A Study Of PF-06410293 (Adalimumab-Pfizer) And Adalimumab (Humira®) In Combination With Methotrexate In Subjects With Active Rheumatoid Arthritis (REFLECTIONS B538-02).

A PHASE 3 RANDOMIZED, DOUBLE-BLIND STUDY ASSESSING THE EFFICACY AND SAFETY OF PF-06410293 AND ADALIMUMAB IN COMBINATION WITH METHOTREXATE IN SUBJECTS WITH MODERATELY TO SEVERELY ACTIVE RHEUMATOID ARTHRITIS WHO HAVE HAD AN INADEQUATE RESPONSE TO METHOTREXATE

The study will assess the efficacy, safety, and immunogenicity of PF-06410293 and adalimumab in combination with methotrexate in subjects with moderately to severly active rheumatoid arthritis who have had an inadequate response to methotrexate.

In an additional optional portion of the study, during open label Treatment Period 3 (TP3), a subset of subjects used a Prefilled Pen (PFP) to administer up to 3 injections of their study treatment (PF-06410293) at home.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Biological: PF-06410293; Biological: Adalimumab

• Study Type: Interventional
• Enrollment (Actual): 597
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Southport, Queensland, Australia, 4215
      • Paradise Arthritis & Rheumatology Pty Ltd
  • South Australia
    • Woodville South, South Australia, Australia, 5011
      • The Queen Elizabeth Hospital
  • Western Australia
    • Victoria Park, Western Australia, Australia, 6100
      • RK Will Pty Ltd
• Brazil
  • Paraná
    • Curitiba, Paraná, Brazil, 80440-080
      • EDUMED Educação em Saúde S/S Ltda
• Bulgaria
  • Plovdiv, Bulgaria, 4000
    • MHAT Plovdiv AD
  • Plovdiv, Bulgaria, 4002
    • University Multiprofile Hospital for Active Treatment (UMHAT) Kaspela EOOD
  • Sofia, Bulgaria, 1612
    • UMHAT "Sv. Ivan Rilski" EAD
  • Sofia, Bulgaria, 1612
    • University Multiprofile Hospital for Active Treatment "Sv. Ivan Rilski" EAD
• Colombia
  • Bogota, Colombia
    • Fundacion Instituto de Reumatologia Fernando Chalem
• Czechia
  • Bruntal, Czechia, 792 01
    • Lekarna Na vrsku
  • Bruntal, Czechia, 792 01
    • Revmatologie Bruntal, s.r.o.
  • Hlucin, Czechia, 748 01
    • L.K.N. Arthrocentrum, s.r.o.
  • Ostrava, Czechia, 702 00
    • Lekarna Vesalion
  • Pardubice, Czechia, 530 02
    • BENU Lekarna
  • Pardubice, Czechia, 530 02
    • CCBR-SYNARC, a.s.
  • Praha 2, Czechia, 128 50
    • Revmatologicky Ustav
  • Uherske Hradiste, Czechia, 686 01
    • Medical Plus, S.R.O.
  • Uherske Hradiste, Czechia, 686 01
    • Lekarna Hradebni s.r.o.
• Estonia
  • Tallinn, Estonia, 10117
    • Innomedica OÜ
  • Tallinn, Estonia, 11312
    • East Tallinn Central Hospital
• Georgia
  • Tbilisi, Georgia, 0159
    • Tbilisi Heart and Vascular Clinic Ltd
  • Tbilisi, Georgia, 0102
    • V.Tsitlanadze Scientifically-Practical Rheumatology Center LTD
  • Tbilisi, Georgia, 0105
    • V.Tsitlanadze Scientifically-Practical Rheumatology Center
  • Tbilisi, Georgia, 0112
    • LTD Israeli-Georgian Medical Research Clinic Helsicore"
  • Tbilisi, Georgia, 0159
    • LTD Cardio-Reanimation Center
  • Tbilisi, Georgia, 0160
    • LTD Altravita
  • Tbilisi, Georgia, 0160
    • LTD.MediClubGeorgia
  • Tbilisi, Georgia, 0177
    • JSC Medical Corporation Evex
  • Ajaria
    • Batumi, Ajaria, Georgia, 6010
      • LTD "Unimed Adjara"
  • Kakheti
    • Telavi, Kakheti, Georgia, 2200
      • Unimedi Kakheti Ltd, Telavi Referral Hospital
• Germany
  • Berlin, Germany, 14059
    • Schlosspark-Klinik
  • Hildesheim, Germany, 31134
    • Gemeinschaftspraxis Dr. von Hinüber/Dr. Demary
  • München, Germany, 80336
    • Klinikum der Universität München
  • München, Germany, 81541
    • Praxiszentrum St. Bonifatius
  • Planegg, Germany, 82152
    • Rheumapraxis Dr. Martin Welcker und Kollegen
  • Püttlingen, Germany, 66346
    • Knappschaftsklinikum Saar GmbH
  • Ratingen, Germany, 40878
    • Rheumazentrum Ratingen
• Hungary
  • Budapest, Hungary, 1036
    • Qualiclinic Kft.
  • Veszprem, Hungary, 8200
    • VITAL MEDICAL CENTER Orvosi es Fogorvosi Kozpont
  • Hajdú-bihar
    • Debrecen, Hajdú-bihar, Hungary, H-4032
      • Debreceni Egyetem Klinikai Kozpont
• Japan
  • Fukuoka, Japan, 810-8563
    • National Hospital Organization Kyushu Medical Center
  • Fukuoka, Japan, 810-0001
    • Kondo clinic for rheumatism and orthopaedics
  • Aichi
    • Anjo-shi, Aichi, Japan, 446-8602
      • Anjo Kosei Hospital
  • Gunma
    • Takasaki, Gunma, Japan, 370-0053
      • Inoue Hospital
  • Hokkaido
    • Asahikawa, Hokkaido, Japan, 070-8644
      • National Hospital Organization Asahikawa Medical Center
    • Asahikawa, Hokkaido, Japan, 078-8243
      • Katayama Orthopaedic Rheumatology Clinic
    • Sapporo, Hokkaido, Japan, 060-8648
      • Hokkaido University Hospital
    • Sapporo, Hokkaido, Japan, 060-8604
      • Sapporo City General Hospital
  • Hyogo
    • Kato, Hyogo, Japan, 673-1462
      • Matsubara Mayflower Hospital
  • Nagasaki
    • Omura, Nagasaki, Japan, 856-8562
      • National Hospital Organization Nagasaki Medical Center
  • Saitama
    • Kawagoe, Saitama, Japan, 350-8550
      • Saitama Medical Center
    • Tokorozawa, Saitama, Japan, 359-1111
      • Hirose Clinic
• Korea, Republic of
  • Gwangju, Korea, Republic of, 61469
    • Chonnam National University Hospital
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital, Yonsei University Health System
  • Seoul, Korea, Republic of, 05030
    • Konkuk University Medical Center
  • Seoul, Korea, Republic of, 133-817
    • Hanyang University Seoul Hospital
• Lithuania
  • Kaunas, Lithuania, LT-50161
    • LSMUL Kauno klinikos
  • Klaipeda, Lithuania, LT-92288
    • Klaipedos Universitetine Ligonine
  • Vilnius, Lithuania, LT-08661
    • Vilniaus Universiteto ligonines Santariskiu Klinikos
• Mexico
  • Ciudad de Mexico, Mexico, CP 07760
    • Consultorio de Reumatologia
  • BAJA California
    • Mexicali, BAJA California, Mexico, 21100
      • Consultorio Medico Privado de Reumatologia
• New Zealand
  • Hamilton, New Zealand, 3204
    • Waikato Hospital
  • Wellington, New Zealand, 6021
    • Wellington Hospital, Capital Coast District Health Board
  • South Canterbury
    • Timaru, South Canterbury, New Zealand, 7940
      • MedLab
    • Timaru, South Canterbury, New Zealand, 7940
      • Timaru Hospital
    • Timaru, South Canterbury, New Zealand, 7940
      • Timaru Rheumatology Studies
• Peru
  • Arequipa, Peru, CP656
    • Unidad de Investigación en Medicina Interna y Enfermedades Críticas
  • Arequipa, Arequipa, Peru, 04020
    • Oficina Administrativa
  • Lima, Peru, Lima 31
    • Clinica Medica Cayetano Heredia
  • Lima, Peru, Lima 21
    • ABK REUMA SRL-Medicentro Biociencias Peru SRL
  • Lima, Peru, Lima 33
    • Centro de Investigación para el Estudio de Enfermedades Reumáticas
  • Lima, Peru, Lima 33
    • Instituto de Ginecología y Reproducción & Cirugía Mínimamente Invasiva
  • Lima, Lima, Peru, Lima 33
    • Oficina Administrativa
• Poland
  • Bialystok, Poland, 15-099
    • Gabinet Internistyczno-Reumatologiczny Piotr Adrian Klimiuk
  • Bialystok, Poland, 15-351
    • NZOZ Zdrowie Osteo-Medic s.c.
  • Elblag, Poland, 82-300
    • NZOZ Centrum Reumatologiczne Indywidualna Specjalistyczna Praktyka Lekarska Lek. Med. Barbara Bazela
  • Elblag, Poland, 82-300
    • Centrum Kliniczno-Badawcze J.Brzezicki, B. Gornikiewicz-Brzezicka Lekarze Spolka Partnerska
  • Gdynia, Poland, 81-537
    • Synexus Polska Sp. z o.o. Oddzial w Gdyni
  • Katowice, Poland, 40-040
    • Synexus Polska Sp. z o.o. Oddzial w Katowicach
  • Katowice, Poland, 40-081
    • Centrum Medyczne Pratia Katowice
  • Lublin, Poland, 20-582
    • Zespol Poradni Specjalistycznych "REUMED" Filia nr 2
  • Nadarzyn, Poland, 05-830
    • NZOZ Lecznica MAK-MED. S.C.
  • Poznan, Poland, 61-397
    • Prywatna Praktyka Lekarska Prof. UM dr hab. med. Pawel Hrycaj
  • Torun, Poland, 87-100
    • Niepubliczny Zaklad Opieki Zdrowotnej ''Nasz Lekarz''
  • Warszawa, Poland, 02-106
    • MTZ Clinical Research Sp. z o.o.
  • Warszawa, Poland, 01-518
    • Centrum Medyczne AMED
  • Warszawa, Poland, 01-192
    • Synexus Polska Sp. z o.o. Oddzial w Warszawie
  • Warszawa, Poland, 02-118
    • ''Rheuma Medicus'' Zakład Opieki Zdrowotnej
  • Wroclaw, Poland, 50-381
    • Synexus Polska Sp. z o.o. Oddział we Wroclawiu
• Russian Federation
  • Izhevsk, Russian Federation, 426035
    • LLC Alliance Biomedical Ural group
  • Kemerovo, Russian Federation, 650000
    • GAUZ of Kemerovo Region "Regional clinical hospital for war veterans"
  • Kursk, Russian Federation, 305007
    • GMU Kursk Regional Clinical Hospital of the Healthcare Committee of the Kursk Region
  • Moscow, Russian Federation, 119049
    • Municipal Clinical Hospital No. 1 Named after N.I. Pirogov
  • Moscow, Russian Federation, 129327
    • GBUZ of city of Moscow City clinical hospital n.a. A.K.Eramishantsev of Ministry of Healthcare of
  • Orenburg, Russian Federation, 460018
    • Regional Clinical Hospital
  • Orenburg, Russian Federation, 460000
    • Orenburg State Medical Academy
  • Ryazan, Russian Federation, 390026
    • GBOU VPO Ryazan State Medical University Named after Academician I.P. Pavlov
  • Ryazan, Russian Federation, 390026
    • GBU of Ryazan region Regional clinical cardiology dispanser
  • Saint-Petersburg, Russian Federation, 190068
    • Spb GBUZ "Clinical rheumatology hospital # 25" City CDC prevention of osteoporosis
  • Saratov, Russian Federation, 410053
    • GUZ " Regional clinical hospital"
  • Vladimir, Russian Federation, 600023
    • GBUZ VO Regional clinical hospital
  • Yaroslavl, Russian Federation, 150002
    • GBKUZ of Yaroslavl region "City hospital n. a. N.A. Semashko"
  • Republic OF Karelia
    • Petrozavodsk, Republic OF Karelia, Russian Federation, 185019
      • GBUZ Republican hospital n.a. V.A. Baranov
• Serbia
  • Belgrade, Serbia, 11000
    • Institute of Rheumatology
  • Belgrade, Serbia, 11000
    • Military Medical Academy,
  • Niska Banja, Serbia, 18205
    • Institute for Treatment and Rehabilitation Niska Banja
  • Novi Sad, Serbia, 21112
    • Special Hospital for Rheumatic Diseases Novi Sad
• South Africa
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 2193
      • Charlotte Maxeke Johannesburg Academic Hospital
    • Kempton Park, Gauteng, South Africa, 1619
      • Clinresco Centres (Pty) Ltd
  • Kwa-zulu Natal
    • Durban, Kwa-zulu Natal, South Africa, 4001
      • St. Augustine's Hospital
  • Western CAPE
    • Cape Town, Western CAPE, South Africa, 7500
      • Panorama Medical Centre
    • Cape Town, Western CAPE, South Africa, 7405
      • Arthritis Clinical Research Trials, Dr. C.E Spargo and Dr. R.B Bhorat Practice
• Spain
  • A Coruña, Spain, 15006
    • Hospital Universitario A Coruña
  • Madrid, Spain, 28034
    • Hospital Universitario Ramón y Cajal
  • Sevilla, Spain, 41010
    • Hospital Infanta Luisa
  • Madrid
    • Fuenlabrada, Madrid, Spain, 28942
      • Hospital Universitario de Fuenlabrada
  • Vizcaya
    • Barakaldo, Vizcaya, Spain, 48903
      • Hospital Universitario Cruces
• Taiwan
  • Taichung, Taiwan, 40447
    • China Medical University Hospital
  • Taichung, Taiwan, 40201
    • Chung Shan Medical University Hospital
  • Taipei, Taiwan, 11031
    • Taipei Medical University Hospital
• Ukraine
  • Kyiv, Ukraine, 03680
    • Kyivska miska klinichna likarnia #6
  • Lviv, Ukraine, 79010
    • Lvivskyi oblasnyi klinichnyi diahnostychnyi tsentr,
  • Lviv, Ukraine, 79011
    • Komunalna 4-a miska klinichna likarnia m. Lvova,
  • M. Kharkiv, Ukraine, 61176
    • Komunalnyi zaklad okhorony zdorovia "Kharkivska miska klinichna likarnia #8"
  • M. Kyiv,, Ukraine, 04107
    • Komunalnyi zaklad Kyivskoi oblasnoi rady "Kyivska oblasna klinichna likarnia",
  • Odesa, Ukraine, 65026
    • Bahatoprofilnyi medychnyi tsentr (Universytetska klinika #1)
  • Sumy, Ukraine, 40022
    • Komunalnyi zaklad Sumskoi oblasnoi rady "Sumska oblasna klinichna
  • Vinnytsia, Ukraine, 21018
    • Vinnytska oblasna klinichna likarnia im. M.I.Pyrohova revmatolohichne viddilennia
  • Zaporizhzhia, Ukraine, 69600
    • Komunalna ustanova "Zaporizka oblasna klinichna likarnia" Zaporizkoi oblasnoi rady
• United Kingdom
  • Hampshire
    • Basingstoke, Hampshire, United Kingdom, RG24 9NA
      • Basingstoke and North Hampshire Hospital, Hampshire Hospitals NHS Foundation Trust
  • Merseyside
    • Wirral, Merseyside, United Kingdom, CH49 5PE
      • Arrowe Park Hospital, Wirral University Teaching Hospitals NHS Foundation Trust
  • Somerset
    • Bath, Somerset, United Kingdom, BA1 1RL
      • Royal United Hospital Bath NHS Foundation Trust ,Royal National Hospital for Rheumatic Diseases
  • WEST Yorkshire
    • Leeds, WEST Yorkshire, United Kingdom, LS7 4SA
      • The Leeds Institute of Rheumatic and Musculoskeletal Medicine
• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • ArthroCare, Arthritis Care & Research P.C.
    • Glendale, Arizona, United States, 85306
      • Arizona Arthritis & Rheumatology Associates, PC
    • Phoenix, Arizona, United States, 85032
      • Arizona Arthritis & Rheumatology Associates, PC
  • California
    • Fullerton, California, United States, 92835
      • St. Jude Hospital Yorba Linda dba St. Joseph Heritage Healthcare
    • San Leandro, California, United States, 94578
      • East Bay Rheumatology Medical Group, Inc.
    • Thousand Oaks, California, United States, 91360
      • Westlake Medical Research
    • Upland, California, United States, 91786
      • Inland Rheumatology Clinical Trials, Inc.
    • Victorville, California, United States, 92395
      • Desert Valley Medical Group
  • Delaware
    • Newark, Delaware, United States, 19713
      • Javed Rheumatology Associates, Inc
  • Florida
    • Aventura, Florida, United States, 33180
      • Arthritis and Rheumatic Disease Specialties
    • Clearwater, Florida, United States, 33765
      • Robert W. Levin, MD, PA
    • Daytona Beach, Florida, United States, 32117
      • International Medical Research
    • Gainesville, Florida, United States, 32607
      • Southeastern Integrated Medical, PL, d/b/a Florida Medical Research
    • Gainesville, Florida, United States, 32607
      • SIMED Arthritis Center
    • Orlando, Florida, United States, 32806
      • Rheumatology Associates of Central Florida, P.A.
    • Sarasota, Florida, United States, 34239
      • Sarasota Arthritis Research Center
    • Vero Beach, Florida, United States, 32960
      • Alastair C. Kennedy, MD
    • Vero Beach, Florida, United States, 32960
      • Indian River Primary Care
  • Idaho
    • Boise, Idaho, United States, 83702
      • St Luke's Intermountain Research Center
    • Meridian, Idaho, United States, 83642
      • St Luke' s Clinic
  • Iowa
    • Cedar Rapids, Iowa, United States, 52403
      • Physician's Clinic of Iowa, P.C.
  • Kentucky
    • Bowling Green, Kentucky, United States, 42101
      • Graves-Gilbert Clinic Bowling Green
  • Maryland
    • Wheaton, Maryland, United States, 20902
      • The Center for Rheumatology and Bone Research
  • Michigan
    • Battle Creek, Michigan, United States, 49015
      • Bronson Internal Medicine and Rheumatology
  • Mississippi
    • Tupelo, Mississippi, United States, 38801
      • North Mississippi Medical Clinics, Inc. - Clinical Research
  • Nebraska
    • Lincoln, Nebraska, United States, 68516
      • Physician Research Collaboration, LLC
    • Omaha, Nebraska, United States, 68114
      • Westroads Clinical Research, Inc.
  • New Jersey
    • Voorhees, New Jersey, United States, 08043
      • Arthritis, Rheumatic & Back Disease Associates, P.A.
  • New York
    • New York, New York, United States, 10016
      • Manhattan Medical Research
    • Orchard Park, New York, United States, 14127
      • Buffalo Rheumatology and Medicine PLLC
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • Physicians East PA
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Cincinnati Rheumatic Disease Study Group, Inc.
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center for Clinical Research
    • Wyomissing, Pennsylvania, United States, 19610
      • Clinical Research of Reading, LLC
  • South Carolina
    • Charleston, South Carolina, United States, 29406
      • Low Country Rheumatology, PA
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Regional Health Clinical Research
    • Rapid City, South Dakota, United States, 57701
      • Regional Medical Clinic - Rheumatology
  • Tennessee
    • Jackson, Tennessee, United States, 38305
      • West Tennessee Research Institute
    • Memphis, Tennessee, United States, 38119
      • Ramesh C Gupta, M.D.
  • Texas
    • Amarillo, Texas, United States, 79124
      • Amarillo Center for Clinical Research, Ltd.
    • Austin, Texas, United States, 78731
      • Austin Regional Clinic
    • Dallas, Texas, United States, 75231
      • Metroplex Clinical Research Center
    • Houston, Texas, United States, 77090
      • The Clinical Research Institute of Houston, LLC
    • League City, Texas, United States, 77573
      • Accurate Clinical Research
    • Mesquite, Texas, United States, 75150
      • SouthWest Rheumatology Research, LLC
    • Shenandoah, Texas, United States, 77380
      • Northwest Diagnostic Clinic, PA
  • Virginia
    • Chesapeake, Virginia, United States, 23320
      • Center for Arthritis and Rheumatic Diseases, P.C.
  • Washington
    • Wenatchee, Washington, United States, 98801
      • Wenatchee Valley Hospitals & Clinics
  • West Virginia
    • Beckley, West Virginia, United States, 25801
      • Rheumatology and Pulmonary Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of rheumatoid arthritis based on 2010 ACR/EULAR criteria for at least 4 months.
• At least 6 tender (of 68 assessed) and 6 swollen (of 66 assessed) joints at screening and baseline.
• Hs-CRP equal or greater than 8 mg/L.
• Must have received methotrexate for at least 12 weeks and been on a stable dose for at least 4 weeks prior to the first study dose.

Exclusion Criteria:

• Evidence of untreated or inadequately treated latent or active TB.
• Evidence of uncontrolled, clinically significant diseases, including moderate or severe heart failure (NYHA Class III/IV) or malignancy in the previous 5 years.
• History of infection requiring hospitalization or parenteral antimicrobial therapy within 6 months prior to first dose of study drug.
• May have received no more than 2 doses of one biologic therapy (other than adalimumab or lymphocyte depleting therapy).
• Any second DMARD must be washed out prior to the first study dose.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: PF-06410293	Biological: PF-06410293; PF-06410293 will be administered with a uniform dose regimen, which is SC injection at a dose of 40 mg every other week, throughout the study treatment.; Other Names: Adalimumab-Pfizer
ACTIVE_COMPARATOR: Adalimumab	Biological: Adalimumab; Adalimumab will be administered with a uniform dose regimen, which is SC injection at a dose of 40 mg every other week, throughout the study treatment.; Other Names: Adalimumab-European Union, Humira®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12: Period 1	ACR20 is a categorical variable indicating a 20% or greater improvement in tender and swollen joint counts and 20% or greater improvement in 3 of the 5 other ACR-core set measures: patient's assessment of arthritis pain (PAAP); patient's global assessment of arthritis (PGA); physician's global assessment of arthritis (PGAA); high sensitivity C-reactive protein (hs-CRP); and Health Assessment Questionnaire - Disability Index (HAQ-DI).	Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With an American College of Rheumatology 20% (ACR20) Response at Other Time Points Other Than Week 12: Period 1	ACR20 is a categorical variable indicating a 20% or greater improvement in tender and swollen joint counts and 20% or greater improvement in 3 of the 5 other ACR-core set measures: patient's assessment of arthritis pain (PAAP); patient's global assessment of arthritis (PGA); physician's global assessment of arthritis (PGAA); high sensitivity C-reactive protein (hs-CRP); and Health Assessment Questionnaire - Disability Index (HAQ-DI).	Weeks 2, 4, 6, 8, 18 and 26 (pre-dose)
Number of Participants With an American College of Rheumatology 20% (ACR20) Response: Period 2	ACR20 is a categorical variable indicating a 20% or greater improvement in tender and swollen joint counts and 20% or greater improvement in 3 of the 5 other ACR-core set measures: patient's assessment of arthritis pain (PAAP); patient's global assessment of arthritis (PGA); physician's global assessment of arthritis (PGAA); high sensitivity C-reactive protein (hs-CRP); and Health Assessment Questionnaire - Disability Index (HAQ-DI).	Weeks 26, 30, 36, 44 and 52 (pre-dose)
Number of Participants With an American College of Rheumatology 20% (ACR20) Response: Period 3	ACR20 is a categorical variable indicating a 20% or greater improvement in tender and swollen joint counts and 20% or greater improvement in 3 of the 5 other ACR-core set measures: patient's assessment of arthritis pain (PAAP); patient's global assessment of arthritis (PGA); physician's global assessment of arthritis (PGAA); high sensitivity C-reactive protein (hs-CRP); and Health Assessment Questionnaire - Disability Index (HAQ-DI).	Weeks 52, 56, 66, 76 and 78
Number of Participants With an American College of Rheumatology 50% (ACR50) Response: Period 1	ACR50 is a categorical variable indicating a 50% or greater improvement in tender and swollen joint counts and 50% or greater improvement in 3 of the 5 other ACR-core set measures: patient's assessment of arthritis pain (PAAP); patient's global assessment of arthritis (PGA); physician's global assessment of arthritis (PGAA); high sensitivity C-reactive protein (hs-CRP); and Health Assessment Questionnaire - Disability Index (HAQ-DI).	Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose)
Number of Participants With an American College of Rheumatology 50% (ACR50) Response: Period 2	ACR50 is a categorical variable indicating a 50% or greater improvement in tender and swollen joint counts and 50% or greater improvement in 3 of the 5 other ACR-core set measures: patient's assessment of arthritis pain (PAAP); patient's global assessment of arthritis (PGA); physician's global assessment of arthritis (PGAA); high sensitivity C-reactive protein (hs-CRP); and Health Assessment Questionnaire - Disability Index (HAQ-DI).	Weeks 26, 30, 36, 44 and 52 (pre-dose)
Number of Participants With an American College of Rheumatology 50% (ACR50) Response: Period 3	ACR50 is a categorical variable indicating a 50% or greater improvement in tender and swollen joint counts and 50% or greater improvement in 3 of the 5 other ACR-core set measures: patient's assessment of arthritis pain (PAAP); patient's global assessment of arthritis (PGA); physician's global assessment of arthritis (PGAA); high sensitivity C-reactive protein (hs-CRP); and Health Assessment Questionnaire - Disability Index (HAQ-DI).	Weeks 52, 56, 66, 76 and 78
Number of Participants With an American College of Rheumatology 70% (ACR70) Response: Period 1	ACR70 is a categorical variable indicating a 70% or greater improvement in tender and swollen joint counts and 70% or greater improvement in 3 of the 5 other ACR-core set measures: patient's assessment of arthritis pain (PAAP); patient's global assessment of arthritis (PGA); physician's global assessment of arthritis (PGAA); high sensitivity C-reactive protein (hs-CRP); and Health Assessment Questionnaire - Disability Index (HAQ-DI).	Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose)
Number of Participants With an American College of Rheumatology 70% (ACR70) Response: Period 2	ACR70 is a categorical variable indicating a 70% or greater improvement in tender and swollen joint counts and 70% or greater improvement in 3 of the 5 other ACR-core set measures: patient's assessment of arthritis pain (PAAP); patient's global assessment of arthritis (PGA); physician's global assessment of arthritis (PGAA); high sensitivity C-reactive protein (hs-CRP); and Health Assessment Questionnaire - Disability Index (HAQ-DI).	Weeks 26, 30, 36, 44 and 52 (pre-dose)
Number of Participants With an American College of Rheumatology 70% (ACR70) Response: Period 3	ACR70 is a categorical variable indicating a 70% or greater improvement in tender and swollen joint counts and 70% or greater improvement in 3 of the 5 other ACR-core set measures: patient's assessment of arthritis pain (PAAP); patient's global assessment of arthritis (PGA); physician's global assessment of arthritis (PGAA); high sensitivity C-reactive protein (hs-CRP); and Health Assessment Questionnaire - Disability Index (HAQ-DI).	Weeks 52, 56, 66, 76 and 78
Change From Baseline in Tender Joint Count: Period 1	Sixty-eight (68) joints were assessed by an independent blinded joint assessor to determine the number of joints that were considered tender. The 68 joints assessed were: upper body including temporomandibular, sternoclavicular, acromioclavicular; upper extremity including shoulder, elbow, wrist (radiocarpal, carpal and carpometacarpal considered as 1 unit), metacarpophalangeals (MCP I, II, III, IV, V), thumb interphalangeal, proximal interphalangeals (PIP II, III, IV, V), and distal interphalangeals (DIP II, III, IV, V); lower extremity including hip, knee, ankle, tarsus (subtalar, transverse tarsal and tarsometatarsal considered as 1 unit), metatarsophalangeals (MTP I, II, III, IV, V), great toe interphalangeal, proximal and distal interphalangeals combined (PIP and DIP II, III, IV, V).	Baseline, Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose)
Change From Baseline in Tender Joint Count: Period 2	Sixty-eight (68) joints were assessed by an independent blinded joint assessor to determine the number of joints that were considered tender. The 68 joints assessed were: upper body including temporomandibular, sternoclavicular, acromioclavicular; upper extremity including shoulder, elbow, wrist (radiocarpal, carpal and carpometacarpal considered as 1 unit), metacarpophalangeals (MCP I, II, III, IV, V), thumb interphalangeal, proximal interphalangeals (PIP II, III, IV, V), and distal interphalangeals (DIP II, III, IV, V); lower extremity including hip, knee, ankle, tarsus (subtalar, transverse tarsal and tarsometatarsal considered as 1 unit), metatarsophalangeals (MTP I, II, III, IV, V), great toe interphalangeal, proximal and distal interphalangeals combined (PIP and DIP II, III, IV, V).	Baseline, Weeks 26, 30, 36, 44 and 52 (pre-dose)
Change From Baseline in Tender Joint Count: Period 3	Sixty-eight (68) joints were assessed by an independent blinded joint assessor to determine the number of joints that were considered tender. The 68 joints assessed were: upper body including temporomandibular, sternoclavicular, acromioclavicular; upper extremity including shoulder, elbow, wrist (radiocarpal, carpal and carpometacarpal considered as 1 unit), metacarpophalangeals (MCP I, II, III, IV, V), thumb interphalangeal, proximal interphalangeals (PIP II, III, IV, V), and distal interphalangeals (DIP II, III, IV, V); lower extremity including hip, knee, ankle, tarsus (subtalar, transverse tarsal and tarsometatarsal considered as 1 unit), metatarsophalangeals (MTP I, II, III, IV, V), great toe interphalangeal, proximal and distal interphalangeals combined (PIP and DIP II, III, IV, V).	Baseline, Weeks 52, 56, 66, 76 and 78
Change From Baseline in Swollen Joint Count: Period 1	Sixty-six (66) joints were assessed for swelling, the same as those listed for tender joint count, excluding the right and left hip joints.	Baseline, Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose)
Change From Baseline in Swollen Joint Count: Period 2	Sixty-six (66) joints were assessed for swelling, the same as those listed for tender joint count, excluding the right and left hip joints.	Baseline, Weeks 26, 30, 36, 44 and 52 (pre-dose)
Change From Baseline in Swollen Joint Count: Period 3	Sixty-six (66) joints were assessed for swelling, the same as those listed for tender joint count, excluding the right and left hip joints.	Baseline, Weeks 52, 56, 66, 76 and 78
Change From Baseline in Physician's Global Assessment of Arthritis (PGAA): Period 1	The investigator assessed how the participant's overall arthritis appeared at the time of the visit. This was an evaluation based on the participant's disease symptoms, functional capacity and physical examination, and independent of the participant's reported assessments of PGA (patient's global assessment of arthritis) and PAAP (patient's assessment of arthritis pain). The investigator's response was recorded using a 100 mm visual analog scale (VAS), with the 0 mm end labeled "None" and the 100 mm end labeled "Extreme".	Baseline, Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose)
Change From Baseline in Physician's Global Assessment of Arthritis (PGAA): Period 2	The investigator assessed how the participant's overall arthritis appeared at the time of the visit. This was an evaluation based on the participant's disease symptoms, functional capacity and physical examination, and independent of the participant's reported assessments of PGA (patient's global assessment of arthritis) and PAAP (patient's assessment of arthritis pain). The investigator's response was recorded using a 100 mm visual analog scale (VAS), with the 0 mm end labeled "None" and the 100 mm end labeled "Extreme".	Baseline, Weeks 26, 30, 36, 44 and 52 (pre-dose)
Change From Baseline in Physician's Global Assessment of Arthritis (PGAA): Period 3	The investigator assessed how the participant's overall arthritis appeared at the time of the visit. This was an evaluation based on the participant's disease symptoms, functional capacity and physical examination, and independent of the participant's reported assessments of PGA (patient's global assessment of arthritis) and PAAP (patient's assessment of arthritis pain). The investigator's response was recorded using a 100 mm visual analog scale (VAS), with the 0 mm end labeled "None" and the 100 mm end labeled "Extreme".	Baseline, Weeks 52, 56, 66, 76 and 78
Change From Baseline in Patient's Assessment of Arthritis Pain (PAAP): Period 1	Participants assessed the severity of their arthritis pain using a 100 mm Visual Analog Scale (VAS) by placing a mark on the scale between 0 (no pain) and 100 (most severe pain), which corresponded to the magnitude of their pain.	Baseline, Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose)
Change From Baseline in Patient's Assessment of Arthritis Pain (PAAP): Period 2	Participants assessed the severity of their arthritis pain using a 100 mm Visual Analog Scale (VAS) by placing a mark on the scale between 0 (no pain) and 100 (most severe pain), which corresponded to the magnitude of their pain.	Baseline, Weeks 26, 30, 36, 44 and 52 (pre-dose)
Change From Baseline in Patient's Assessment of Arthritis Pain (PAAP): Period 3	Participants assessed the severity of their arthritis pain using a 100 mm Visual Analog Scale (VAS) by placing a mark on the scale between 0 (no pain) and 100 (most severe pain), which corresponded to the magnitude of their pain.	Baseline, Weeks 52, 56, 66, 76 and 78
Change From Baseline in Patient's Global Assessment of Arthritis (PGA): Period 1	Participants answered the following question, "Considering all the ways your arthritis affects you, how are you feeling today?" The participant's response was recorded using a 100 mm visual analog scale (VAS), with the 0 mm end labeled "Very Well" and the 100 mm end labeled "Very Poorly".	Baseline, Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose)
Change From Baseline in Patient's Global Assessment of Arthritis (PGA): Period 2	Participants answered the following question, "Considering all the ways your arthritis affects you, how are you feeling today?" The participant's response was recorded using a 100 mm visual analog scale (VAS), with the 0 mm end labeled "Very Well" and the 100 mm end labeled "Very Poorly".	Baseline, Weeks 26, 30, 36, 44 and 52 (pre-dose)
Change From Baseline in Patient's Global Assessment of Arthritis (PGA): Period 3	Participants answered the following question, "Considering all the ways your arthritis affects you, how are you feeling today?" The participant's response was recorded using a 100 mm visual analog scale (VAS), with the 0 mm end labeled "Very Well" and the 100 mm end labeled "Very Poorly".	Baseline, Weeks 52, 56, 66, 76 and 78
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI): Period 1	HAQ-DI assesses the degree of difficulty a participant had experienced during the past week in 8 domains of daily activities: dressing and grooming, arising, eating, walking, hygiene, reach, grip and other activities. Each activity category consisted of 2-3 items. For each question in the questionnaire, the level of difficulty was scored from 0 to 3 with 0 representing "no difficulty", 1 as "some difficulty", 2 as "much difficulty", and 3 as "unable to do". Any activity that required assistance from another individual or required the use of an assistive device would adjust to a minimum score of 2 to represent a more limited functional status. Overall score was computed as the sum of scores divided by the number of domains answered. Total possible score range was 0-3 with 0 representing "no difficulty", 1 as "some difficulty", 2 as "much difficulty", and 3 as "unable to do". Higher score indicate more difficulty in performing daily living activities.	Baseline, Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose)
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI): Period 2	HAQ-DI assesses the degree of difficulty a participant had experienced during the past week in 8 domains of daily activities: dressing and grooming, arising, eating, walking, hygiene, reach, grip and other activities. Each activity category consisted of 2-3 items. For each question in the questionnaire, the level of difficulty was scored from 0 to 3 with 0 representing "no difficulty", 1 as "some difficulty", 2 as "much difficulty", and 3 as "unable to do". Any activity that required assistance from another individual or required the use of an assistive device would adjust to a minimum score of 2 to represent a more limited functional status. Overall score was computed as the sum of scores divided by the number of domains answered. Total possible score range was 0-3 with 0 representing "no difficulty", 1 as "some difficulty", 2 as "much difficulty", and 3 as "unable to do". Higher score indicate more difficulty in performing daily living activities.	Baseline, Weeks 26, 30, 36, 44 and 52 (pre-dose)
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI): Period 3	HAQ-DI assesses the degree of difficulty a participant had experienced during the past week in 8 domains of daily activities: dressing and grooming, arising, eating, walking, hygiene, reach, grip and other activities. Each activity category consisted of 2-3 items. For each question in the questionnaire, the level of difficulty was scored from 0 to 3 with 0 representing "no difficulty", 1 as "some difficulty", 2 as "much difficulty", and 3 as "unable to do". Any activity that required assistance from another individual or required the use of an assistive device would adjust to a minimum score of 2 to represent a more limited functional status. Overall score was computed as the sum of scores divided by the number of domains answered. Total possible score range was 0-3 with 0 representing "no difficulty", 1 as "some difficulty", 2 as "much difficulty", and 3 as "unable to do". Higher score indicate more difficulty in performing daily living activities.	Baseline, Weeks 52, 56, 66, 76 and 78
Change From Baseline in High-Sensitivity C-Reactive Protein (Hs-CRP): Period 1	Serum samples were analyzed to determine the level of hs-CRP, which was an acute-phase reactant.	Baseline, Weeks1, 2, 4, 6, 8, 12, 18 and 26 (pre-dose)
Change From Baseline in High-Sensitivity C-Reactive Protein (Hs-CRP): Period 2	Serum samples were analyzed to determine the level of hs-CRP, which was an acute-phase reactant.	Baseline, Weeks 26, 30, 36, 44 and 52 (pre-dose)
Change From Baseline in High-Sensitivity C-Reactive Protein (Hs-CRP): Period 3	Serum samples were analyzed to determine the level of hs-CRP, which was an acute-phase reactant.	Baseline, Weeks 52, 56, 66, 76 and 78
Change From Baseline in Disease Activity Score-28 (4 Components Based on High-Sensitivity C-Reactive Protein) (DAS28-4 [CRP]): Period 1	The DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-4 (CRP) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed, high-sensitivity C-reactive protein (hs-CRP) and patient's global assessment of arthritis (PGA). DAS28-4 (CRP) was calculated as 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 ln(CRP [mg/L] +1) + 0.014 (PGA [mm]) + 0.96. Higher score indicate more disease activity. The possible lowest score is 0.96. The possible highest score is difficult to be determined, due to indeterminable nature of hs-CRP level; assuming hs-CRP level is 0 to 500 mg/L, the possible highest score would be 6.8 (when hs-CRP is 0) to 9.04 (when hs-CRP is 500 mg/L).	Baseline, Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose)
Change From Baseline in Disease Activity Score-28 (4 Components Based on High-Sensitivity C-Reactive Protein) (DAS28-4 [CRP]): Period 2	The DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-4 (CRP) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed, high-sensitivity C-reactive protein (hs-CRP) and patient's global assessment of arthritis (PGA). DAS28-4 (CRP) was calculated as 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 ln(CRP [mg/L] +1) + 0.014 (PGA [mm]) + 0.96. Higher score indicate more disease activity. The possible lowest score is 0.96. The possible highest score is difficult to be determined, due to indeterminable nature of hs-CRP level; assuming hs-CRP level is 0 to 500 mg/L, the possible highest score would be 6.8 (when hs-CRP is 0) to 9.04 (when hs-CRP is 500 mg/L).	Baseline, Weeks 26, 30, 36, 44 and 52 (pre-dose)
Change From Baseline in Disease Activity Score-28 (4 Components Based on High-Sensitivity C-Reactive Protein) (DAS28-4 [CRP]): Period 3	The DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-4 (CRP) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed, high-sensitivity C-reactive protein (hs-CRP) and patient's global assessment of arthritis (PGA). DAS28-4 (CRP) was calculated as 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 ln(CRP [mg/L] +1) + 0.014 (PGA [mm]) + 0.96. Higher score indicate more disease activity. The possible lowest score is 0.96. The possible highest score is difficult to be determined, due to indeterminable nature of hs-CRP level; assuming hs-CRP level is 0 to 500 mg/L, the possible highest score would be 6.8 (when hs-CRP is 0) to 9.04 (when hs-CRP is 500 mg/L).	Baseline, Weeks 52, 56, 66, 76 and 78
Number of Participants Achieving European League Against Rheumatism (EULAR) Response: Period 1	EULAR response was based on DAS28 EULAR response criteria. Good response was achieved if DAS28 improvement from baseline >1.2 and DAS28 =<3.2. Moderate response was achieved if DAS28 improvement from baseline >0.6 to =<1.2 and DAS28 =<5.1; or DAS improvement from baseline >1.2 and DAS28 >3.2. No response was achieved if DAS improvement from baseline =<0.6 (no matter present DAS28 score); or DAS improvement from baseline >0.6 to =<1.2 and DAS28 >5.1.	Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose)
Number of Participants Achieving European League Against Rheumatism (EULAR) Response: Period 2	EULAR response was based on DAS28 EULAR response criteria. Good response was achieved if DAS28 improvement from baseline >1.2 and DAS28 =<3.2. Moderate response was achieved if DAS28 improvement from baseline >0.6 to =<1.2 and DAS28 =<5.1; or DAS improvement from baseline >1.2 and DAS28 >3.2. No response was achieved if DAS improvement from baseline =<0.6 (no matter present DAS28 score); or DAS improvement from baseline >0.6 to =<1.2 and DAS28 >5.1.	Weeks 26, 30, 36, 44 and 52 (pre-dose)
Number of Participants Achieving European League Against Rheumatism (EULAR) Response: Period 3	EULAR response was based on DAS28 EULAR response criteria. Good response was achieved if DAS28 improvement from baseline >1.2 and DAS28 =<3.2. Moderate response was achieved if DAS28 improvement from baseline >0.6 to =<1.2 and DAS28 =<5.1; or DAS improvement from baseline >1.2 and DAS28 >3.2. No response was achieved if DAS improvement from baseline =<0.6 (no matter present DAS28 score); or DAS improvement from baseline >0.6 to =<1.2 and DAS28 >5.1.	Weeks 52, 56, 66, 76 and 78
Number of Participants Achieving Disease Activity Score Remission (DAS <2.6): Period 1	The DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-4 (CRP) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed, high-sensitivity C-reactive protein (hs-CRP) and patient's global assessment of arthritis (PGA). DAS28-4 (CRP) was calculated as 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 ln(CRP [mg/L] +1) + 0.014 (PGA [mm]) + 0.96. The possible lowest score is 0.96. The possible highest score is difficult to be determined, due to indeterminable nature of hs-CRP level; assuming hs-CRP level is 0 to 500 mg/L, the possible highest score would be 6.8 (when hs-CRP is 0) to 9.04 (when hs-CRP is 500 mg/L). Higher score indicate more disease activity; DAS28-4 (CRP) <2.6 indicates remission.	Baseline, Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose)
Number of Participants Achieving Disease Activity Score Remission (DAS <2.6): Period 2	The DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-4 (CRP) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed, high-sensitivity C-reactive protein (hs-CRP) and patient's global assessment of arthritis (PGA). DAS28-4 (CRP) was calculated as 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 ln(CRP [mg/L] +1) + 0.014 (PGA [mm]) + 0.96. The possible lowest score is 0.96. The possible highest score is difficult to be determined, due to indeterminable nature of hs-CRP level; assuming hs-CRP level is 0 to 500 mg/L, the possible highest score would be 6.8 (when hs-CRP is 0) to 9.04 (when hs-CRP is 500 mg/L). Higher score indicate more disease activity; DAS28-4 (CRP) <2.6 indicates remission.	Weeks 26, 30, 36, 44 and 52 (pre-dose)
Number of Participants Achieving Disease Activity Score Remission (DAS <2.6): Period 3	The DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-4 (CRP) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed, high-sensitivity C-reactive protein (hs-CRP) and patient's global assessment of arthritis (PGA). DAS28-4 (CRP) was calculated as 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 ln(CRP [mg/L] +1) + 0.014 (PGA [mm]) + 0.96. The possible lowest score is 0.96. The possible highest score is difficult to be determined, due to indeterminable nature of hs-CRP level; assuming hs-CRP level is 0 to 500 mg/L, the possible highest score would be 6.8 (when hs-CRP is 0) to 9.04 (when hs-CRP is 500 mg/L). Higher score indicate more disease activity; DAS28-4 (CRP) <2.6 indicates remission.	Weeks 52, 56, 66, 76 and 78
Number of Participants Achieving American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Response：Period 1	Participants were considered to be in ACR/EULAR remission when either of the following criteria was met: scores on the tender joint count, swollen joint count, hs-CRP (mg/dL) and PGA (0-10 cm scale) were all =<1; or the score on the simplified disease activity index (SDAI) was =<3.3. SDAI score was the sum of tender joint count (28), swollen joint count (28), PGA (0-10 cm scale), physician's global assessment of arthritis (PGAA, 0-10 cm scale) and hs-CRP (mg/dL).	Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose)
Number of Participants Achieving American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Response: Period 2	Participants were considered to be in ACR/EULAR remission when either of the following criteria was met: scores on the tender joint count, swollen joint count, hs-CRP (mg/dL) and PGA (0-10 cm scale) were all =<1; or the score on the simplified disease activity index (SDAI) was =<3.3. SDAI score was the sum of tender joint count (28), swollen joint count (28), PGA (0-10 cm scale), physician's global assessment of arthritis (PGAA, 0-10 cm scale) and hs-CRP (mg/dL).	Weeks 26, 30, 36, 44 and 52 (pre-dose)
Number of Participants Achieving American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Response: Period 3	Participants were considered to be in ACR/EULAR remission when either of the following criteria was met: scores on the tender joint count, swollen joint count, hs-CRP (mg/dL) and PGA (0-10 cm scale) were all =<1; or the score on the simplified disease activity index (SDAI) was =<3.3. SDAI score was the sum of tender joint count (28), swollen joint count (28), PGA (0-10 cm scale), physician's global assessment of arthritis (PGAA, 0-10 cm scale) and hs-CRP (mg/dL).	Weeks 52, 56, 66, 76 and 78
Serum Concentration Versus Time Summary: Period 1		Pre-dose on Days 1, 15, 43, 85 and 183, and at any time during Day 8 visit
Serum Concentration Versus Time Summary: Period 2		Pre-dose on Days 183, 211, 253 and 365
Serum Concentration Versus Time Summary: Period 3		Pre-dose on Days 365, 393, 463, 547 and 575
Number of Participants With Positive Anti-drug Antibodies (ADA) and Neutralizing Antibodies (NAb): Period 1	Serum samples were analyzed for the presence or absence of ADA using a semi-quantitative electrochemiluminescent (ECL) assay, and ADA positive was defined as ADA titer >=1.88. Serum samples tested positive for ADA were further analyzed for the presence or absence of NAb using a semi-quantitative cell-based assay, and NAb positive was defined as NAb titer >=0.70.	Baseline up to Week 26 (pre-dose)
Number of Participants With Positive Anti-drug Antibodies (ADA) and Neutralizing Antibodies (NAb): Period 2	Serum samples were analyzed for the presence or absence of ADA using a semi-quantitative electrochemiluminescent (ECL) assay, and ADA positive was defined as ADA titer >=1.88. Serum samples tested positive for ADA were further analyzed for the presence or absence of NAb using a semi-quantitative cell-based assay, and NAb positive was defined as NAb titer >=0.70.	Week 26 dosing up to Week 52 (pre-dose)
Number of Participants With Positive Anti-drug Antibodies (ADA) and Neutralizing Antibodies (NAb): Period 3	Serum samples were analyzed for the presence or absence of ADA using a semi-quantitative electrochemiluminescent (ECL) assay, and ADA positive was defined as ADA titer >=1.88. Serum samples tested positive for ADA were further analyzed for the presence or absence of NAb using a semi-quantitative cell-based assay, and NAb positive was defined as NAb titer >=0.70.	Week 52 dosing up to follow-up visit (Week 92)
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Treatment Related TEAEs: Period 1	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 AEs for Period 1 were events between first dose of study drug in Period 1 and up to Week 26 pre-dose assessments that were absent before treatment or that worsened relative to pre-treatment state. Treatment-related TEAE was any untoward medical occurrence attributed to study drug. AEs included both serious and non-serious AEs.	Baseline (Day 1) up to Week 26 (pre-dose)
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Treatment Related TEAEs: Period 2	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 AEs for Period 2 were events between first dose of study drug in Period 2 and up to Week 52 pre-dose assessments that were absent before treatment or that worsened relative to prior state. Treatment-related TEAE was any untoward medical occurrence attributed to study drug. AEs included both serious and non-serious AEs.	Week 26 dosing up to Week 52 (pre-dose)
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Treatment Related TEAEs: Period 3	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 AEs for Period 3 were events between first dose of study drug in Period 3 and up to Week 92 visit that were absent before treatment or that worsened relative to prior state. Treatment-related TEAE was any untoward medical occurrence attributed to study drug. AEs included both serious and non-serious AEs.	Week 52 dosing up to follow-up visit (Week 92)
Number of Participants With Laboratory Abnormalities: Period 1	Laboratory evaluation included hematology, clinical chemistry, and urinalysis. Each parameter was evaluated against commonly used and widely accepted criteria. Number of participants with any laboratory abnormality during Period 1 (without regard to baseline abnormality) is presented.	Baseline (Day 1) up to Week 26 (pre-dose)
Number of Participants With Laboratory Abnormalities: Period 2	Laboratory evaluation included hematology, clinical chemistry, and urinalysis. Each parameter was evaluated against commonly used and widely accepted criteria. Number of participants with any laboratory abnormality during Period 2 (without regard to baseline abnormality) is presented.	Week 26 dosing up to Week 52 (pre-dose)
Number of Participants With Laboratory Abnormalities: Period 3	Laboratory evaluation included hematology, clinical chemistry, and urinalysis. Each parameter was evaluated against commonly used and widely accepted criteria. Number of participants with any laboratory abnormality during Period 3 (without regard to baseline abnormality) is presented.	Week 52 dosing up to follow-up visit (Week 92)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieved Delivery Success in Sub-study	A sub-study was conducted to determine whether participants or their non-healthcare professional caregivers could safely and effectively administer PF-06410293 with the sponsor's prefilled pen (PFP) device.	Weeks 56, 58, 60, 62, 64, 66

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Kay J, Bock AE, Rehman M, Zhang W, Zhang M, Iikuni N, Alvarez DF. Use of multibiomarker disease activity scores in biosimilarity studies for the treatment of patients with rheumatoid arthritis. RMD Open. 2022 Sep;8(2):e002423. doi: 10.1136/rmdopen-2022-002423.
• Fleischmann RM, Bock AE, Zhang W, Godfrey CM, Vranic I, Cronenberger C, Dokoupilova E. Usability Study of PF-06410293, an Adalimumab Biosimilar, by Prefilled Pen: Open-Label, Single-Arm, Sub-Study of a Phase 3 Trial in Patients with Rheumatoid Arthritis. Rheumatol Ther. 2022 Jun;9(3):839-850. doi: 10.1007/s40744-022-00439-8. Epub 2022 Mar 18.
• Fleischmann RM, Alvarez DF, Bock AE, Cronenberger C, Vranic I, Zhang W, Alten R. Long-term efficacy, safety, and immunogenicity of the adalimumab biosimilar, PF-06410293, in patients with rheumatoid arthritis after switching from reference adalimumab (Humira(R)) or continuing biosimilar therapy: week 52-92 data from a randomized, double-blind, phase 3 trial. Arthritis Res Ther. 2021 Sep 25;23(1):248. doi: 10.1186/s13075-021-02626-4.
• Fleischmann RM, Alvarez DF, Bock AE, Cronenberger C, Vranic I, Zhang W, Alten R. Randomised study of PF-06410293, an adalimumab (ADL) biosimilar, compared with reference ADL for the treatment of active rheumatoid arthritis: results from weeks 26-52, including a treatment switch from reference ADL to PF-06410293. RMD Open. 2021 Apr;7(2):e001578. doi: 10.1136/rmdopen-2021-001578.
• Huizinga TWJ, Torii Y, Muniz R. Adalimumab Biosimilars in the Treatment of Rheumatoid Arthritis: A Systematic Review of the Evidence for Biosimilarity. Rheumatol Ther. 2021 Mar;8(1):41-61. doi: 10.1007/s40744-020-00259-8. Epub 2020 Dec 1.
• Fleischmann RM, Alten R, Pileckyte M, Lobello K, Hua SY, Cronenberger C, Alvarez D, Bock AE, Sewell KL. A comparative clinical study of PF-06410293, a candidate adalimumab biosimilar, and adalimumab reference product (Humira(R)) in the treatment of active rheumatoid arthritis. Arthritis Res Ther. 2018 Aug 15;20(1):178. doi: 10.1186/s13075-018-1676-y.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 25, 2015
• Primary Completion (ACTUAL): August 31, 2016
• Study Completion (ACTUAL): December 6, 2017

Study Registration Dates

• First Submitted: June 19, 2015
• First Submitted That Met QC Criteria: June 19, 2015
• First Posted (ESTIMATE): June 24, 2015

Study Record Updates

• Last Update Posted (ACTUAL): January 23, 2019
• Last Update Submitted That Met QC Criteria: January 18, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: rheumatoid arthritis; adalimumab; Phase 3
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Anti-Inflammatory Agents; Antirheumatic Agents; Adalimumab
• Other Study ID Numbers: B5381002; B5381002, REFLECTIONS B538-02; 2014-000352-29 (EUDRACT_NUMBER); ADALIMUMAB (OTHER: Alias Study 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.