Safety and Efficacy of Pf-06650833 In Subjects With Rheumatoid Arthritis, With An Inadequate Response To Methotrexate
A 12 WEEK RANDOMIZED, DOUBLE-BLIND, DOUBLE DUMMY, PARALLEL GROUP, ACTIVE AND PLACEBO-CONTROLLED, MULTICENTER STUDY TO ASSESS THE EFFICACY AND SAFETY PROFILE OF PF-06650833 IN SUBJECTS WITH ACTIVE RHEUMATOID ARTHRITIS WITH AN INADEQUATE RESPONSE TO METHOTREXATE
3 other identifiers
interventional
269
19 countries
103
Brief Summary
This is a Phase 2, multicenter, randomized, double blind, double dummy, placebo and active-controlled, parallel group study to assess the efficacy and safety of PF 06650833 at Week 12 in subjects with moderate-severe, active, RA who have had an inadequate response to MTX. PF-06650833 or matching placebo tablets will be administered orally QD under fasting conditions, and tofacitinib or matching tofacitinib placebo tablets will be administered orally BID for 12 weeks in a blinded fashion.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2 rheumatoid-arthritis
Started Nov 2016
103 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 13, 2016
CompletedStudy Start
First participant enrolled
November 10, 2016
CompletedFirst Posted
Study publicly available on registry
December 19, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 15, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
August 15, 2018
CompletedResults Posted
Study results publicly available
February 27, 2020
CompletedFebruary 27, 2020
February 1, 2020
1.8 years
October 13, 2016
July 29, 2019
February 12, 2020
Conditions
Outcome Measures
Primary Outcomes (1)
Change From Baseline in the Simplified Disease Activity Index (SDAI) at Week 12
The SDAI is a continuous composite measure derived from components of the American College of Rheumatology (ACR) Core Dataset.The SDAI was calculated using the following formula: SDAI = Tender / Painful Joint Count(TJC) (using 28 joints) + Swollen Joint Count (SJC) (using 28 joints) + Patient Global Assessment of Arthritis (PtGA) (0-10 cm scale) + Physician's Global Assessment of Arthritis (PhGA) (0-10 cm scale) + high sensitivity C-reactive protein (hsCRP) (mg/dL). SDAI total score= 0-86. SDAI \<=3.3 indicates disease remission, \>3.4 to 11 = low disease activity, \>11 to 26 = moderate disease activity, and \>26 = high disease activity. The primary analysis utilized a Bayesian ANCOVA model with an informative placebo prior distribution with borrowing from tofacitinib historical placebo data. The confidence interval was credible interval in this statistical analysis. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Baseline and Week 12
Secondary Outcomes (33)
Change From Baseline in SDAI at Weeks 4 and 8
Baseline, Weeks 4 and 8
Percentage of Participants With SDAI Low Disease Activity Score (LDAS) (SDAI <=11) at 4, 8, and 12 Weeks
Weeks 4, 8 and 12
Percentage of Participants With SDAI Remission (SDAI <=3.3) at 4, 8, and 12 Weeks
Weeks 4, 8 and 12
Percentage of Participants With Disease Activity Score-28 (4 Components Based on Erythrocyte Sedimentation Rate) (DAS28-4 [ESR]) LDAS (DAS28 <3.2) at 4, 8, and 12 Weeks
Weeks 4, 8 and 12
Percentage of Participants With DAS28-3 (ESR) LDAS (DAS28 <3.2) at 4, 8, and 12 Weeks
Weeks 4, 8 and 12
- +28 more secondary outcomes
Study Arms (6)
Arm 1: 20 mg QD
EXPERIMENTALPF-06650833 , 20 mg QD
Arm 2: 60 mg QD
EXPERIMENTALPF-06650833, 60 mg QD
Arm 3: 200 mg QD
EXPERIMENTALPf-06650833, 200 mg QD
Arm 4: 400 mg QD
EXPERIMENTALPF-06650833, 400 mg QD
Placebo
PLACEBO COMPARATORPlacebo, 0 mg BID
Arm 5: Tofacitinib
ACTIVE COMPARATORTofacitinib 5 mg BID
Interventions
Eligibility Criteria
You may qualify if:
- Male and female (including WOCBP) subjects between the ages of 18 and 75 years, inclusive.
- Diagnosis of RA and meeting the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for RA with a Total Score ≥6/10.
- The subject has active disease at both Screening and Baseline, as defined by both:
- joints tender or painful on motion, AND
- joints swollen; and fulfills 1 of the following 2 criteria at Screening:
- High sensitivity C reactive protein (hsCRP) \>7 mg/L at screening
- Erythrocyte sedimentation rate (ESR) (Westergren method) \>28 mm/hr;
- Meets Class I, II or III of the ACR 1991 Revised Criteria for Global Functional Status in RA.
- Subjects must be ACPA positive between screening and randomization.
- Subjects must have been taking oral MTX for at least 3 months at an adequate dose to determine that the subject had an inadequate response to MTX
- Up to 50 % of subjects may have received one (and only one) approved TNF-inhibiting biologic agent administered that was inadequately effective and/or not tolerated. The anti-TNF biologic could also have been discontinued due to lack of continued access.
You may not qualify if:
- Subjects with a known immunodeficiency disorder or a first degree relative with a hereditary immunodeficiency.
- Subjects with any of the following infections or infections history:
- Any infection requiring treatment within 2 weeks prior to screening (Visit 1).
- Any infection requiring hospitalization, parenteral antimicrobial therapy within 60 days, or as otherwise judged to be an opportunistic infection or clinically significant by the investigator, within the past 6 months.
- Infected joint prosthesis at any time with the prosthesis still in situ.
- Recurrent (more than one episode) herpes zoster or disseminated (a single episode) herpes zoster or disseminated (a single episode) herpes simplex.
- Subjects will be screened for HIV. Subjects who test positive for HIV will be excluded from the study.
- Subjects will be screened for hepatitis B virus infection and will be excluded if positive for hepatitis B surface antigen (HBsAg). Subjects with HBsAg negative testing but who test positive for hepatitis B core antibody (HBcAb) must have further testing for hepatitis B surface antibody (HBsAb). If HBsAb is negative, the subject will be excluded from the study.
- Subjects with clinically significant active hepatic disease or hepatic impairment by laboratory assessment.
- Subjects will be screened for hepatitis C virus (HCV Ab). Subjects with positive HCV Ab tests will be reflex tested for HCV ribonucleic acid (HCV RNA). Only subjects with negative HCV Ab or HCV RNA will be allowed to enroll in the study.
- Evidence of active or latent, untreated or inadequately treated infection with Mycobacterium tuberculosis (TB)
- Pre-existing chronic autoimmune disease.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Pfizerlead
Study Sites (103)
Clinical and Translational Research Center of Alabama, PC
Tuscaloosa, Alabama, 35406, United States
Dory Hardy, PharmD
Tucson, Arizona, 85723, United States
Southern Arizona VA Health care System
Tucson, Arizona, 85723, United States
Robert W. Levin, MD,PA
Clearwater, Florida, 33765, United States
Millennium Research
Ormond Beach, Florida, 32174, United States
Arthritis & Rheumatic Care Center
South Miami, Florida, 33143, United States
Qps-Mra, Llc
South Miami, Florida, 33143, United States
Medical Associates of North Georgia
Canton, Georgia, 30115, United States
Graves Gilbert Clinic
Bowling Green, Kentucky, 42101, United States
Arthritis and Diabetes Clinic, Inc.
Monroe, Louisiana, 71203, United States
Ramesh C Gupta, M.D.
Memphis, Tennessee, 38119, United States
Accurate Clinical Management, LLC
Baytown, Texas, 77521, United States
Accurate Clinical Management, LLC
Houston, Texas, 77004, United States
Accurate Clinical Management, LLC
Houston, Texas, 77084, United States
DM Clinical Research
Tomball, Texas, 77375, United States
Canberra Hospital
Garran, Australian Capital Territory, 2605, Australia
Genesis Research Services
Broadmeadow, New South Wales, 2292, Australia
General Hospital "Prim.dr.Abdulah Nakas"
Sarajevo, Kanton Sarajevo, 71000, Bosnia and Herzegovina
University Clinical Center Republic of Srpska
Banja Luka, Republika Srpska, 78000, Bosnia and Herzegovina
Health Center Gradiska
Gradiška, Republika Srpska, 78400, Bosnia and Herzegovina
UMHAT Kaspela
Plovdiv, 4001, Bulgaria
MHAT Liulin
Sofia, 1336, Bulgaria
UMHAT "Sv.Ivan Rilski", Clinic of rheumatology
Sofia, 1612, Bulgaria
Medical Center Synexus Sofia EOOD
Sofia, 1784, Bulgaria
Specialized Hospital for Active Treatment of Oncology Diseases EAD, Department of Imaging Diagnostic
Sofia, 1784, Bulgaria
Poliklinika K-centar
Zagreb, City of Zagreb, 10000, Croatia
Medicinski centar Kuna&Peric
Zagreb, 10000, Croatia
CCBR Ostrava s.r.o.
Ostrava, 702 00, Czechia
Revmatologicka ambulance
Prague, 140 00, Czechia
Medical Plus s.r.o.
Uherské Hradiště, 68601, Czechia
LTD Israeli-Georgian Medical Research Clinic HELSICORE
Tbilisi, 0112, Georgia
LTD " Diagnostic Service "
Tbilisi, 0159, Georgia
Ltd Institute of Clinical Cardiology
Tbilisi, 0159, Georgia
LTD Unimedi Kakheti
Tbilisi, 0159, Georgia
LTD "MediClubGeorgia"
Tbilisi, 0160, Georgia
Ltd "Medicore"
Tbilisi, 0186, Georgia
Unimedi Kakheti LTD
Telavi, 2200, Georgia
Knappschaftsklinikum Saar GmbH
Püttlingen, 66346, Germany
Revita Reumatologiai Rendelo
Budapest, 1027, Hungary
Pest Megyei Flor Ferenc Korhaz
Kistarcsa, 2143, Hungary
CRU Hungary Ltd.
Miskolc, 3529, Hungary
Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont
Szeged, 6725, Hungary
Csongrad Megyei Dr. Bugyi Istvan Korhaz, Mozgasszervi Rehabilitacios Osztaly
Szentes, 6600, Hungary
VITAL MEDICAL CENTER Orvosi es Fogorvosi Kozpont
Veszprém, 8200, Hungary
Private Practice - Dr. Miguel Cortes Hernandez
Cuernavaca, Morelos, 62290, Mexico
Centro Peninsular de Investigacion Clinica S.C.P
Mérida, Yucatán, 97000, Mexico
Kohler & Milstein Research S.A de C.V
Mérida, Yucatán, 97070, Mexico
Centro de Alta Especialidad en Reumatología e Investigación del Potosi, S.C.
San Luis Potosí City, 78213, Mexico
Szpital Specjalistyczny nr 1 w Bytomiu
Bytom, 41-902, Poland
Synexus Polska Sp. z o.o. Oddzial w Gdansku
Gdansk, 80-382, Poland
Synexus Polska Sp z o.o. Oddzial w Gdyni
Gdynia, 81-537, Poland
McBk S.C.
Grodzisk Mazowiecki, 05-825, Poland
Synexus Polska Sp.Zo.o.
Katowice, 40-040, Poland
Prywatna Praktyka Lekarska Prof. UM Dr hab. Med. Pawel Hrycaj
Poznan, 61-397, Poland
Synexus Polska Sp. z o.o.
Warsaw, 01-192, Poland
Reumatika Centrum Reumatologii NZOZ
Warsaw, 02-691, Poland
Synexus Polska Sp. z o.o. Oddział we Wroclawiu
Wroclaw, 50-381, Poland
Centrul Medical Unirea
Bucharest, 010306, Romania
Med Life
Bucharest, 010719, Romania
Centrul Medical Sana
Bucharest, 011025, Romania
Euroclinic Hospital
Bucharest, 014461, Romania
Spitalul Clinic de Recuperare Iasi
Iași, 700661, Romania
Spitalul Clinic Judetean de Urgenta Tirgu Mures
Târgu Mureş, 540136, Romania
FSBEI HE "Kazan State Medical University" MoH of RF
Kazan', 420064, Russia
FSBEI HE "Kazan State Medical University" MoH of RF
Kazan', 420103, Russia
FSBSI "Scientific Research Institute of Rheumatology n.a. V.A. Nasonova"
Moscow, 115522, Russia
SBHI of Moscow City Clinical Hospital # 1 n.a. N.I. Pirogov of Moscow Healthcare Department
Moscow, 119049, Russia
FSBHI Central Clinical Hospital of Russian Academy of Sciences
Moscow, 119333, Russia
State Budgetary Institution of Ryazan Region "Regional clinical cardiology dispensary"
Ryazan, 390026, Russia
LLC "Sanavita"
Saint Petersburg, 190031, Russia
Saint Petersburg State Budgetary Institution of Health Care "Clinical Rheumatology Hospital #25"
Saint Petersburg, 190068, Russia
LLC "Sanavita"
Saint Petersburg, 195257, Russia
SBHI of VR "Regional Clinical Hospital"
Vladimir, 600023, Russia
Institute of Rheumatology
Belgrade, 11000, Serbia
Military Medical Academy
Belgrade, 11000, Serbia
Institute for Treatment and Rehabilitation "Niska Banja"
Niška Banja, 18205, Serbia
Special Hospital for Rheumatic Diseases Novi Sad
Novi Sad, 21112, Serbia
Reumacentrum s.r.o.
Partizánske, Trenčín Region, 958 01, Slovakia
AAGS s.r.o., Reumatologicka ambulancia
Dunajská Streda, 92901, Slovakia
Nemocnica Kosice-Saca, a.s.1.sukromna nemocnica
Kosice-Saca, 040 15, Slovakia
Neštátna Reumatologická ambulancia
Považská Bystrica, 017 01, Slovakia
REUMEX s.r.o. Reumatologicka ambulancia
Rimavská Sobota, 979 01, Slovakia
Reumatologicka ambulancia, MUDr. Pavol Polak s.r.o.
Žilina, 010 01, Slovakia
Seoul National University hospital
Seoul, 03080, South Korea
Hanyang University Seoul hospital
Seoul, 04763, South Korea
Konkuk University Medical Center
Seoul, 05030, South Korea
The Catholic University of Korea, Seoul St.Mary's Hospital
Seoul, 06591, South Korea
Complejo Hospitalario Universitario de Santiago de Compostela
Santiago de Compostela, A Coruna, 15706, Spain
HM Hospital Nuestra Señora de La Esperanza
Santiago de Compostela, A Coruña, 15705, Spain
Hospital Universitario Cruces
Barakaldo, Vizcaya, 48903, Spain
Hospital Universitario A Coruña
A Coruña, 15006, Spain
Hospital Quironsalud Infanta Luisa
Seville, 41010, Spain
China Medical University Hospital
Taichung, 40447, Taiwan
National Taiwan University Hospital
Taipei, 10043, Taiwan
Taipei Medical University Hospital
Taipei, 110, Taiwan
Komunalnyi likuvalno-profilaktychnyi zaklad "Chernihivska oblasna likarnia",
Chernihiv, 14029, Ukraine
Derzhavna ustanova "Natsionalnyi instytut terapii imeni L.T. Maloi
Kharkiv, 61039, Ukraine
Komunalne nekomertsiine pidpryiemstvo "Konsultatyvno-diahnostychnyi tsentr"
Kyiv, 01103, Ukraine
Medychnyi tsentr tovarystva z obmezhenoiu vidpovidalnistiu "Revmotsentr", m. Kyiv
Kyiv, 04070, Ukraine
Derzhavna ustanova "Instytut herontolohii imeni D.F. Chebotarova
Kyiv, 04114, Ukraine
Poltavska oblasna klinichna likarnia im. M.V. Sklifosovskoho,
Poltava, 36011, Ukraine
Ternopilska universytetska likarnia, revmatolohichne viddilennia, Derzhavnyi vyshchyi navchalnyi
Ternopil, 46002, Ukraine
Vinnytska oblasna klinichna likarnia im. M.I.Pyrohova, revmatolohichne viddilennia
Vinnytsia, 21018, Ukraine
Related Links
MeSH Terms
Conditions
Interventions
Condition 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 2
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 13, 2016
First Posted
December 19, 2016
Study Start
November 10, 2016
Primary Completion
August 15, 2018
Study Completion
August 15, 2018
Last Updated
February 27, 2020
Results First Posted
February 27, 2020
Record last verified: 2020-02
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.