joint counts) at both Screening Visit and Baseline Visit (Visit 1).
- Have moderate to severe disease activity as defined by CDAI\>10 and DAS28-4(ESR) ≥3.2 at Baseline Visit.
- Have taken an oral MTX treatment regimen (15-25mg/week) continuously for at least 4 months prior to the screening visit and has taken a stable weekly dose of oral MTX with supplemental folic acid or folinic acid for at least 4 weeks prior to the baseline visit (conversion from parenteral MTX to oral MTX will require stabilization of the treatment regimen for at least 1 month).
- Subjects must screen negative for active tuberculosis or inadequately treated tuberculosis infection (active or latent).
You may not qualify if:
- Pregnant female subjects; breastfeeding female subjects; male subjects with partners currently pregnant; male subjects able to father children and female subjects of childbearing potential who are unwilling or unable to use 2 highly effective methods of contraception as outlined in this protocol for the duration of the study and for at least 3 months after the last dose of investigational product.
- Subjects with infection or infection history; subjects with any current malignancy or a history of malignancy (except adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ); subjects with history of, or current evidence for, severe gastrointestinal narrowing (pathologic or iatrogenic); and subjects with history of documented diverticulitis.
- Subjects with a history of insufficient response to ≥2 biologics, regardless of the class.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Pfizerlead
Study Sites (136)
Rheumatology Associates of North Alabama, PC
Huntsville, Alabama, 35801-4418, United States
Arthrocare, Arthritiscare & Research, PC
Gilbert, Arizona, 85234, United States
SunValley Arthritis Center, Ltd.
Peoria, Arizona, 85381, United States
CHI St. Vincent Medical Group Hot Springs
Hot Springs, Arkansas, 71913, United States
Med Investigations, Inc
Fair Oaks, California, 95628, United States
HCP Clinical Research, LLC
Huntington Beach, California, 92646, United States
Sierra Rheumatology
Roseville, California, 95661, United States
Pacific Arthritis Center Medical Group
Santa Maria, California, 93454, United States
Robin K. Dore, MD, Inc.
Tustin, California, 92780, United States
Inland Rheumatology and Osteoporosis Medical Group
Upland, California, 91786, United States
Inland Rheumatology Clinical Trials, Inc.
Upland, California, 91786, United States
Desert Valley Medical Group
Victorville, California, 92395, United States
AARDS Research Inc
Aventura, Florida, 33180, United States
RASF-Clinical Research Inc
Boca Raton, Florida, 33486, United States
Omega Research Consultants
DeBary, Florida, 32713, United States
University of Florida College of Medicine - Jacksonville - Rheumatology Research
Jacksonville, Florida, 32207, United States
University of Florida, Rheumatology at ACC
Jacksonville, Florida, 32209, United States
Center for Arthritis and Rheumatic Diseases
Miami, Florida, 33173, United States
Jeffrey Alper, MD
Naples, Florida, 34102, United States
Medallion Clinical Research Institute, LLC
Naples, Florida, 34102, United States
Suncoast Clinical Research, Inc.
New Port Richey, Florida, 34652, United States
Florida Arthritis & Osteoporosis Center
Port Richey, Florida, 34668, United States
Gulf Coast Medical Center
Port Richey, Florida, 34668, United States
West Broward Rheumatology Associates, Inc.
Tamarac, Florida, 33321, United States
USF Health Morsani Center for Advanced Healthcare
Tampa, Florida, 33612, United States
BayCare Medical Group, Inc
Tampa, Florida, 33614, United States
Institute of Arthritis Research
Idaho Falls, Idaho, 83404, United States
Quincy Medical Group
Quincy, Illinois, 62301, United States
Beacon Medical Group Rheumatology Main Street
Granger, Indiana, 46530, United States
Diagnostic Rheumatology and Research, PC
Indianapolis, Indiana, 46227, United States
Ochsner Clinic Baton Rouge
Baton Rouge, Louisiana, 70836, United States
Phase III Clinical Research
Fall River, Massachusetts, 02720, United States
Clinical Pharmacology Study Group
Worcester, Massachusetts, 01605, United States
Bronson Internal Medicine and Rheumatology
Battle Creek, Michigan, 49015, United States
Western Michigan University Homer Stryker MD
Kalamazoo, Michigan, 49007, United States
North Mississippi Medical Clinics, Inc. - Clinical Research
Tupelo, Mississippi, 38801, United States
Arthritis & Osteoporosis Associates
Freehold, New Jersey, 07728, United States
Radnet
Marlton, New Jersey, 08053, United States
Arthritis, Rheumatic & Back Disease Associates, P.A.
Voorhees Township, New Jersey, 08043, United States
Open MRI & Diagnostic Imaging of Wall
Wall, New Jersey, 07719, United States
AAIR Research Center
Rochester, New York, 14618, United States
Physicians East, PA
Greenville, North Carolina, 27834, United States
PMG Research of Salisbury
Salisbury, North Carolina, 28144, United States
Trinity Health Center-Medical Arts
Minot, North Dakota, 58701, United States
Group Health Associates
Cincinnati, Ohio, 45236, United States
Cincinnati Rheumatic Disease Study Group, Inc.
Cincinnati, Ohio, 45242, United States
STAT Research, Inc.
Dayton, Ohio, 45417, United States
Health Research of Oklahoma
Oklahoma City, Oklahoma, 73103, United States
Oklahoma Medical Research Foundation (OMRF)
Oklahoma City, Oklahoma, 73104, United States
Lynn Health Science Institute
Oklahoma City, Oklahoma, 73112, United States
East Penn Rheumatology Associates, P.C.
Bethlehem, Pennsylvania, 18015, United States
Altoona Center for Clinical Research
Duncansville, Pennsylvania, 16635, United States
Piedmont Arthritis Clinic
Greenville, South Carolina, 29601, United States
Articularis Healthcare Group dba ACME Research
Orangeburg, South Carolina, 29118, United States
Articularis Healthcare Group d/b/a Low Country Rheumatology
Summerville, South Carolina, 29486, United States
Pioneer Research Solutions, Inc.
Cypress, Texas, 77429, United States
Metroplex Clinical Research Center
Dallas, Texas, 75231, United States
Center for Arthritis and Rheumatic Diseases
Chesapeake, Virginia, 23320, United States
Center for Arthritis and Rheumatic Diseases
Suffolk, Virginia, 23435, United States
Genesis Research Services Pty Ltd
Broadmeadow, New South Wales, 2292, Australia
Optimus Clinical Research Pty Ltd
Kogarah, New South Wales, 2217, Australia
Rheumatology Research Unit
Maroochydore, Queensland, 4558, Australia
Emeritus Research
Melbourne, Victoria, 3124, Australia
ReumaClinic
Genk, 3600, Belgium
AZ Delta
Roeselare, 8800, Belgium
University Multiprofile Hospital for Active Treatment Dr. G. Stranski EAD
Pleven, 5800, Bulgaria
Multiprofile Hospital for Active Treatment - Plovdiv AD, Rheumatology Department
Plovdiv, 4000, Bulgaria
Multiprofile Hospital for Active Treatment Trimontium OOD
Plovdiv, 4000, Bulgaria
University Multiprofile Hospital for Active Treatment - Kaspela EOOD
Plovdiv, 4001, Bulgaria
National Multiprofile Transport Hospital Tsar Boris III
Sofia, 1233, Bulgaria
Medical Centre Synexus Sofia EOOD
Sofia, 1784, Bulgaria
CCBR Czech Brno, s.r.o.
Brno, Czech Republic, 602 00, Czechia
LEKARNA LANCIER s.r.o.
Brno, 602 00, Czechia
Lekarna Na Lidicke
Brno, 602 00, Czechia
Revmacentrum MUDr. Mostera, s.r.o., Revmatologie a interna
Brno, 615 00, Czechia
CCBR Ostrava, s.r.o.
Ostrava, 702 00, Czechia
Lekarna Rezidence Nova Karolina
Ostrava, 702 00, Czechia
Revmatologicky ustav, Lekrna
Prague, 128 50, Czechia
Revmatologicky ustav
Prague, 128 50, Czechia
Lekarna Hradebni s.r.o.
UherskĂ© HradiÅ¡tÄ›, 686 01, Czechia
MEDICAL PLUS, s.r.o. Revmatologicka a osteologicka ambulance
UherskĂ© HradiÅ¡tÄ›, 686 01, Czechia
PV - MEDICAL s.r.o., Revmatologicka ambulance
ZlĂn, 760 01, Czechia
Revmavita s.r.o, Lekarna
ZlĂn, 760 01, Czechia
Hamburger Rheuma Forschungszentrum I
Hamburg, 22391, Germany
DRC Gyogyszervizsgalo Kozpont Kft.
BalatonfĂ¼red, 8230, Hungary
Revita Rendelo
Budapest, 1027, Hungary
Qualiclinic Kft.
Budapest, 1036, Hungary
CRU Hungary Kft.
Miskolc, 3529, Hungary
Morales Vargas Centro de Investigacion SC (Consultorio Anexo)
LeĂ³n, Guanajuato, 37000, Mexico
Centro de Investigacion y Tratamiento Reumatologico SC Consultorio Medico de Reumatologia (CINTRE)
Mexico City, Mexico City, 11850, Mexico
Mary Mediatrix Medical Center
Lipa City, Batangas, 4217, Philippines
Far Eastern University - Nicanor Reyes Medical Foundation, Marian Medical Arts Bldg
Quezon City, National Capital Region, 1118, Philippines
Zdrowie OSTEO-MEDIC s.c. L i A. Racewicz, A i J. Supronik
Bialystok, 15-351, Poland
ClinicMed Daniluk, Nowak. Sp. j.
Bialystok, 15-879, Poland
Nzoz Bif - Med
Bytom, 41-902, Poland
Centrum Medyczne Pratia Krakow
Krakow, 30-002, Poland
Malopolskie Centrum Medyczne S.C.
Krakow, 30-510, Poland
NZOZ Lecznica MAK-MED. S.C.
Nadarzyn, 05-830, Poland
MTZ Clinical Research Sp. z o.o.
Warsaw, 02-106, Poland
Federal State Budgetary Scientific Institution "Research Institute of Rheumatology
Moscow, 115522, Russia
FSBEI HE "Orenburg State Medical University" of MoH RF
Orenburg, 460000, Russia
FSBEI HE "Orenburg State Medical University" of MoH RF
Orenburg, 460018, Russia
FSBIH "Clinical Hospital #122 n.a. L.G. Sokolov" of FMBA of Russia
Saint Petersburg, 194291, Russia
SPb SBIH "Consultative-Diagnostic Centre #85"
Saint Petersburg, 198260, Russia
SBIH "Samara Regional Clinical Hospital n.a. V.D. Seredavin"
Samara, 443095, Russia
NSHI "Departmental Hospital at Smolensk station OJSC "Russian Railways"
Smolensk, 214025, Russia
SAHI YR Clinical Hospital of Emergency Medical Care n.a. N.V. Soloviev
Yaroslavl, 150003, Russia
State Budgetary Institution of Healthcare of Yaroslavl Region "Regional Clinical Hospital"
Yaroslavl, 150062, Russia
AAGS s.r.o.
DunajskĂ¡ Streda, 929 01, Slovakia
MEDMAN s.r.o.
Martin, 03601, Slovakia
REUMACENTRUM s.r.o.
PartizĂ¡nske, 958 01, Slovakia
MUDr. Zuzana Cizmarikova, s.r.o.
Poprad, 05801, Slovakia
Reumex s.r.o
RimavskĂ¡ Sobota, 979 01, Slovakia
St. Augustine's Hospital
Durban, KwaZulu-Natal, 4001, South Africa
Clinical Trial Pharmacy, KyungHee University Hospital
Seoul, 02447, South Korea
KyungHee University Hospital
Seoul, 02447, South Korea
CTC Pharmacy, Seoul National University Hospital
Seoul, 03080, South Korea
Seoul National University Hospital
Seoul, 03080, South Korea
Konkuk University Medical Center
Seoul, 05030, South Korea
Clinical Trial Pharmacy, The Catholic University of Korea, Seoul St. Mary's Hospital
Seoul, 06591, South Korea
The Catholic University of Korea Seoul, St. Mary's Hospital
Seoul, 06591, South Korea
Complejo Hospitalario Universitario de Santiago
Santiago de Compostela, A Coruna, 15706, Spain
Hospital Universitario de Cruces
Barakaldo, Vizcaya, 48903, Spain
Hospital Infanta Luisa
Seville, 41010, Spain
Countess of Chester Hospital NHS Foundation Trust
Chester, Cheshire, CH2 1UL, United Kingdom
Pharmacy (dispensary)
Chester, Cheshire, CH2 1UL, United Kingdom
Countess of Chester Hospital NHS Foundation Trust
Ellesmere Port, Cheshire, CH65 6SG, United Kingdom
Hampshire Hospitals NHS Foundation Trust
Basingstoke, Hampshire, RG24 9NA, United Kingdom
Pharmacy, Hampshire Hospitals NHS Foundation Trust
Basingstoke, Hampshire, RG24 9NA, United Kingdom
Department of Rheumatology, Wirral University Teaching Hospital NHS Foundation Trust
Metropolitan Borough of Wirral, Merseyside, CH49 5PE, United Kingdom
Pharmacy Department, Wirral University Teaching Hospital NHS Foundation Trust
Metropolitan Borough of Wirral, Merseyside, CH49 5PE, United Kingdom
Wirral University Teaching Hospital NHS Foundation Trust
Metropolitan Borough of Wirral, Merseyside, CH49 5PE, United Kingdom
Pharmacy Department
Dudley, WEST Midlands, DY1 2HQ, United Kingdom
The Dudley Group NHS Foundation Trust
Dudley, WEST Midlands, DY1 2HQ, United Kingdom
Pharmacy
Manchester, M23 9LT, United Kingdom
University Hospital of South Manchester NHS Foundation Trust
Manchester, M23 9LT, United Kingdom
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PMID: 36600185DERIVEDFleischmann R, Haraoui B, Buch MH, Gold D, Sawyerr G, Shi H, Diehl A, Lee K. Analysis of Disease Activity Metrics in a Methotrexate Withdrawal Study among Patients with Rheumatoid Arthritis Treated with Tofacitinib plus Methotrexate. Rheumatol Ther. 2023 Apr;10(2):375-386. doi: 10.1007/s40744-022-00511-3. Epub 2022 Dec 19.
PMID: 36534208DERIVEDWinthrop 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.
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Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Pfizer ClinicalTrials.gov Call Center
- Organization
- Pfizer Inc.
Study Officials
- STUDY DIRECTOR
Pfizer CT.gov Call Center
Pfizer
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 4
- 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 11, 2016
First Posted
July 13, 2016
Study Start
September 1, 2016
Primary Completion
November 19, 2018
Study Completion
December 17, 2018
Last Updated
December 4, 2019
Results First Posted
December 4, 2019
Record last verified: 2019-11
Data Sharing
- IPD Sharing
- Will share
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.