Methotrexate Withdrawal Study of Tofacitinib Modified Release Formulation in Subjects With Rheumatoid Arthritis

November 13, 2019 updated by: Pfizer

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

694

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Broadmeadow, New South Wales, Australia, 2292
        • Genesis Research Services Pty Ltd
      • Kogarah, New South Wales, Australia, 2217
        • Optimus Clinical Research Pty Ltd
    • Queensland
      • Maroochydore, Queensland, Australia, 4558
        • Rheumatology Research Unit
    • Victoria
      • Melbourne, Victoria, Australia, 3124
        • Emeritus Research
  • Belgium
      • Genk, Belgium, 3600
        • ReumaClinic
      • Roeselare, Belgium, 8800
        • Az Delta
  • Bulgaria
      • Pleven, Bulgaria, 5800
        • University Multiprofile Hospital for Active Treatment Dr. G. Stranski EAD
      • Plovdiv, Bulgaria, 4000
        • Multiprofile Hospital for Active Treatment Trimontium OOD
      • Plovdiv, Bulgaria, 4000
        • Multiprofile Hospital for Active Treatment - Plovdiv AD, Rheumatology Department
      • Plovdiv, Bulgaria, 4001
        • University Multiprofile Hospital for Active Treatment - Kaspela EOOD
      • Sofia, Bulgaria, 1784
        • Medical Centre Synexus Sofia EOOD
      • Sofia, Bulgaria, 1233
        • National Multiprofile Transport Hospital Tsar Boris III
  • Czechia
      • Brno, Czechia, 602 00
        • LEKARNA LANCIER s.r.o.
      • Brno, Czechia, 602 00
        • Lekarna Na Lidicke
      • Brno, Czechia, 615 00
        • Revmacentrum MUDr. Mostera, s.r.o., Revmatologie a interna
      • Ostrava, Czechia, 702 00
        • Lekarna Rezidence Nova Karolina
      • Ostrava, Czechia, 702 00
        • CCBR Ostrava, s.r.o.
      • Praha 2, Czechia, 128 50
        • Revmatologicky Ustav
      • Praha 2, Czechia, 128 50
        • Revmatologicky ustav, Lekrna
      • Uherske Hradiste, Czechia, 686 01
        • Lekarna Hradebni s.r.o.
      • Uherske Hradiste, Czechia, 686 01
        • MEDICAL PLUS, s.r.o. Revmatologicka a osteologicka ambulance
      • Zlin, Czechia, 760 01
        • PV - MEDICAL s.r.o., Revmatologicka ambulance
      • Zlin, Czechia, 760 01
        • Revmavita s.r.o, Lekarna
    • Czech Republic
      • Brno, Czech Republic, Czechia, 602 00
        • CCBR Czech Brno, s.r.o.
  • Germany
      • Hamburg, Germany, 22391
        • Hamburger Rheuma Forschungszentrum I
  • Hungary
      • Balatonfured, Hungary, 8230
        • DRC Gyogyszervizsgalo Kozpont Kft.
      • Budapest, Hungary, 1036
        • Qualiclinic Kft.
      • Budapest, Hungary, 1027
        • Revita Rendelo
      • Miskolc, Hungary, 3529
        • CRU Hungary Kft.
  • Korea, Republic of
      • Seoul, Korea, Republic of, 03080
        • Seoul National University Hospital
      • Seoul, Korea, Republic of, 05030
        • Konkuk University Medical Center
      • Seoul, Korea, Republic of, 02447
        • KyungHee University Hospital
      • Seoul, Korea, Republic of, 02447
        • Clinical Trial Pharmacy, KyungHee University Hospital
      • Seoul, Korea, Republic of, 03080
        • CTC Pharmacy, Seoul National University Hospital
      • Seoul, Korea, Republic of, 06591
        • Clinical Trial Pharmacy, The Catholic University of Korea, Seoul St. Mary's Hospital
      • Seoul, Korea, Republic of, 06591
        • The Catholic University of Korea Seoul, St. Mary's Hospital
  • Mexico
    • Ciudad DE Mexico
      • Mexico, Ciudad DE Mexico, Mexico, 11850
        • Centro de Investigacion y Tratamiento Reumatologico SC Consultorio Medico de Reumatologia (CINTRE)
    • Guanajuato
      • Leon, Guanajuato, Mexico, 37000
        • Morales Vargas Centro de Investigacion SC (Consultorio Anexo)
  • Philippines
    • Batangas
      • Lipa City, Batangas, Philippines, 4217
        • Mary Mediatrix Medical Center
    • Metro Manila
      • Quezon City, Metro Manila, Philippines, 1118
        • Far Eastern University - Nicanor Reyes Medical Foundation, Marian Medical Arts Bldg
  • Poland
      • Bialystok, Poland, 15-351
        • Zdrowie OSTEO-MEDIC s.c. L i A. Racewicz, A i J. Supronik
      • Bialystok, Poland, 15-879
        • ClinicMed Daniluk, Nowak. Sp. j.
      • Bytom, Poland, 41-902
        • Nzoz Bif - Med
      • Krakow, Poland, 30-510
        • Malopolskie Centrum Medyczne s.c.
      • Krakow, Poland, 30-002
        • Centrum Medyczne Pratia Krakow
      • Nadarzyn, Poland, 05-830
        • NZOZ Lecznica MAK-MED. S.C.
      • Warszawa, Poland, 02-106
        • MTZ Clinical Research Sp. z o.o.
  • Russian Federation
      • Moscow, Russian Federation, 115522
        • Federal State Budgetary Scientific Institution "Research Institute of Rheumatology
      • Orenburg, Russian Federation, 460000
        • FSBEI HE "Orenburg State Medical University" of MoH RF
      • Orenburg, Russian Federation, 460018
        • FSBEI HE "Orenburg State Medical University" of MoH RF
      • Saint Petersburg, Russian Federation, 198260
        • SPb SBIH "Consultative-Diagnostic Centre #85"
      • Saint-Petersburg, Russian Federation, 194291
        • FSBIH "Clinical Hospital #122 n.a. L.G. Sokolov" of FMBA of Russia
      • Samara, Russian Federation, 443095
        • SBIH "Samara Regional Clinical Hospital n.a. V.D. Seredavin"
      • Smolensk, Russian Federation, 214025
        • NSHI "Departmental Hospital at Smolensk station OJSC "Russian Railways"
      • Yaroslavl, Russian Federation, 150003
        • SAHI YR Clinical Hospital of Emergency Medical Care n.a. N.V. Soloviev
      • Yaroslavl, Russian Federation, 150062
        • State Budgetary Institution of Healthcare of Yaroslavl Region "Regional Clinical Hospital"
  • Slovakia
      • Dunajska Streda, Slovakia, 929 01
        • AAGS s.r.o.
      • Martin, Slovakia, 03601
        • MEDMAN s.r.o.
      • Partizanske, Slovakia, 958 01
        • Reumacentrum s.r.o.
      • Poprad, Slovakia, 05801
        • MUDr. Zuzana Cizmarikova, s.r.o.
      • Rimavska Sobota, Slovakia, 979 01
        • Reumex s.r.o
  • South Africa
    • Kwazulu Natal
      • Durban, Kwazulu Natal, South Africa, 4001
        • St. Augustine's Hospital
  • Spain
      • Sevilla, Spain, 41010
        • Hospital Infanta Luisa
    • A Coruna
      • Santiago de Compostela, A Coruna, Spain, 15706
        • Complejo Hospitalario Universitario de Santiago
    • Vizcaya
      • Baracaldo, Vizcaya, Spain, 48903
        • Hospital Universitario de Cruces
  • United Kingdom
      • Manchester, United Kingdom, M23 9LT
        • University Hospital of South Manchester NHS Foundation Trust
      • Manchester, United Kingdom, M23 9LT
        • Pharmacy
    • Cheshire
      • Chester, Cheshire, United Kingdom, CH2 1UL
        • Countess Of Chester Hospital NHS Foundation Trust
      • Chester, Cheshire, United Kingdom, CH2 1UL
        • Pharmacy (dispensary)
      • Ellesmere Port, Cheshire, United Kingdom, CH65 6SG
        • Countess Of Chester Hospital NHS Foundation Trust
    • Hampshire
      • Basingstoke, Hampshire, United Kingdom, RG24 9NA
        • Hampshire Hospitals NHS Foundation Trust
      • Basingstoke, Hampshire, United Kingdom, RG24 9NA
        • Pharmacy, Hampshire Hospitals NHS Foundation Trust
    • Merseyside
      • Wirral, Merseyside, United Kingdom, CH49 5PE
        • Department of Rheumatology, Wirral University Teaching Hospital NHS Foundation Trust
      • Wirral, Merseyside, United Kingdom, CH49 5PE
        • Pharmacy Department, Wirral University Teaching Hospital NHS Foundation Trust
      • Wirral, Merseyside, United Kingdom, CH49 5PE
        • Wirral University Teaching Hospital NHS Foundation Trust
    • WEST Midlands
      • Dudley, WEST Midlands, United Kingdom, DY1 2HQ
        • Pharmacy Department
      • Dudley, WEST Midlands, United Kingdom, DY1 2HQ
        • The Dudley Group NHS Foundation Trust
  • United States
    • Alabama
      • Huntsville, Alabama, United States, 35801-4418
        • Rheumatology Associates of North Alabama, PC
    • Arizona
      • Gilbert, Arizona, United States, 85234
        • Arthrocare, Arthritiscare & Research, PC
      • Peoria, Arizona, United States, 85381
        • SunValley Arthritis Center, Ltd.
    • Arkansas
      • Hot Springs, Arkansas, United States, 71913
        • CHI St. Vincent Medical Group Hot Springs
    • California
      • Fair Oaks, California, United States, 95628
        • Med Investigations, Inc
      • Huntington Beach, California, United States, 92646
        • HCP Clinical Research, LLC
      • Roseville, California, United States, 95661
        • Sierra Rheumatology
      • Santa Maria, California, United States, 93454
        • Pacific Arthritis Center Medical Group
      • Tustin, California, United States, 92780
        • Robin K. Dore, MD, Inc.
      • Upland, California, United States, 91786
        • Inland Rheumatology Clinical Trials, Inc.
      • Upland, California, United States, 91786
        • Inland Rheumatology and Osteoporosis Medical Group
      • Victorville, California, United States, 92395
        • Desert Valley Medical Group
    • Florida
      • Aventura, Florida, United States, 33180
        • AARDS Research Inc
      • Boca Raton, Florida, United States, 33486
        • RASF-Clinical Research Inc
      • DeBary, Florida, United States, 32713
        • Omega Research Consultants
      • Jacksonville, Florida, United States, 32207
        • University of Florida College of Medicine - Jacksonville - Rheumatology Research
      • Jacksonville, Florida, United States, 32209
        • University of Florida, Rheumatology at ACC
      • Miami, Florida, United States, 33173
        • Center for Arthritis and Rheumatic Diseases
      • Naples, Florida, United States, 34102
        • Jeffrey Alper, MD
      • Naples, Florida, United States, 34102
        • Medallion Clinical Research Institute, LLC
      • New Port Richey, Florida, United States, 34652
        • Suncoast Clinical Research, Inc.
      • Port Richey, Florida, United States, 34668
        • Florida Arthritis & Osteoporosis Center
      • Port Richey, Florida, United States, 34668
        • Gulf Coast Medical Center
      • Tamarac, Florida, United States, 33321
        • West Broward Rheumatology Associates, Inc.
      • Tampa, Florida, United States, 33612
        • USF Health Morsani Center For Advanced Healthcare
      • Tampa, Florida, United States, 33614
        • BayCare Medical Group, Inc
    • Idaho
      • Idaho Falls, Idaho, United States, 83404
        • Institute of Arthritis Research
    • Illinois
      • Quincy, Illinois, United States, 62301
        • Quincy Medical Group
    • Indiana
      • Granger, Indiana, United States, 46530
        • Beacon Medical Group Rheumatology Main Street
      • Indianapolis, Indiana, United States, 46227
        • Diagnostic Rheumatology And Research, PC
    • Louisiana
      • Baton Rouge, Louisiana, United States, 70836
        • Ochsner Clinic Baton Rouge
    • Massachusetts
      • Fall River, Massachusetts, United States, 02720
        • Phase III Clinical Research
      • Worcester, Massachusetts, United States, 01605
        • Clinical Pharmacology Study Group
    • Michigan
      • Battle Creek, Michigan, United States, 49015
        • Bronson Internal Medicine and Rheumatology
      • Kalamazoo, Michigan, United States, 49007
        • Western Michigan University Homer Stryker MD
    • Mississippi
      • Tupelo, Mississippi, United States, 38801
        • North Mississippi Medical Clinics, Inc. - Clinical Research
    • New Jersey
      • Freehold, New Jersey, United States, 07728
        • Arthritis & Osteoporosis Associates
      • Marlton, New Jersey, United States, 08053
        • Radnet
      • Voorhees, New Jersey, United States, 08043
        • Arthritis, Rheumatic & Back Disease Associates, P.A.
      • Wall, New Jersey, United States, 07719
        • Open MRI & Diagnostic Imaging of Wall
    • New York
      • Rochester, New York, United States, 14618
        • AAIR Research Center
    • North Carolina
      • Greenville, North Carolina, United States, 27834
        • Physicians East, PA
      • Salisbury, North Carolina, United States, 28144
        • PMG Research of Salisbury
    • North Dakota
      • Minot, North Dakota, United States, 58701
        • Trinity Health Center-Medical Arts
    • Ohio
      • Cincinnati, Ohio, United States, 45236
        • Group Health Associates
      • Cincinnati, Ohio, United States, 45242
        • Cincinnati Rheumatic Disease Study Group, Inc.
      • Dayton, Ohio, United States, 45417
        • STAT Research, Inc.
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73112
        • Lynn Health Science Institute
      • Oklahoma City, Oklahoma, United States, 73103
        • Health Research of Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Oklahoma Medical Research Foundation (OMRF)
    • Pennsylvania
      • Bethlehem, Pennsylvania, United States, 18015
        • East Penn Rheumatology Associates, P.C.
      • Duncansville, Pennsylvania, United States, 16635
        • Altoona Center for Clinical Research
    • South Carolina
      • Greenville, South Carolina, United States, 29601
        • Piedmont Arthritis Clinic
      • Orangeburg, South Carolina, United States, 29118
        • Articularis Healthcare Group dba ACME Research
      • Summerville, South Carolina, United States, 29486
        • Articularis Healthcare Group d/b/a Low Country Rheumatology
    • Texas
      • Cypress, Texas, United States, 77429
        • Pioneer Research Solutions, Inc.
      • Dallas, Texas, United States, 75231
        • Metroplex Clinical Research Center
    • Virginia
      • Chesapeake, Virginia, United States, 23320
        • Center for Arthritis and Rheumatic Diseases
      • Suffolk, Virginia, United States, 23435
        • Center for Arthritis and Rheumatic Diseases

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: CP-690,550 and methotrexate
Open-label tofacitinib tablet and blinded methotrexate capsule
Drug: CP-690,550

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.

Other Names:
  • tofacitinib
Drug: Methotrexate

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.
Placebo Comparator: CP-690,550 and placebo
open-label tofacitinib tablet and blinded matching placebo for methotrexate capsule
Drug: Placebo
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Time Frame: Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), 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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Double Blind Phase: Change From Randomization in DAS28-4 ESR at Week 36
Time Frame: Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Week 36
DAS28 is a measure of disease activity in participants with rheumatoid arthritis. DAS28-4 (ESR) was calculated from SJC and TJC using 28 joints count, ESR (mm/hr) and PtGA on a 100 millimeter (mm) VAS (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 36
Double Blind Phase: Change From Randomization in DAS28-4 (C-reactive Protein [CRP]) at Weeks 36 and 48
Time Frame: Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48
DAS28 is a measure of disease activity in participants with rheumatoid arthritis. DAS28-4 (CRP) was calculated from SJC and TJC using 28 joints count, CRP (milligrams per liter [mg/L]) and PtGA on a 100 mm VAS (VAS: scores ranging from 0 mm [very well] to 100 mm [worst], higher scores indicate worse health condition). Total DAS28-4 (CRP) score range: 0 (none) to 9.4 (extreme disease activity), higher score indicated more disease activity. DAS28-4 (CRP) <= 3.2 implied low disease activity and > 3.2 to <=5.1 implied moderate disease activity, >5.1 implied high disease activity, and DAS28-4 (CRP) < 2.6 implied remission. DAS28-4 (CRP) = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.36*ln(CRP in mg/L +1) + 0.014*PtGA in mm+ 0.96; 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), Weeks 36 and 48
Double Blind Phase: Change From Randomization in Clinical Disease Activity Index (CDAI) at Weeks 36 and 48
Time Frame: Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48
CDAI was calculated from tender and swollen joints using 28 joint count, PtGA and physician global assessment of arthritis (PhyGA). PtGA and PhyGA both were assessed on 0-10 centimeter (cm) VAS scale (VAS: scores ranging from 0 cm [very well] to 10 cm [worst]), where higher scores indicated greater affliction due to disease activity). CDAI total score ranged from 0 to 76, where higher scores indicated higher disease activity. CDAI score of <=10 indicated low disease activity and a score of <= 2.8 indicated remission. CDAI = (28TJC) + (28SJC) + (PhyGA in cm) + (PtGA in cm).
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
Time Frame: Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48
SDAI was calculated from tender and swollen joints using 28 joint count, PtGA, PhyGA and CRP (in mg/dL). PtGA and PhyGA both were assessed on 0-10 cm VAS scale (VAS: scores ranging from 0 cm [very well] to 10 cm [worst]), where higher scores indicated greater affliction due to disease activity). SDAI total score ranged from 0 to 86, where higher scores indicated higher disease activity. SDAI score of <=11 indicates low disease activity and a score of <=3.3 indicates remission. SDAI = (28TJC) + (28SJC) + (PhyGA in cm) + (PtGA in cm) + (CRP in mg/dL).
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
Time Frame: Weeks 36 and 48
DAS28 is a measure of disease activity in participants with rheumatoid arthritis. DAS28-4 (ESR) was calculated from SJC and TJC using 28 joints count, ESR (mm/hr) and PtGA on a 100 mm VAS (VAS: scores ranging from 0 mm [very well] to 100 mm [worst], higher scores indicated 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) <=3.2 implied low disease activity and >3.2 to <=5.1 implied moderate disease activity, >5.1 implied high disease activity, and DAS28-4 (ESR) <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.
Weeks 36 and 48
Double Blind Phase: Percentage of Participants With LDA Assessed by DAS28-4 (CRP) <=3.2 at Weeks 36 and 48
Time Frame: Weeks 36 and 48
DAS28 is a measure of disease activity in participants with rheumatoid arthritis. DAS28-4 (CRP) was calculated from SJC and TJC using 28 joints count, CRP (mg/L) and PtGA on a 100 mm VAS (VAS: scores ranging from 0 mm [very well] to 100 mm [worst], higher scores indicate worse health condition). Total DAS28-4 (CRP) score range: 0 (none) to 9.4 (extreme disease activity), higher score indicated more disease activity. DAS28-4 (CRP) <=3.2 implied low disease activity and >3.2 to <=5.1 implied moderate disease activity, >5.1 implied high disease activity, and DAS28-4 (CRP) <2.6 implied remission. DAS28-4 (CRP) = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.36*ln(CRP in mg/L +1) + 0.014*PtGA in mm+ 0.96; ln = natural logarithm, sqrt = square root of.
Weeks 36 and 48
Double Blind Phase: Percentage of Participants With LDA Assessed by CDAI <=10 at Weeks 36 and 48
Time Frame: Weeks 36 and 48
CDAI was calculated from tender and swollen joints using 28 joint count, PtGA and PhyGA. PtGA and PhyGA both were assessed on 0-10 cm VAS scale (VAS: scores ranging from 0 cm [very well] to 10 cm [worst]), where higher scores indicated greater affliction due to disease activity). CDAI total score ranged from 0 to 76, where higher scores indicated higher disease activity. CDAI score of <=10 indicated low disease activity and a score of <= 2.8 indicated remission. Percentage of participants with CDAI <=10 were reported. CDAI = (28TJC) + (28SJC) + (PhyGA in cm) + (PtGA in cm).
Weeks 36 and 48
Double Blind Phase: Percentage of Participants With LDA Assessed by SDAI <=11 at Weeks 36 and 48
Time Frame: Weeks 36 and 48
SDAI was calculated from tender and swollen joints using 28 joint count, PtGA, PhyGA and CRP (in mg/dL). PtGA and PhyGA both were assessed on 0-10 cm VAS scale (VAS: scores ranging from 0 cm [very well] to 10 cm [worst]), where higher scores indicated greater affliction due to disease activity). SDAI total score ranged from 0 to 86, where higher scores indicated higher disease activity. SDAI score of <=11 indicated low disease activity and a score of <=3.3 indicated remission. SDAI = (28TJC) + (28SJC) + (PhyGA in cm) + (PtGA in cm) + (CRP in mg/dL).
Weeks 36 and 48
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
Time Frame: Weeks 36 and 48
ACR-EULAR Boolean remission was when a participant satisfied all of the following: tender joint count, swollen joint count (both based on a 28-joint assessment), CRP (in mg/dL), and PtGA (VAS: 0 cm [very well] to 10 cm [worst], higher scores indicated worse health condition) and all scores were <=1.
Weeks 36 and 48
Double Blind Phase: Percentage of Participants With Remission Assessed by DAS28-4 (ESR) Less Than [<] 2.6 at Weeks 36 and 48
Time Frame: Weeks 36 and 48
DAS28 is a measure of disease activity in participants with rheumatoid arthritis. DAS28-4 (ESR) was calculated from SJC and TJC using 28 joints count, ESR (mm/hr) and PtGA on a 100 mm VAS (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) <= 3.2 implied low disease activity and >3.2 to <=5.1 implied moderate disease activity, >5.1 implied high disease activity, and DAS28-4 (ESR) <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. Percentage of participants with DAS remission (DAS28-4-ESR<2.6) were reported in this outcome measure.
Weeks 36 and 48
Double Blind Phase: Percentage of Participants With Remission Assessed by DAS28-4 (CRP) <2.6 at Weeks 36 and 48
Time Frame: Weeks 36 and 48
DAS28 is a measure of disease activity in participants with rheumatoid arthritis. DAS28-4 (CRP) was calculated from SJC and TJC using 28 joints count, CRP (mg/L) and PtGA on a 100 mm VAS (VAS: scores ranging from 0 mm [very well] to 100 mm [worst], higher scores indicate worse health condition). Total DAS28-4 (CRP) score range: 0 (none) to 9.4 (extreme disease activity), higher score indicated more disease activity. DAS28-4 (CRP) <=3.2 implied low disease activity and >3.2 to <=5.1 implied moderate disease activity, >5.1 implied high disease activity, and DAS28-4 (CRP) <2.6 implied remission. DAS28-4 (CRP) = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.36*ln(CRP in mg/l +1) + 0.014*PtGA in mm+ 0.96. Percentage of participants with DAS remission (DAS28-4-CRP<2.6) were reported in this outcome measure.
Weeks 36 and 48
Double Blind Phase: Percentage of Participants With Remission Assessed by CDAI <=2.8 at Weeks 36 and 48
Time Frame: Weeks 36 and 48
CDAI was calculated from tender and swollen joints using 28 joint count, PtGA and PhyGA. PtGA and PhyGA both were assessed on 0-10 cm VAS scale (VAS: scores ranging from 0 cm [very well] to 10 cm [worst]), where higher scores indicated greater affliction due to disease activity). CDAI total score ranged from 0 to 76, where higher scores indicated higher disease activity. CDAI score of <=10 indicated low disease activity and a score of <= 2.8 indicated remission. CDAI = (28TJC) + (28SJC) + (PhyGA in cm) + (PtGA in cm).
Weeks 36 and 48
Double Blind Phase: Percentage of Participants With Remission Assessed by SDAI <=3.3 at Weeks 36 and 48
Time Frame: Weeks 36 and 48
SDAI was calculated from tender and swollen joints using 28 joint count, PtGA, PhyGA and CRP (in mg/dL). PtGA and PhyGA both were assessed on 0-10 cm VAS scale (VAS: scores ranging from 0 cm [very well] to 10 cm [worst]), where higher scores indicated greater affliction due to disease activity). SDAI total score ranged from 0 to 86, where higher scores indicated higher disease activity. SDAI score of <=11 indicates low disease activity and a score of <=3.3 indicates remission. SDAI = (28TJC) + (28SJC) + (PhyGA in cm) + (PtGA in cm) + (CRP in mg/dL).
Weeks 36 and 48
Double Blind Phase: Percentage of Participants Achieving an American College of Rheumatology 20 Percent (%) (ACR20) Response at Weeks 36 and 48
Time Frame: Baseline (Day 1), Weeks 36 and 48
Participants with 20% improvement in tender and swollen joint counts and 20% improvement in at least 3 of the 5 measures: PtGA, PhyGA, participant's assessment of arthritis pain, Health Assessment Questionnaire-Disability Index (HAQ-DI) and CRP. PtGA: participant assessed health on VAS, 0 mm (very well) to 100 mm (worst health condition), higher scores = worse condition. PhyGA: physician judged participants' pain on VAS, 0 (no pain) to 100 mm (extreme pain), higher scores = more pain. Participant's assessment of arthritis pain: participant assessed pain on VAS, 0 mm (no pain) to 100 mm (most severe pain), higher score = more pain. HAQ-DI: functional disability evaluation, score: 0 (no difficulty) to 3 (extreme difficulty), higher score implied more disability. The improvement was relative to baseline (Day 1).
Baseline (Day 1), Weeks 36 and 48
Double Blind Phase: Percentage of Participants Achieving an American College of Rheumatology 50% (ACR50) Response at Weeks 36 and 48
Time Frame: Baseline (Day 1), Weeks 36 and 48
Participants with 50% improvement in tender and swollen joint counts and 50% improvement in at least 3 of the 5 measures: PtGA, PhyGA, participant's assessment of arthritis pain, HAQ-DI and CRP. PtGA: participant assessed health on VAS, 0 mm (very well) to 100 mm (worst health condition), higher scores = worse condition. PhyGA: physician judged participants' pain on VAS, 0 (no pain) to 100 mm (extreme pain), higher scores = more pain. Participant's assessment of arthritis pain: participant assessed pain on VAS, 0 mm (no pain) to 100 mm (most severe pain), higher score = more pain. HAQ-DI: functional disability evaluation, score: 0 (no difficulty) to 3 (extreme difficulty), higher score implied more disability. The improvement was relative to baseline (Day 1).
Baseline (Day 1), Weeks 36 and 48
Double Blind Phase: Percentage of Participants Achieving an American College of Rheumatology 70% (ACR70) Response at Weeks 36 and 48
Time Frame: Baseline (Day 1), Weeks 36 and 48
Participants with 70% improvement in tender and swollen joint counts and 70% improvement in at least 3 of the 5 measures: PtGA, PhyGA, participant's assessment of arthritis pain, HAQ-DI and CRP. PtGA: participant assessed health on VAS, 0 mm (very well) to 100 mm (worst health condition), higher scores = worse condition. PhyGA: physician judged participants' pain on VAS, 0 (no pain) to 100 mm (extreme pain), higher scores = more pain. Participant's assessment of arthritis pain: participant assessed pain on VAS, 0 mm (no pain) to 100 mm (most severe pain), higher score = more pain. HAQ-DI: functional disability evaluation, score: 0 (no difficulty) to 3 (extreme difficulty), higher score implied more disability. The improvement was relative to baseline (Day 1).
Baseline (Day 1), Weeks 36 and 48
Double Blind Phase: Change From Randomization in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Weeks 36 and 48
Time Frame: Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48
HAQ-DI assesses the degree of difficulty a participant has experienced during the past week in 8 domains of daily living activities: dressing/grooming; arising; eating; walking; reach; grip; hygiene; and other activities.. There were total of 30 items distributed in these 8 domains. Each item was scored on a 4-point scale from 0 to 3: 0= no difficulty; 1= some difficulty; 2= much difficulty; 3= unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0 (least difficulty) and 3 (extreme difficulty), where higher scores indicate more difficulty while performing daily living activities.
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 the Short Form 36 (SF-36) Health Survey 8 Domain Scores at Weeks 36 and 48
Time Frame: Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48
SF-36 is a participant reported standardized survey designed to assess generic health related quality of life. It consisted of 36 items evaluating 8 aspects of functional health and well-being: physical functioning, role physical, bodily pain, social functioning, mental health, role emotional, vitality, and general health perception. The score range for each of the 8 health aspects was from 0 (poor health) to 100 (better health), higher scores indicating good health condition. Scores of 8 health aspects were summarized to derive the 2 component scores (physical component scores [PCS], mental component scores [MCS]) ranging from 0 (worst) to 100 (best), where higher PCS/MCS indicated good health condition.
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 the SF-36 Health Survey Component Scores at Weeks 36 and 48
Time Frame: Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48
SF-36 is a participant reported standardized survey designed to assess generic health related quality of life. It consisted of 36 items evaluating 8 aspects of functional health and well-being: physical functioning, role physical, bodily pain, social functioning, mental health, role emotional, vitality, and general health perception. The score range for each of the 8 health aspects was from 0 (poor health) to 100 (better health), higher scores indicating good health condition. Scores of 8 health aspects were summarized aggregated to derive the two 2 component scores PCS and MCS ranging from 0 (worst) to 100 (best), where higher PCS/MCS indicated good health condition.
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 the Work Productivity and Activity Impairment (WPAI) Scores at Week 36 and 48
Time Frame: Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Week 36 and 48
WPAI is 6-question participant rated questionnaire to determine the impact of rheumatoid arthritis and yields 4 types of outcomes: absenteeism (work time missed), presenteeism (impairment while working), work productivity loss (overall work impairment), and daily activity impairment (activity impairment) for a period of 7 days prior to a visit. These 4 outcomes are expressed as an impairment percentage (range from 0 to 100), with higher numbers indicating greater impairment and less productivity.
Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Week 36 and 48
Double Blind Phase: Change From Randomization in the European Quality of Life - 5 Dimensions Questionnaire (EQ-5D) Scores at Weeks 36 and 48
Time Frame: Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48
EQ-5D was a participant completed instrument designed to assess impact on quality of life in terms of a single utility score in 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. 3 possible answers for mobility: 1=no problem in walking, 2=moderate problems in walking, 3= confined to bed; self-care: 1=no problem, 2=moderate problems, 3= unable to wash/dress; usual activities: 1=no problem, 2=moderate problems, 3= unable to do usual activities; pain and discomfort: 1=no pain or discomfort, 2=moderate pain or discomfort, 3= extreme pain or discomfort; anxiety and depression: 1=not anxious or depressed, 2=moderately anxious or depressed, 3= extremely anxious or depressed. The 5-dimensional systems are converted into a single index utility score between 0 and 1, where higher score indicated a better health state.
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 the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Scores at Weeks 36 and 48
Time Frame: Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48
The FACIT-Fatigue scale was a participant completed questionnaire consisted of 13 items that assessed fatigue. Each item was scored on a scale of 0 (maximum fatigue) to 4 (no fatigue), higher scores indicate less fatigue. Total FACIT-fatigue score was obtained by addition of scores from 13 items, giving a possible overall range from 0 (maximum fatigue) to 52 (no fatigue). Higher FACIT-fatigue scores indicated lower level of fatigue, better participant status.
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 Achieving an Improvement of at Least 0.22 Units in HAQ-DI at Weeks 36 and 48
Time Frame: Baseline (Day 1), Weeks 36 and 48
HAQ-DI assesses the degree of difficulty a participant has experienced during the past week in 8 domains of daily living activities: dressing/grooming; arising; eating; walking; reach; grip; hygiene; and other activities.. There were total of 30 items distributed in these 8 domains. Each item was scored on a 4-point scale from 0 to 3: 0= no difficulty; 1= some difficulty; 2= much difficulty; 3= unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0 (least difficulty) and 3 (extreme difficulty), where higher scores indicate more difficulty while performing daily living activities. Percentage of participants with an improvement of at least 0.22 units in HAQ scores from baseline (Day 1) to Weeks 36 and 48 were reported in this outcome measure.
Baseline (Day 1), Weeks 36 and 48

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs
Time Frame: For OL Phase: Baseline up to Week 24; For DB Phase: Week 24 up to Week 52 (up to 28 days after last dose)
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to Week 52 (up to 28 days after last dose) that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non-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
Time Frame: For OL Phase: Baseline up to Week 24; For DB Phase: Week 24 up to Week 48
Abnormality criteria: Hemoglobin (Hb),Hematocrit,Erythrocytes(Ery): <0.8*LLN;Ery. Mean corpuscular volume <0.9*lower limit of normal (LLN), >1.1*upper limit of normal (ULN); Platelets:<0.5*LLN,>1.75*ULN;WBCs:<0.6*LLN,>1.5*ULN; Lymphocytes/WBCs, Neutrophils/WBCs:<0.8*LLN,>1.2* ULN;Basophils,Basophils/WBCs,Eosinophils,Eosinophils/WBCs,Monocytes, Monocytes/WBCs: >1.2*ULN;Prothrombin Time, Prothrombin Intl. Normalized Ratio:>1.1*ULN; ESR:>1.5*ULN; Bilirubin,Direct Bilirubin,Indirect Bilirubin: >1.5*ULN; Aspartate Aminotransferase (AT),Alanine AT,Gamma Glutamyl Transferase,Alkaline Phosphatase:>3.0*ULN; Protein, Albumin: <0.8*LLN, >1.2x ULN; Blood Urea Nitrogen, Creatinine, Triglycerides: >1.3*ULN;HDL Cholesterol:<0.8*LLN;Sodium <0.95*LLN, >1.05*ULN;Potassium, Chloride, Calcium, Bicarbonate: <0.9*LLN, >1.1*ULN; Glucose: <0.6*LLN, >1.5*ULN; Creatine Kinase: >2.0*ULN; Cholesterol:>1.3*ULN;Specific Gravity:<1.003;pH:<4.5; urine glucose,Ketones,urine protein,urine Hb,WBCs Esterase: >=1.
For OL Phase: Baseline up to Week 24; For DB Phase: Week 24 up to Week 48

Collaborators and Investigators

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Sponsor

Pfizer

Publications and helpful links

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General Publications

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Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 1, 2016

Primary Completion (Actual)

November 19, 2018

Study Completion (Actual)

December 17, 2018

Study Registration Dates

First Submitted

July 11, 2016

First Submitted That Met QC Criteria

July 11, 2016

First Posted (Estimate)

July 13, 2016

Study Record Updates

Last Update Posted (Actual)

December 4, 2019

Last Update Submitted That Met QC Criteria

November 13, 2019

Last Verified

November 1, 2019

More Information

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Other Study ID Numbers

  • A3921192
  • 2016-001825-15 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

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.

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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