A Study Comparing Upadacitinib (ABT-494) to Placebo and to Adalimumab in Adults With Rheumatoid Arthritis Who Are on a Stable Dose of Methotrexate and Who Have an Inadequate Response to Methotrexate (SELECT-COMPARE)

A Phase 3, Randomized, Double-Blind Study Comparing Upadacitinib (ABT-494) to Placebo and to Adalimumab in Subjects With Moderately to Severely Active Rheumatoid Arthritis Who Are on a Stable Background of Methotrexate (MTX) and Who Have an Inadequate Response to MTX (MTX-IR)

The purpose of this study was to assess efficacy, including inhibition of radiographic progression, and safety with upadacitinib versus placebo and versus an active comparator, adalimumab, in adults with with moderately to severely active rheumatoid arthritis (RA) who are on a stable background of methotrexate (MTX and who have an inadequate response to MTX.

Study Overview

• Status: Active, not recruiting
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Placebo for Upadacitinib; Drug: Upadacitinib; Drug: Placebo for Adalimumab; Drug: Adalimumab

Detailed Description

This study consists of a 48-week double-blind treatment period (Period 1) and a long-term extension period (Period 2).

Period 1 is a 48-week randomized, double-blind, parallel-group, placebo-controlled and active comparator-controlled period designed to compare the safety and efficacy of upadacitinib versus placebo, and versus adalimumab. Participants will be randomized in a 2:2:1 ratio to one of three treatment groups:

• Placebo (up to Week 26)
• Upadacitinib 15 mg once daily (QD)
• Adalimumab 40 mg every other week (eow)

Participants randomized to placebo who do not achieve a ≥ 20% improvement in tender joint count (TJC) and swollen joint count (SJC) at Weeks 14, 18, or 22 compared to Baseline will be switched to blinded upadacitinib treatment. At Week 26, all participants still receiving placebo will be switched to blinded upadacitinib treatment regardless of clinical response.

Participants randomized to adalimumab who do not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline will be switched to blinded upadacitinib. Participants still receiving adalimumab at Week 26 who do not achieve low disease activity (LDA) according to Clinical Disease Activity Index (CDAI; LDA is defined as CDAI ≤ 10) will be switched to blinded upadacitinib treatment to Week 48.

Participants randomized to upadacitinib who do not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline will be switched to blinded adalimumab; participants still receiving upadacitinib at Week 26 who do not achieve LDA (CDAI ≤ 10) will be switched to blinded adalimumab treatment to Week 48.

Participants who complete the Week 48 visit (end of Period 1) will enter the long-term extension phase of the study (Period 2), for up to 5 years. Participants will continue study treatment as assigned at the end of Period 1. Starting at the Week 48 and thereafter, at least 20% improvement in both TJC and SJC compared to Baseline is required to remain on study drug. Anyone who does not fulfill this criterion at 2 consecutive visits (starting at Week 48) will be discontinued.

• Study Type: Interventional
• Enrollment (Actual): 1629
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1128
    • Mautalen Salud e Investigacion /ID# 142843
  • Buenos Aires, Argentina, 1180
    • Fundacion Sanatorio Guemes /ID# 148405
  • Buenos Aires, Argentina, 1428
    • Consultorio Reumatologic Pampa /ID# 144853
  • Buenos Aires, Argentina, 1431
    • Cemic /Id# 148404
  • Buenos Aires, Argentina, C1015ABO
    • Org Medica de Investigacion /ID# 144855
  • Cordoba, Argentina, 5000
    • Inst. Rheumatologic Strusberg /ID# 145601
  • Cordoba, Argentina, 5900
    • Consultora Integral de Salud S /ID# 144856
  • Rosario, Santa FE, Argentina, 2000
    • Instituto CAICI /ID# 144854
  • Salta, Argentina, 4400
    • Cordis S.A. /Id# 152622
  • San Fernando, Argentina, 1646
    • Iari /Id# 151293
  • San Miguel de Tucuman, Argentina, 4000
    • Centro Integral de Reumatologi /ID# 142845
  • San Miguel de Tucuman, Argentina, 4000
    • Centro Medico Privado/Reuma /ID# 142842
  • Santa Fe, Argentina, 2000
    • Centro de Enfermedades /ID# 153542
  • Buenos Aires
    • Capital Federal, Buenos Aires, Argentina, 1046
      • Aprillus Asistencia e Investig /ID# 148406
• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital /ID# 144857
  • Victoria
    • Camberwell, Victoria, Australia, 3124
      • Emeritus Research /ID# 142848
• Austria
  • Graz, Austria, 8036
    • LKH-Univ. Klinikum Graz /ID# 142851
• Belarus
  • Minsk, Belarus, 220013
    • First City Clinical Hospital /ID# 158011
• Belgium
  • Mons, Belgium, 7000
    • CHU Ambroise Pare /ID# 152953
  • Bruxelles-Capitale
    • Woluwe-Saint-Lambert, Bruxelles-Capitale, Belgium, 1200
      • Cliniques Universitaires Saint Luc /ID# 142858
  • Hainaut
    • Charleroi, Hainaut, Belgium, 6000
      • Rhumaconsult SPRL /ID# 142860
  • Liege
    • Liège, Liege, Belgium, 4000
      • CHU de Liege /ID# 148401
  • Oost-Vlaanderen
    • Gent, Oost-Vlaanderen, Belgium, 9000
      • UZ Gent /ID# 142859
• Bosnia and Herzegovina
  • Sarajevo, Bosnia and Herzegovina, 71000
    • Clinical Center University of Sarajevo /ID# 142865
  • Republika Srpska
    • Banja Luka, Republika Srpska, Bosnia and Herzegovina, 78000
      • University Clinical Centre of the Republic of Srpska /ID# 142862
    • Banja Luka, Republika Srpska, Bosnia and Herzegovina, 78000
      • University Clinical Centre of the Republic of Srpska /ID# 142863
• Brazil
  • Rio de Janeiro, Brazil, 22271-100
    • CCBR Brasil /ID# 150918
  • Goias
    • Goiânia, Goias, Brazil, 74110-120
      • CIP - Centro Internacional de Pesquisa /ID# 142872
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 30130-100
      • Hc Ufmg /Id# 142868
  • Parana
    • Curitiba, Parana, Brazil, 80030-110
      • Ceti - Centro de Estudos Em Terapias Inovadoras Ltda /Id# 142871
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90035-903
      • Hospital de Clinicas de Porto Alegre /ID# 142870
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90480-000
      • LMK Sevicos Medicos S/S /ID# 142869
  • Sao Paulo
    • São Paulo, Sao Paulo, Brazil, 04266-010
      • CEPIC - Centro Paulista de Investigação Clínica e Serviços Médicos Ltda /ID# 142867
• Bulgaria
  • Plovdiv, Bulgaria, 4000
    • MHAT Trimontsium /ID# 142874
  • Plovdiv, Bulgaria, 4000
    • UMHAT Pulmed OOD /ID# 142877
  • Plovdiv, Bulgaria, 4001
    • MHAT Kaspela /ID# 142873
  • Sofia, Bulgaria, 1612
    • Diagnostic Consultative Center /ID# 142875
  • Sofia, Bulgaria, 1612
    • UMHAT Sv. Ivan Rilski /ID# 142876
• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3A IM3
      • Manitoba Clinic /ID# 161434
    • Winnipeg, Manitoba, Canada, R3N 0K6
      • Ciads /Id# 142880
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada, A1C 5B8
      • St. Clare's Mercy Hospital /ID# 142879
  • Ontario
    • Hamilton, Ontario, Canada, L8N 1Y2
      • Adachi Medicine Prof. Corp /ID# 154205
    • Thornhill, Ontario, Canada, L4J 1W3
      • CA Ctr for Clin Trials CCCT /ID# 157379
  • Quebec
    • Sainte-foy, Quebec, Canada, G1V 3M7
      • Groupe de Recherche en Maladies Osseuses /ID# 142878
• Chile
  • Concepcion, Chile, 4070038
    • Reg. Clinical Hosptial Concepcion /ID# 151271
  • Osorno, Chile, 1710216
    • Corp de Beneficencia Osorno /ID# 147941
  • Providencia-santiago, Chile, 7510186
    • Someal /Id# 144704
  • Puerto Varas, Chile, 5550170
    • Quantum Research LTDA. /ID# 142893
  • Santiago, Chile, 7500588
    • Quantum Research Stgo. /ID# 157933
  • Santiago, Chile, 7510047
    • Soc. de Prestaciones medicas y Paramedicas Goecke /ID# 142890
  • Santiago, Chile, 7640881
    • Clinica DermaCross /ID# 142892
  • Santiago, Chile, 8207257
    • Investigaciones Medicas SSMSO /ID# 151686
  • Santiago, Chile, 8420383
    • Centro Inter Estud Clin CIEC /ID# 144777
  • Temuco, Chile, 4790928
    • Centro Medico de Reumatologia /ID# 148402
  • Vina Del Mar, Chile, 2520997
    • Cinvec /Id# 144705
  • Araucania
    • Temuco, Araucania, Chile, 4781156
      • Ctr de Inv Clinica del Sur /ID# 142888
• Colombia
  • Barranquilla, Colombia, 80002
    • Ctr Int de Reum del Caribe SAS /ID# 142894
  • Bogota, Colombia, 110221
    • Riesgo de Fractura S.A - CAYRE /ID# 142896
  • Bogota DC, Colombia
    • Fund Inst de Reum F. Chalem /ID# 149847
  • Bucaramanga, Colombia, 680003
    • Medicity S.A.S. /ID# 144860
  • Medellín, Colombia, 50021
    • Centro Integral de Reumatologi /ID# 142897
  • Cundinamarca
    • Bogota, Cundinamarca, Colombia, 110221
      • Centro de Investigacion en Reumatologia y Especialidades Medicas- CIREEM SAS /ID# 142898
• Croatia
  • Split, Croatia, 21000
    • Klinicki bolnicki centar Split /ID# 152530
  • Zagreb, Croatia, 10000
    • Clinical Hospital Dubrava /ID# 142900
  • Zagreb, Croatia, 10000
    • Medical Center Kuna-Peric /ID# 142901
  • Zagreb, Croatia, 10000
    • Poliklinika Bonifarm /ID# 142899
  • Primorsko-goranska Zupanija
    • Rijeka, Primorsko-goranska Zupanija, Croatia, 51000
      • Klinicki bolnicki centar Rijeka /ID# 160232
• Czechia
  • Brno, Czechia, 611 41
    • REVMACLINIC s.r.o. /ID# 142906
  • Bruntál, Czechia, 79201
    • Revmatologie Bruntal, s.r.o /ID# 142903
  • Kladno, Czechia, 272 01
    • Revmatologicka a interni ambul /ID# 142907
  • Ostrava, Czechia, 702 00
    • Revmatologie MUDr. Klara Sirov /ID# 142908
  • Pardubice, Czechia, 530 02
    • Arthromed, s.r.o. /ID# 144706
  • Moravskoslezsky Kraj
    • Hlučín, Moravskoslezsky Kraj, Czechia, 748 01
      • L.K.N. Arthrocentrum, s.r.o /ID# 145961
  • Olomoucky Kraj
    • Olomouc, Olomoucky Kraj, Czechia, 779 00
      • CTCenter MaVe, s.r.o. /ID# 142905
  • Praha 2
    • Prague 2, Praha 2, Czechia, 128 00
      • Revmatologicky ustav Praha /ID# 142904
  • Praha 4
    • Prague 4, Praha 4, Czechia, 140 00
      • Nuselská poliklinika, Revmatologie /ID# 144862
    • Prague 4, Praha 4, Czechia, 140 00
      • Revmatologická ambulance /ID# 145963
    • Prague 4, Praha 4, Czechia, 140 00
      • Thomayerova nemocnice /ID# 145962
• Denmark
  • Silkeborg, Denmark, 8600
    • Regionhospital Silkeborg /ID# 142914
  • Midtjylland
    • Aarhus N, Midtjylland, Denmark, 8200
      • Aarhus University Hospital /ID# 158838
• Estonia
  • Pärnu, Estonia, 80010
    • Paernu Hospital /ID# 142921
  • Tallinn, Estonia, 10138
    • East Tallinn Central Hospital /ID# 142923
  • Tallinn, Estonia, 13419
    • North Estonian Medical Centre /ID# 145454
  • Harjumaa
    • Tallinn, Harjumaa, Estonia, 10128
      • Center of Clinical and Basic Research /ID# 142922
  • Tartumaa
    • Tartu, Tartumaa, Estonia, 50406
      • MediTrials /ID# 151870
• France
  • Bordeaux, France, 33076
    • CHU Bordeaux-Hopital Pellegrin /ID# 145618
  • Caen, France, 14033
    • Hopital de la Cote de Nacre /ID# 145616
  • Clermont Ferrand, France, 63000
    • CHU Gabriel Montpied /ID# 145619
  • Marseille, France, 13005
    • Hopital de la Conception /ID# 142926
  • Paris, France, 75651
    • Hopital Pitie Salpetriere /ID# 145605
  • Rennes, France, 35203
    • CHU de Rennes - Hospital Sud /ID# 151957
  • Strasbourg, France, 67200
    • CHU Strasbourg Hautepierre Hos /ID# 144708
  • Haute-Garonne
    • Toulouse, Haute-Garonne, France, 31059
      • Hopital Universitaire Purpan /ID# 144707
  • Hauts-de-France
    • Lille CEDEX, Hauts-de-France, France, 59045
      • CHRU Lille - Hôpital Claude Huriez /ID# 151312
  • Herault
    • Montpellier CEDEX 5, Herault, France, 34295
      • Hopital Saint Eloi /ID# 142925
• Germany
  • Chemnitz, Germany, 9126
    • Med Versorgungszentrum AGILOME /ID# 154975
  • Hamburg, Germany, 20095
    • Rheumaforschungszentrum II /ID# 142930
  • Munich, Germany, 80337
    • LMU Klinikum der Universität München /ID# 142931
  • Nordrhein-Westfalen
    • Herne, Nordrhein-Westfalen, Germany, 44649
      • Rheumazentrum Ruhrgebiet /ID# 145620
    • Köln, Nordrhein-Westfalen, Germany, 50937
      • Uniklinik Koln /ID# 145964
  • Schleswig-Holstein
    • Rendsburg, Schleswig-Holstein, Germany, 24768
      • Praxis Walter, Rendsburg /ID# 142932
• Greece
  • Athens, Greece, 11527
    • General Hospital of Athens Ippokratio /ID# 142935
  • Attiki
    • Athens, Attiki, Greece, 115 27
      • General Hospital of Athens Laiko /ID# 142934
    • Athens, Attiki, Greece, 12462
      • University General Hospital Attikon /ID# 142933
• Hong Kong
  • Hong Kong, Hong Kong, 999077
    • Queen Mary Hospital /ID# 142938
  • Tuen Mun, Hong Kong, 999077
    • Tuen Mun Hospital /ID# 142939
• Hungary
  • Budapest, Hungary, 1023
    • Budai Irgalmasrendi Korhaz /ID# 142952
  • Budapest, Hungary, 1027
    • Revita Reumatologiai Rendelo /ID# 142950
  • Budapest, Hungary, 1036
    • Synexus Magyarorszag Kft. /ID# 153061
  • Debrecen, Hungary, 4031
    • Debreceni Egyetem Kenezy Gyula Egyetemi Korhaz /ID# 142948
  • Heviz, Hungary, 8380
    • Hevizgyogyfurdo es Szent Andra /ID# 142949
  • Kiskunhalas, Hungary, 6400
    • Kiskunhalasi Semmelweis Korhaz /ID# 151944
  • Kistarcsa, Hungary, 2143
    • Pest Megyei Flor Ferenc Korhaz /ID# 142954
  • Borsod-Abauj-Zemplen
    • Miskolc, Borsod-Abauj-Zemplen, Hungary, 3529
      • CRU Hungary Egeszsegugyi és Szolgaltato Kft. /ID# 142951
  • Pest
    • Budapest III, Pest, Hungary, 1036
      • Qualiclinic Kft. /ID# 142953
  • Vas
    • Szombathely, Vas, Hungary, 9700
      • Markusovszky Egyetemi Oktatókórház /ID# 145621
  • Veszprem
    • Veszprém, Veszprem, Hungary, 8200
      • Vital Medical Center Orvosi es /ID# 145950
• Ireland
  • Dublin, Ireland, D04 T6F4
    • St Vincent's University Hosp /ID# 142957
• Israel
  • Haifa, Israel, 3109601
    • Rambam Health Care Campus /ID# 152050
  • Haifa, Israel, 3339419
    • Bnai Zion Medical Center /ID# 151958
  • Haifa, Israel, 3436212
    • The Lady Davis Carmel MC /ID# 142960
  • Ramat Gan, Israel, 5262100
    • Sheba Medical Center /ID# 145965
  • Tel-Aviv
    • Tel Aviv-Yafo, Tel-Aviv, Israel, 6423906
      • Tel Aviv Sourasky Medical Ctr /ID# 144709
• Italy
  • Milan, Italy, 20157
    • Azienda Ospedaliera Luigi Sacc /ID# 142966
  • Verona, Italy, 37134
    • A.O.U.I. di Verona Policlinico /ID# 142963
  • Milano
    • Rozzano, Milano, Italy, 20089
      • Istituto Clinico Humanitas /ID# 147528
  • Piemonte
    • Turin, Piemonte, Italy, 10126
      • AOU Citta della Salute Scienza /ID# 150070
• Kazakhstan
  • Astana, Kazakhstan, 010009
    • JSC Nat Scientific Med Res Ctr /ID# 142971
  • Karaganda, Kazakhstan, 100008
    • Karaganda State Medical Univ /ID# 153433
  • Semey, Kazakhstan, 071403
    • Semey State Medical University /ID# 152659
  • Shymkent, Kazakhstan, 160000
    • Regional Clinical Hospital /ID# 147168
• Korea, Republic of
  • Daegu, Korea, Republic of, 705-718
    • Daegu Catholic University Med /ID# 142973
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital /ID# 142978
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center /ID# 142974
  • Daegu Gwang Yeogsi
    • Daegu, Daegu Gwang Yeogsi, Korea, Republic of, 41944
      • Kyungpook National Univ Hosp /ID# 162073
  • Daejeon Gwang Yeogsi
    • Jung-gu, Daejeon Gwang Yeogsi, Korea, Republic of, 35015
      • Chungnam National University Hospital /ID# 142977
  • Incheon Gwang Yeogsi
    • Jung-gu, Incheon Gwang Yeogsi, Korea, Republic of, 22332
      • Inha University Hospital /ID# 150886
  • Jeonranamdo
    • Gwangju, Jeonranamdo, Korea, Republic of, 61469
      • Chonnam National University Hospital /ID# 142975
  • Seoul Teugbyeolsi
    • Seongdong-gu, Seoul Teugbyeolsi, Korea, Republic of, 04763
      • Hanyang University Seoul Hospi /ID# 142979
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 06591
      • Cath Univ Seoul St Mary's Hosp /ID# 142976
• Latvia
  • Adazi, Latvia, 2164
    • LTD M+M Centers /ID# 142984
  • Daugavpils, Latvia, 5417
    • Daugavpils Regional Hospital /ID# 142982
  • Liepaja, Latvia, 3401
    • D.Saulites-Kandevicas PP /ID# 142985
  • Riga, Latvia, 1005
    • Clinic ORTO /ID# 142983
  • Riga, Latvia, 1038
    • Riga East Clinical Univ Hosp /ID# 142981
• Lithuania
  • Vilnius, Lithuania, LT-08661
    • Vilnius University Hospital /ID# 142987
  • Kaunas
    • Kovno, Kaunas, Lithuania, 50009
      • Hosp Lithuanian Univ Health Sc /ID# 142986
• Malaysia
  • Batu Caves, Malaysia, 68100
    • Hospital Selayang /ID# 156756
  • Kuching, Malaysia, 93586
    • Hospital Umum Sarawak /ID# 142990
  • Putrajaya, Malaysia, 62250
    • Hospital Putrajaya /ID# 142989
  • Seremban, Malaysia, 70300
    • Hospital Tuanku Ja afar /ID# 142988
  • Kelantan
    • Kota Bharu, Kelantan, Malaysia, 15586
      • Hospital Raja Perempuan Zainab II /ID# 157862
• Mexico
  • Chihuahua, Mexico, 31000
    • Invest y Biomed de Chihuahua /ID# 142996
  • Mexico City, Mexico, 03100
    • RM Pharma Specialists, S.A de C.V /ID# 142994
  • Mexico City, Mexico, 06090
    • Hospital de Jesús Nazareno /ID# 142993
  • Mérida, Mexico, 97000
    • Centro Peninsular de Investiga /ID# 148159
  • Ciudad De Mexico
    • Cuauhtemoc, Ciudad De Mexico, Mexico, 06700
      • Clinstile, S.A. de C.V. /ID# 144866
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64320
      • Hosp. Univ. Dr. Jose E. Gonz /ID# 142992
• New Zealand
  • Nelson, New Zealand, 7010
    • Porter Rheumatology Ltd /ID# 143001
  • Timaru, New Zealand, 7910
    • Timaru Medical Specialists Ltd /ID# 143000
  • Waikato
    • Hamilton, Waikato, New Zealand, 3204
      • Waikato Hospital /ID# 143002
• Poland
  • Bialystok, Poland, 15-879
    • ClinicMed Badurski i wspolnicy SJ /ID# 163300
  • Poznan, Poland, 60-425
    • Solumed Sp. zoo Cent Medyczne /ID# 152783
  • Warsaw, Poland, 02-118
    • Rheuma Medicus /ID# 143007
  • Dolnoslaskie
    • Wrocław, Dolnoslaskie, Poland, 51-685
      • WroMedica I. Bielicka, A. Strzalkowska s.c. /ID# 145622
  • Kujawsko-pomorskie
    • Toruń, Kujawsko-pomorskie, Poland, 87-100
      • NZOZ Nasz Lekarz /ID# 143004
  • Lubelskie
    • Lublin, Lubelskie, Poland, 20-607
      • REUMED Sp.z o.o. Filia nr 1 /ID# 148189
  • Malopolskie
    • Cracow, Malopolskie, Poland, 30-149
      • Malopolskie Centrum Kliniczne /ID# 152782
    • Krakow, Malopolskie, Poland, 30-510
      • Pratia MCM Krakow /ID# 143005
  • Mazowieckie
    • Grodzisk Mazowiecki, Mazowieckie, Poland, 05-825
      • McBk Sc /Id# 143003
    • Warszawa, Mazowieckie, Poland, 02-507
      • Centralny Szpital Kliniczny MSWiA w Warszawie /ID# 151960
    • Warszawa, Mazowieckie, Poland, 03-291
      • Centrum Medyczne AMED Warszawa Targowek /ID# 157621
  • Podlaskie
    • Białystok, Podlaskie, Poland, 15-351
      • Osteo-Medic spolka cywilna /ID# 143006
  • Pomorskie
    • Gdynia, Pomorskie, Poland, 81-384
      • Synexus Polska Sp. z o.o. Oddz. Poznan /ID# 163293
    • Gdynia, Pomorskie, Poland, 81-384
      • Synexus Polska Sp. z o.o. Oddz. Poznan /ID# 163294
    • Gdynia, Pomorskie, Poland, 81-384
      • Synexus Polska Sp. z o.o. Oddz. Poznan /ID# 163295
  • Slaskie
    • Katowice, Slaskie, Poland, 40-282
      • Silmedic Sp z o.o /ID# 152914
• Portugal
  • Braga, Portugal, 4710-243
    • CCA Braga - Hospital de Braga /ID# 148317
  • Lisbon, Portugal, 1998-018
    • Hospital CUF Descobertas /ID# 160539
  • Porto, Portugal, 4200-319
    • Centro Hospitalar de Sao Joao, EPE /ID# 152871
  • Viana Do Castelo, Portugal, 4901-858
    • Unidade Local De Saude Do Alto Minho /ID# 143009
  • Lisboa
    • Lisbon, Lisboa, Portugal, 1050-034
      • Instituto Portugues De Reumatologia /ID# 148316
  • Porto
    • Vila Nova De Gaia, Porto, Portugal, 4434-502
      • Centro Hospitalar De Vila Nova /ID# 143010
• Puerto Rico
  • Ponce, Puerto Rico, 00716
    • Ponce School of Medicine /ID# 151961
  • San Juan, Puerto Rico, 00909
    • GCM Medical Group /ID# 143011
• Romania
  • Bucuresti, Romania, 011172
    • Spitalul Clinic Sf. Maria /ID# 144868
  • Bucuresti, Romania, 011172
    • Spitalul Clinic Sf. Maria /ID# 144869
  • Bucuresti, Romania, 011172
    • Spitalul Clinic Sf. Maria /ID# 145966
  • Iasi, Romania, 700656
    • Spitalul Clinic de Recuperare /ID# 144867
  • Oradea, Romania, 410028
    • Ecomed SRL /ID# 144870
  • Bucuresti
    • Bucharest, Bucuresti, Romania, 020475
      • Spitalul Clinic Dr. I. Cantacuzino /ID# 143012
    • Bucharest, Bucuresti, Romania, 020475
      • Spitalul Clinic Dr. I. Cantacuzino /ID# 143017
• Russian Federation
  • Ivanovo, Russian Federation, 153005
    • Сity Clinical Hospital #4 /ID# 143023
  • Moscow, Russian Federation, 117997
    • Russian National Research Medi /ID# 143028
  • Moscow, Russian Federation, 125284
    • City Clinical Hospital Botkina /ID# 145628
  • Moscow, Russian Federation, 127473
    • Moscow State Univ Med and Dent /ID# 145623
  • Nizhnij Novgorod, Russian Federation, 603005
    • City Clinical Hospital #5 /ID# 148318
  • Orenburg, Russian Federation, 460000
    • Orenburg State Medical Academy /ID# 143018
  • Ryazan, Russian Federation, 390026
    • Ryazan State Medical Universit /ID# 143031
  • St. Petersburg, Russian Federation, 192242
    • II Dzhan Research Center /ID# 143027
  • St. Petersburg, Russian Federation, 193015
    • NW State Med Univ NA Mechnikov /ID# 143022
  • UFA, Russian Federation, 450005
    • Republican clinical hospital n /ID# 145626
  • Ulyanovsk, Russian Federation, 432018
    • Ulyanovsk Regional Clin Hosp /ID# 143030
  • Moskva
    • Korolev, Moskva, Russian Federation, 141060
      • Family Outpatient clinic#4,LLC /ID# 148319
    • Moscow, Moskva, Russian Federation, 119049
      • Clinical Hospital No.1 n.a. N.I.Pirogov /ID# 143138
  • Permskiy Kray
    • Perm, Permskiy Kray, Russian Federation, 614109
      • Perm Clinical Center of FMBA /ID# 145627
  • Stavropol Skiy Kray
    • Pyatigorsk, Stavropol Skiy Kray, Russian Federation, 357500
      • LLC Novaya Klinika /ID# 143019
  • Tatarstan, Respublika
    • Kazan, Tatarstan, Respublika, Russian Federation, 420012
      • Kazan State Medical University /ID# 144871
  • Tverskaya Oblast
    • Tver, Tverskaya Oblast, Russian Federation, 170036
      • Tver Regional Clinical Hosp. /ID# 143026
• Serbia
  • Beograd
    • Belgrade, Beograd, Serbia, 11000
      • Institute for Rheumatology /ID# 143032
    • Belgrade, Beograd, Serbia, 11000
      • Institute for Rheumatology /ID# 143035
    • Belgrade, Beograd, Serbia, 11000
      • Institute for Rheumatology /ID# 143036
    • Belgrade, Beograd, Serbia, 11000
      • Institute for Rheumatology /ID# 143037
  • Vojvodina
    • Novi Sad, Vojvodina, Serbia, 21101
      • Special Hospital for Rheuma /ID# 143034
    • Novi Sad, Vojvodina, Serbia, 21137
      • Clinical Center of Vojvodina /ID# 143033
• Slovakia
  • Martin, Slovakia, 036 01
    • MEDMAN s.r.o. /ID# 143045
  • Nové Mesto Nad Váhom, Slovakia, 915 01
    • Reumatologická ambulancia Reum.hapi s.r.o. /ID# 147169
  • Partizanske, Slovakia, 958 01
    • REUMACENTRUM s.r.o. /ID# 143041
  • Pieštany, Slovakia, 921 01
    • Slovak research center Team Member, Thermium s.r.o. /ID# 147614
  • Rimavska Sobota, Slovakia, 97 101
    • Reumex, s.r.o. /ID# 143043
  • Sabinov, Slovakia, 083 01
    • Reumatologicka ambulancia /ID# 144873
  • Stará Lubovna, Slovakia, 06401
    • TIMMED spol. s r.o. /ID# 144872
  • Topolcany, Slovakia, 955 01
    • Reumatologicka ambulancia, LER /ID# 143044
  • Zvolen, Slovakia, 960 01
    • ALBAMED s.r.o. /ID# 143042
• South Africa
  • Eastern Cape
    • Port Elizabeth, Eastern Cape, South Africa, 6045
      • Greenacres Hospital /ID# 144710
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 2193
      • Wits Clinical Research Site /ID# 148320
    • Pretoria, Gauteng, South Africa, 0001
      • University of Pretoria /ID# 148353
    • Pretoria, Gauteng, South Africa, 0132
      • Jakaranda Hosp, Emmed Research /ID# 143046
    • Pretoria, Gauteng, South Africa, 0132
      • Jakaranda Hosp, Emmed Research /ID# 145968
  • Kwazulu-Natal
    • Durban, Kwazulu-Natal, South Africa, 4001
      • St. Augustine's Hospital /ID# 143047
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7130
      • Synexus Helderberg Clinical Tr /ID# 148322
    • Cape Town, Western Cape, South Africa, 7405
      • Arthritis Clinical Research Tr /ID# 144874
    • Cape Town, Western Cape, South Africa, 7530
      • Tiervlei Trial Centre /ID# 153085
    • Stellenbosch, Western Cape, South Africa, 7600
      • Winelands Medical Research Ctr /ID# 143048
• Spain
  • A Coruna, Spain, 15006
    • Comple Hosp Univ de A Coruna /ID# 143051
  • Cordoba, Spain, 14004
    • Hospital Universitario Reina S /ID# 153566
  • Santiago de Compostela, Spain, 15702
    • Clinica Gaias /ID# 143052
  • Santiago de Compostela, Spain, 15706
    • Complejo Hosp Santiago /ID# 153727
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • H. Un. Marques de Valdecilla /ID# 143050
• Taiwan
  • Kaohsiung, Taiwan, 80708
    • Kaohsiung Medical University /ID# 143059
  • Kaohsiung, Taiwan, 833
    • Kaohsiung Chang Gung Memorial Hospital /ID# 143055
  • New Taipei City, Taiwan, 22060
    • Far Eastern Memorial Hospital /ID# 143061
  • Taichung City, Taiwan, 40201
    • Chung Shan Medical University /ID# 143060
  • Taipei City, Taiwan, 11217
    • Taipei Veterans General Hosp /ID# 157940
  • Taoyuan City, Taiwan, 33305
    • Linkou Chang Gung Memorial Ho /ID# 143057
  • Taichung
    • Taichung City, Taichung, Taiwan, 40447
      • China Medical University Hosp /ID# 143058
  • Taipei
    • Taipei City, Taipei, Taiwan, 10002
      • National Taiwan Univ Hosp /ID# 143056
• Turkey
  • Cerrahpasa, Turkey, 34098
    • Istanbul Universitesi Cerrahpa /ID# 156088
  • Istanbul, Turkey, 34147
    • Istanbul Fizik Tedavi Rehabilitasyon Egitim ve Arastırma Hastanesi /ID# 143063
  • Izmir, Turkey, 35360
    • Izmir Katip Celebi Ataturk Training & Research Hospital /ID# 143062
• Ukraine
  • Ivano-frankivsk, Ukraine, 76018
    • Regional Clinical Hospital /ID# 152025
  • Kiev, Ukraine, 03680
    • NSC-Strazhesko Ist Cardiology /ID# 152030
  • Lviv, Ukraine, 79007
    • Lviv Municipal City Clinical /ID# 143068
  • Odesa, Ukraine, 65026
    • Odessa National Medical Univ /ID# 143072
  • Zaporizhia, Ukraine, 69600
    • Zaporizhzhia Regional Clinical /ID# 143069
  • Kyiv
    • Kiev, Kyiv, Ukraine, 04070
      • LLC Revmocentr /ID# 143067
  • Lvivska Oblast
    • Lviv, Lvivska Oblast, Ukraine, 79013
      • Lviv Regional Clinical Hospita /ID# 154450
  • Vinnytska Oblast
    • Vinnytsia, Vinnytska Oblast, Ukraine, 21018
      • Vinnytsia Regional Clinical Hospital n.a. M.I.Pyrogov /ID# 143071
• United Kingdom
  • Portsmouth, United Kingdom, PO6 3LY
    • Queen Alexandra Hospital /ID# 143077
  • Warrington, United Kingdom, WA5 1LZ
    • Warrington + Halton Hosp NHS /ID# 143075
  • London, City Of
    • London, London, City Of, United Kingdom, NW3 2QG
      • The Royal Free Hospital /ID# 143074
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35216
      • Achieve Clinical Research, LLC /ID# 143136
  • Arizona
    • Mesa, Arizona, United States, 85202
      • AZ Arthritis and Rheum Assoc /ID# 143130
    • Peoria, Arizona, United States, 85381
      • SunValley Arthritis Center, Lt /ID# 143123
    • Phoenix, Arizona, United States, 85018
      • Elite Clinical Studies, LLC /ID# 144881
    • Phoenix, Arizona, United States, 85032-9306
      • AZ Arthritis and Rheum Researc /ID# 143080
    • Phoenix, Arizona, United States, 85032-9306
      • AZ Arthritis and Rheum Researc /ID# 143121
    • Phoenix, Arizona, United States, 85032
      • AZ Arthritis & Rheuma Research /ID# 143131
    • Phoenix, Arizona, United States, 85053-4061
      • Arizona Research Center, Inc. /ID# 144877
    • Sun City, Arizona, United States, 85351
      • AZ Arthritis & Rheum Research /ID# 156093
    • Tucson, Arizona, United States, 85719-1478
      • University of Arizona Cancer Center - North Campus /ID# 143114
  • California
    • Beverly Hills, California, United States, 90211
      • Osteoporosis Medical Center /ID# 153935
    • Encino, California, United States, 91436
      • T. Joseph Raoof, MD, Inc. /ID# 144884
    • Escondido, California, United States, 92025
      • Rheumatology Ctr of San Diego /ID# 153747
    • Hemet, California, United States, 92543
      • C.V. Mehta MD, Med Corporation /ID# 143116
    • La Jolla, California, United States, 92037
      • Allergy and Rheum Med Clin /ID# 146083
    • La Mesa, California, United States, 91942
      • Kotha and Kotha /ID# 161046
    • La Mesa, California, United States, 91942
      • TriWest Research Associates- La Mesa /ID# 143115
    • Los Alamitos, California, United States, 90720-5402
      • Valerius Med Grp & Res Ctr /ID# 143120
    • Los Angeles, California, United States, 11373
      • Discovery MM Services, Inc /ID# 163504
    • Palm Desert, California, United States, 92260
      • Desert Medical Advances /ID# 143097
    • Roseville, California, United States, 95661
      • Sierra Rheumatology /ID# 155672
    • Tustin, California, United States, 92780
      • Robin K. Dore MD, Inc /ID# 143090
    • Whittier, California, United States, 90606
      • Medvin Clinical Research /ID# 148362
  • Colorado
    • Colorado Springs, Colorado, United States, 80920
      • Arthritis Assoc & Osteo Ctr /ID# 143122
    • Fort Collins, Colorado, United States, 80528
      • Arthritis and Rheum Clin N. CO /ID# 156094
  • Florida
    • Aventura, Florida, United States, 33180
      • AARDS Research, Inc. /ID# 154190
    • Boynton Beach, Florida, United States, 33472
      • ZASA Clinical Research /ID# 143134
    • Clearwater, Florida, United States, 33765
      • Clinical Res of West FL, Inc. /ID# 143112
    • Daytona Beach, Florida, United States, 32117
      • International Medical Research /ID# 143132
    • Miami, Florida, United States, 33014
      • Lakes Research, LLC /ID# 145630
    • Miami, Florida, United States, 33142
      • FL Med Ctr and Research, Inc. /ID# 143081
    • Miami, Florida, United States, 33173
      • Ctr Arthritis & Rheumatic Dise /ID# 143135
    • Miami Lakes, Florida, United States, 33016-1501
      • Precision Research Org, LLC /ID# 143092
    • Ocoee, Florida, United States, 34761-4547
      • Advanced Clin Res of Orlando /ID# 154617
    • Orlando, Florida, United States, 32806
      • Rheum Assoc of Central FL /ID# 145632
    • Orlando, Florida, United States, 32810
      • Omega Research Consultants /ID# 145635
    • Orlando, Florida, United States, 32819
      • HMD Research LLC /ID# 163292
    • Palm Harbor, Florida, United States, 34684-2672
      • Arthritis Research of Florida /ID# 143125
    • Palm Harbor, Florida, United States, 34684
      • Arthritis Center, Inc. /ID# 145647
    • Saint Petersburg, Florida, United States, 33705
      • St. Anthony Comprehsve Res Ins /ID# 143095
    • Tampa, Florida, United States, 33603
      • Clinical Research West FL /ID# 148358
    • Tampa, Florida, United States, 33609
      • SW FL Clin Res Ctr, Tampa, FL /ID# 143117
    • Tampa, Florida, United States, 33614-7101
      • BayCare Medical Group, Inc. /ID# 143085
    • Venice, Florida, United States, 34292
      • Lovelace Scientific Resources /ID# 143106
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Arthritis and Rheumatology /ID# 155668
    • Gainesville, Georgia, United States, 30501
      • Arthritis Center of North GA /ID# 155258
    • Lawrenceville, Georgia, United States, 30045
      • North Georgia Rheumatology Grp /ID# 147170
  • Idaho
    • Meridian, Idaho, United States, 83642
      • Advanced Clinical Research /ID# 153090
  • Illinois
    • Chicago, Illinois, United States, 60640
      • Great Lakes Clinical Trials /ID# 148357
  • Maryland
    • Frederick, Maryland, United States, 21204
      • Arthritis Treatment Center /ID# 155260
    • Wheaton, Maryland, United States, 20902
      • The Center for Rheumatology & /ID# 151356
  • Massachusetts
    • Worcester, Massachusetts, United States, 01605
      • Clinical Pharmacology Study Gr /ID# 143082
  • Michigan
    • Lansing, Michigan, United States, 48910
      • Advanced Rheumatology, PC /ID# 143118
    • Saint Clair Shores, Michigan, United States, 48081
      • Shores Rheumatology, PC /ID# 162977
  • Minnesota
    • Duluth, Minnesota, United States, 55805
      • St. Luke's Hospital /ID# 156750
  • Mississippi
    • Tupelo, Mississippi, United States, 38801
      • North Mississippi Med Clinics /ID# 145636
  • Nebraska
    • Lincoln, Nebraska, United States, 68516
      • Physician Res. Collaboration /ID# 143087
    • Omaha, Nebraska, United States, 68114
      • Quality Clinical Research Inc. /ID# 156394
  • New Jersey
    • Toms River, New Jersey, United States, 08755
      • Atlantic Coast Research /ID# 148355
    • Toms River, New Jersey, United States, 08755
      • Ocean Rheumatology, PA /ID# 143111
    • Voorhees, New Jersey, United States, 08043
      • Arthritis Rheumatic Back Disorder /ID# 143102
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Albuquerque Clinical Trials, Inc /ID# 143083
    • Las Cruces, New Mexico, United States, 88011
      • Arthritis and Osteo Assoc /ID# 143127
  • New York
    • Potsdam, New York, United States, 13676
      • St. Lawrence Health System /ID# 161619
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Joint & Muscle Research Instit /ID# 143119
    • Charlotte, North Carolina, United States, 28210-8508
      • DJL Clinical Research, PLLC /ID# 143101
    • Durham, North Carolina, United States, 27704
      • EmergeOrtho, P.A. /ID# 143100
    • Leland, North Carolina, United States, 28451
      • Cape Fear Arthritis Care /ID# 148361
    • New Bern, North Carolina, United States, 28562
      • Coastal Carolina Health Care /ID# 148359
    • Raleigh, North Carolina, United States, 27617
      • Shanahan Rheuma & Immuno /ID# 145643
  • Ohio
    • Dayton, Ohio, United States, 45409
      • Clinical Research Solutions, LLC /ID# 154619
    • Toledo, Ohio, United States, 43606
      • Arthritis Assoc of NW Ohio /ID# 143094
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74135
      • Healthcare Research Consultant /ID# 143129
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Ctr Clinical Res /ID# 143110
    • Wyomissing, Pennsylvania, United States, 19610
      • Clinical Research Ctr Reading /ID# 143133
  • South Carolina
    • Columbia, South Carolina, United States, 29204
      • Columbia Arthritis Center /ID# 153730
    • Greenville, South Carolina, United States, 29601
      • Innovative Clinical Research /ID# 145637
    • Summerville, South Carolina, United States, 29486-7887
      • Articularis Healthcare Group, Inc d/b/a Low Country Rheumatology /ID# 143091
  • Tennessee
    • Kingsport, Tennessee, United States, 37660
      • Arthritis Associates, PLLC /ID# 155490
    • Knoxville, Tennessee, United States, 37909
      • Rheumatology Consultants, PLLC /ID# 153731
    • Memphis, Tennessee, United States, 38119
      • Dr. Ramesh Gupta /ID# 143099
  • Texas
    • Austin, Texas, United States, 78731
      • Austin Regional Clinic /ID# 143084
    • Beaumont, Texas, United States, 77701
      • Diagnostic Group Integrated He /ID# 148356
    • Dallas, Texas, United States, 75231
      • Arthritis Care and Diagnostic /ID# 150677
    • Dallas, Texas, United States, 75231
      • Metroplex Clinical Research /ID# 145631
    • Edinburg, Texas, United States, 78539
      • Doctor's Hosp at Renaissance /ID# 154616
    • El Paso, Texas, United States, 79935
      • MedResearch Inc. /ID# 154618
    • Houston, Texas, United States, 77004
      • Accurate Clinical Management /ID# 145644
    • Houston, Texas, United States, 77034
      • Accurate Clinical Research /ID# 145645
    • Houston, Texas, United States, 77065
      • Rheumatology Clinic of Houston /ID# 150921
    • Houston, Texas, United States, 77074
      • Houston Institute for Clin Res /ID# 144879
    • Houston, Texas, United States, 77098-5294
      • Pioneer Research Solutions, Inc. /ID# 145640
    • Killeen, Texas, United States, 76549
      • Arthritis Consultants, P.A. /ID# 144880
    • Lubbock, Texas, United States, 79424
      • Arthritis & Osteoporosis Assoc /ID# 147364
    • Lufkin, Texas, United States, 75904-3132
      • P&I Clinical Research /ID# 161625
    • Mesquite, Texas, United States, 75150
      • SW Rheumatology Res. LLC /ID# 143126
    • Missouri City, Texas, United States, 77459-4750
      • Discovery MM Services, Inc. /ID# 162578
    • Missouri City, Texas, United States, 77459-4750
      • Discovery MM Services, Inc. /ID# 163183
    • Missouri City, Texas, United States, 77459-4750
      • Discovery MM Services, Inc. /ID# 163184
    • San Antonio, Texas, United States, 78215
      • Sun Research Institute /ID# 159539
    • San Antonio, Texas, United States, 78229
      • Accurate Clinical Management /ID# 143089
    • San Antonio, Texas, United States, 78232
      • Arthritis & Osteo Ctr of S. TX /ID# 143103
    • Tomball, Texas, United States, 77375
      • DM Clinical Research /ID# 151357
  • Virginia
    • Arlington, Virginia, United States, 22205
      • Arthritis Clinic of N. VA, P.C /ID# 143109
    • Chesapeake, Virginia, United States, 23320
      • Ctr for Arth and Rheum Disease /ID# 143113
  • Washington
    • Spokane, Washington, United States, 99204
      • Arthritis Northwest, PLLC /ID# 143088
    • Vancouver, Washington, United States, 98664
      • The Vancouver Clinic, INC. PS /ID# 143107
  • West Virginia
    • South Charleston, West Virginia, United States, 25309
      • West Virginia Research Inst /ID# 153088
  • Wisconsin
    • Franklin, Wisconsin, United States, 53132
      • Rheumatology and Immunotherapy Center /ID# 145646

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult male or female, at least 18 years old.
• Diagnosis of RA for greater than or equal to 3 months.
• Subjects must have been on oral or parenteral methotrexate (MTX) therapy greater than or equal to 3 months and on a stable prescription of greater than or equal to 15 to 25 mg/week (or greater than or equal to 10 mg/week in subjects intolerant of MTX at doses greater than or equal to 12.5 mg/week) for at least 4 weeks prior to the first dose of study drug. In addition all subjects should take a dietary supplement of folic acid or folinic acid throughout the study participation.
• Meets the following minimum disease activity criteria: greater than or equal to 6 swollen joints (based on 66 joint counts) and greater than or equal to 6 tender joints (based on 68 joint counts) at Screening and Baseline Visits.
• At least one of the following at Screening: greater than or equal to 3 bone erosions on x-ray OR greater than or equal to 1 bone erosion and a positive rheumatoid factor OR greater than or equal to 1 bone erosion and a positive anti-cyclic citrullinated peptide autoantibodies.
• Subjects with prior exposure to only one biological disease-modifying anti-rheumatic drugs (bDMARD) (except adalimumab) may be enrolled (up to 20% of total study population) if they have documented evidence of intolerance to the bDMARD or limited exposure (less than 3 months), but required washout periods need to be satisfied.
• Except for MTX, subject must have discontinued all conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs).

Exclusion Criteria:

• Prior exposure to any Janus kinase (JAK) inhibitor (including but not limited to tofacitinib, baricitinib, and filgotinib).
• Subjects who have been exposed to adalimumab or who are considered inadequate responders to bDMARD therapy as determined by the Investigator.
• History of inflammatory joint disease other than RA. History of secondary Sjogren's Syndrome is permitted.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo followed by ABT-494; Participants were to receive placebo to upadacitinib orally once daily (QD) and placebo to adalimumab by subcutaneous injection once every two weeks (eow) for up to 26 weeks. Participants who did not achieve a ≥ 20% improvement in tender joint count (TJC) and swollen joint count (SJC) at Weeks 14, 18, or 22 compared to Baseline were to be switched to 15 mg upadacitinib orally QD. At Week 26, all remaining participants were to be switched to 15 mg upadacitinib QD until Week 48 (end of Period 1). Participants who complete Period 1 will continue to receive 15 mg upadacitinib orally QD for up to 5 years in Period 2.	Drug: Placebo for Upadacitinib; Tablets taken orally once a day; Drug: Upadacitinib; Tablets taken orally once a day; Other Names: ABT-494; Drug: Placebo for Adalimumab; Administered by subcutaneous injection once every other week
Active Comparator: Adalimumab; Participants were to receive placebo to upadacitinib orally QD and 40 mg adalimumab by subcutaneous injection eow for up to 48 weeks in Period 1. Participants who did not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline were to be switched to 15 mg upadacitinib orally QD. At Week 26 remaining participants who did not achieve low disease activity (defined as Clinical Disease Activity Index [CDAI] ≤ 10) were to be switched to 15 mg upadacitinib orally QD until Week 48. Participants who complete Period 1 will continue to receive the same treatment assigned at the end of Period 1 (15 mg upadacitinib QD or 40 mg adalimumab eow) for up to 5 years in Period 2.	Drug: Placebo for Upadacitinib; Tablets taken orally once a day; Drug: Upadacitinib; Tablets taken orally once a day; Other Names: ABT-494; Drug: Adalimumab; Administered by subcutaneous injection once every other week; Other Names: Humira
Experimental: Upadacitinib; Participants were to receive 15 mg upadacitinib orally QD and placebo to adalimumab by subcutaneous injection eow for up to 48 weeks in Period 1. Participants who did not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline were to be switched to 40 mg adalimumab eow. At Week 26 remaining participants who did not achieve low disease activity (defined as CDAI ≤ 10) were to be switched to 40 mg adalimumab eow until Week 48. Participants who complete Period 1 will continue to receive the same treatment assigned at the end of Period 1 (15 mg upadacitinib QD or 40 mg adalimumab eow) for up to 5 years in Period 2.	Drug: Upadacitinib; Tablets taken orally once a day; Other Names: ABT-494; Drug: Placebo for Adalimumab; Administered by subcutaneous injection once every other week; Drug: Adalimumab; Administered by subcutaneous injection once every other week; Other Names: 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	The primary endpoint for United States (US)/Food and Drug Administration (FDA) regulatory purposes was ACR 20% response (ACR20) at Week 12. Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR20 response criteria: ≥ 20% improvement in 68-tender joint count;; ≥ 20% improvement in 66-swollen joint count; and; ≥ 20% improvement in at least 3 of the 5 following parameters:Physician global assessment of disease activityPatient global assessment of disease activityPatient assessment of painHealth Assessment Questionnaire - Disability Index (HAQ-DI)High-sensitivity C-reactive protein (hsCRP).	Baseline and Week 12
Percentage of Participants Achieving Clinical Remission (CR) Based on DAS28(CRP) at Week 12	The primary endpoint for European Union (EU)/European Medicines Agency (EMA) regulatory purposes was clinical remission, based on a Disease Activity Score 28 (DAS28)-CRP score of < 2.6 at Week 12. The DAS28 is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity. A DAS28 score less than 2.6 indicates clinical remission.	Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 12	The Short Form 36-Item Health Survey (SF-36) Version 2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The physical component score is a weighted combination of the 8 subscales with positive weighting for physical functioning, role-physical, bodily pain, and general health. The PCS was calculated using norm-based scoring so that 50 is the average score and the standard deviation equals 10. Higher scores are associated with better functioning/quality of life; a positive change from baseline score indicates an improvement.	Baseline and Week 12
Percentage of Participants Achieving Low Disease Activity Based on CDAI at Week 12	Low disease activity based on the clinical disease activity index (CDAI) is defined as a CDAI score ≤ 10. CDAI is a composite index for assessing disease activity based on the summation of the total tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), patient global assessment of disease activity measured on a VAS from 0 to 10 cm, and physician global assessment of disease activity measured on a VAS from 0 to 10 cm. The total CDAI score ranges from 0 to 78 with higher scores indicating higher disease activity.	Week 12
Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12	Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR50 response criteria: ≥ 50% improvement in 68-tender joint count;; ≥ 50% improvement in 66-swollen joint count; and; ≥ 50% improvement in at least 3 of the 5 following parameters:Physician global assessment of disease activityPatient global assessment of disease activityPatient assessment of painHealth Assessment Questionnaire - Disability Index (HAQ-DI)High-sensitivity C-reactive protein (hsCRP).	Baseline and Week 12
Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 12	Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR70 response criteria: ≥ 70% improvement in 68-tender joint count;; ≥ 70% improvement in 66-swollen joint count; and; ≥ 70% improvement in at least 3 of the 5 following parameters:Physician global assessment of disease activityPatient global assessment of disease activityPatient assessment of painHealth Assessment Questionnaire - Disability Index (HAQ-DI)High-sensitivity C-reactive protein (hsCRP).	Baseline and Week 12
Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12	The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire that measures the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and errands and chores) over the past week. Participants assessed their ability to do each task on a scale from 0 (without any difficulty) to 3 (unable to do). Scores were averaged to provide an overall score ranging from 0 to 3, where 0 represents no disability and 3 represents very severe, high-dependency disability. A negative change from Baseline in the overall score indicates improvement.	Baseline and Week 12
Change From Baseline in DAS28 (CRP) at Week 12	The DAS28 is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity. A negative change from Baseline in DAS28 (CRP) indicates improvement in disease activity.	Baseline and Week 12
Change From Baseline in Modified Total Sharp Score (mTSS) at Week 26	The mTSS measures the level of joint damage from radiographs of the hands and feet, assessed by 2 independent, blinded readers. mTSS is calculated as the sum of the total joint erosion score and total joint space narrowing (JSN) score. Joint erosion severity was assessed in 16 joints in each hand and wrist and 6 joints in each foot. Each joint was scored from 0 (no erosion) to 5 for hands/wrists or to 10 for feet (complete collapse). The total erosion score ranges from 0 to 280 (worst). JSN was assessed in 15 joints of each hand and wrist, and 6 joints of each foot, including subluxation, from 0 (normal) to 4 (complete loss of joint space, bony ankylosis, or luxation). The total JSN score ranges from 0 to 168 (worst). The mTSS is the sum of the joint erosion and JSN scores and ranges from 0 (normal) to 448 (worst). A negative change from Baseline in mTSS indicates improvement in joint damage whereas a change from Baseline greater than 0 indicates progression.	Baseline and Week 26
Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 12	The DAS28(CRP) is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity. A DAS28(CRP) score less than or equal to 3.2 indicates low disease activity.	Week 12
Change From Baseline in Duration of Morning Stiffness at Week 12	Participants were asked to indicate the time it took for them to get as limber as possible after awakening with morning stiffness over the past 7 days. A negative change from Baseline indicates improvement.	Baseline and Week 12
Change From Baseline in in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F)	The FACIT Fatigue scale is a 13-item tool that measures an individual's level of fatigue during their usual daily activities over the past 7 days. Each of the fatigue and impact of fatigue items are measured on a four point Likert scale. The FACIT Fatigue Scale is the sum of the individual 13 scores and ranges from 0 to 52 where higher scores indicate better the quality of life. A positive change from Baseline indicates improvement.	Baseline and Week 12
Change From Baseline in Patient's Assessment of Pain at Week 12	Participants were asked to indicate the severity of their arthritis pain within the previous week on a visual analog scale (VAS) from 0 to 100. A score of 0 indicates "no pain" and a score of 100 indicates "worst possible pain." A negative change from Baseline indicates improvement.	Baseline and Week 12
Percentage of Participants With No Radiographic Progression at Week 26	No radiographic progression is defined as a change from Baseline in mTSS ≤ 0. The mTSS measures the level of joint damage from radiographs of the hands and feet, which were assessed by 2 independent, blinded readers. mTSS is calculated as the sum of the total joint erosion score and total joint space narrowing (JSN) score and ranges from 0 (normal) to 448 (worst). Joint erosion severity was assessed in 16 joints in each hand and wrist and 6 joints in each foot. Each joint was scored from 0 (no erosion) to 5 for hands/wrists or to 10 for feet (complete collapse). The total erosion score ranges from 0 to 280 (worst). Joint space narrowing (JSN) was assessed in 15 joints of each hand and wrist, and 6 joints of each foot, including subluxation, from 0 (normal) to 4 (complete loss of joint space, bony ankylosis, or luxation). The total JSN score ranges from 0 to 168 (worst).	Baseline and Week 26

Collaborators and Investigators

• Sponsor: AbbVie

Publications and helpful links

General Publications

• Bergman M, Buch MH, Tanaka Y, Citera G, Bahlas S, Wong E, Song Y, Zueger P, Ali M, Strand V. Routine Assessment of Patient Index Data 3 (RAPID3) in Patients with Rheumatoid Arthritis Treated with Long-Term Upadacitinib Therapy in Five Randomized Controlled Trials. Rheumatol Ther. 2022 Dec;9(6):1517-1529. doi: 10.1007/s40744-022-00483-4. Epub 2022 Sep 20.
• Yamaoka K, Tanaka Y, Kameda H, Khan N, Sasaki N, Harigai M, Song Y, Zhang Y, Takeuchi T. The Safety Profile of Upadacitinib in Patients with Rheumatoid Arthritis in Japan. Drug Saf. 2021 Jun;44(6):711-722. doi: 10.1007/s40264-021-01067-x. Epub 2021 May 27.
• Cohen SB, van Vollenhoven RF, Winthrop KL, Zerbini CAF, Tanaka Y, Bessette L, Zhang Y, Khan N, Hendrickson B, Enejosa JV, Burmester GR. Safety profile of upadacitinib in rheumatoid arthritis: integrated analysis from the SELECT phase III clinical programme. Ann Rheum Dis. 2021 Mar;80(3):304-311. doi: 10.1136/annrheumdis-2020-218510. Epub 2020 Oct 28. Erratum In: Ann Rheum Dis. 2021 May;80(5):e83.
• Nader A, Mohamed MF, Winzenborg I, Doelger E, Noertersheuser P, Pangan AL, Othman AA. Exposure-Response Analyses of Upadacitinib Efficacy and Safety in Phase II and III Studies to Support Benefit-Risk Assessment in Rheumatoid Arthritis. Clin Pharmacol Ther. 2020 Apr;107(4):994-1003. doi: 10.1002/cpt.1671. Epub 2019 Nov 30.
• Peterfy CG, Strand V, Friedman A, Hall S, Mysler E, Durez P, Baraliakos X, Enejosa JV, Shaw T, Li Y, Chen S, Song IH. Inhibition of structural joint damage progression with upadacitinib in rheumatoid arthritis: 1-year outcomes from the SELECT phase 3 program. Rheumatology (Oxford). 2022 Aug 3;61(8):3246-3256. doi: 10.1093/rheumatology/keab861.
• Fleischmann R, Pangan AL, Song IH, Mysler E, Bessette L, Peterfy C, Durez P, Ostor AJ, Li Y, Zhou Y, Othman AA, Genovese MC. Upadacitinib Versus Placebo or Adalimumab in Patients With Rheumatoid Arthritis and an Inadequate Response to Methotrexate: Results of a Phase III, Double-Blind, Randomized Controlled Trial. Arthritis Rheumatol. 2019 Nov;71(11):1788-1800. doi: 10.1002/art.41032. Epub 2019 Aug 28.
• Mysler E, Tanaka Y, Kavanaugh A, Aletaha D, Taylor PC, Song IH, Shaw T, Song Y, DeMasi R, Ali M, Fleischmann R. Impact of initial therapy with upadacitinib or adalimumab on achievement of 48-week treatment goals in patients with rheumatoid arthritis: post hoc analysis of SELECT-COMPARE. Rheumatology (Oxford). 2022 Aug 26:keac477. doi: 10.1093/rheumatology/keac477. Online ahead of print.
• Strand V, Tundia N, Bergman M, Ostor A, Durez P, Song IH, Enejosa J, Schlacher C, Song Y, Fleischmann R. Upadacitinib improves patient-reported outcomes vs placebo or adalimumab in patients with rheumatoid arthritis: results from SELECT-COMPARE. Rheumatology (Oxford). 2021 Dec 1;60(12):5583-5594. doi: 10.1093/rheumatology/keab158.
• Fleischmann RM, Blanco R, Hall S, Thomson GTD, Van den Bosch FE, Zerbini C, Bessette L, Enejosa J, Li Y, Song Y, DeMasi R, Song IH. Switching between Janus kinase inhibitor upadacitinib and adalimumab following insufficient response: efficacy and safety in patients with rheumatoid arthritis. Ann Rheum Dis. 2021 Apr;80(4):432-439. doi: 10.1136/annrheumdis-2020-218412. Epub 2020 Nov 4.
• Fleischmann RM, Genovese MC, Enejosa JV, Mysler E, Bessette L, Peterfy C, Durez P, Ostor A, Li Y, Song IH. Safety and effectiveness of upadacitinib or adalimumab plus methotrexate in patients with rheumatoid arthritis over 48 weeks with switch to alternate therapy in patients with insufficient response. Ann Rheum Dis. 2019 Nov;78(11):1454-1462. doi: 10.1136/annrheumdis-2019-215764. Epub 2019 Jul 30.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2015
• Primary Completion (Actual): October 27, 2017
• Study Completion (Anticipated): September 30, 2027

Study Registration Dates

• First Submitted: December 10, 2015
• First Submitted That Met QC Criteria: December 10, 2015
• First Posted (Estimate): December 14, 2015

Study Record Updates

• Last Update Posted (Actual): April 24, 2023
• Last Update Submitted That Met QC Criteria: April 20, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Arthritis; Anti-inflammatory agents; Musculoskeletal disease; Antirheumatic agents; Joint disease
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Protein Kinase Inhibitors; Janus Kinase Inhibitors; Adalimumab; Upadacitinib
• Other Study ID Numbers: M14-465; 2022-501017-31-00 (Other Identifier: EU CT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols, analyses plans, clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
• IPD Sharing Time Frame: For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
• IPD Sharing Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous independent scientific research, and will be provided following review and approval of a research proposal and statistical analysis plan and execution of a data sharing statement. Data requests can be submitted at any time after approval in the US and/or EU and a primary manuscript is accepted for publication. For more information on the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No