A Study of Tocilizumab as Monotherapy and in Combination With Methotrexate Versus Methotrexate in Patients With Early Moderate to Severe Rheumatoid Arthritis

A Multi-center, Randomized, Double-blind, Parallel Group Study of the Safety, Disease Remission and Prevention of Structural Joint Damage During Treatment With Tocilizumab (TCZ), as a Monotherapy and in Combination With Methotrexate (MTX), Versus Methotrexate in Patients With Early, Moderate to Severe Rheumatoid Arthritis

This randomized, double-blind, parallel group study will assess the safety, disease remission, and prevention of structural joint damage in patients with early moderate to severe rheumatoid arthritis treated with tocilizumab as monotherapy or in combination with methotrexate, versus methotrexate alone. Patients will be randomized to receive either (A) tocilizumab (8 mg/kg iv every 4 weeks) plus placebo, (B) tocilizumab (8 mg/kg iv every 4 weeks) plus methotrexate (7.5-20 mg po weekly), (C) tocilizumab (4 mg/kg iv every 4 weeks) plus methotrexate (7.5-20 mg po weekly), or (D) placebo plus methotrexate (7.5-20 mg po weekly). Patients in groups C and D who have not achieved low disease activity at week 52 can receive tocilizumab 8 mg/kg iv every 4 weeks. Anticipated time on study treatment is 104 weeks.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Tocilizumab; Drug: Placebo to methotrexate; Drug: Methotrexate; Drug: Placebo to tocilizumab

• Study Type: Interventional
• Enrollment (Actual): 1162
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1015ABO
    • Organización Médica de Investigación
  • Buenos Aires, Argentina, C1428DQG
    • Inst. de Rehabilitacion Psicofisica; Reumathology
  • Rosario, Argentina, S2000PBJ
    • Caici; Rheumatology
  • San Miguel, Argentina, T4000AXL
    • Centro Medico Privado de Reumatologia; Reumathology
• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital; Rheumatology
  • Queensland
    • Maroochydore, Queensland, Australia, 4558
      • Sunshine Coast Rheumatology Research Unit
  • South Australia
    • Woodville, South Australia, Australia, 5011
      • Queen Elizabeth Hospital; Rheumatology
  • Tasmania
    • Hobart, Tasmania, Australia, 7100
      • Menzies Research Institute
  • Victoria
    • Malvern, Victoria, Australia, 3144
      • Cabrini Medical Centre; Rheumatology
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Worthing Hospital
• Austria
  • Innsbruck, Austria, 6020
    • Lkh innsbruck - univ. Klinikum innsbruck - Tiroler landeskrankenanstalten ges.m.b.h.; Innere Medizin
  • Wien, Austria, 1100
    • Kaiser Franz Josef Spital; Ii. Medizinische Abt.
  • Wien, Austria, 1130
    • Krankenhaus der stadt wien hietzing; ii. Med. Abt. / zentrum für rheumatologie
• Brazil
  • GO
    • Goiania, GO, Brazil, 74653-050
      • Hospital das Clinicas - UFG;Reumatologia
    • Goiania, GO, Brazil, 74110010
      • Centro Internacional de Pesquisa; Reumatologia
  • MG
    • Juiz de Fora, MG, Brazil, 36036-330
      • Centro Mineiro de Pesquisa - CMIP
  • PR
    • Curtiba, PR, Brazil, 80030-110
      • Centro de Estudos em Terapias Inovadoras - CETI
  • RS
    • Porto Alegre, RS, Brazil, 90610-000
      • Hospital São Lucas - PUCRS
  • SP
    • Campinas, SP, Brazil, 13059-900
      • Hospital e Maternidade Celso Pierro - PUCCamp; Reumatologia
    • Sao Paulo, SP, Brazil, 04026-000
      • Universidade Federal de Sao Paulo - UNIFESP; Reumatologia
    • Sao Paulo, SP, Brazil, 04266-010
      • Centro Paulista de Investigacao Clinica - CEPIC
• Canada
  • Quebec, Canada, G1W 4R4
    • Centre Re Recherche Saint-Louis
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 3Y1
      • Laurel Medical Clinic
    • Vancouver, British Columbia, Canada, V5Z 1L7
      • Arthritis Research Centre
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3A 1M3
      • Manitoba Clinic
  • Newfoundland and Labrador
    • St John's, Newfoundland and Labrador, Canada, A1A 5E8
      • Nexus Clinical Research Centre
  • Ontario
    • Hamilton, Ontario, Canada, L8N 1Y2
      • Dr. William G. Bensen Medicine Professional Corporation
    • Kitchener, Ontario, Canada, N2M 5N6
      • K-W Musculoskeletal Research
    • London, Ontario, Canada, N6A 4V2
      • St. Joseph'S Health Care Centre; Rheumatology
    • Ottawa, Ontario, Canada, K1H 1A2
      • Rheumatology Research Associates
    • St. Catharines, Ontario, Canada, L2N 7E4
      • Niagara Peninsula Arthritis Centre
  • Quebec
    • Montreal, Quebec, Canada, H2L 1S6
      • Institut de Rhumatologie de Montreal
    • Montreal, Quebec, Canada, H1T 2M4
      • Hopital Maisonneuve- Rosemont; Rheumatology
    • Trois-rivieres, Quebec, Canada, G8Z 1Y2
      • Centre De Recherche Musculo-Squelettique
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7K 0H6
      • Saskatoon Osteoporosis Centre
• China
  • Beijing, China, 10029
    • China-Japan Friendship Hospital
  • Beijing, China, 100853
    • General Hospital of Chinese PLA; Department of Hematology
  • Guangzhou, China, 510630
    • The Third Affiliated Hospital of Sun Yat-Sen University
  • Shanghai, China, 200127
    • Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
• Colombia
  • Bogota, Colombia
    • Riesgo De Fractura; Rheumatology
  • Medellin, Colombia
    • Reumalab Sas; Rheumatology
  • Medellin-Antioquia, Colombia
    • Hospital Pablo Tobón Uribe
• Denmark
  • Køge, Denmark, 4600
    • Sjællands Universitetshospital, Køge; Reumatologisk Afdeling
• Finland
  • Helsinki, Finland, 00290
    • Helsinki University Central Hospital; Rheumatology Clinic
  • Hyvinkää, Finland, 05800
    • Kiljavan Lääketutkimus Oy
• France
  • Cahors, France, 46005
    • CH Jean Rougier; Rhumato Reed Fonctionnelle
  • Marseille, France, 13285
    • Fondation Hopital Saint Joseph; Rhumatologie
  • Montpellier, France, 34295
    • Hopital Lapeyronie; Immunologie Rhumatologie
  • Mulhouse, France, 68070
    • Hopital emile muller; Rhumatologie
  • Orleans, France, 45032
    • Hopital Porte Madeleine; Service de Rhumatologie
  • Paris, France, 75651
    • Ch Pitie Salpetriere; Rhumatologie
  • Toulouse, France, 31059
    • Hopital Purpan; Rhumatologie
• Germany
  • Bad Nauheim, Germany, 61231
    • Kerckhoff-Klinik; Rheumatologie&klin.Immunologie
  • Baden-Baden, Germany, 76530
    • Rheuma-Zentrum Baden-Baden Gmbh; Klinik Für Innere Medizin-Rheumatologie
  • Berlin, Germany, 10117
    • Campus Charité Mitte Charité Centrum 12. Med.Klinik Abt.Rheumatologie u.Klin.Immunologie
  • Berlin, Germany, 14059
    • Schlosspark Klinik; Abt. Rheumatologie
  • Dresden, Germany, 01307
    • Universitätsklinikum "Carl Gustav Carus"; Medizinische Klinik III
  • Erlangen, Germany, 91056
    • Dres. Florian Schuch, Ruediger de la Camp, Martin Hammerschmidt u.w.
  • Hamburg, Germany, 22081
    • Schön Klinik Hamburg-Eilbek Klinik für Rheumatologie
  • Heidelberg, Germany, 69120
    • Rheumapraxis PD Dr.med. Bernhard Heilig
  • Herne, Germany, 44652
    • Rheumazentrum-Ruhrgebiet, St. Josefs-Krankenhaus; Rheumatologie
  • Hildesheim, Germany, 31134
    • Gemeinschaftspraxis Dr. Von Hinueber/Dr. Demary; Rheumatologie
  • Köln, Germany, 50924
    • Klinik der Uni zu Köln; Klinik für Innere Medizin
  • München, Germany, 80336
    • Klinikum der Universität München; Bereich Pettenkoferstr.; Rheumaeinheit der medizinischen Klinik IV
  • Osnabrück, Germany, 49074
    • Rheumapraxis an der Hase
  • Ratingen, Germany, 40882
    • Evangelisches Fachkrankenhaus; Rheumaklinik
  • Würzburg, Germany, 97080
    • Universitätsklinikum Würzburg; Medizinische Klinik und Poliklinik II; Rheumatologie/Immunologie
• Greece
  • Athens, Greece, 115 27
    • Laiko General Hospital; Hematology Clinic
  • Larissa, Greece, 411 10
    • University General Hospital of Larissa; Rheumatology Unit
• Guatemala
  • Guatemala City, Guatemala, 01010
    • Clinica Medica Del Dr Eduardo Alfredo Samayoa
  • Guatemala City, Guatemala, 01010
    • Private Practice
  • Guatemala City, Guatemala, 01015
    • Reuma-Centro
• Hong Kong
  • Hong Kong, Hong Kong
    • Pamela Youde Nethersole Eastern Hospital; Department of Medicine
  • Hong Kong, Hong Kong, 852
    • QUEEN MARY HOSPITAL; Division of Rheumatology & Clinical Immunology
  • Tuen Mun, Hong Kong
    • Tuen Mun Hospital; Medicine & Geriatrics
• Hungary
  • Budapest, Hungary, 1027
    • Budai Irgalmasrendi Kórház KHT. II. Reumatológia
  • Debrecen, Hungary, 4032
    • Debreceni Egyetem Orvos- és Egészségtudományi Centrum; Belgyógyászati Intézet, Reumatológiai Tanszék
  • Eger, Hungary, 3300
    • Markhot Ferenc Hospital; Dep. of Rheumatology
• Ireland
  • Cork, Ireland
    • Cork Uni Hospital; Dept of Rheumatology
  • Dublin, Ireland, 24
    • Adelaide and Meath Hospital; Rheumatology Department
  • Dublin, Ireland, 4
    • St.Vincent's University Hospital; Rheumatology Department
• Israel
  • Afula, Israel, 18101
    • Haemek Hospital; Rheumatology
  • Ashkelon, Israel, 78306
    • Barzilai; Rheumatology
  • Haifa, Israel, 3339419
    • Bnei Zion Medical Center; Rheumatology
  • Jerusalem, Israel, 91240
    • Hadassah Mount Scopus Hospital; Rheumatology
  • Jerusalem, Israel, 9112001
    • Hadassah University Hospital, Ein Karem; Rheumatology
  • Kfar Saba, Israel, 44281
    • Meir Medical Center; Internal Dept A
  • Ramat Gan, Israel, 5262000
    • Chaim Sheba Medical Center; Rheumatology
  • Ramat-Gan, Israel, 52621
    • Chaim Sheba Medical Center; Interna Dept B
• Italy
  • Campania
    • Napoli, Campania, Italy, 80131
      • Policlinico Universitario; Cattedra Di Reumatologia, Edificio 3
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40136
      • Istituto Ortopedico Rizzoli; Unità di Reumatologia
    • Reggio Emilia, Emilia-Romagna, Italy, 42100
      • Arcispedale Santa Maria Nuova; Reumatologia
  • Lazio
    • Roma, Lazio, Italy, 00128
      • Campus Bio-Medico; Immunologia e Allergologia
    • Roma, Lazio, Italy, 00161
      • Policlinico Umberto I - Universita' La Sapienza ; Cattedra Di Reumatologia - Dept. Terapia Medica
  • Liguria
    • Genova, Liguria, Italy, 16132
      • Università Degli Studi Di Genova - Dimi; Reumatologia
  • Lombardia
    • Magenta, Lombardia, Italy, 20013
      • Ospedale Di Magenta Fornaroli; U.O. Di Reumatologia
    • Milano, Lombardia, Italy, 20157
      • ASST FATEBENEFRATELLI SACCO; Reumatologia (Sacco)
  • Piemonte
    • Torino, Piemonte, Italy, 10154
      • Ospedale S. Giovanni Bosco; S.C. A Direzione Uni Ria Di Immunologia Clinica
  • Sardegna
    • Monserrato, Sardegna, Italy, 09042
      • Policlinico Universitario Di Cagliari
• Macedonia, The Former Yugoslav Republic of
  • Skopje, Macedonia, The Former Yugoslav Republic of, 1000
    • Clinic of Rheumatology; Clinical Centre Skopje
• Mexico
  • Guadalajara, Mexico, 44690
    • Centro de Estudios de Investigacion Basica Y Clinica S.C.; Reumatologia
  • Mexicali, Mexico, 21100
    • Unidad de Reumatologia Rehabilitacion Integral; Centro Medico Del Angel
  • Mexico, Mexico, 44620
    • Unidad De Enfermedades; Cronico Degenerativas, SC.
  • Miexico City, Mexico, 06700
    • Cliditer SA de CV
  • Morelia, Mexico, 58070
    • Centro de Investigación Clínica de Morelia, S.C.; Reumatologia
  • Saltillo, Mexico, 25000
    • Hospital Universitario de Saltillo
  • Torreon, Mexico, 27000
    • Unidad de Enfermedades Reumaticas y Cronicodegenerativas
  • Sinaloa
    • Culiacán Rosales, Sinaloa, Mexico, 80000
      • Centro de Investigación de Tratamientos Innovadores de Sinaloa (CITI)
• New Zealand
  • Auckland, New Zealand
    • North Shore Hospital, STAR Unit; Rheumatology Department
  • Hamilton, New Zealand, 3240
    • Waikato Hospital; Rheumatology Outpatients
  • Timaru, New Zealand, 7910
    • Timaru Hospital
• Panama
  • Panama City, Panama, 32400
    • Centro de Infusion Marbella; Consultorios Royal Center Num 214
• Peru
  • Lima, Peru, Lima 21
    • Abk Reuma Srl- Medicentro
  • Lima, Peru, LIMA 14
    • Centro especializado de rehabilitacion fisica y del dolor cerfid - unidad de inv. En reumatologia
  • San Juan de Miraflores, Peru, 15801
    • Centro de Investigaciones Medicas/Hospital Maria Auxiliadora
• Philippines
  • Manila, Philippines, 1003
    • Jose Reyes Memorial Medical Center
  • Manila, Philippines, 1000
    • Philippine General Hospital; Rheumatology
  • Manila, Philippines, 1015
    • Uni of Santo Tomas Hospital; Rheumatology
• Poland
  • Bytom, Poland, 41-902
    • Szpital Specjalistyczny Nr 1; Oddzial Reumatologii I Rehabilitacji
  • Elblag, Poland, 82-300
    • Wojewodzki Szpital Zespolony; Oddzial Reumatologii
  • Lublin, Poland, 20-607
    • NZOZ REUMED Sp. z o.o.
  • Poznan, Poland, 60-218
    • Medyczne Centrum Hetmanska; Indywidualna Specjalistyczna Praktyka Lekarska
  • Szczecin, Poland, 71-252
    • Klinika Reumatologii I Chorób Wewn. Pum W Szczecinie; Samodzielny Publiczny Szpital Kliniczny Nr 1
  • Warszawa, Poland, 02-637
    • Instytut Reumatologii im. Prof. Dr hab. Eleonory Reicher; Oddzial Wczesnej Diagnostyki Stawow
• Portugal
  • Coimbra, Portugal, 3000-075
    • HUC; Servico de Reumatologia
  • Lisboa, Portugal, 1649-035
    • Hospital de Santa Maria; Servico de Reumatologia
  • Porto, Portugal, 4200-319
    • Hospital de Sao Joao; Servico de Reumatologia
• Puerto Rico
  • Ponce, Puerto Rico, 00716
    • Ponce School of Medicine; Caimed Center
• Russian Federation
  • Ekaterinburg, Russian Federation, 620102
    • Municipal Autonomous Institution of Healthcare "City Clinical Hospital #40"
  • Moscow, Russian Federation, 115522
    • FSBI "Scientific Research Institute of Rheumatology" of russian Academy of Medical Sciences
  • Moscow, Russian Federation, 105203
    • FSBI "National medico-surgical Centre n.a. N.I. Pirogov" of the Ministry of Healthcare
  • Moscow, Russian Federation, 115682
    • FSBI "FSCC of particularized sorts of medical care and medical technologies of FMBA"
  • Moscow, Russian Federation, 119049
    • SBIH of Moscow "City clinical hospital #1 n.a. N.I. Pirogov" of Moscow Healthcare Department
  • Moscow, Russian Federation, 129327
    • SBIH of Moscow "City Clinical Hospital #20 of Moscow Healthcare Department"
  • Ryazan, Russian Federation, 390011
    • Ryazan State Medical University named after I.P.Pavlov
  • Saint-Petersburg, Russian Federation, 195067
    • SBEI of HPE "Northwestern State Medical University n.a. I.I.Mechnikov" of MoH of RF
  • Saratov, Russian Federation, 410002
    • State institution of healthcare "Regional hospital for war veterans"
  • Tula, Russian Federation, 300053
    • State Institution of Healthcare of Tula Region "Tula Regional Clinical Hospital"
  • Voronezh, Russian Federation, 394066
    • Budget Institution of Healthcare of Voronezh Region "Voronezh Regional Clinical Hospital #1"
  • Yaroslavl, Russian Federation, 150030
    • State Institution of Healthcare of Yaroslavl Region Clinical Hospital #8
• Singapore
  • Singapore, Singapore, 117599
    • National University Hospital; Dept of Medicine
• South Africa
  • Bloemfontein, South Africa, 9301
    • Netcare Private Hospital
  • Durban, South Africa, 4001
    • St Augustines Hospital; Rheumatology
  • Port Elizabeth, South Africa, 6045
    • Greenacres Hospital
  • Pretoria, South Africa, 0083
    • Clinical Research Unit
  • Stellenbosch, South Africa, 7600
    • Winelands Research Centre
• Spain
  • Cordoba, Spain, 14004
    • Hospital Universitario Reina Sofia; Servicio de Reumatologia
  • Guadalajara, Spain, 19002
    • Hospital General Universitario de Guadalajara; Servicio de Reumatologia
  • Madrid, Spain, 28006
    • Hospital Universitario de la Princesa; Servicio de Reumatologia
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocio; Servicio de Reumatologia
  • Sevilla, Spain, 41014
    • Hospital Univ. Nuestra Señora de Valme; Servicio de Reumatologia
  • Asturias
    • Oviedo, Asturias, Spain, 33006
      • Hospital Univ. Central de Asturias; Servicio de Reumatologia
  • Badajoz
    • Merida, Badajoz, Spain, 06800
      • Hospital de Merida ;Servicio de Reumatologia
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Universitario Marques de Valdecilla; Servicio de Reumatologia
  • Las Palmas
    • Las Palmas de Gran Canaria, Las Palmas, Spain, 35016
      • Hospital Universitario Materno Infantil de Gran Canaria; Servicio de Reumatologia
  • Madrid
    • San Sebastian de los Reyes, Madrid, Spain, 28702
      • Hospital Infanta Sofia; Servicio de Reumatologia
• Sweden
  • Huddinge, Sweden, SE-141 86
    • Karolinska University Hospital, Huddinge; Rheumatology
  • Stockholm, Sweden, 171 76
    • Karolinska Sjukhuset; Reumatologkliniken D2-1
• Thailand
  • Bangkok, Thailand, 10330
    • Chulalongkorn Hospital; Division of Rheumatology - Medicine
  • Bangkok, Thailand, 10400
    • Phramongkutklao Hospital; Dept. of Medicine, Rheumatology
  • Bangkok, Thailand, 10400
    • Ramathibodi Hospital, Mahidol Uni ; Allergy, Immunology & Rheumatology, Dept of Medicine
  • Songkhla, Thailand, 90110
    • Songklanagarind Hospital; Department of Internal Medicine, Division of Rheumatology
• Turkey
  • Istanbul, Turkey, 34098
    • Iu Cerrahpasa Tip Fakultesi Ic Hastaliklari Anabilim Dali; Romatoloji Bilim Dali
• United Kingdom
  • Cambridge, United Kingdom, CB2 2QQ
    • Addenbrooke'S Hospital; Rheumatology Research Unit
  • Cannock, United Kingdom, WS11 5XY
    • Cannock Chase Hospital; Rheumatology
  • Derby, United Kingdom, DE22 3NE
    • Royal Derby Hospital
  • Dudley, United Kingdom, DY1 2HQ
    • Russells Hall Hospital; Rheumatology Department
  • Maidstone, United Kingdom, ME16 9QQ
    • Maidstone Hospital; Dept of Rheumatology
  • Manchester, United Kingdom, M41 5SL
    • Trafford General Hospital; Rheumatology
  • Newcastle Upon Tyne, United Kingdom, NE1 4LP
    • Royal Victoria Infirmary; Clinical Research Facility
  • North Shields, United Kingdom, NE29 8NH
    • North Tyneside General Hospital
  • Sheffield, United Kingdom, S10 2JF
    • Royal Hallamshire Hospital; Rheumatology
  • Stoke-on-trent, United Kingdom, ST6 7AG
    • Haywood Hospital; Staffordshire Rheumatology Centre
  • Torquay, United Kingdom, TQ2 7AA
    • Torbay Hospital; Dept of Rhematology
  • Wirral, United Kingdom, CH49 5PE
    • Arrowe Park Hospital; Rheumatology Dept
• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Pinnacle Research Group; Llc, Central
    • Huntsville, Alabama, United States, 35801
      • Rheumatology Associates of North Alabama
    • Tuscaloosa, Alabama, United States, 35406
      • Clnical & Translational Reseach Center for Alabama, PC
  • Arizona
    • Mesa, Arizona, United States, 85208
      • Arthrocare, Arthritis Care and Research, P.C.
    • Peoria, Arizona, United States, 85381
      • Sun Valley Arthritis Center
  • California
    • Huntington Beach, California, United States, 92646
      • Talbert Medical Group
    • La Jolla, California, United States, 92037
      • Uni of California - San Diego; Division of Rheumatology
    • Los Alamitos, California, United States, 90720
      • Valerius Medical Group & Research Ctr of Greater Long Beach
    • San Diego, California, United States, 92101
      • Sharp Rees-Stealy Medical Group
    • San Diego, California, United States, 92108
      • San Diego Arthritis Med Clnc
  • Colorado
    • Denver, Colorado, United States, 80230-7127
      • Denver Arthritis Clinic
  • Connecticut
    • Bridgeport, Connecticut, United States, 06606
      • Joao Nascimento
    • Trumbull, Connecticut, United States, 06611
      • New England Research Associates
  • Florida
    • Orange Park, Florida, United States, 32073
      • Arthritis/Osteoporosis Treatment Center
    • Palm Harbor, Florida, United States, 34684
      • Arthritis Center Palm Harbor
    • Palm Harbor, Florida, United States, 34684
      • Arthritis Rsrch of Florida, Inc.
    • Tampa, Florida, United States, 33614
      • Burnette & Silverfield, MDS
  • Illinois
    • Moline, Illinois, United States, 61265
      • Quad City Rheumatology, Sc
    • Morton Grove, Illinois, United States, 60053
      • Illinois Bone & Joint Inst.
    • Springfield, Illinois, United States, 62703
      • Springfield Clinic
    • Vernon Hills, Illinois, United States, 60061
      • Deerbrook Medical Associates
  • Iowa
    • Cedar Rapids, Iowa, United States, 52401
      • Physician'S Clinic of Iowa
  • Kansas
    • Wichita, Kansas, United States, 67208
      • Via Christi Clinic, PA
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • Baton Rouge Clinic, Amc
  • Maryland
    • Cumberland, Maryland, United States, 21502
      • Osteoporosis & Clinical Trials Center
  • Massachusetts
    • Worcester, Massachusetts, United States, 01605
      • UMASS Memorial Medical Center
  • Michigan
    • Kalamazoo, Michigan, United States, 49009
      • Borgess Rheumatology
    • Lansing, Michigan, United States, 48910
      • Fiechtner Research Inc
    • Petoskey, Michigan, United States, 49770
      • Harbor Arthritis Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55416
      • Park Nicollet Inst. ; Rtrc
  • Mississippi
    • Flowood, Mississippi, United States, 39232
      • Jackson Arthritis Clinic
    • Tupelo, Mississippi, United States, 38802
      • North Mississippi Medical Ctr; Internal Medicine Associates
  • Missouri
    • Florissant, Missouri, United States, 63031
      • Depaul Medical Group-SSM Healthcare
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth-Hitchcock Medical Center, Rheumatology 5C
  • New Jersey
    • Clifton, New Jersey, United States, 07012
      • NJP Clinical Research
    • Haddon Heights, New Jersey, United States, 08035
      • Mark Fisher Md, Facr, Llc
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Albuquerque Center for Rheumatology
    • Las Cruces, New Mexico, United States, 88011
      • Arthritis and Osteoporosis Associates of New Mexico
  • New York
    • Syracuse, New York, United States, 13210
      • Arthritis Health Associates; Clinical Research
  • North Carolina
    • Asheville, North Carolina, United States, 28803
      • Asheville Arthritis & Osteoporosis Center, PA
    • Durham, North Carolina, United States, 27704
      • Durham Rheumatology
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University; Dept of Immunology
    • Middleburg Heights, Ohio, United States, 44130
      • Southwest Rheumatology & Research Group, LLC
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma Medical Research Foundation
    • Oklahoma City, Oklahoma, United States, 73103
      • Health Research of Oklahoma, Llc
    • Tulsa, Oklahoma, United States, 74135
      • Healthcare Research Consultants
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18015
      • East Penn Rheumatology Associates, Pc
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center for Clinical Research
    • Wyomissing, Pennsylvania, United States, 19610
      • Clinical Research Center of Reading
  • South Carolina
    • Greenville, South Carolina, United States, 29601
      • Piedmont Arthritis Clinic
  • Texas
    • Amarillo, Texas, United States, 79124
      • Amarillo Center for Clinical Research
    • Houston, Texas, United States, 77074
      • Houston Inst. For Clinical Research
    • Houston, Texas, United States, 77034
      • Accurate Clinical Research
    • Lubbock, Texas, United States, 79424
      • Arthritis & Osteoporosis Associates, LLP
    • San Antonio, Texas, United States, 78217
      • Texas Arthritis Research Center; Center for Arthritis & Rheumatic Diseases
    • Sugar Land, Texas, United States, 77479
      • Texas Research Center
    • Waco, Texas, United States, 76710
      • Arthritis & Osteoporosis Clinic
  • Washington
    • Spokane, Washington, United States, 99204
      • Arthritis Northwest, Spokane
    • Tacoma, Washington, United States, 98405
      • Tacoma Center for Arthritis Research
    • Wenatchee, Washington, United States, 98801
      • Wenatchee Valley Hospital & Clinics
  • Wisconsin
    • Glendale, Wisconsin, United States, 53217
      • Rheumatic Disease Center

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:

• Adult patients ≥ 18 years of age.
• Rheumatoid arthritis of ≤ 2 years duration.
• Disease Activity Score 28 (DAS28) > 3.2.
• Swollen joint count (SJC) ≥ 4 of 66 joints, tender joint count (TJC) ≥ 6 of 68 joints.
• Rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide (anti-CCP) positive (if RF and anti-CCP negative > 1 erosion required at screening).
• Erythrocyte sedimentation rate (ESR) ≥ 28 mm/h or C-reactive protein (CRP) ≥ 10 mg/L at screening.

Exclusion Criteria:

• Previous treatment with tocilizumab.
• Previous treatment with methotrexate or biologic agent.
• Rheumatic autoimmune disease other than rheumatoid arthritis (RA).
• History of or current inflammatory joint disease other than RA.
• Functional class IV as defined by the American College of Rheumatology (ACR) Classification of Functional Status in RA.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: (A) Tocilizumab 8 mg/kg + placebo to methotrexate; Patients received tocilizumab 8 mg/kg iv every 4 weeks + placebo to methotrexate orally once a week for 104 weeks.	Drug: Tocilizumab; Tocilizumab was supplied in vials.; Other Names: RoActemra; Actemra; Drug: Placebo to methotrexate; Patients received placebo to methotrexate orally once a week.
EXPERIMENTAL: (B) Tocilizumab 8 mg/kg + methotrexate; Patients received tocilizumab 8 mg/kg iv every 4 weeks + methotrexate orally once a week for 104 weeks.	Drug: Tocilizumab; Tocilizumab was supplied in vials.; Other Names: RoActemra; Actemra; Drug: Methotrexate; Initially, patients received methotrexate 7.5 mg (3, 2.5 mg tablets) orally once a week. If a patient had swollen or tender joints, the dose was increased to 15 mg and 20 mg weekly, at the Week 4 and Week 8 visits, respectively.
EXPERIMENTAL: (C) Tocilizumab 4 mg/kg + methotrexate; Patients received tocilizumab 4 mg/kg iv every 4 weeks + methotrexate orally once a week for 104 weeks.	Drug: Tocilizumab; Tocilizumab was supplied in vials.; Other Names: RoActemra; Actemra; Drug: Methotrexate; Initially, patients received methotrexate 7.5 mg (3, 2.5 mg tablets) orally once a week. If a patient had swollen or tender joints, the dose was increased to 15 mg and 20 mg weekly, at the Week 4 and Week 8 visits, respectively.
ACTIVE_COMPARATOR: (D) Placebo to tocilizumab + methotrexate; Patients received placebo tocilizumab intravenously (iv) every 4 weeks + methotrexate orally once a week for 104 weeks.	Drug: Methotrexate; Initially, patients received methotrexate 7.5 mg (3, 2.5 mg tablets) orally once a week. If a patient had swollen or tender joints, the dose was increased to 15 mg and 20 mg weekly, at the Week 4 and Week 8 visits, respectively.; Drug: Placebo to tocilizumab; Placebo to tocilizumab was supplied in vials.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With a Disease Activity Score 28 (DAS28) Remission Response at Week 24	A participant has a DAS28 remission response if their DAS28 < 2.6. The DAS28 is a combined index for measuring disease activity in rheumatic arthritis (RA) and includes swollen and tender joint counts, erythrocyte sedimentation rate (ESR), and general health (GH) status. The index is calculated with the following formula: DAS28 = (0.56 × √(TJC28)) + (0.28 × √(SJC28)) + (0.7 × log(ESR)) + (0.014 × GH), where TJC28 = tender joint count and SJC28 = swollen joint count, each on 28 joints. GH = a patient's global assessment of disease activity in the previous 24 hours on a 100 mm visual analog scale (left end = no disease activity [symptom-free and no arthritis symptoms], right end = maximum disease activity [maximum arthritis disease activity]). When ESR equaled 0 mm/hr, it was set to 1 mm/hr. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity.	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With a Disease Activity Score 28 (DAS28) Remission Response at Week 52		Week 52
Percentage of Patients With an Improvement ≥ 20%, 50%, or 70% in American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline to Weeks 24 and 52	Improvement must be seen in tender (68) and swollen (66) joint counts. Joints were assessed and classified as swollen/not swollen and tender/not tender by pressure and joint manipulation. Improvement must also be seen in at least 3 of the following 5 parameters: Separate patient and physician assessments of patient disease activity in the previous 24 hours on a visual analog scale (VAS, the extreme left end of the line "no disease activity" [symptom-free and no arthritis symptoms] and the extreme right end "maximum disease activity"; patient assessment of pain in previous the 24 hours on a VAS (extreme left end of the line "no pain" and the extreme right end "unbearable pain"); Health Assessment Questionnaire-Disability Index (20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do); and C-reactive protein (CRP), or erythrocyte sedimentation rate if CRP was missing.	Baseline to Weeks 24 and 52
Change From Baseline in Modified Total Sharp Score (mTSS) at Week 52	The mTSS is a measure of joint damage and includes measures of joint erosion (JE) and joint space narrowing (JSN). The JE score, using the van der Heijde modification, measures erosion severity in 32 hand joints and 12 foot joints. Each hand joint is scored from 0 to 5 and each foot joint is scored from 0 to 10; the total score ranges from 0 to 280. Each joint is scored according to the surface area involved. A score of 10 indicates extensive loss of bone from more than one-half of the articulating bone; a score of 0 indicates no erosion. The JSN score measures the severity of JSN in 30 hand joints (15 per hand) and 12 foot joints (6 per foot). Each joint, including subluxation, is scored from 0 to 4; the total score ranges from 0 to 168. A higher score indicates more joint space narrowing. The mTSS ranges from 0 to 448 (280+168). A higher mTSS score indicates greater damage. A negative change score indicates improvement.	Baseline to Week 52
Change From Baseline in Modified Sharp Erosion Score at Week 52		Baseline to Week 52
Change From Baseline in Sharp Joint Space Narrowing Score at Week 52		Baseline to Week 52
Percentage of Participants With a Major Clinical Response at Week 52	A major clinical response is defined as an ACR70 response that is maintained for 6 consecutive months (24 weeks) for any 24-week period between Week 2 and Week 52.	Baseline to Week 52
Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Weeks 24 and 52	The Stanford HAQ-DI is a patient completed questionnaire specific for rheumatoid arthritis. The HAQ-DI assesses how well the patient is able to perform 8 activities: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. The patient answers 20 questions with 1 of 4 responses with the past week as the time frame: 0=without difficulty, 1=with some difficulty, 2=with much difficulty, and 3=unable to do. The highest score for any question in a category determines the category score. The total score ranges from 0 (no disability) to 3 (completely disabled). A negative change score indicates improvement.	Baseline to Weeks 24 and 52
Change From Baseline in Short Form 36 (SF-36) Physical Component Summary (PCS) Scores at Weeks 24 and 52	The SF-36 Health Survey (Version 2) is a standardized questionnaire consisting of 36 questions that measures patient-reported symptoms on 8 dimensions; it is used to assess health-related quality of life (HRQoL). The Physical Component Summary (PCS) score summarizes the subscales Physical Functioning, Role-Physical, Bodily Pain, and General Health. The Mental Component Summary (MCS) score summarizes the subscales Vitality, Social Functioning, Role-Emotional, and Mental Health. Each score was scaled from 0 to 100. A positive change score indicates better HRQoL.	Baseline to Weeks 24 and 52

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Burmester GR, Rigby WF, van Vollenhoven RF, Kay J, Rubbert-Roth A, Blanco R, Kadva A, Dimonaco S. Tocilizumab combination therapy or monotherapy or methotrexate monotherapy in methotrexate-naive patients with early rheumatoid arthritis: 2-year clinical and radiographic results from the randomised, placebo-controlled FUNCTION trial. Ann Rheum Dis. 2017 Jul;76(7):1279-1284. doi: 10.1136/annrheumdis-2016-210561. Epub 2017 Apr 7.
• Burmester GR, Rigby WF, van Vollenhoven RF, Kay J, Rubbert-Roth A, Kelman A, Dimonaco S, Mitchell N. Tocilizumab in early progressive rheumatoid arthritis: FUNCTION, a randomised controlled trial. Ann Rheum Dis. 2016 Jun;75(6):1081-91. doi: 10.1136/annrheumdis-2015-207628. Epub 2015 Oct 28.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 31, 2009
• Primary Completion (ACTUAL): May 31, 2012
• Study Completion (ACTUAL): January 28, 2014

Study Registration Dates

• First Submitted: November 3, 2009
• First Submitted That Met QC Criteria: November 3, 2009
• First Posted (ESTIMATE): November 4, 2009

Study Record Updates

• Last Update Posted (ACTUAL): July 26, 2017
• Last Update Submitted That Met QC Criteria: June 28, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Methotrexate
• Other Study ID Numbers: WA19926; 2009-012759-12