A Study of PF-06438179 (Infliximab-Pfizer) and Infliximab in Combination With Methotrexate in Subjects With Active Rheumatoid Arthritis (REFLECTIONS B537-02).

Rheumatoid Arthritis Clinical Trial

Official title:

A Phase 3 Randomized, Double-blind Study Assessing The Efficacy And Safety Of Pf-06438179 And Infliximab In Combination With Methotrexate In Subjects With Moderately To Severely Active Rheumatoid Arthritis Who Have Had An Inadequate Response To Methotrexate

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02222493
• Other study ID #: B5371002
• Secondary ID: REFLECTIONS B537
• Status: Completed
• Phase: Phase 3
• Start date: August 26, 2014
• Est. completion date: June 1, 2017

Study information

• Verified date: April 2018
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study will assess the efficacy and safety of PF-06438179 and infliximab in combination with methotrexate in subjects with active rheumatoid arthritis who have had an inadequate response to methotrexate.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 650
• Est. completion date: June 1, 2017
• Est. primary completion date: June 29, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 10 mg/L.

Must have received methotrexate for at least 12 weeks and be on a stable dose for at least 4 weeks.

Exclusion Criteria:

Evidence of untreated or inadequately treated latent or active TB.

Evidence or history of moderate or severe heart failure (NYHA Class III/IV)

Infection requiring hospitalization or parenteral antimicrobial therapy judged clinically significant by the investigator within 6 months prior to first dose of study drug.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Biological:
• PF-06438179
PF-06438179 will be administered by intravenous infusion at an initial dose of 3 mg/kg at 0, 2 and 6 weeks, then every 8 weeks.
• Infliximab
Infliximab will be administered by intravenous infusion at an initial dose of 3 mg/kg at 0, 2 and 6 weeks, then every 8 weeks.

Locations

Country	Name	City	State
Australia	CliniPath Pathology	Osborne Park	Western Australia
Australia	Gold Coast Private Hospital Pty Ltd	Southport	Queensland
Australia	HPS Pharmacies	Southport	Queensland
Australia	Paradise Arthritis and Rheumatology Pty Ltd	Southport	Queensland
Australia	R.K. Will Pty Ltd	Victoria Park	Western Australia
Australia	The Queen Elizabeth Hospital	Woodville South	South Australia
Bosnia and Herzegovina	University Hospital Clinical Center Banja Luka	Banja Luka
Bosnia and Herzegovina	Clinical Center University of Sarajevo	Sarajevo	Kanton Sarajevo
Bosnia and Herzegovina	General Hospital "Prim.dr.Abdulah Nakas"	Sarajevo	Kanton Sarajevo
Bosnia and Herzegovina	University Clinical Center Tuzla	Tuzla	Tuzlanski Kanton
Brazil	CETI - Centro de Estudos em Terapias Inovadoras	Curitiba	Paraná
Brazil	Hospital Israelita Albert Einstein	São Paulo
Bulgaria	Multiprofile Hospital for Active Treatment Trimontium OOD	Plovdiv
Bulgaria	University Multiprofile Hospital for Active Treatment (UMHAT) "Kaspela" EOOD	Plovdiv
Bulgaria	University Multiprofile Hospital for Active Treatment (UMHAT) "Sv. Ivan Rilski" EAD	Sofia
Canada	Clinical Research and Arthritis Center	Windsor	Ontario
Czechia	CCBR Czech Brno, s.r.o.	Brno
Czechia	Lekarna Lancier, s.r.o.	Brno
Czechia	BENU Lekarna	Pardubice
Czechia	CCBR-SYNARC a.s.	Pardubice
Czechia	Lekarna U Robina, s.r.o.	Praha
Czechia	CCBR Czech Prague, s.r.o.	Praha 3
Czechia	Lekarna Hradebni s.r.o.	Uherske Hradiste
Czechia	MEDICAL PLUS, s.r.o.	Uherske Hradiste
Georgia	LTD Adapti	Tbilisi
Georgia	LTD MediClubGeorgia	Tbilisi
Georgia	LTD Medulla" Chemotherapy and Immunotherapy Clinic	Tbilisi
Georgia	LTD Tbilisi Central Hospital	Tbilisi
Georgia	LTD Unimedi Kakheti	Tbilisi
Georgia	Tbilisi Heart and Vascular Clinic LTD	Tbilisi
Germany	Schlosspark-Klinik	Berlin
Germany	Klinikum der Universität München	München
Germany	Elisabeth-Klinik gGmbH	Olsberg
Germany	Knappschaftsklinikum Saar GmbH	Puettlingen
Germany	Rheumazentrum Ratingen	Ratingen
Guatemala	Centro de Nutricion y Rehabilitacion Cardiorespiratoria, S.A. (NUCARE)	Guatemala
Guatemala	Clínica Médica especializada en Medicina Interna	Guatemala
Guatemala	Clínica Médica Especializada en Medicina Interna y Reumatología	Guatemala
Guatemala	Therapeutic Research Institute and Lab S.A	Guatemala
Hungary	DRC Gyógyszervizsgáló Központ Kft.	Balatonfüred
Hungary	Qualiclinic Kft.	Budapest
Israel	Rambam Health Care Campus	Haifa
Israel	Hadassah Medical Organization, Hadassah Medical Center, Ein-Karem	Jerusalem
Israel	Meir Medical Center	Kfar Saba
Japan	Mazda Hospital	Aki-gun	Hiroshima
Japan	Anjo Kosei Hospital	Anjo-shi	Aichi
Japan	National Hospital Organization Chiba-East Hospital	Chiba
Japan	St. Luke's International Hospital	Chuo-ku	Tokyo
Japan	Kondo clinic for rheumatism and orthopaedics	Fukuoka
Japan	National Hospital Organization Kyushu Medical Center	Fukuoka
Japan	Aso Iizuka Hospital	Iiduka	Fukuoka
Japan	Matsubara Mayflower Hospital	Katoh	Hyogo
Japan	Saitama Medical Center	Kawagoe-shi	Saitama
Japan	Kumamoto Orthopaedic Hospital	Kumamoto
Japan	Kurashiki Sweet Hospital	Kurashiki	Okayama
Japan	Toho University Ohashi Medical Center	Meguro-ku	Tokyo
Japan	National Hospital Organization Nagasaki Medical Center	Omura	Nagasaki
Japan	National Hospital Organization Sagamihara National Hospital	Sagamihara	Kanagawa
Japan	Hokkaido University Hospital	Sapporo	Hokkaido
Japan	Sapporo City General Hospital	Sapporo	Hokkaido
Japan	Sasebo Chuo Hospital	Sasebo	Nagasaki
Japan	Showa University Hospital	Shinagawa-ku	Tokyo
Japan	National Hospital Organization Shizuoka Medical Center	Sunto-gun	Shizuoka
Japan	Inoue Hospital	Takasaki	Gunma
Japan	Hirose Clinic	Tokorozawa-shi	Saitama
Japan	Yuaikai Tomishiro Central Hospital	Tomigusuku	Okinawa
Japan	Yokohama Minami Kyosai Hospital	Yokohama	Kanagawa
Jordan	Jordan Hospital	Amman
Jordan	King Abdullah University Hospital	Irbid
Korea, Republic of	Chungnam National University Hospital	Daejeon
Korea, Republic of	Chonnam National University Hospital	Gwangju
Korea, Republic of	Hanyang University Seoul Hospital	Seoul
Korea, Republic of	Konkuk University Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Lithuania	LSMUL Kauno klinikos	Kaunas
Mexico	Unidad Reumatologica Las Americas S.C.P	Merida	Yucatan
Mexico	Centro de Alta Especialidad en Reumatología e Investigación del Potosí, S.C.	San Luis De Potosí	SAN LUIS DE Potosi
Mexico	Unidad de Investigaciones Reumatológicas A.C - Hospital Central "Dr. Ignacio Morones Prieto"	Zona Universitaria	SAN LUIS DE Potosi
Morocco	El Ayachi Hospital	Salé
Morocco	Groupe Radiologique de Salé	Salé
Morocco	Laboratoire les Arcades d'Analyses Médicales	Salé
Peru	Centro de diagnóstico por imágenes, Radiología General y Especial	Arequipa
Peru	Unidad de Investigación en Medicina Interna y Enfermedades Críticas	Arequipa
Peru	Centro de Investigación Reumatología CAA	Lima
Peru	Clinica Medica Cayetano Heredia	Lima
Peru	Servicio de Inmunología y Reumatología	Lima
Peru	Hospital María Auxiliadora - Centro de Investigaciones Medicas	San juan de Miraflores	Lima
Peru	Instituto de Ginecología y Reproducción & Cirugía Mínimamente Invasiva	Santiago de Surco	Lima
Philippines	Southern Philippines Medical Center	Davao	Davao DEL SUR
Philippines	Mary Mediatrix Medical Center	Lipa City	Batangas
Philippines	Makati Medical Center	Makati	Metro Manila
Philippines	Medical Center Manila	Manila
Philippines	Philippine General Hospital	Manila
Philippines	St. Luke's Medical Center	Quezon
Poland	Szpital Uniwersytecki nr 2 im. dr. Jana Biziela w Bydgoszczy	Bydgoszcz
Poland	Szpital Specjalistyczny im. J. Dietla Malopolskie Centrum Reumatologii Immunologii i Rehabilitacji	Krakow
Poland	NZOZ Lecznica MAK-MED. S.C.	Nadarzyn
Poland	Twoja Przychodnia - Centrum Medyczne Nowa Sol	Nowa Sol
Poland	MTZ Clinical Research Sp. z o.o.	Warszawa
Romania	Spitalul Clinic Judetean de Urgenta Galati "Sf. Apostol Andrei"	Galati
Romania	Spitalul Clinic de Recuperare Iasi	Iasi
Romania	Spitalul Clinic Judetean de Urgenta Targu Mures	Targu Mures
Russian Federation	GAUZ of Kemerovo Region "Regional clinical hospital for war veterans"	Kemerovo
Russian Federation	KGBUZ "Krasnoyarsk Interdistrict Clinical Hospital #20 n.a. I.S.Berzon"	Krasnoyarsk
Russian Federation	Krasnoyarsk State Medical University n.a.Prof.V.F.Voyno-Yasenetsky	Krasnoyarsk
Russian Federation	GMU " Kursk regional clinical hospital" of the Committee of Healthcare of the Kursk region	Kursk
Russian Federation	GBUZ of city of Moscow	Moscow
Russian Federation	GBUZ "Republican hospital n.a. V.A.Baranov"	Petrozavodsk	Republic OF Karelia
Russian Federation	GBOU of Ryazan region "Regional clinical hospital"	Ryazan
Russian Federation	GBOU VPO "Ryazan State medical university n.a. academician I.P.Pavlov"	Ryazan
Russian Federation	GBOUVPO "Ryazan State Medical University n.a. Academician I.P.Pavlov"	Ryazan
Russian Federation	GBU of Ryazan region "Regional clinical cardiology dispanser"	Ryazan
Russian Federation	Spb GBUZ "Clinical rheumatology hospital # 25" City CDC prevention of osteoporosis	Saint-Petersburg
Russian Federation	GUZ "Regional clinical hospital"	Saratov
Russian Federation	GBUZ VO 'Regional clinical hospital"	Vladimir
Russian Federation	GBKUZ of Yaroslavl region "City hospital n. a. N.A. Semashko"	Yaroslavl
Serbia	Clinical Hospital Center Bezanijska Kosa	Belgrade
Serbia	Military Medical Academy	Belgrade
Serbia	Institute for Treatment and Rehabilitation "Niska Banja"	Niska Banja
South Africa	Arthritis Clinical Research Unit	Cape Town	Western CAPE
South Africa	Vincent Pallotti Hospital	Cape Town	Western CAPE
South Africa	Charlotte Maxeke Johannesburg Academic Hospital	Johannesburg	Gauteng
South Africa	Emmed Research	Pretoria	Gauteng
South Africa	Jakaranda Hospital	Pretoria	Gauteng
Tunisia	Mohamed Kassab Institute of orthopedics	Manouba
Tunisia	Rabta Hospital	Tunis
Ukraine	Derzhavna ustanova "Ukrainskyi derzhavnyi naukovo-doslidnyi instytut	Dnipropetrovsk
Ukraine	Oblasna klinichna likarnia, revmatolohichne viddilennia, Derzhavnyi vyshchyi navchalnyi zaklad	Ivano-Frankivsk
Ukraine	Komunalnyi zaklad okhorony zdorovia "Kharkivska miska klinichna likarnia #8"	Kharkiv
Ukraine	Khmelnytska oblasna likarnia	Khmelnytskyi
Ukraine	Kyivska miska klinichna likarnia #6	Kyiv
Ukraine	Klinichnyi hospital Derzhavnoi prykordonnoi sluzhby Ukrainy	Lviv
Ukraine	Komunalnyi zaklad "Kryvorizka miska klinichna likarnia #2" Dnipropetrovskoi oblasnoi rady"	M. Kryvyi Rih
Ukraine	Komunalnyi zaklad Sumskoi oblasnoi rady "Sumska oblasna klinichna likarnia"	M. Sumy
Ukraine	Vinnytska oblasna klinichna likarnia im. M.I.Pyrohova, revmatolohichne	M. Vinnytsia
Ukraine	Bahatoprofilnyi medychnyi tsentr (Universytetska klinika #1)	Odesa
Ukraine	Komunalna ustanova "Odeska oblasna klinichna likarnia"	Odesa
Ukraine	Komunalna ustanova "Zaporizka oblasna klinichna likarnia" Zaporizkoi oblasnoi rady	Zaporizhzhia
United Kingdom	Maidstone Hospital, Maidstone and Tunbridge wells NHS Trust	Maidstone
United Kingdom	Wrightington Hospital	Wigan	Lancashire
United States	Austin Regional Clinic	Austin	Texas
United States	Arthritis and Rheumatic Disease Specialties	Aventura	Florida
United States	Ochsner Clinic Baton Rouge	Baton Rouge	Louisiana
United States	Western Michigan University Homer Stryker MD School of Medicine Center for Clinical Research	Battle Creek	Michigan
United States	Achieve Clinical Research, LLC	Birmingham	Alabama
United States	Gilbert-Graves Clinic	Bowling Green	Kentucky
United States	Graves-Gilbert Clinic Bowling Green	Bowling Green	Kentucky
United States	Physician's Clinic of Iowa, P.C.	Cedar Rapids	Iowa
United States	Low Country Rheumatology, PA	Charleston	South Carolina
United States	Metroplex Clinical Research Center	Dallas	Texas
United States	International Medical Research	Daytona Beach	Florida
United States	Altoona Center for Clinical Research	Duncansville	Pennsylvania
United States	St. Jude Hospital Yorba Linda DBA St. Joseph Heritage Healthcare	Fullerton	California
United States	Accurate Clinical Research, Inc.	Houston	Texas
United States	West Tennessee Research Institute	Jackson	Tennessee
United States	Arthritis & Osteoporosis Medical Center	La Palma	California
United States	Ramesh C Gupta, MD	Memphis	Tennessee
United States	Advanced Clinical Research	Meridian	Idaho
United States	Advance Medical Research Services Corporation	Miami	Florida
United States	San Marcus Research Clinic, Inc.	Miami	Florida
United States	Trinity Health Center-Medical Arts	Minot	North Dakota
United States	Arthritis and Diabetes Clinic, Inc.	Monroe	Louisiana
United States	Accurate Clinical Research	Nassau Bay	Texas
United States	Javed Rheumatology Associates, Inc	Newark	Delaware
United States	Pharmacy Services, Sentara Leigh Hospital	Norfolk	Virginia
United States	Sentara Medical Group, Clinical Research	Norfolk	Virginia
United States	Methodist Medical Center of IL	Peoria	Illinois
United States	Sun Valley Arthritis Center, Ltd.	Peoria	Arizona
United States	Arizona Arthritis & Rheumatology Associates, P.C.	Phoenix	Arizona
United States	Regional Health Clinical Research	Rapid City	South Dakota
United States	Regional Medical Clinic	Rapid City	South Dakota
United States	Harbin Clinic	Rome	Georgia
United States	Sarasota Arthritis Research Center	Sarasota	Florida
United States	The Seattle Arthritis Clinic	Seattle	Washington
United States	Clinical and Translational Research Center of Alabama, PC	Tuscaloosa	Alabama
United States	Inland Rheumatology Clinical Trials, Inc.	Upland	California
United States	Alastair C. Kennedy, MD	Vero Beach	Florida
United States	Indian River Primary Care	Vero Beach	Florida
United States	Desert Valley Medical Group	Victorville	California
United States	Arthritis, Rheumatic & Back Disease Associates	Voorhees	New Jersey
United States	The Center for Rheumatology and Bone Research	Wheaton	Maryland
United States	Clinical Research Center of Reading, LLC	Wyomissing	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Australia,  Bosnia and Herzegovina,  Brazil,  Bulgaria,  Canada,  Czechia,  Georgia,  Germany,  Guatemala,  Hungary,  Israel,  Japan,  Jordan,  Korea, Republic of,  Lithuania,  Mexico,  Morocco,  Peru,  Philippines,  Poland,  Romania,  Russian Federation,  Serbia,  South Africa,  Tunisia,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 14: Period 1	ACR20 response: greater than or equal to (>=) 20 percent (%) improvement in tender joint count (TJC); >= 20% improvement in swollen joint count (SJC); and >= 20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity (PGA); physician global assessment of disease activity; self-assessed disability (health assessment questionnaire-disability index [HAQ-DI]); and C-Reactive Protein (CRP).	Week 14
Secondary	Number of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 2, 4, 6, 12, 22 and 30 (Pre-dose): Period 1	ACR20 response: >=20% improvement in tender joint count; >=20% improvement in swollen joint count; and >=20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; HAQ-DI and CRP.	Week 2, 4, 6, 12, 22 and 30 (pre-dose)
Secondary	Number of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 38, 46 and 54 (Pre-dose): Period 2	ACR20 response: >=20% improvement in tender joint count; >=20% improvement in swollen joint count; and >=20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; HAQ-DI and CRP.	Week 38, 46 and 54 (pre-dose)
Secondary	Number of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 62, 70 and 78: Period 3	ACR20 response: >=20% improvement in tender joint count; >=20% improvement in swollen joint count; and >=20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; HAQ-DI and CRP.	Week 62, 70 and 78
Secondary	Number of Participants With an American College of Rheumatology 50% (ACR50) and ACR 70% Response at Week 2, 4, 6, 12, 14, 22 and 30 (Pre-dose): Period 1	ACR50 response: >=50% improvement in tender joint count, >=50% improvement in swollen joint count improvement and >=50% in at least 3 of 5 remaining ACR core measures: participant assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, HAQ-DI and CRP. ACR70 response: >=70% improvement in tender joint count, >=70% improvement in swollen joint count improvement and >=70% in at least 3 of 5 remaining ACR core measures: participant assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, HAQ-DI and CRP.	Week 2, 4, 6, 12, 14, 22 and 30 (pre-dose)
Secondary	Number of Participants With an American College of Rheumatology 50% (ACR50) and ACR 70% Response at Week 38, 46 and 54 (Pre-dose): Period 2	ACR50 response: >=50% improvement in tender joint count, >=50% improvement in swollen joint count improvement and >=50% in at least 3 of 5 remaining ACR core measures: participant assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, HAQ-DI and CRP. ACR70 response: >=70% improvement in tender joint count, >=70% improvement in swollen joint count improvement and >=70% in at least 3 of 5 remaining ACR core measures: participant assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, HAQ-DI and CRP.	Week 38, 46 and 54 (pre-dose)
Secondary	Number of Participants With an American College of Rheumatology 50% (ACR50) and ACR 70% Response at Week 62, 70 and 78: Period 3	ACR50 response: >=50% improvement in tender joint count, >=50% improvement in swollen joint count improvement and >=50% in at least 3 of 5 remaining ACR core measures: participant assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, HAQ-DI and CRP. ACR70 response: >=70% improvement in tender joint count, >=70% improvement in swollen joint count improvement and >=70% in at least 3 of 5 remaining ACR core measures: participant assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, HAQ-DI and CRP.	Week 62, 70 and 78
Secondary	Change From Baseline in Disease Activity Score-CRP (4 Variables) (DAS28-4 [CRP]) and HAQ-DI at Week 2, 4, 6, 12, 14, 22 and 30: Period 1	DAS28 is measure of disease activity in participants. DAS28-4 (CRP): calculated from SJC, TJC, CRP(mg/L) and PGA (participant rated disease activity on visual analogue scale [VAS] from 0 to 100 mm; high score=worse health). Total score range of DAS28-4 (CRP): 0 to 9.4(0=no activity; 9.4=extreme disease activity), higher score=more disease activity. DAS28-4(CRP) less than (<)2.6=remission, <3.2=low disease activity, >=3.2-5.1=moderate disease activity and greater than (>) 5.1=high disease activity. HAQ-DI assess degree of difficulty a participant experienced (past week) in 8 domain of daily activities: dressing and grooming, arising, eating, walking, hygiene, reach, grip and other activities. Each item scored on a 4-point scale ranging from 0 to 3(0=no difficulty; 3=extreme difficulty). Overall score: sum of domain scores/number of domains answered. Total possible score range (0=least difficulty; 3=extreme difficulty); high scores=more difficulty in performing daily living activities.	Baseline (Day 1), Week 2, 4, 6, 12, 14, 22 and 30
Secondary	Change From Baseline in Disease Activity Score-CRP (4 Variables) (DAS28-4 [CRP]) and HAQ-DI at Week 38, 46 and 54: Period 2	DAS28 is measure of disease activity in participants. DAS28-4 (CRP): calculated from SJC, TJC, CRP(mg/L) and PGA (participant rated disease activity on VAS from 0 to 100 millimeter [mm]; high score=worse health). Total score range of DAS28-4 (CRP): 0 to 9.4(0=no activity; 9.4=extreme disease activity), higher score=more disease activity. DAS28-4(CRP) <2.6=remission, <3.2=low disease activity, >=3.2-5.1=moderate disease activity and >5.1=high disease activity. HAQ-DI assess degree of difficulty a participant experienced (past week) in 8 domain of daily activities: dressing and grooming, arising, eating, walking, hygiene, reach, grip and other activities. Each item scored on a 4-point scale ranging from 0 to 3(0=no difficulty; 3=extreme difficulty). Overall score: sum of domain scores/number of domains answered. Total possible score range (0=least difficulty; 3=extreme difficulty); high scores=more difficulty in performing daily living activities.	Baseline (Week 30 pre-dose), Week 38, 46 and 54
Secondary	Change From Baseline in Disease Activity Score-CRP (4 Variables) (DAS28-4 [CRP]) and HAQ-DI at Week 62, 70 and 78: Period 3	DAS28 is measure of disease activity in participants. DAS28-4 (CRP): calculated from SJC, TJC, CRP(mg/L) and PGA (participant rated disease activity on VAS from 0 to 100 mm; high score=worse health). Total score range of DAS28-4 (CRP): 0 to 9.4(0=no activity; 9.4=extreme disease activity), higher score=more disease activity. DAS28-4(CRP) <2.6=remission, <3.2=low disease activity, >=3.2-5.1=moderate disease activity and >5.1=high disease activity. HAQ-DI assess degree of difficulty a participant experienced (past week) in 8 domain of daily activities: dressing and grooming, arising, eating, walking, hygiene, reach, grip and other activities. Each item scored on a 4-point scale ranging from 0 to 3(0=no difficulty; 3=extreme difficulty). Overall score: sum of domain scores/number of domains answered. Total possible score range (0=least difficulty; 3=extreme difficulty); high scores=more difficulty in performing daily living activities.	Baseline (Week 54 pre-dose), Week 62, 70 and 78
Secondary	Number of Participants Achieving American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) and Disease Activity Score (DAS <2.6) Remission: Period 1	ACR/EULAR remission was considered if the scores on tender joint count, swollen joint count, hs-CRP (mg/dL), and patient's global assessment of arthritis (PGA) all were less than or equal to (=<) 1 or the score on the simplified disease activity index (SDAI) was =<3.3. SDAI was calculated as the sum of number of tender and swollen joint count (using 28 joints), PGA, physician global assessment, and CRP (mg/dL). PGA was assessed on a 10 mm VAS ranging from 0 (very well) to 10 (very poor), where higher scores indicate worse health condition. Physician global assessment was recorded on a 10 mm VAS ranging from 0 (very well) to 10 (very poor), where higher scores indicated more disease activity. DAS28 calculated from number of swollen joints and painful joints using the 28 joints count, CRP (mg/dL) and PGA using a 10 mm-VAS from 0 (very well) to 10 (very poor), where higher scores indicate worse health condition. DAS28 <3.2: low disease activity, DAS28 <2.6: remission.	Week 2, 4, 6, 12, 14, 22 and Week 30 (pre-dose)
Secondary	Number of Participants Achieving American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) and Disease Activity Score (DAS <2.6) Remission: Period 2	ACR/EULAR remission was considered if the scores on tender joint count, swollen joint count, hs-CRP (mg/dL), and PGA all were =<1 or the score on the SDAI was =<3.3. SDAI was calculated as the sum of number of tender and swollen joint count (using 28 joints), PGA, physician global assessment, and CRP (mg/dL). PGA was assessed on a 10 mm VAS ranging from 0 (very well) to 10 (very poor), where higher scores indicate worse health condition. Physician global assessment was recorded on a 10 mm VAS ranging from 0 (very well) to 10 (very poor), where higher scores indicated more disease activity. DAS28 calculated from number of swollen joints and painful joints using the 28 joints count, CRP (mg/dL) and PGA using a 10 mm-VAS from 0 (very well) to 10 (very poor), where higher scores indicate worse health condition. DAS28 <3.2: low disease activity, DAS28 <2.6: remission.	Week 38, 46 and 54 (pre-dose)
Secondary	Number of Participants Achieving American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) and Disease Activity Score (DAS <2.6) Remission: Period 3	ACR/EULAR remission was considered if the scores on tender joint count, swollen joint count, hs-CRP (mg/dL), and PGA all were =<1 or the score on the SDAI was =<3.3. SDAI was calculated as the sum of number of tender and swollen joint count (using 28 joints), PGA, physician global assessment, and CRP (mg/dL). PGA was assessed on a 10 mm VAS ranging from 0 (very well) to 10 (very poor), where higher scores indicate worse health condition. Physician global assessment was recorded on a 10 mm VAS ranging from 0 (very well) to 10 (very poor), where higher scores indicated more disease activity. DAS28 calculated from number of swollen joints and painful joints using the 28 joints count, CRP (mg/dL) and PGA using a 10 mm-VAS from 0 (very well) to 10 (very poor), where higher scores indicate worse health condition. DAS28 <3.2: low disease activity, DAS28 <2.6: remission.	Week 62, 70 and 78
Secondary	Number of Participants With European League Against Rheumatism (EULAR) Response: Period 1	EULAR response was based on DAS28 EULAR response criteria which was defined as good response = DAS28 change of >1.2 with DAS28 =<3.2; moderate response = DAS28 change of >0.6 to =<1.2 with DAS28 >3.2-5.1 and no-response = DAS28 change of =<0.6 with DAS28 >5.1.	Week 2, 4, 6, 12, 14, 22 and Week 30 (pre-dose)
Secondary	Number of Participants With European League Against Rheumatism (EULAR) Response: Period 2	EULAR response was based on DAS28 EULAR response criteria which was defined as good response = DAS28 change of >1.2 with DAS28 =<3.2; moderate response = DAS28 change of >0.6 to =<1.2 with DAS28 >3.2-5.1 and no-response = DAS28 change of =<0.6 with DAS28 >5.1.	Week 38, 46 and Week 54 (pre-dose)
Secondary	Number of Participants With European League Against Rheumatism (EULAR) Response: Period 3	EULAR response was based on DAS28 EULAR response criteria which was defined as good response = DAS28 change of >1.2 with DAS28 =<3.2; moderate response = DAS28 change of >0.6 to =<1.2 with DAS28 >3.2-5.1 and no-response = DAS28 change of =<0.6 with DAS28 >5.1.	Week 62, 70 and Week 78
Secondary	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 were events between first dose of study drug and up to Week 30 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 in a participant who received study drug. AEs included both serious and non-serious adverse events.	Baseline (Day 1) up to Week 30
Secondary	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 were events between first dose of study drug and up to Week 54 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 in a participant who received study drug. AEs included both serious and non-serious adverse events.	Baseline (Week 30 pre-dose) up to Week 54
Secondary	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 were events between first dose of study drug and up to Week 78 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 in a participant who received study drug. AEs included both serious and non-serious adverse events.	Baseline (Week 54 pre-dose) up to Week 78
Secondary	Number of Participants With Treatment Emergent Adverse Events (TEAEs) of Grade 3 or Higher Severity: Period 1	AEs were graded in accordance with National Cancer Institute (NCI) Common Terminology Criteria for AEs (CTCAE) Version 4.03 as Grades 1= mild, Grade 2= moderate, Grade 3= severe, Grade 4= life threatening AEs and Grade 5= death related to AE. AEs of Grade 3 and higher severity are reported in this outcome measure.	Baseline (Day 1) up to Week 30
Secondary	Number of Participants With Treatment Emergent Adverse Events (TEAEs) of Grade 3 or Higher Severity: Period 2	AEs were graded in accordance with National Cancer Institute (NCI) Common Terminology Criteria for AEs (CTCAE) Version 4.03 as Grades 1= mild, Grade 2= moderate, Grade 3= severe, Grade 4= life threatening AEs and Grade 5= death related to AE. AEs of Grade 3 and higher severity are reported in this outcome measure.	Baseline (Week 30 pre-dose) up to Week 54
Secondary	Number of Participants With Treatment Emergent Adverse Events (TEAEs) of Grade 3 or Higher Severity: Period 3	AEs were graded in accordance with National Cancer Institute (NCI) Common Terminology Criteria for AEs (CTCAE) Version 4.03 as Grades 1= mild, Grade 2= moderate, Grade 3= severe, Grade 4= life threatening AEs and Grade 5= death related to AE. AEs of Grade 3 and higher severity are reported in this outcome measure.	Baseline (Week 54 pre-dose) up to Week 78
Secondary	Number of Participants With Laboratory Abnormalities: Period 1	Criteria for abnormality:hematology: hemoglobin, hematocrit, red blood cell count, lymphocytes, neutrophils: <0.8*lower limit of normal (LLN); platelets: >1.75*upper limit of normal (ULN); white blood cell count: <0.6*LLN; basophils, eosinophils, monocytes: >1.2*ULN. liver function: bilirubin: >1.5*ULN; aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase: >3.0*ULN; protein, albumin: <0.8*LLN>	Baseline (Day 1) up to Week 30
Secondary	Number of Participants With Laboratory Abnormalities: Period 2	Criteria for abnormality:hematology: hemoglobin, hematocrit, red blood cell count, lymphocytes, neutrophils: <0.8*lower limit of normal (LLN); platelets: >1.75*upper limit of normal (ULN); white blood cell count: <0.6*LLN; basophils, eosinophils, monocytes: >1.2*ULN. liver function: bilirubin: >1.5*ULN; aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase: >3.0*ULN; protein, albumin: <0.8*LLN>	Baseline (Week 30 pre-dose) up to Week 54
Secondary	Number of Participants With Laboratory Abnormalities: Period 3	Criteria for abnormality:hematology: hemoglobin, hematocrit, red blood cell count, lymphocytes, neutrophils: <0.8*lower limit of normal (LLN); platelets: >1.75*upper limit of normal (ULN); white blood cell count: <0.6*LLN; basophils, eosinophils, monocytes: >1.2*ULN. liver function: bilirubin: >1.5*ULN; aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase: >3.0*ULN; protein, albumin: <0.8*LLN>	Baseline (Week 54 pre-dose) up to Week 78
Secondary	Change From Baseline in Tender Joint Count and Swollen Joint Count at Week 2, 4, 6, 12, 14, 22 and 30: Period 1	Tender joint count was an assessment of 68 joints (upper body, upper extremity, and lower extremity). Each joint's response to pressure/motion was assessed as: Present or Absent. Swollen joint count was an assessment of 66 joints (upper body, upper extremity, and lower extremity). Each joint was assessed for swelling as: Present or Absent.	Baseline (Day 1), Week 2, 4, 6, 12, 14, 22 and Week 30
Secondary	Change From Baseline in Tender Joint Count and Swollen Joint Count at Week 38, 46 and 54: Period 2	Tender joint count was an assessment of 68 joints (upper body, upper extremity, and lower extremity). Each joint's response to pressure/motion was assessed as: Present or Absent. Swollen joint count was an assessment of 66 joints (upper body, upper extremity, and lower extremity). Each joint was assessed for swelling as: Present or Absent.	Baseline (Week 30 pre-dose), Week 38, 46 and Week 54
Secondary	Change From Baseline in Tender Joint Count and Swollen Joint Count at Week 62, 70 and 78: Period 3	Tender joint count was an assessment of 68 joints (upper body, upper extremity, and lower extremity). Each joint's response to pressure/motion was assessed as: Present or Absent. Swollen joint count was an assessment of 66 joints (upper body, upper extremity, and lower extremity). Each joint was assessed for swelling as: Present or Absent.	Baseline (Week 54 pre-dose), Week 62, 70 and 78
Secondary	Change From Baseline in Patient's Assessment of Arthritis Pain (PAAP), Patient's Global Assessment of Arthritis (PGA) and Physician's Global Assessment of Arthritis (PGAA) at Week 2, 4, 6, 12, 14, 22, 30: Period 1	PAAP: Participants assessed the severity of their arthritis pain by using a 100 mm VAS ranging from 0 (no pain) to 100 (most severe pain), which corresponded to the magnitude of their pain, where higher scores indicated more pain. PGA: Participants were asked the following question, "Considering all the ways your arthritis affects you, how are you feeling today?" and their response was recorded on a 100 mm VAS ranging from 0 (very well) to 100 (very poor), where higher scores indicated worse health condition. PGAA: Participants were assessed how their overall arthritis appears at the time of the visit. The evaluation was based on the participant's disease signs, functional capacity and physical examination, and was independent of the PAAP and PGA assessments. The physician's response was recorded using a 100 mm VAS ranging from 0 (very well) to 100 (very poor), where higher scores indicated more disease activity.	Baseline (Day 1), Week 2, 4, 6, 12, 14, 22 and 30
Secondary	Change From Baseline in Patient's Assessment of Arthritis Pain (PAAP), Patient's Global Assessment of Arthritis (PGA) and Physician's Global Assessment of Arthritis (PGAA) at Week 38, 46 and 54: Period 2	PAAP: Participants assessed the severity of their arthritis pain by using a 100 mm VAS ranging from 0 (no pain) to 100 (most severe pain), which corresponded to the magnitude of their pain, where higher scores indicated more pain. PGA: Participants were asked the following question, "Considering all the ways your arthritis affects you, how are you feeling today?" and their response was recorded on a 100 mm VAS ranging from 0 (very well) to 100 (very poor), where higher scores indicated worse health condition. PGAA: Participants were assessed how their overall arthritis appears at the time of the visit. The evaluation was based on the participant's disease signs, functional capacity and physical examination, and was independent of the PAAP and PGA assessments. The physician's response was recorded using a 100 mm VAS ranging from 0 (very well) to 100 (very poor), where higher scores indicated more disease activity.	Baseline (Week 30 pre-dose), Week 38, 46 and 54
Secondary	Change From Baseline in Patient's Assessment of Arthritis Pain (PAAP), Patient's Global Assessment of Arthritis (PGA) and Physician's Global Assessment of Arthritis (PGAA) at Week 62, 70 and 78: Period 3	PAAP: Participants assessed the severity of their arthritis pain by using a 100 mm VAS ranging from 0 (no pain) to 100 (most severe pain), which corresponded to the magnitude of their pain, where higher scores indicated more pain. PGA: Participants were asked the following question, "Considering all the ways your arthritis affects you, how are you feeling today?" and their response was recorded on a 100 mm VAS ranging from 0 (very well) to 100 (very poor), where higher scores indicated worse health condition. PGAA: Participants were assessed how their overall arthritis appears at the time of the visit. The evaluation was based on the participant's disease signs, functional capacity and physical examination, and was independent of the PAAP and PGA assessments. The physician's response was recorded using a 100 mm VAS ranging from 0 (very well) to 100 (very poor), where higher scores indicated more disease activity.	Baseline (Week 54 pre-dose), Week 62, 70 and 78
Secondary	Change From Baseline in High Sensitivity C-Reactive Protein (Hs-CRP) Concentration at Week 2, 4, 6, 12, 14, 22 and 30: Period 1		Baseline (Day 1), Week 2, 4, 6, 12, 14, 22 and 30
Secondary	Change From Baseline in High Sensitivity C-Reactive Protein (Hs-CRP) Concentration at Week 38, 46 and 54: Period 2		Baseline (Week 30 pre-dose), Week 38, 46 and 54
Secondary	Change From Baseline in High Sensitivity C-Reactive Protein (Hs-CRP) Concentration at Week 62, 70 and 78: Period 3		Baseline (Week 54 pre-dose), Week 62, 70 and 78
Secondary	Number of Participants With Positive Anti-drug Antibodies (ADA) and Neutralizing Antibodies (Nab) Status: Period 1	ADA positive results was defined as ADA titer level >=1.30 and NAb positive was defined as NAb titer level >=0.70.	Baseline (Day 1) up to Week 30
Secondary	Number of Participants With Positive Anti-drug Antibodies (ADA) and Neutralizing Antibodies (Nab) Status: Period 2	ADA positive results was defined as ADA titer level >=1.30 and NAb positive was defined as NAb titer level >=0.70.	Baseline (Week 30 pre-dose) up to Week 54
Secondary	Number of Participants With Positive Anti-drug Antibodies (ADA) and Neutralizing Antibodies (Nab) Status: Period 3	ADA positive results was defined as ADA titer level >=1.30 and NAb positive was defined as NAb titer level >=0.70.	Baseline (Week 54 pre-dose) up to Week 78
Secondary	Serum Concentration Versus Time Summary: Period 1		Pre dose on Day 1, 15, 43, 99, 155 and 211; 2 hours post dose on Day 1 and 99; and 336 hours post dose on Day 29
Secondary	Serum Concentration Versus Time Summary: Period 2		Pre dose on Day 211, 267, 379 and 547
Secondary	Serum Concentration Versus Time Summary: Period 3		Pre dose on Day 379, 435 and 547

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