Clinical trial NCT02831855: Methotrexate Withdrawal Study of Tofacitinib Modified Release Formulation in Subjects With Rheumatoid Arthritis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Rheumatoid Arthritis
Keywords: Rheumatoid Arthritis
Tofacitinib
CP-690,550
Xeljanz
methotrexate withdrawal
withdrawal study
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2016-07-13
Enrollment: 694
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: 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.


Eligibility criteria: Key Inclusion Criteria

- 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).

Key Exclusion Criteria

* 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.

Primary outcomes:
measure: 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
timeFrame: Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Week 48
Secondary outcomes:
measure: Double Blind Phase: Change From Randomization in DAS28-4 ESR at Week 36
timeFrame: Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Week 36
measure: Double Blind Phase: Change From Randomization in DAS28-4 (C-reactive Protein [CRP]) at Weeks 36 and 48
timeFrame: Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48
measure: Double Blind Phase: Change From Randomization in Clinical Disease Activity Index (CDAI) at Weeks 36 and 48
timeFrame: Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48
measure: Double Blind Phase: Change From Randomization in Simplified Disease Activity Index (SDAI) at Weeks 36 and 48
timeFrame: Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48
measure: 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
timeFrame: Weeks 36 and 48
measure: Double Blind Phase: Percentage of Participants With LDA Assessed by DAS28-4 (CRP) <=3.2 at Weeks 36 and 48
timeFrame: Weeks 36 and 48
measure: Double Blind Phase: Percentage of Participants With LDA Assessed by CDAI <=10 at Weeks 36 and 48
timeFrame: Weeks 36 and 48
measure: Double Blind Phase: Percentage of Participants With LDA Assessed by SDAI <=11 at Weeks 36 and 48
timeFrame: Weeks 36 and 48
measure: Double Blind Phase: Percentage of Participants With Remission Assessed by American College of Rheumatology-European League Against Rheumatism (ACR-EULAR) Boolean at Weeks 36 and 48
timeFrame: Weeks 36 and 48
measure: Double Blind Phase: Percentage of Participants With Remission Assessed by DAS28-4 (ESR) Less Than [<] 2.6 at Weeks 36 and 48
timeFrame: Weeks 36 and 48
measure: Double Blind Phase: Percentage of Participants With Remission Assessed by DAS28-4 (CRP) <2.6 at Weeks 36 and 48
timeFrame: Weeks 36 and 48
measure: Double Blind Phase: Percentage of Participants With Remission Assessed by CDAI <=2.8 at Weeks 36 and 48
timeFrame: Weeks 36 and 48
measure: Double Blind Phase: Percentage of Participants With Remission Assessed by SDAI <=3.3 at Weeks 36 and 48
timeFrame: Weeks 36 and 48
measure: Double Blind Phase: Percentage of Participants Achieving an American College of Rheumatology 20 Percent (%) (ACR20) Response at Weeks 36 and 48
timeFrame: Baseline (Day 1), Weeks 36 and 48
measure: Double Blind Phase: Percentage of Participants Achieving an American College of Rheumatology 50% (ACR50) Response at Weeks 36 and 48
timeFrame: Baseline (Day 1), Weeks 36 and 48
measure: Double Blind Phase: Percentage of Participants Achieving an American College of Rheumatology 70% (ACR70) Response at Weeks 36 and 48
timeFrame: Baseline (Day 1), Weeks 36 and 48
measure: Double Blind Phase: Change From Randomization in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Weeks 36 and 48
timeFrame: Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48
measure: Double Blind Phase: Change From Randomization in the Short Form 36 (SF-36) Health Survey 8 Domain Scores at Weeks 36 and 48
timeFrame: Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48
measure: Double Blind Phase: Change From Randomization in the SF-36 Health Survey Component Scores at Weeks 36 and 48
timeFrame: Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48
measure: Double Blind Phase: Change From Randomization in the Work Productivity and Activity Impairment (WPAI) Scores at Week 36 and 48
timeFrame: Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Week 36 and 48
measure: Double Blind Phase: Change From Randomization in the European Quality of Life - 5 Dimensions Questionnaire (EQ-5D) Scores at Weeks 36 and 48
timeFrame: Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48
measure: Double Blind Phase: Change From Randomization in the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Scores at Weeks 36 and 48
timeFrame: Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48
measure: Double Blind Phase: Percentage of Participants Achieving an Improvement of at Least 0.22 Units in HAQ-DI at Weeks 36 and 48
timeFrame: Baseline (Day 1), Weeks 36 and 48
Other outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs
timeFrame: For OL Phase: Baseline up to Week 24; For DB Phase: Week 24 up to Week 52 (up to 28 days after last dose)
measure: Number of Participants With Abnormal Laboratory Parameters
timeFrame: For OL Phase: Baseline up to Week 24; For DB Phase: Week 24 up to Week 48
Locations:
city: Huntsville
country: United States
facility: Rheumatology Associates of North Alabama, PC
state: Alabama
city: Gilbert
country: United States
facility: Arthrocare, Arthritiscare & Research, PC
state: Arizona
city: Peoria
country: United States
facility: SunValley Arthritis Center, Ltd.
state: Arizona
city: Hot Springs
country: United States
facility: CHI St. Vincent Medical Group Hot Springs
state: Arkansas
city: Fair Oaks
country: United States
facility: Med Investigations, Inc
state: California
city: Huntington Beach
country: United States
facility: HCP Clinical Research, LLC
state: California
city: Roseville
country: United States
facility: Sierra Rheumatology
state: California
city: Santa Maria
country: United States
facility: Pacific Arthritis Center Medical Group
state: California
city: Tustin
country: United States
facility: Robin K. Dore, MD, Inc.
state: California
city: Upland
country: United States
facility: Inland Rheumatology and Osteoporosis Medical Group
state: California
city: Upland
country: United States
facility: Inland Rheumatology Clinical Trials, Inc.
state: California
city: Victorville
country: United States
facility: Desert Valley Medical Group
state: California
city: Aventura
country: United States
facility: AARDS Research Inc
state: Florida
city: Boca Raton
country: United States
facility: RASF-Clinical Research Inc
state: Florida
city: DeBary
country: United States
facility: Omega Research Consultants
state: Florida
city: Jacksonville
country: United States
facility: University of Florida College of Medicine - Jacksonville - Rheumatology Research
state: Florida
city: Jacksonville
country: United States
facility: University of Florida, Rheumatology at ACC
state: Florida
city: Miami
country: United States
facility: Center for Arthritis and Rheumatic Diseases
state: Florida
city: Naples
country: United States
facility: Jeffrey Alper, MD
state: Florida
city: Naples
country: United States
facility: Medallion Clinical Research Institute, LLC
state: Florida
city: New Port Richey
country: United States
facility: Suncoast Clinical Research, Inc.
state: Florida
city: Port Richey
country: United States
facility: Florida Arthritis & Osteoporosis Center
state: Florida
city: Port Richey
country: United States
facility: Gulf Coast Medical Center
state: Florida
city: Tamarac
country: United States
facility: West Broward Rheumatology Associates, Inc.
state: Florida
city: Tampa
country: United States
facility: USF Health Morsani Center for Advanced Healthcare
state: Florida
city: Tampa
country: United States
facility: BayCare Medical Group, Inc
state: Florida
city: Idaho Falls
country: United States
facility: Institute of Arthritis Research
state: Idaho
city: Quincy
country: United States
facility: Quincy Medical Group
state: Illinois
city: Granger
country: United States
facility: Beacon Medical Group Rheumatology Main Street
state: Indiana
city: Indianapolis
country: United States
facility: Diagnostic Rheumatology and Research, PC
state: Indiana
city: Baton Rouge
country: United States
facility: Ochsner Clinic Baton Rouge
state: Louisiana
city: Fall River
country: United States
facility: Phase III Clinical Research
state: Massachusetts
city: Worcester
country: United States
facility: Clinical Pharmacology Study Group
state: Massachusetts
city: Battle Creek
country: United States
facility: Bronson Internal Medicine and Rheumatology
state: Michigan
city: Kalamazoo
country: United States
facility: Western Michigan University Homer Stryker MD
state: Michigan
city: Tupelo
country: United States
facility: North Mississippi Medical Clinics, Inc. - Clinical Research
state: Mississippi
city: Freehold
country: United States
facility: Arthritis & Osteoporosis Associates
state: New Jersey
city: Marlton
country: United States
facility: Radnet
state: New Jersey
city: Voorhees
country: United States
facility: Arthritis, Rheumatic & Back Disease Associates, P.A.
state: New Jersey
city: Wall
country: United States
facility: Open MRI & Diagnostic Imaging of Wall
state: New Jersey
city: Rochester
country: United States
facility: AAIR Research Center
state: New York
city: Greenville
country: United States
facility: Physicians East, PA
state: North Carolina
city: Salisbury
country: United States
facility: PMG Research of Salisbury
state: North Carolina
city: Minot
country: United States
facility: Trinity Health Center-Medical Arts
state: North Dakota
city: Cincinnati
country: United States
facility: Group Health Associates
state: Ohio
city: Cincinnati
country: United States
facility: Cincinnati Rheumatic Disease Study Group, Inc.
state: Ohio
city: Dayton
country: United States
facility: STAT Research, Inc.
state: Ohio
city: Oklahoma City
country: United States
facility: Health Research of Oklahoma
state: Oklahoma
city: Oklahoma City
country: United States
facility: Oklahoma Medical Research Foundation (OMRF)
state: Oklahoma
city: Oklahoma City
country: United States
facility: Lynn Health Science Institute
state: Oklahoma
city: Bethlehem
country: United States
facility: East Penn Rheumatology Associates, P.C.
state: Pennsylvania
city: Duncansville
country: United States
facility: Altoona Center for Clinical Research
state: Pennsylvania
city: Greenville
country: United States
facility: Piedmont Arthritis Clinic
state: South Carolina
city: Orangeburg
country: United States
facility: Articularis Healthcare Group dba ACME Research
state: South Carolina
city: Summerville
country: United States
facility: Articularis Healthcare Group d/b/a Low Country Rheumatology
state: South Carolina
city: Cypress
country: United States
facility: Pioneer Research Solutions, Inc.
state: Texas
city: Dallas
country: United States
facility: Metroplex Clinical Research Center
state: Texas
city: Chesapeake
country: United States
facility: Center for Arthritis and Rheumatic Diseases
state: Virginia
city: Suffolk
country: United States
facility: Center for Arthritis and Rheumatic Diseases
state: Virginia
city: Broadmeadow
country: Australia
facility: Genesis Research Services Pty Ltd
state: New South Wales
city: Kogarah
country: Australia
facility: Optimus Clinical Research Pty Ltd
state: New South Wales
city: Maroochydore
country: Australia
facility: Rheumatology Research Unit
state: Queensland
city: Melbourne
country: Australia
facility: Emeritus Research
state: Victoria
city: Genk
country: Belgium
facility: ReumaClinic
city: Roeselare
country: Belgium
facility: AZ Delta
city: Pleven
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment Dr. G. Stranski EAD
city: Plovdiv
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment - Plovdiv AD, Rheumatology Department
city: Plovdiv
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment Trimontium OOD
city: Plovdiv
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment - Kaspela EOOD
city: Sofia
country: Bulgaria
facility: National Multiprofile Transport Hospital Tsar Boris III
city: Sofia
country: Bulgaria
facility: Medical Centre Synexus Sofia EOOD
city: Brno
country: Czechia
facility: CCBR Czech Brno, s.r.o.
state: Czech Republic
city: Brno
country: Czechia
facility: LEKARNA LANCIER s.r.o.
city: Brno
country: Czechia
facility: Lekarna Na Lidicke
city: Brno
country: Czechia
facility: Revmacentrum MUDr. Mostera, s.r.o., Revmatologie a interna
city: Ostrava
country: Czechia
facility: CCBR Ostrava, s.r.o.
city: Ostrava
country: Czechia
facility: Lekarna Rezidence Nova Karolina
city: Praha 2
country: Czechia
facility: Revmatologicky ustav, Lekrna
city: Praha 2
country: Czechia
facility: Revmatologicky ustav
city: Uherske Hradiste
country: Czechia
facility: Lekarna Hradebni s.r.o.
city: Uherske Hradiste
country: Czechia
facility: MEDICAL PLUS, s.r.o. Revmatologicka a osteologicka ambulance
city: Zlin
country: Czechia
facility: PV - MEDICAL s.r.o., Revmatologicka ambulance
city: Zlin
country: Czechia
facility: Revmavita s.r.o, Lekarna
city: Hamburg
country: Germany
facility: Hamburger Rheuma Forschungszentrum I
city: Balatonfured
country: Hungary
facility: DRC Gyogyszervizsgalo Kozpont Kft.
city: Budapest
country: Hungary
facility: Revita Rendelo
city: Budapest
country: Hungary
facility: Qualiclinic Kft.
city: Miskolc
country: Hungary
facility: CRU Hungary Kft.
city: Seoul
country: Korea, Republic of
facility: Clinical Trial Pharmacy, KyungHee University Hospital
city: Seoul
country: Korea, Republic of
facility: KyungHee University Hospital
city: Seoul
country: Korea, Republic of
facility: CTC Pharmacy, Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Konkuk University Medical Center
city: Seoul
country: Korea, Republic of
facility: Clinical Trial Pharmacy, The Catholic University of Korea, Seoul St. Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea Seoul, St. Mary's Hospital
city: Mexico
country: Mexico
facility: Centro de Investigacion y Tratamiento Reumatologico SC Consultorio Medico de Reumatologia (CINTRE)
state: Ciudad DE Mexico
city: Leon
country: Mexico
facility: Morales Vargas Centro de Investigacion SC (Consultorio Anexo)
state: Guanajuato
city: Lipa City
country: Philippines
facility: Mary Mediatrix Medical Center
state: Batangas
city: Quezon City
country: Philippines
facility: Far Eastern University - Nicanor Reyes Medical Foundation, Marian Medical Arts Bldg
state: Metro Manila
city: Bialystok
country: Poland
facility: Zdrowie OSTEO-MEDIC s.c. L i A. Racewicz, A i J. Supronik
city: Bialystok
country: Poland
facility: ClinicMed Daniluk, Nowak. Sp. j.
city: Bytom
country: Poland
facility: Nzoz Bif - Med
city: Krakow
country: Poland
facility: Centrum Medyczne Pratia Krakow
city: Krakow
country: Poland
facility: Malopolskie Centrum Medyczne S.C.
city: Nadarzyn
country: Poland
facility: NZOZ Lecznica MAK-MED. S.C.
city: Warszawa
country: Poland
facility: MTZ Clinical Research Sp. z o.o.
city: Moscow
country: Russian Federation
facility: Federal State Budgetary Scientific Institution "Research Institute of Rheumatology
city: Orenburg
country: Russian Federation
facility: FSBEI HE "Orenburg State Medical University" of MoH RF
city: Orenburg
country: Russian Federation
facility: FSBEI HE "Orenburg State Medical University" of MoH RF
city: Saint Petersburg
country: Russian Federation
facility: SPb SBIH "Consultative-Diagnostic Centre #85"
city: Saint-Petersburg
country: Russian Federation
facility: FSBIH "Clinical Hospital #122 n.a. L.G. Sokolov" of FMBA of Russia
city: Samara
country: Russian Federation
facility: SBIH "Samara Regional Clinical Hospital n.a. V.D. Seredavin"
city: Smolensk
country: Russian Federation
facility: NSHI "Departmental Hospital at Smolensk station OJSC "Russian Railways"
city: Yaroslavl
country: Russian Federation
facility: SAHI YR Clinical Hospital of Emergency Medical Care n.a. N.V. Soloviev
city: Yaroslavl
country: Russian Federation
facility: State Budgetary Institution of Healthcare of Yaroslavl Region "Regional Clinical Hospital"
city: Dunajska Streda
country: Slovakia
facility: AAGS s.r.o.
city: Martin
country: Slovakia
facility: MEDMAN s.r.o.
city: Partizanske
country: Slovakia
facility: REUMACENTRUM s.r.o.
city: Poprad
country: Slovakia
facility: MUDr. Zuzana Cizmarikova, s.r.o.
city: Rimavska Sobota
country: Slovakia
facility: Reumex s.r.o
city: Durban
country: South Africa
facility: St. Augustine's Hospital
state: Kwazulu Natal
city: Santiago de Compostela
country: Spain
facility: Complejo Hospitalario Universitario de Santiago
state: A Coruna
city: Baracaldo
country: Spain
facility: Hospital Universitario de Cruces
state: Vizcaya
city: Sevilla
country: Spain
facility: Hospital Infanta Luisa
city: Chester
country: United Kingdom
facility: Countess of Chester Hospital NHS Foundation Trust
state: Cheshire
city: Chester
country: United Kingdom
facility: Pharmacy (dispensary)
state: Cheshire
city: Ellesmere Port
country: United Kingdom
facility: Countess of Chester Hospital NHS Foundation Trust
state: Cheshire
city: Basingstoke
country: United Kingdom
facility: Hampshire Hospitals NHS Foundation Trust
state: Hampshire
city: Basingstoke
country: United Kingdom
facility: Pharmacy, Hampshire Hospitals NHS Foundation Trust
state: Hampshire
city: Wirral
country: United Kingdom
facility: Department of Rheumatology, Wirral University Teaching Hospital NHS Foundation Trust
state: Merseyside
city: Wirral
country: United Kingdom
facility: Pharmacy Department, Wirral University Teaching Hospital NHS Foundation Trust
state: Merseyside
city: Wirral
country: United Kingdom
facility: Wirral University Teaching Hospital NHS Foundation Trust
state: Merseyside
city: Dudley
country: United Kingdom
facility: Pharmacy Department
state: WEST Midlands
city: Dudley
country: United Kingdom
facility: The Dudley Group NHS Foundation Trust
state: WEST Midlands
city: Manchester
country: United Kingdom
facility: Pharmacy
city: Manchester
country: United Kingdom
facility: University Hospital of South Manchester NHS Foundation Trust
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
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