TO ASSESS THE EFFICACY AND SAFETY OF PF-06650833, PF-06651600, AND TOFACITINIB ALONE AND IN COMBINATION IN PARTICIPANTS WITH ACTIVE RHEUMATOID ARTHRITIS WITH AN INADEQUATE RESPONSE TO METHOTREXATE
Rheumatoid Arthritis
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring Rheumatoid Arthritis
Eligibility Criteria
Inclusion Criteria:
- Male or female participants between the ages of 18 and 70 years.
- Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
- 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 participant has active disease at both Screening and Randomization, as defined by both: ≥6 joints tender or painful on motion, AND ≥6 joints swollen; and fulfills 1 of the following 2 criteria: High sensitivity C reactive protein (hsCRP) >7 mg/L at Screening (Visit 1) as performed by the central laboratory OR Erythrocyte sedimentation rate (ESR) (Westergren method) >28 mm h.
Exclusion Criteria:
- Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or IP administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study.
- Participants with a known immunodeficiency disorder or a first degree relative with a hereditary immunodeficiency.
- Participants with any active or latent infections.
- Participants with positive hepatitis B surface antigen (HBsAg).
- Participants with positive HCV Ab tests will be reflex tested for HCV ribonucleic acid (HCV RNA).
- Any history of either untreated or inadequately treated latent or active tuberculosis (TB) infection, current treatment for active or latent TB infection or evidence of currently active TB,
- History of a major organ transplant (eg, heart, lung, kidney and liver) or hematopoietic stem cell/marrow transplant.
- History of severe allergic or anaphylactoid reaction to kinase inhibitors, or corticosteroid preparations.
- Known history of diverticulitis or symptomatic diverticulosis, perineal abscess or fistulae.
- Participants with malignancy or history of malignancy (including lymphoma, leukemia, or lymphoproliferative disease).
- Pre-existing chronic autoimmune disease (eg, inflammatory bowel disease, systemic lupus erythematosus, moderate-severe atopic dermatitis, dermatomyositis) other than RA. Secondary Sjogren's Syndrome (due to RA) may be included.
- Participants with fibromyalgia will be excluded.
- Previous treatment with total lymphoid irradiation.
- Participants with an oral, tympanic, or temporal temperature of 38°C (100.4°F) or higher at baseline.
- Participants may not receive any live/attenuated vaccine from 30 days prior to randomization during the course of the study, or for 30 days after the last dose of study medication. Participants who have current routine household contact with children who have received varicella or oral polio vaccine within 2 months of first study dose are also excluded.
- History of any lymphoproliferative disorder.
- Have hearing loss with progression over the previous 5 years, sudden hearing loss, or middle or inner ear disease.
- History of any prior deep vein thrombosis (DVT) or pulmonary embolism [PE].
- Recent (within 6 months of screening) myocardial infarction, coronary revascularization, or percutaneous angioplasty with or without placement of a coronary artery stent; acute coronary syndrome; chronic uncompensated heart failure or New York Heart Association Functional Class III or IV; left ventricular assist devices; implanted defibrillators.
- Current severe chronic renal insufficiency or renal failure as defined by persistent (on repeated measurements) eGFR <60 mL/min per 1.73 m2 based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) calculation.
- Any known coagulopathy or hypercoagulant syndrome.
- Presence of any of the following laboratory abnormalities at screening or within the 3 months prior to first study dose:
Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels ≥1.5 x the upper limit of normal (ULN); Participants with a history of Gilbert's syndrome may have a direct bilirubin measured and would be eligible for this study provided the direct bilirubin is ≤ ULN and other liver function assessments are normal; Absolute neutrophil count of <1.5 x 109/L (<1500/mm3). Participants with cyclic (benign ethnic) neutropenia will be excluded; Absolute lymphocyte count of <0.5 x 109/L (<500/mm3); Absolute white blood cell (WBC) count of <3.0 x 109/L (<3000/mm3); Hemoglobin <9.0 g/dL (90 g/L); Platelet count ≤100 x 109/L (100,000 cells/mm3) or ≥1000 x 109/L (1,000,000 cells/mm3); Thrombocytopenia, as defined by a platelet count <100 x 109/L (<100,000/mm3) at screening visit or within the 3 months prior to first study dose. [Screening laboratory tests with abnormal results may be repeated once to confirm abnormal results. If results return to normal protocol acceptable limits within the 4-week screening period, the participant may enter the study].
- Grade 3 or greater laboratory abnormality based on the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 toxicity scale, except for the following that are allowed: Grade 3 prothrombin time (PT) secondary to warfarin treatment; Grade 3 partial thromboplastin time (PTT) due to lupus anticoagulant and not related to liver disease or anti-coagulant therapy.
- Participants previously treated with a biologic DMARD (except for up to 25% of participants who may have been treated with 1, and only 1 prior TNF inhibitor) or any other recent DMARD treatment (eg, a JAK inhibitor), or participants currently treated with any other prohibited medications will be excluded.
- Prior use of tofacitinib or other JAK inhibitor in the context of a clinical trial is excluded. Concomitant use of tofacitinib (other than as prescribed by the randomization scheme) or other JAK inhibitor is prohibited.
- Participants who have previously been treated with other, non-TNFa inhibiting biologic DMARDs [including, abatacept (Orencia®), tocilizumab (Actemra®), Sarilumab (Kevzara®), anakinra (Kineret®), rituximab (Rituxan®) or other selective B lymphocyte depleting agents, or other lymphocyte depleting agents/therapies (such as alemtuzab [CamPath®], natalizumab (Tysabri®), alkylating agents [eg, cyclophosphamide or chlorambucil], total lymphoid irradiation) are excluded from participation in the study.
- Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of IP used in this study (whichever is longer).
- Any 12-lead electrocardiogram (ECG) performed prior to randomization that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results.
Sites / Locations
- ,,UMHAT - Georgi Stranski" EAD
- Medical Diagnostic Laboratory Rusev EOOD
- MHAT Plovdiv AD
- DCC Sveti Georgi EOOD
- Independent Medical Diagnostic Laboratory Mediscan EOOD
- "Medical Center-Teodora" EOOD
- UMHAT "Kanev" AD
- Medical Center "Spectar" OOD
- MHAT "Lyulin" EAD
- "DCC 17 - Sofia" EOOD
- Medical Center "N.I. Pirogov" EOOD
- UMHAT "Sveti Ivan Rilski" EAD
- Manitoba Clinic
- Centre de Rhumatologie de l'Est du Quebec (CREQ)
- Centro Radiologico San Vicente de Paul
- CTR Estudios
- Enroll SpA
- Centro Radiologico Plaza Baquedano
- IMARED
- Centro de Estudios Reumatologicos (CER)
- CCR Czech a.s.
- REVMACLINIC s.r.o.
- Revmacentrum MUDr. Mostera, s.r.o.
- HV Medical s.r.o., ORL ambulance pro deti a dospele
- MRI Lekarsky servis s.r.o.
- Poliklinika AMO - Audiologie
- CCR Ostrava, s.r.o.
- Vesalion s.r.o.
- Mestka nemocnice Ostrava
- ORL - sluchadla s.r.o.
- Poliklinika Vektor
- Revmatologicky ustav
- Thomayerova nemocnice
- ORL ambulance
- Uherskohradistska nemocnice, a.s.
- Medical Plus s.r.o.
- JSC "Evex Hospitals"
- LTD "Cardioclinic - Digomi Medical Center"
- LTD "Institute of Clinical Cardiology"
- LTD "MediClub Georgia"
- LTD "Multi-Profile Clinic Consilium Medulla"
- Trial Pharma Kft.
- Vasutegeszsegugyi Nonprofit Kozhasznu Tarsasag
- Betegapolo Irgalmasrend Budai Irgalmasrendi Korhaz
- Mammut Egeszsegkozpont, Ful-orr- gegeszet
- Betegapolo Irgalmasrend Budai Irgalmasrendi Korhaz
- Budai Irgalmasrendi Korhaz
- Revita Reumatologiai Rendelo
- Qualiclinic Kft.
- Affidea Magyarorszag Kft.
- Affidea Magyarország Kft. Bank Center Központ
- Magyar Honvédség Egészségügyi Központ
- Affidea Magyarorszag Kft. Vaci Greens Egeszsegkozpont
- Mediszintech Audiologia Kft.
- Debreceni Egyetem Klinikai Kozpont
- Debreceni Egyetem Klinikai Központ
- Sanitas Diagnosztikai es Rehabilitacios Kozpont
- Pest Megyei Flór Ferenc Kórház Fül- Orr- Gégészet és Gyermek Fül-Orr-Gégészet
- Pest Megyei Flór Ferenc Kórház Reumatológiai es Fizioterápiás Osztály
- Huniko Kereskedelmi és Egészségügyi Szolgáltató Kft.
- Szegedi Tudomanyegyetem Reumatologiai Klinika
- Szegedi Tudomanyegyetem
- Szent-Gyorgyi Albert Klinikai Kozpont
- Csolnoky Ferenc Korhaz, Ful- Orr- Gegeszeti Osztaly
- VITAL MEDICAL CENTER (VITÁL-MEDICINA Kft.)
- Podlaskie Centrum Sluchu i Mowy Sluchmed
- Nzoz Zdrowie Osteo-Medic
- Lar-Med
- NZOZ Kendron
- Tomma Diagnostyka obrazowa
- ClinicMed Daniluk, Nowak Sp. J.
- Nzoz McD Voxel
- Klinika Foniatrii i Audiologii, Szpital Uniwersytecki Nr 2 im. Dr Jana Biziela w Bydgoszczy
- Klinika Reumatologii i Ukladowych Chorob Tkanki Lacznej
- Centrum Medyczne Pratia Gdynia
- Portowy Zaklad Opieki Zdrowotnej Sp. z o.o.
- Centrum Medyczne Enel-Med., Oddzial Alfa Plaza - Gdynia
- MCBK
- Samodzielny Publiczny Specjalistyczny Szpital Zachodni im. sw. Jana Pawla II
- Malopolskie Badania Kliniczne
- LUX MED.
- Centrum Badan Klinicznych JCI
- Centrum medyczne PLEJADY
- LUXMED
- Pratia MCM Krakow
- Centrum Medycyny Profilaktycznej Sp. z o. o.
- Centrum Medyczne iMed24
- FONMED
- Twoja Przychodnia - Centrum Medyczne Nowa Sol
- LIVMED Sp. z.o.o.
- Ai Centrum Medyczne
- Tomma Diagnostyka Obrazowa S.A.
- GEERS Dobry Sluch
- Prywatna Praktyka Lekarska Prof. dr hab. med. Pawel Hrycaj
- Pracownia Rezonansu Magnetycznego i RTG
- Centrum Mowy i Sluchu Medincus
- Rex Medica Sport
- Medycyna Kliniczna
- Tomma Diagnostyka Obrazowa
- "MTZ CLINICAL RESEARCH" Spolka z ograniczona odpowiedzialnoscia
- "Reumatika - Centrum Reumatologii" NZOZ
- ArtAna Anna Piotrowska
- Spoldzielnia Pracy Specjalistow Rentgenologow im. prof. W. Zawadowskiego
- Szpital LUX MED
- Dermatovenerologicka ambulancia
- ROMJAN, s.r.o.
- ORL ambulancia RHINO s.r.o.
- Klinika dermatovenerologie UNLP
- ARTROMAC n. o.
- Oddelenie radiodiagnostiky a zobrazovacich metod, UNLP
- Poliklinika Terasa s.r.o.
- Dermabene, s.r.o
- MEDMAN, s. r. o.,
- ORL ML, s.r.o
- Jessenius - Diagnosticke centrum
- Otorinolaryngologicka ambulancia MUDr. Olga Salgova
- PARDERM, s. r. o., Dermatovenerologicka ambulancia
- REUMACENTRUM s.r.o.
- MEDICENTRUM Piestany, s.r.o.
- Narodny ustav reumatickych chorob
- Nemocnica Alexandra Wintera n.o.
- Vseobecna nemocnica Rimavska Sobota
- AZIMED-ORL s.r.o.
- Dg.s.r.o. - Diagnosticke- centrum
- REUMEX s.r.o.
- Spinn, s.r.o.
- Zdravomak s.r.o. Topoľčany
- Clinica Gaias - Santiago
- Grupo Hospitalario La Rosaleda - Hospital Nuestra Senora de la Esperanza
- Hospital General Universitario de Elche
- Clinica Sagrada Familia
- Hospital Clinico Universitario Santiago de Compostela
- Hospital Quironsalud Infanta Luisa
- Communal non-profit enterprise "Chernihiv Regional Hospital" of Chernihiv Regional Council
- Communal Non-commercial Enterprise of Kharkiv Regional Council
- Medical сепtег of "Medical Clinic "Blagomed" LLC
- Medical Center 'Ok!Clinic+' of International Institute of Clinical Research LLC
- Communal non-profit enterprise "Kyiv City Clinical Hospital #3" of executive body of Kyiv
- Limited Liability Company "Medical Centre "Consilium Medical"
- "Revmocenter" LLC
- Clinic of the State Institution "DF Chebotaryov Institute of Gerontology of the NAMS of Ukraine"
- Communal Non-Commercial Enterprise "Odesa Regional Clinical Hospital" of Odesa Regional Council
- Comunal Enterprise "Poltava Regional Clinical Hospital n. a. M.S. Sklifosovskogo of Poltava
- LLC "Modern Clinic"
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Experimental
Experimental
Experimental
Experimental
Experimental
PF-06650833 + tofacitinib
PF-06650833 + PF-06651600
PF-06650833
PF-06651600
Tofacitinib