Clinical trial NCT02996500: Safety and Efficacy of Pf-06650833 In Subjects With Rheumatoid Arthritis, With An Inadequate Response To Methotrexate
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2016-12-19
Enrollment: 269
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. Male and female (including WOCBP) subjects between the ages of 18 and 75 years, inclusive.
2. 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.
3. The subject has active disease at both Screening and Baseline, as defined by both:

   * 6 joints tender or painful on motion, AND
   * 6 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;
4. Meets Class I, II or III of the ACR 1991 Revised Criteria for Global Functional Status in RA.
5. Subjects must be ACPA positive between screening and randomization.
6. 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
7. 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.

Exclusion Criteria:

1. Subjects with a known immunodeficiency disorder or a first degree relative with a hereditary immunodeficiency.
2. Subjects with any of the following infections or infections history:

   1. Any infection requiring treatment within 2 weeks prior to screening (Visit 1).
   2. 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.
   3. Infected joint prosthesis at any time with the prosthesis still in situ.
   4. Recurrent (more than one episode) herpes zoster or disseminated (a single episode) herpes zoster or disseminated (a single episode) herpes simplex.
   5. Subjects will be screened for HIV. Subjects who test positive for HIV will be excluded from the study.
   6. 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.
   7. Subjects with clinically significant active hepatic disease or hepatic impairment by laboratory assessment.
   8. 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.
3. Evidence of active or latent, untreated or inadequately treated infection with Mycobacterium tuberculosis (TB)
4. Pre-existing chronic autoimmune disease.

Primary outcomes:
measure: Change From Baseline in the Simplified Disease Activity Index (SDAI) at Week 12
timeFrame: Baseline and Week 12
Secondary outcomes:
measure: Change From Baseline in SDAI at Weeks 4 and 8
timeFrame: Baseline, Weeks 4 and 8
measure: Percentage of Participants With SDAI Low Disease Activity Score (LDAS) (SDAI <=11) at 4, 8, and 12 Weeks
timeFrame: Weeks 4, 8 and 12
measure: Percentage of Participants With SDAI Remission (SDAI <=3.3) at 4, 8, and 12 Weeks
timeFrame: Weeks 4, 8 and 12
measure: 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
timeFrame: Weeks 4, 8 and 12
measure: Percentage of Participants With DAS28-3 (ESR) LDAS (DAS28 <3.2) at 4, 8, and 12 Weeks
timeFrame: Weeks 4, 8 and 12
measure: Percentage of Participants With Disease Activity Score-28 (4 Components Based on High-Sensitivity C-Reactive Protein) (DAS28-4 [CRP]) LDAS (DAS28 <3.2) at 4, 8, and 12 Weeks
timeFrame: Weeks 4, 8 and 12
measure: Percentage of Participants With DAS28-3 (CRP) LDAS (DAS28 <3.2) at 4, 8, and 12 Weeks
timeFrame: Weeks 4, 8 and 12
measure: Percentage of Participants With DAS28-4 (ESR) Remission (DAS28 <2.6) at 4, 8 and 12 Weeks
timeFrame: Weeks 4, 8 and 12
measure: Percentage of Participants With DAS28-3 (ESR) Remission (DAS28 <2.6) at 4, 8 and 12 Weeks
timeFrame: Weeks 4, 8 and 12
measure: Percentage of Participants With DAS28-4 (CRP) Remission (DAS28 <2.6) at 4, 8 and 12 Weeks
timeFrame: Weeks 4, 8 and 12
measure: Percentage of Participants With DAS28-3 (CRP) Remission (DAS28 <2.6) at 4, 8 and 12 Weeks
timeFrame: Weeks 4, 8 and 12
measure: Change From Baseline in DAS28-4 (ESR) at 4, 8 and 12 Weeks
timeFrame: Baseline, Weeks 4, 8 and 12
measure: Change From Baseline in DAS28-3 (ESR) at 4, 8 and 12 Weeks
timeFrame: Baseline, Weeks 4, 8 and 12
measure: Change From Baseline in DAS28-4 (CRP) at 4, 8 and 12 Weeks
timeFrame: Baseline, Weeks 4, 8 and 12
measure: Change From Baseline in DAS28-3 (CRP) at 4, 8 and 12 Weeks
timeFrame: Baseline, Weeks 4, 8 and 12
measure: Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at 4, 8 and 12 Weeks
timeFrame: Weeks 4, 8 and 12
measure: Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response at 4, 8 and 12 Weeks
timeFrame: Weeks 4, 8 and 12
measure: Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response at 4, 8 and 12 Weeks
timeFrame: Weeks 4, 8 and 12
measure: Change From Baseline in the Tender/Painful and Swollen Joint Counts at 4, 8 and 12 Weeks
timeFrame: Baseline, Weeks 4, 8 and 12
measure: Change From Baseline in High-Sensitivity C-Reactive Protein (Hs-CRP) at 4, 8 and 12 Weeks
timeFrame: Baseline, Weeks 4, 8 and 12
measure: Change From Baseline in the Physician's Global Assessment of Arthritis (PhGA) at 4, 8, and 12 Weeks
timeFrame: Baseline, Weeks 4, 8 and 12
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Treatment-Related TEAEs
timeFrame: Baseline up to 28 calendar days after the last administration of the investigational product (about 21 months)
measure: Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)
timeFrame: Baseline up to 28 calendar days after the last administration of the investigational product (about 21 months)
measure: Number of Participants With Vital Signs Data Meeting Pre-sepcified Criteria
timeFrame: Baseline up to 28 calendar days after the last administration of the investigational product (about 21 months)
measure: Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-sepcified Criteria
timeFrame: Baseline up to 28 calendar days after the last administration of the investigational product (about 21 months)
measure: Number of Participants With Urinalysis Data Meeting Pre-specified Criteria
timeFrame: Baseline up to 28 calendar days after the last administration of the investigational product (about 21 months)
measure: Change From Baseline in the Patient's Assessment of Arthritis Pain (PAAP) Visual Analogue Scale (VAS) at Weeks 4, 8, 12
timeFrame: Baseline, Weeks 4, 8 and 12
measure: Change From Baseline in the Patient Global Assessment of Arthritis (PtGA) VAS at Weeks 4, 8, 12
timeFrame: Baseline, Weeks 4, 8 and 12
measure: Change From Baseline in the Health Assessment Questionnaire - Disability Index (HAQ-DI) at Weeks 4, 8, and 12
timeFrame: Baseline, Weeks 4, 8 and 12
measure: Change From Baseline in the 36 Item Short Form Health Survey (SF-36) Version 2 (Acute) 8 Domain Scores at Week 12
timeFrame: Baseline and Week 12
measure: Change From Baseline in the Physical Component Score (PCS) and Mental Component Score (MCS) at Week 12
timeFrame: Baseline and Week 12
measure: Change From Baseline in the European Quality of Life 5 Dimensions-3 Level (EQ-5D-3L) Score at Week 12
timeFrame: Baseline and Week 12
measure: Change From Baseline in the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Total Score at Week 12
timeFrame: Baseline and Week 12
Other outcomes:
Locations:
city: Tuscaloosa
country: United States
facility: Clinical and Translational Research Center of Alabama, PC
state: Alabama
city: Tucson
country: United States
facility: Dory Hardy, PharmD
state: Arizona
city: Tucson
country: United States
facility: Southern Arizona VA Health care System
state: Arizona
city: Clearwater
country: United States
facility: Robert W. Levin, MD,PA
state: Florida
city: Ormond Beach
country: United States
facility: Millennium Research
state: Florida
city: South Miami
country: United States
facility: Arthritis & Rheumatic Care Center
state: Florida
city: South Miami
country: United States
facility: Qps-Mra, Llc
state: Florida
city: Canton
country: United States
facility: Medical Associates of North Georgia
state: Georgia
city: Bowling Green
country: United States
facility: Graves Gilbert Clinic
state: Kentucky
city: Monroe
country: United States
facility: Arthritis and Diabetes Clinic, Inc.
state: Louisiana
city: Memphis
country: United States
facility: Ramesh C Gupta, M.D.
state: Tennessee
city: Baytown
country: United States
facility: Accurate Clinical Management, LLC
state: Texas
city: Houston
country: United States
facility: Accurate Clinical Management, LLC
state: Texas
city: Houston
country: United States
facility: Accurate Clinical Management, LLC
state: Texas
city: Tomball
country: United States
facility: DM Clinical Research
state: Texas
city: Garran
country: Australia
facility: Canberra Hospital
state: Australian Capital Territory
city: Broadmeadow
country: Australia
facility: Genesis Research Services
state: New South Wales
city: Sarajevo
country: Bosnia and Herzegovina
facility: General Hospital "Prim.dr.Abdulah Nakas"
state: Kanton Sarajevo
city: Banja Luka
country: Bosnia and Herzegovina
facility: University Clinical Center Republic of Srpska
state: Republika Srpska
city: Gradiska
country: Bosnia and Herzegovina
facility: Health Center Gradiska
state: Republika Srpska
city: Plovdiv
country: Bulgaria
facility: UMHAT Kaspela
city: Sofia
country: Bulgaria
facility: MHAT Liulin
city: Sofia
country: Bulgaria
facility: UMHAT "Sv.Ivan Rilski", Clinic of rheumatology
city: Sofia
country: Bulgaria
facility: Medical Center Synexus Sofia EOOD
city: Sofia
country: Bulgaria
facility: Specialized Hospital for Active Treatment of Oncology Diseases EAD, Department of Imaging Diagnostic
city: Zagreb
country: Croatia
facility: Poliklinika K-centar
state: GRAD Zagreb
city: Zagreb
country: Croatia
facility: Medicinski centar Kuna&Peric
city: Ostrava
country: Czechia
facility: CCBR Ostrava s.r.o.
city: Praha
country: Czechia
facility: Revmatologicka ambulance
city: Uherske Hradiste
country: Czechia
facility: Medical Plus s.r.o.
city: Tbilisi
country: Georgia
facility: LTD Israeli-Georgian Medical Research Clinic HELSICORE
city: Tbilisi
country: Georgia
facility: LTD " Diagnostic Service "
city: Tbilisi
country: Georgia
facility: Ltd Institute of Clinical Cardiology
city: Tbilisi
country: Georgia
facility: LTD Unimedi Kakheti
city: Tbilisi
country: Georgia
facility: LTD "MediClubGeorgia"
city: Tbilisi
country: Georgia
facility: Ltd "Medicore"
city: Telavi
country: Georgia
facility: Unimedi Kakheti LTD
city: Puettlingen
country: Germany
facility: Knappschaftsklinikum Saar GmbH
city: Budapest
country: Hungary
facility: Revita Reumatologiai Rendelo
city: Kistarcsa
country: Hungary
facility: Pest Megyei Flor Ferenc Korhaz
city: Miskolc
country: Hungary
facility: CRU Hungary Ltd.
city: Szeged
country: Hungary
facility: Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont
city: Szentes
country: Hungary
facility: Csongrad Megyei Dr. Bugyi Istvan Korhaz, Mozgasszervi Rehabilitacios Osztaly
city: Veszprem
country: Hungary
facility: VITAL MEDICAL CENTER Orvosi es Fogorvosi Kozpont
city: Seoul
country: Korea, Republic of
facility: Seoul National University hospital
city: Seoul
country: Korea, Republic of
facility: Hanyang University Seoul hospital
city: Seoul
country: Korea, Republic of
facility: Konkuk University Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St.Mary's Hospital
city: Cuernavaca
country: Mexico
facility: Private Practice - Dr. Miguel Cortes Hernandez
state: Morelos
city: Merida
country: Mexico
facility: Centro Peninsular de Investigacion Clinica S.C.P
state: Yucatan
city: Merida
country: Mexico
facility: Kohler & Milstein Research S.A de C.V
state: Yucatan
city: San Luis Potosí
country: Mexico
facility: Centro de Alta Especialidad en Reumatología e Investigación del Potosi, S.C.
city: Bytom
country: Poland
facility: Szpital Specjalistyczny nr 1 w Bytomiu
city: Gdansk
country: Poland
facility: Synexus Polska Sp. z o.o. Oddzial w Gdansku
city: Gdynia
country: Poland
facility: Synexus Polska Sp z o.o. Oddzial w Gdyni
city: Grodzisk Mazowiecki
country: Poland
facility: McBk S.C.
city: Katowice
country: Poland
facility: Synexus Polska Sp.Zo.o.
city: Poznan
country: Poland
facility: Prywatna Praktyka Lekarska Prof. UM Dr hab. Med. Pawel Hrycaj
city: Warszawa
country: Poland
facility: Synexus Polska Sp. z o.o.
city: Warszawa
country: Poland
facility: Reumatika Centrum Reumatologii NZOZ
city: Wroclaw
country: Poland
facility: Synexus Polska Sp. z o.o. Oddział we Wroclawiu
city: Bucuresti
country: Romania
facility: Centrul Medical Unirea
city: Bucuresti
country: Romania
facility: Med Life
city: Bucuresti
country: Romania
facility: Centrul Medical Sana
city: Bucuresti
country: Romania
facility: Euroclinic Hospital
city: Iasi
country: Romania
facility: Spitalul Clinic de Recuperare Iasi
city: Tirgu Mures
country: Romania
facility: Spitalul Clinic Judetean de Urgenta Tirgu Mures
city: Kazan
country: Russian Federation
facility: FSBEI HE "Kazan State Medical University" MoH of RF
city: Kazan
country: Russian Federation
facility: FSBEI HE "Kazan State Medical University" MoH of RF
city: Moscow
country: Russian Federation
facility: FSBSI "Scientific Research Institute of Rheumatology n.a. V.A. Nasonova"
city: Moscow
country: Russian Federation
facility: SBHI of Moscow City Clinical Hospital # 1 n.a. N.I. Pirogov of Moscow Healthcare Department
city: Moscow
country: Russian Federation
facility: FSBHI Central Clinical Hospital of Russian Academy of Sciences
city: Ryazan
country: Russian Federation
facility: State Budgetary Institution of Ryazan Region "Regional clinical cardiology dispensary"
city: Saint-Petersburg
country: Russian Federation
facility: LLC "Sanavita"
city: Saint-Petersburg
country: Russian Federation
facility: LLC "Sanavita"
city: St. Petersburg
country: Russian Federation
facility: Saint Petersburg State Budgetary Institution of Health Care "Clinical Rheumatology Hospital #25"
city: Vladimir
country: Russian Federation
facility: SBHI of VR "Regional Clinical Hospital"
city: Belgrade
country: Serbia
facility: Institute of Rheumatology
city: Belgrade
country: Serbia
facility: Military Medical Academy
city: Niska Banja
country: Serbia
facility: Institute for Treatment and Rehabilitation "Niska Banja"
city: Novi Sad
country: Serbia
facility: Special Hospital for Rheumatic Diseases Novi Sad
city: Partizanske
country: Slovakia
facility: Reumacentrum s.r.o.
state: Trenciansky Kraj.
city: Dunajska Streda
country: Slovakia
facility: AAGS s.r.o., Reumatologicka ambulancia
city: Kosice-Saca
country: Slovakia
facility: Nemocnica Kosice-Saca, a.s.1.sukromna nemocnica
city: Považská Bystrica
country: Slovakia
facility: Neštátna Reumatologická ambulancia
city: Rimavska Sobota
country: Slovakia
facility: REUMEX s.r.o. Reumatologicka ambulancia
city: Zilina
country: Slovakia
facility: Reumatologicka ambulancia, MUDr. Pavol Polak s.r.o.
city: Santiago de Compostela
country: Spain
facility: Complejo Hospitalario Universitario de Santiago de Compostela
state: A Coruna
city: Santiago de Compostela
country: Spain
facility: HM Hospital Nuestra Señora de La Esperanza
state: A Coruña
city: Barakaldo
country: Spain
facility: Hospital Universitario Cruces
state: Vizcaya
city: A Coruña
country: Spain
facility: Hospital Universitario A Coruña
city: Sevilla
country: Spain
facility: Hospital Quironsalud Infanta Luisa
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Medical University Hospital
city: Chernihiv
country: Ukraine
facility: Komunalnyi likuvalno-profilaktychnyi zaklad "Chernihivska oblasna likarnia",
city: Kharkiv
country: Ukraine
facility: Derzhavna ustanova "Natsionalnyi instytut terapii imeni L.T. Maloi
city: Kyiv
country: Ukraine
facility: Komunalne nekomertsiine pidpryiemstvo "Konsultatyvno-diahnostychnyi tsentr"
city: Kyiv
country: Ukraine
facility: Medychnyi tsentr tovarystva z obmezhenoiu vidpovidalnistiu "Revmotsentr", m. Kyiv
city: Kyiv
country: Ukraine
facility: Derzhavna ustanova "Instytut herontolohii imeni D.F. Chebotarova
city: Poltava
country: Ukraine
facility: Poltavska oblasna klinichna likarnia im. M.V. Sklifosovskoho,
city: Ternopil
country: Ukraine
facility: Ternopilska universytetska likarnia, revmatolohichne viddilennia, Derzhavnyi vyshchyi navchalnyi
city: Vinnytsia
country: Ukraine
facility: Vinnytska oblasna klinichna likarnia im. M.I.Pyrohova, revmatolohichne viddilennia
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: