A Study to Compare Upadacitinib (ABT-494) Monotherapy to Methotrexate (MTX) Monotherapy in Adults With Rheumatoid Arthritis (RA) Who Have Not Previously Taken Methotrexate (SELECT-EARLY)

June 21, 2023 updated by: AbbVie

A Phase 3, Randomized, Double-Blind Study Comparing Upadacitinib (ABT-494) Once Daily Monotherapy to Methotrexate (MTX) Monotherapy in MTX-Naïve Subjects With Moderately to Severely Active Rheumatoid Arthritis

The objectives of Period 1 were the following:

  • To compare the safety and efficacy of upadacitinib 7.5 mg once daily (QD) monotherapy (for participants in Japan only), 15 mg QD monotherapy, and 30 mg QD monotherapy versus weekly methotrexate monotherapy for the treatment of signs and symptoms of RA in methotrexate-naïve adults with moderately to severely active RA;
  • To compare the efficacy of upadacitinib 15 mg QD monotherapy and upadacitinib 30 mg QD monotherapy versus weekly methotrexate monotherapy for prevention of structural progression in methotrexate-naïve adults with moderately to severely active RA.

The objective of Period 2 is to evaluate the long-term safety, tolerability, and efficacy of upadacitinib 7.5 mg QD (for participants in Japan only), 15 mg QD, and 30 mg QD in adults with RA who have completed Period 1.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This study includes 2 periods (a 48-week double-blind treatment period and a long-term extension period) and a Japan substudy. In Period 1 participants will be randomized in a 1:1:1 ratio to treatment Groups 2, 3, and 4 below, except for participants from Japan, who will be randomized in a 2:1:1:1 ratio to Groups 1, 2, 3, and 4:

  • Group 1: Upadacitinib 7.5 mg once daily (QD) monotherapy (participants in Japan only)
  • Group 2: Upadacitinib 15 mg QD monotherapy
  • Group 3: Upadacitinib 30 mg QD monotherapy
  • Group 4: Methotrexate monotherapy

Rescue therapy is defined for Weeks 12 through 24, Week 26, and Weeks 36 through 40. Starting at Week 12 through Week 24, participants who do not achieve ≥ 20% improvement in both tender joint count (TJC) and swollen joint count (SJC) compared with baseline at two consecutive visits will continue on their blinded therapy and the Investigator should optimize (initiate or increase) background RA medications: non-steroidal anti-inflammatory drug(s) (NSAIDs), corticosteroids (oral ≤ 10 mg/day prednisone equivalent or prednisone equivalent ≤ 0.5 mg/kg/day for 3 consecutive days) and/or low-potency analgesics.

Rescue therapy for participants who meet the following criteria at Week 26 are as follows:

Participants who do not achieve clinical remission (CR) based on Clinical Disease Activity Index (CDAI) (defined as a CDAI score ≤ 2.8):

  • but achieve ≥ 20% improvement in both TJC and SJC compared with baseline will continue on blinded study drug and the Investigator should optimize (initiate or increase) background RA medications: NSAIDs, corticosteroids (oral ≤ 10 mg/day prednisone equivalent and up to 2 local injections), low-potency analgesics and conventional synthetic disease-modifying anti-rheumatic drug(s) (csDMARDs) (only 1 of the following: sulfasalazine, hydroxychloroquine or chloroquine) throughout the remainder of Period 1 and until the study is unblinded.
  • and do not achieve ≥ 20% improvement in both TJC and SJC compared with baseline and originally assigned to methotrexate will be re-randomized in a 1:1 ratio to receive blinded upadacitinib 15 mg QD or upadacitinib 30 mg QD (participants in Japan will be randomized 1:1:1 to receive upadacitinib 7.5 mg QD, 15 mg QD, or 30 mg QD) while continuing methotrexate treatment in a blinded manner until the study is unblinded. Participants originally assigned to upadacitinib will add methotrexate 10 mg/week (7.5 mg for Japan) to upadacitinib in a blinded manner and will remain on upadacitinib plus methotrexate 10 mg/week (7.5 mg for Japan) until the study is unblinded.

Starting at Week 36 through Week 40, participants who do not achieve ≥ 20% improvement in both TJC and SJC compared with baseline at two consecutive visits will continue on their blinded therapy and the Investigator should optimize (initiate or increase) background RA medications: NSAIDs, corticosteroids (oral ≤ 10 mg/day prednisone equivalent or prednisone equivalent ≤ 0.5 mg/kg/day for 3 consecutive days and up to 2 local injections), low-potency analgesics and csDMARDs (only 1 of the following: sulfasalazine, hydroxychloroquine or chloroquine).

Participants who complete the Week 48 visit (end of Period 1) will enter the long-term extension, Period 2 (212 weeks) and continue study treatment per assignment at the end of Period 1 in a blinded fashion. When the last participant completes the last visit of Period 1 (Week 48), study drug assignment in both periods may be unblinded, and participants will be dispensed study drug in an open-label fashion until the completion of Period 2. Starting with Protocol Amendment 6, participants receiving upadacitinib 15 mg and 30 mg QD will receive open-label upadacitinib 15 mg QD, and participants receiving methotrexate will receive open-label methotrexate.

A global analysis will be conducted for the comparisons of the primary and secondary efficacy endpoints between the upadacitinib 15 mg QD and 30 mg QD treatment groups versus the methotrexate treatment group for all participants (excluding the Japan specific upadacitinib 7.5 mg treatment group). Analyses will be conducted separately for United States (US)/Food and Drug Administration (FDA), European Union (EU)/European Medicines Agency (EMA), and Japan/Pharmaceuticals and Medical Devices Agency (PMDA) regulatory purposes, each according to a pre-specified sequence of primary and ranked secondary endpoints.

A separate Japan sub-study analysis will be conducted for the comparisons of the efficacy endpoints between the upadacitinib 7.5 mg QD, 15 mg QD, and 30 mg QD treatment groups versus the methotrexate treatment group for participants enrolled in Japan only.

Study Type

Interventional

Enrollment (Actual)

1002

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Buenos Aires, Argentina, C1015ABO
        • Org Medica de Investigacion /ID# 143142
      • Cordoba, Argentina, 5900
        • Consultora Integral de Salud S /ID# 143144
      • San Miguel de Tucuman, Argentina, 4000
        • Centro Integral de Reumatologi /ID# 143143
      • San Miguel de Tucuman, Argentina, 4000
        • Centro Medico Privado/Reuma /ID# 143140
    • Buenos Aires
      • Capital Federal, Buenos Aires, Argentina, 1046
        • Aprillus Asistencia e Investig /ID# 149179
      • San isidro, Buenos Aires, Argentina, 1646
        • Iari /Id# 148595
    • Santa FE
      • Rosario, Santa FE, Argentina, 2000
        • Instituto CAICI /ID# 143141
  • Australia
    • New South Wales
      • Camperdown, New South Wales, Australia, 2050
        • Royal Prince Alfred Hospital /ID# 143149
    • Queensland
      • Maroochydore, Queensland, Australia, 4558
        • Rheumatology Research Unit /ID# 143147
    • South Australia
      • Woodville, South Australia, Australia, 5011
        • The Queen Elizabeth Hospital /ID# 143148
    • Tasmania
      • Hobart, Tasmania, Australia, 7000
        • Southern Clinical Research Pty /ID# 143150
    • Victoria
      • Camberwell, Victoria, Australia, 3124
        • Emeritus Research /ID# 143146
  • Belarus
      • Minsk, Belarus, 220013
        • First City Clinical Hospital /ID# 159020
      • Minsk, Belarus, 220116
        • City Clinical Hospital #9 /ID# 145650
  • Belgium
      • Genk, Belgium, 3600
        • ReumaClinic Genk /ID# 143159
      • Mons, Belgium, 7000
        • CHU Ambroise Pare /ID# 152955
    • Hainaut
      • Charleroi, Hainaut, Belgium, 6000
        • Rhumaconsult SPRL /ID# 143158
    • Oost-Vlaanderen
      • Aalst, Oost-Vlaanderen, Belgium, 9300
        • Algemeen Stedelijk Ziekenhuis /ID# 153504
      • Gent, Oost-Vlaanderen, Belgium, 9000
        • UZ Gent /ID# 143157
  • Bosnia and Herzegovina
      • Sarajevo, Bosnia and Herzegovina, 71000
        • Clinical Center University of Sarajevo /ID# 143164
    • Republika Srpska
      • Banja Luka, Republika Srpska, Bosnia and Herzegovina, 78000
        • University Clinical Centre of the Republic of Srpska /ID# 143161
      • Banja Luka, Republika Srpska, Bosnia and Herzegovina, 78000
        • University Clinical Centre of the Republic of Srpska /ID# 143162
  • Brazil
      • Rio de Janeiro, Brazil, 22271-100
        • CCBR Brasil /ID# 150925
    • Goias
      • Goiânia, Goias, Brazil, 74110-120
        • CIP - Centro Internacional de Pesquisa /ID# 143171
    • Parana
      • Curitiba, Parana, Brazil, 80030-110
        • Ceti - Centro de Estudos Em Terapias Inovadoras Ltda /Id# 143169
    • Rio Grande Do Sul
      • Porto Alegre, Rio Grande Do Sul, Brazil, 90035-903
        • Hospital de Clinicas de Porto Alegre /ID# 143168
      • Porto Alegre, Rio Grande Do Sul, Brazil, 90480-000
        • LMK Sevicos Medicos S/S /ID# 143167
    • Sao Paulo
      • São Paulo, Sao Paulo, Brazil, 04266-010
        • CEPIC - Centro Paulista de Investigação Clínica e Serviços Médicos Ltda /ID# 143166
  • Bulgaria
      • Plovdiv, Bulgaria, 4000
        • MHAT Trimontsium /ID# 143173
      • Plovdiv, Bulgaria, 4000
        • UMHAT Pulmed OOD /ID# 143176
      • Plovdiv, Bulgaria, 4001
        • MHAT Kaspela /ID# 143172
      • Sofia, Bulgaria, 1612
        • Diagnostic Consultative Center /ID# 143174
      • Sofia, Bulgaria, 1612
        • UMHAT Sv. Ivan Rilski /ID# 143175
  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T5M 0H4
        • Rheumatology Research Assoc /ID# 143206
    • Manitoba
      • Winnipeg, Manitoba, Canada, R3A IM3
        • Manitoba Clinic /ID# 143203
      • Winnipeg, Manitoba, Canada, R3N 0K6
        • Ciads /Id# 143205
    • Ontario
      • Thornhill, Ontario, Canada, L4J 1W3
        • CA Ctr for Clin Trials CCCT /ID# 159080
    • Quebec
      • Rimouski, Quebec, Canada, G5L 8W1
        • Ctr. de Rheum de l'est du QC /ID# 151317
  • Chile
      • Puerto Varas, Chile, 5550170
        • Quantum Research LTDA. /ID# 143210
      • Santiago, Chile, 7500588
        • Quantum Research Stgo. /ID# 145651
      • Santiago, Chile, 7510047
        • Soc. de Prestaciones medicas y Paramedicas Goecke /ID# 143209
      • Santiago, Chile, 8207257
        • Investigaciones Medicas SSMSO /ID# 151685
      • Vina Del Mar, Chile
        • Centro de Estudios Clinicos Qu /ID# 152913
    • Araucania
      • Temuco, Araucania, Chile, 4781156
        • Ctr de Inv Clinica del Sur /ID# 143208
    • Santiago
      • Providencia, Santiago, Chile, 7510186
        • Someal /Id# 143207
  • China
    • Anhui
      • Bengbu, Anhui, China, 233099
        • 1st Aff Hosp of Bengbu Med Col /ID# 162974
    • Fujian
      • Xiamen, Fujian, China, 361003
        • The 1st Aff Hosp Xiamen Univ /ID# 162076
    • Guangdong
      • Shantou, Guangdong, China, 515041
        • 1st Aff Hosp of Shantou Univ /ID# 162968
  • Colombia
      • Barranquilla, Colombia, 80002
        • Ctr Int de Reum del Caribe SAS /ID# 143211
      • Bogota, Colombia, 110221
        • Riesgo de Fractura S.A - CAYRE /ID# 143212
      • Bogota, Colombia, 110221
        • Simedics IPS SAS /ID# 152572
      • Bogotá, Colombia
        • Fund Inst de Reum F. Chalem /ID# 159544
      • Bucaramanga, Colombia, 680003
        • Medicity S.A.S. /ID# 143213
    • Cundinamarca
      • Bogota, Cundinamarca, Colombia, 110221
        • Centro de Investigacion en Reumatologia y Especialidades Medicas- CIREEM SAS /ID# 143214
  • Croatia
      • Split, Croatia, 21000
        • Klinicki bolnicki centar Split /ID# 143216
      • Zagreb, Croatia, 10000
        • Clinical Hospital Dubrava /ID# 143217
      • Zagreb, Croatia, 10000
        • Medical Center Kuna-Peric /ID# 143218
      • Zagreb, Croatia, 10000
        • Poliklinika Bonifarm /ID# 143215
  • Czechia
      • Breclav, Czechia, 690 02
        • RHEUMA s.r.o. /ID# 143230
      • Brno, Czechia, 638 00
        • Revmatologie, s.r.o. /ID# 143223
      • Bruntál, Czechia, 79201
        • Revmatologie Bruntal, s.r.o /ID# 143220
      • Slany, Czechia, 274 01
        • Nemocnice Slany /ID# 143221
      • Uherské Hradište, Czechia, 686 01
        • Medical Plus, s.r.o. /ID# 143219
    • Moravskoslezsky Kraj
      • Hlučín, Moravskoslezsky Kraj, Czechia, 748 01
        • L.K.N. Arthrocentrum, s.r.o /ID# 143224
    • Olomoucky Kraj
      • Olomouc, Olomoucky Kraj, Czechia, 779 00
        • CTCenter MaVe, s.r.o. /ID# 143226
    • Praha 4
      • Prague, Praha 4, Czechia, 140 59
        • Thomayerova nemocnice /ID# 143228
      • Prague 4, Praha 4, Czechia, 140 00
        • Nuselská poliklinika, Revmatologie /ID# 143232
      • Prague 4, Praha 4, Czechia, 140 00
        • Nuselská poliklinika, Revmatologie /ID# 143233
    • Zlin
      • Zlín 1, Zlin, Czechia, 760 01
        • PV MEDICAL Services s.r.o. /ID# 143234
  • Estonia
      • Pärnu, Estonia, 80010
        • Paernu Hospital /ID# 143238
      • Tallinn, Estonia, 10138
        • East Tallinn Central Hospital /ID# 143240
      • Tallinn, Estonia, 13419
        • North Estonian Medical Centre /ID# 145456
    • Harjumaa
      • Tallinn, Harjumaa, Estonia, 10128
        • Center of Clinical and Basic Research /ID# 143239
  • Germany
      • Hamburg, Germany, 20095
        • Rheumaforschungszentrum II /ID# 143247
      • Hamburg, Germany, 22081
        • Schoen Klinikum Hamburg Eilbek /ID# 143251
      • Munich, Germany, 80337
        • LMU Klinikum der Universität München /ID# 143249
    • Nordrhein-Westfalen
      • Herne, Nordrhein-Westfalen, Germany, 44649
        • Rheumazentrum Ruhrgebiet /ID# 145652
      • Köln, Nordrhein-Westfalen, Germany, 50937
        • Uniklinik Koln /ID# 143248
    • Schleswig-Holstein
      • Rendsburg, Schleswig-Holstein, Germany, 24768
        • Praxis Walter, Rendsburg /ID# 143250
  • Greece
    • Attiki
      • Athens, Attiki, Greece, 12462
        • University General Hospital Attikon /ID# 143252
  • Guatemala
      • Ciudad de Guatemala, Guatemala, 01010
        • Clinicas Hospital Herrera Ller /ID# 153715
      • Ciudad de Guatemala, Guatemala, 10010
        • Creer /Id# 153713
      • Ciudad de Guatemala, Guatemala, 1011
        • Clin Especializada Med Interna /ID# 153716
      • Ciudad de Guatemala, Guatemala, 1021
        • Clinica Medica Reumatologia /ID# 153714
      • Ciudad de Guatemala, Guatemala, 1021
        • Clinica Medica Reumatologia /ID# 153931
  • Hong Kong
      • Hong Kong, Hong Kong, 999077
        • Queen Mary Hospital /ID# 143255
      • Tuen Mun, Hong Kong, 999077
        • Tuen Mun Hospital /ID# 143256
  • Hungary
      • Heviz, Hungary, 8380
        • Hevizgyogyfurdo es Szent Andra /ID# 143257
      • Kistarcsa, Hungary, 2143
        • Pest Megyei Flor Ferenc Korhaz /ID# 143260
      • Szekesfehervar, Hungary, 8000
        • Fejer Megyei Szent Gyorgy Korh /ID# 144724
    • Borsod-Abauj-Zemplen
      • Miskolc, Borsod-Abauj-Zemplen, Hungary, 3529
        • CRU Hungary Egeszsegugyi és Szolgaltato Kft. /ID# 143258
    • Pest
      • Budapest, Pest, Hungary, 1036
        • Qualiclinic Kft. /ID# 143259
    • Vas
      • Szombathely, Vas, Hungary, 9700
        • Markusovszky Egyetemi Oktatókórház /ID# 143261
  • Ireland
      • Dublin, Ireland, D04 T6F4
        • St Vincent's University Hosp /ID# 143262
  • Israel
      • Ashkelon, Israel, 78278
        • Barzilai Medical Center /ID# 144725
      • Haifa, Israel, 3109601
        • Rambam Health Care Campus /ID# 143263
      • Ramat Gan, Israel, 5262100
        • Sheba Medical Center /ID# 145975
  • Italy
      • Milan, Italy, 20157
        • Azienda Ospedaliera Luigi Sacc /ID# 143270
      • Pavia, Italy, 27100
        • Fondazione IRCCS Policlinico /ID# 143265
      • Verona, Italy, 37134
        • A.O.U.I. di Verona Policlinico /ID# 143266
    • Milano
      • Rozzano, Milano, Italy, 20089
        • Istituto Clinico Humanitas /ID# 147531
  • Japan
      • Beppu, Japan, 874 - 001
        • National Hospital Organization Beppu Medical Center /ID# 161058
      • Chiba, Japan, 260-8712
        • NHO Chiba-East-Hospital /ID# 148035
      • Fukui, Japan, 910-0068
        • Sugimoto Rheumatology and Internal Medicine Clinic /ID# 148047
      • Fukuoka, Japan, 814-0002
        • Shono Rheumatism Clinic /ID# 148046
      • Kato, Japan, 673-1462
        • Matsubara Mayflower Hospital /ID# 148033
      • Kurume, Japan, 830-8543
        • St. Mary's Hospital /ID# 148038
      • Kyoto, Japan, 615-8256
        • Kagawa University Hospital /ID# 148016
      • Miyagi, Japan, 981-0112
        • Yu Family Clinic /ID# 148048
      • Nagoya, Japan, 457-8511
        • Daido Hospital /ID# 160868
      • Nagoya, Japan, 464-0071
        • Kondo Clinic for Ortho & Rheum /ID# 148032
      • Nishimura, Japan, 649-2211
        • Shirahama Hamayu Hospital /ID# 148253
      • Oita, Japan, 870-0823
        • Oribe Clinic of Rheumatology and Internal Medicine /ID# 156035
      • Osaka, Japan, 534-0021
        • Osaka City General Hospital /ID# 159617
      • Sanuki, Japan, 769-2321
        • Sanuki Municipal Hospital /ID# 158842
      • Sapporo, Japan, 060-0001
        • Sagawa Akira Rheumatology Clin /ID# 148043
      • Sapporo, Japan, 060-8604
        • Sapporo City General Hospital /ID# 148037
      • Sapporo, Japan, 060-8648
        • Hokkaido University Hospital /ID# 148262
      • Sapporo, Japan, 063-0811
        • Hokkaido Medical Center for Rheumatic Diseases /ID# 148259
      • Sayama, Japan, 350-1305
        • Azuma Rheumatology Clinic /ID# 161050
      • Sendai, Japan, 983-0833
        • Hikarigaoka Spellman Hospital /ID# 148020
      • Takaoka, Japan, 933-0874
        • Takaoka Rheumatic Orthopedic Clinic /ID# 148022
      • Tokyo, Japan, 152-8902
        • National Hospital Organization Tokyo Medical Center /ID# 148040
      • Yotsukaido, Japan, 284-0003
        • National Hospital Organization Shimoshizu National Hospital /ID# 148258
    • Aichi
      • Nagoya-shi, Aichi, Japan, 466-8560
        • Nagoya University Hospital /ID# 148031
      • Toyohashi-shi, Aichi, Japan, 440-8510
        • NHO Toyohashi Medical Center /ID# 161033
    • Chiba
      • Ichihara, Chiba, Japan, 299-0111
        • Teikyo University Chiba Medical Center /ID# 159618
    • Fukuoka
      • Fukuoka-shi, Fukuoka, Japan, 810-8563
        • NHO Kyushu Medical Center /ID# 148263
      • Fukuoka-shi, Fukuoka, Japan, 810-8563
        • NHO Kyushu Medical Center /ID# 148264
    • Hokkaido
      • Asahikawa, Hokkaido, Japan, 070-8644
        • National Hospital Organization Asahikawa Medical Center /ID# 148021
      • Asahikawa, Hokkaido, Japan, 078-8243
        • Katayama Orthopedic Rheumatology Clinic /ID# 148029
    • Hyogo
      • Kobe, Hyogo, Japan, 650-0017
        • Kobe University Hospital /ID# 153461
    • Kanagawa
      • Sagamihara-shi, Kanagawa, Japan, 252-0315
        • National Hospital Organization Sagamihara National Hospital /ID# 148019
    • Kawachinagano-shi
      • Osaka, Kawachinagano-shi, Japan, 586-8521
        • NHO Osaka Minami Med Ctr /ID# 148042
    • Kochi
      • Kochi-shi, Kochi, Japan, 781-0112
        • Bay Side Misato Medical Center /ID# 148256
    • Kumamoto
      • Kumamoto-shi, Kumamoto, Japan, 862-0920
        • Center for Arthritis and Clinical Rheumatology Matsubara Clinic /ID# 148254
      • Kumamoto-shi, Kumamoto, Japan, 862-0976
        • Kumamoto Orthopaedic Hospital /ID# 148054
      • Kumamoto-shi, Kumamoto, Japan, 8628655
        • Kumamoto Shinto General Hospital /ID# 148266
    • Nagasaki
      • Sasebo-city, Nagasaki, Japan, 857-1195
        • Sasebo Chuo Hospital /ID# 148261
    • Niigata
      • Nagaoka-shi, Niigata, Japan, 940-2108
        • Nagaoka Red Cross Hospital /ID# 148018
    • Okayama
      • Okayama-shi, Okayama, Japan, 7008607
        • Japanese Red Cross Okayama Hospital /ID# 159619
    • Osaka
      • Hirakata-shi, Osaka, Japan, 573-1191
        • Kansai Medical University Hospital /ID# 159622
      • Takatsuki -shi, Osaka, Japan, 569-8686
        • Osaka Medical College Hospital /ID# 159624
    • Saitama
      • Kawagoe-shi, Saitama, Japan, 350-8550
        • Saitama Medical Center, Saitama Medical University /ID# 148015
    • Tochigi
      • Shimotsuke-shi, Tochigi, Japan, 329-0498
        • Jichi Medical University Hospital /ID# 159620
    • Tokyo
      • Bunkyo-ku, Tokyo, Japan, 113-8431
        • Juntendo University Hospital /ID# 148050
      • Chuo-ku, Tokyo, Japan, 104-8560
        • St.Luke's International Hospital /ID# 148041
      • Meguro-ku, Tokyo, Japan, 1538515
        • Toho University Ohashi Medical Center /ID# 148027
      • Shinjuku-ku, Tokyo, Japan, 160-8582
        • Keio University Hospital /ID# 148057
    • Yamaguchi
      • Shimonoseki-shi, Yamaguchi, Japan, 752-0976
        • Tokito Clinic Rheumatology and Orthopaedics Surgery /ID# 148052
  • Kazakhstan
      • Astana, Kazakhstan, 010009
        • JSC Nat Scientific Med Res Ctr /ID# 143272
      • Karaganda, Kazakhstan, 100008
        • Karaganda State Medical Univ /ID# 153431
      • Semey, Kazakhstan, 071403
        • Semey State Medical University /ID# 152661
      • Shymkent, Kazakhstan, 160000
        • Regional Clinical Hospital /ID# 147173
  • Latvia
      • Adazi, Latvia, 2164
        • LTD M+M Centers /ID# 143279
  • Lithuania
      • Klaipeda, Lithuania, 92288
        • Klaipeda University Hospital /ID# 143583
      • Vilnius, Lithuania, LT-08661
        • Vilnius University Hospital /ID# 143584
    • Kovno
      • Kaunas, Kovno, Lithuania, 50009
        • Hosp Lithuanian Univ Health Sc /ID# 143582
  • Mexico
      • Chihuahua, Mexico, 31000
        • Invest y Biomed de Chihuahua /ID# 143595
      • Mexico City, Mexico, 03100
        • RM Pharma Specialists, S.A de C.V /ID# 143593
      • Mexico City, Mexico, 06090
        • Unidad de Investigacion de las Enfermedades Reumatologicas SA de CV /ID# 143592
      • Mexico City, Mexico, 11650
        • Centro Especializado en Diabetes, Obesidad y Prevención de Enfermedades Cardiova /ID# 143589
      • Queretaro, Mexico, 76178
        • Centro Reumatologico de Queret /ID# 149493
    • Ciudad De Mexico
      • Cuauhtemoc, Ciudad De Mexico, Mexico, 06700
        • Clinstile, S.A. de C.V. /ID# 143591
      • Mexico City, Ciudad De Mexico, Mexico, 11850
        • CINTRE, Centro de Investigación y Tratamiento Reumatológico SC /ID# 153562
  • New Zealand
      • Auckland, New Zealand, 2025
        • Middlemore Clinical Trials /ID# 143600
      • Nelson, New Zealand, 7010
        • Porter Rheumatology Ltd /ID# 143601
      • Timaru, New Zealand, 7910
        • Timaru Medical Specialists Ltd /ID# 143599
    • Waikato
      • Hamilton, Waikato, New Zealand, 3204
        • Waikato Hospital /ID# 143602
  • Poland
    • Dolnoslaskie
      • Wrocław, Dolnoslaskie, Poland, 51-685
        • WroMedica I. Bielicka, A. Strzalkowska s.c. /ID# 143606
    • Mazowieckie
      • Warsaw, Mazowieckie, Poland, 01-518
        • Centrum Medyczne AMED /ID# 143604
      • Warsaw, Mazowieckie, Poland, 01-869
        • Centrum Medyczne Pratia Warszawa /ID# 143608
    • Pomorskie
      • Gdynia, Pomorskie, Poland, 81-338
        • Centrum Medyczne Pratia Gdynia /ID# 143607
    • Slaskie
      • Katowice, Slaskie, Poland, 40-282
        • Silmedic Sp z o.o /ID# 143605
    • Warminsko-mazurskie
      • Elblag, Warminsko-mazurskie, Poland, 82-300
        • NZOZ Centrum Reumatologiczne /ID# 143603
    • Wielkopolskie
      • Poznań, Wielkopolskie, Poland, 60-218
        • Medyczne Centrum Hetmanska /ID# 144726
  • Portugal
      • Lisboa, Portugal, 1649-035
        • Centro Hospitalar Lisboa Norte, EPE /ID# 143613
      • Porto, Portugal, 4050-111
        • Centro Hospitalar Baixo Vouga /ID# 153726
      • Porto, Portugal, 4200-319
        • Centro Hospitalar de Sao Joao, EPE /ID# 153575
      • Viana Do Castelo, Portugal, 4901-858
        • Unidade Local De Saude Do Alto Minho /ID# 143611
      • Viseu, Portugal, 3504-509
        • Centro Hosp de Tondela-Viseu /ID# 143612
    • Lisboa
      • Lisbon, Lisboa, Portugal, 1050-034
        • Instituto Portugues De Reumatologia /ID# 148313
      • Lisbon, Lisboa, Portugal, 1349-019
        • Centro Hospitalar Lisboa Ocidental, EPE /ID# 151009
    • Porto
      • Vila Nova De Gaia, Porto, Portugal, 4434-502
        • Centro Hospitalar De Vila Nova /ID# 143615
  • Puerto Rico
      • Ponce, Puerto Rico, 00716
        • Ponce School of Medicine /ID# 145657
      • San Juan, Puerto Rico, 00909
        • GCM Medical Group /ID# 143618
      • San Juan, Puerto Rico, 00935
        • School of Medicine University of Puerto Rico-Medical Sciences Campus /ID# 143619
  • Romania
      • Bucuresti, Romania, 011172
        • Spitalul Clinic Sf. Maria /ID# 143623
      • Bucuresti, Romania, 011172
        • Spitalul Clinic Sf. Maria /ID# 143625
      • Bucuresti, Romania, 011172
        • Spitalul Clinic Sf. Maria /ID# 143627
      • Iasi, Romania, 700656
        • Spitalul Clinic de Recuperare /ID# 143620
      • Oradea, Romania, 410028
        • Ecomed SRL /ID# 143629
    • Bucuresti
      • Bucharest, Bucuresti, Romania, 020475
        • Spitalul Clinic Dr. I. Cantacuzino /ID# 143622
  • Russian Federation
      • Moscow, Russian Federation, 117997
        • Russian National Research Medi /ID# 143642
      • Orenburg, Russian Federation, 460018
        • Orenburg Regional Clinical Hos /ID# 143630
      • Petrozavodsk, Russian Federation, 185019
        • Republican Clin Hos n.a. Baran /ID# 143634
      • Ryazan, Russian Federation, 390026
        • Ryazan State Medical Universit /ID# 143646
      • Samara, Russian Federation, 443095
        • Samara Regional Clinical Hosp /ID# 150928
      • UFA, Russian Federation, 450005
        • Reg Clin Hosp n.a. Kuvatova G. /ID# 143632
      • Ulyanovsk, Russian Federation, 432018
        • Ulyanovsk Regional Clin Hosp /ID# 143644
      • Voronezh, Russian Federation, 394036
        • Voronezh State Medical Univers /ID# 150926
    • Moskva
      • Korolev, Moskva, Russian Federation, 141060
        • Family Outpatient clinic#4,LLC /ID# 151010
      • Moscow, Moskva, Russian Federation, 119049
        • Clinical Hospital No.1 n.a. N.I.Pirogov /ID# 143641
    • Novosibirskaya Oblast
      • Novosibirsk, Novosibirskaya Oblast, Russian Federation, 630099
        • LLC Medical Center /ID# 143647
    • Stavropol Skiy Kray
      • Pyatigorsk, Stavropol Skiy Kray, Russian Federation, 357500
        • LLC Novaya Klinika /ID# 143631
    • Tatarstan, Respublika
      • Kazan, Tatarstan, Respublika, Russian Federation, 420012
        • Kazan State Medical University /ID# 143645
    • Tverskaya Oblast
      • Tver, Tverskaya Oblast, Russian Federation, 170036
        • Tver Regional Clinical Hosp. /ID# 143639
  • Serbia
    • Beograd
      • Belgrade, Beograd, Serbia, 11000
        • Clinical Center Serbia /ID# 143649
      • Belgrade, Beograd, Serbia, 11000
        • Clinical Center Serbia /ID# 143650
    • Vojvodina
      • Novi Sad, Vojvodina, Serbia, 21000
        • Special Hospital for Rheuma /ID# 143648
  • Slovakia
      • Martin, Slovakia, 036 01
        • MEDMAN s.r.o. /ID# 143661
      • Nové Mesto Nad Váhom, Slovakia, 915 01
        • Reumatologická ambulancia Reum.hapi s.r.o. /ID# 143657
      • Partizanske, Slovakia, 958 01
        • REUMACENTRUM s.r.o. /ID# 143653
      • Pieštany, Slovakia, 921 01
        • Slovak research center Team Member, Thermium s.r.o. /ID# 143663
      • Puchov, Slovakia, 02001
        • Slovak Research Center /ID# 143659
      • Stará Lubovna, Slovakia, 06401
        • TIMMED spol. s r.o. /ID# 143664
      • Topolcany, Slovakia, 955 01
        • Reumatologicka ambulancia, LER /ID# 143660
      • Trencin, Slovakia, 91101
        • MEDEOS s.r.o. /ID# 143656
      • Trnava, Slovakia, 91701
        • REUMA-GLOBAL, s.r.o. /ID# 143655
      • Zvolen, Slovakia, 960 01
        • ALBAMED s.r.o. /ID# 143654
      • Žiar nad Hronom, Slovakia, 965 01
        • Reuma -MUDr. Maria Palasthyova /ID# 143662
  • Slovenia
      • Ljubljana, Slovenia, 1000
        • Univ Medical Ctr Ljubljana /ID# 143667
  • South Africa
    • Gauteng
      • Pretoria, Gauteng, South Africa, 0132
        • Jakaranda Hosp, Emmed Research /ID# 143668
      • Pretoria, Gauteng, South Africa, 0132
        • Jakaranda Hosp, Emmed Research /ID# 145976
    • Western Cape
      • Cape Town, Western Cape, South Africa, 7405
        • Arthritis Clinical Research Tr /ID# 143670
      • Stellenbosch, Western Cape, South Africa, 7600
        • Winelands Medical Research Ctr /ID# 143669
  • Spain
      • A Coruna, Spain, 15006
        • Comple Hosp Univ de A Coruna /ID# 143672
      • Barcelona, Spain, 08035
        • Hospital Univ Vall d'Hebron /ID# 143675
      • Madrid, Spain, 28040
        • Hospital Clin Univ San Carlos /ID# 143674
      • Santiago de Compostela, Spain, 15702
        • Clinica Gaias /ID# 143673
      • Santiago de Compostela, Spain, 15705
        • Hosp Nuestra Senora Esperanza /ID# 143677
    • Cantabria
      • Santander, Cantabria, Spain, 39008
        • H. Un. Marques de Valdecilla /ID# 143671
  • Switzerland
      • Fribourg, Switzerland, 1708
        • HFR Fribourg - Hopital Canton /ID# 143700
  • Taiwan
      • Dalin, Taiwan, 622
        • Dalin Tzu Chi General Hospital /ID# 153535
    • Taichung
      • Taichung City, Taichung, Taiwan, 40447
        • China Medical University Hosp /ID# 143703
    • Taipei
      • Taipei City, Taipei, Taiwan, 10002
        • National Taiwan Univ Hosp /ID# 143702
  • Tunisia
      • La Marsa, Tunisia, 2046
        • Hopital Mongi Slim /ID# 152870
      • Manouba, Tunisia, 2010
        • Institut Mohamed Kassab /ID# 152869
      • Sousse, Tunisia, 4000
        • Hopital Farhat Hached /ID# 152868
      • Tunis, Tunisia, 1006
        • Charles Nicolle Univ Hosp /ID# 152866
      • Tunis, Tunisia, 1007
        • Hospital La Rabta /ID# 152867
  • Turkey
      • Izmir, Turkey, 35360
        • Izmir Katip Celebi Ataturk Training & Research Hospital /ID# 143704
    • Bursa
      • Osmangazi, Bursa, Turkey, 16080
        • Uludag Universitesi Ataturk Rehabilitasyon ve Uygulama Merkezi /ID# 143705
    • Izmir
      • Konak, Izmir, Turkey, 35180
        • Izmir Tepecik Training and Research Hospital /ID# 157863
  • Ukraine
      • Ivano-frankivsk, Ukraine, 76018
        • Regional Clinical Hospital /ID# 152029
      • Kiev, Ukraine, 03680
        • NSC-Strazhesko Ist Cardiology /ID# 152026
      • Kyiv, Ukraine, 04070
        • LLC Revmocentr /ID# 143710
      • Lviv, Ukraine, 79007
        • MNCE "Lviv City Clinical Hospital #4" /ID# 143711
      • Odesa, Ukraine, 65026
        • Odessa National Medical Univ /ID# 143715
      • Zaporizhia, Ukraine, 69600
        • Zaporizhzhia Regional Clinical /ID# 143712
    • Lvivska Oblast
      • Lviv, Lvivska Oblast, Ukraine, 79013
        • Lviv Regional Clinical Hospita /ID# 154449
    • Vinnytska Oblast
      • Vinnytsia, Vinnytska Oblast, Ukraine, 21018
        • Vinnytsia Regional Clinical Hospital n.a. M.I.Pyrogov /ID# 143714
  • United Kingdom
      • Edinburgh, United Kingdom, EH4 2XU
        • Western General Hospital /ID# 144431
      • Leeds, United Kingdom, LS7 4SA
        • Chapel Allerton Hospital /ID# 143717
      • Portsmouth, United Kingdom, PO6 3LY
        • Queen Alexandra Hospital /ID# 143722
      • Southampton, United Kingdom, SO16 6YD
        • Southampton General Hospital /ID# 143716
    • England
      • Leicester, England, United Kingdom, LE1 5WW
        • Leicester Royal Infirmary /ID# 143718
    • London, City Of
      • London, London, City Of, United Kingdom, E11 1NR
        • Whipps Cross Univ Hospital /ID# 143721
  • United States
    • California
      • La Mesa, California, United States, 91942
        • TriWest Research Associates- La Mesa /ID# 143738
      • Palm Desert, California, United States, 92260
        • Desert Medical Advances /ID# 143730
    • Florida
      • Daytona Beach, Florida, United States, 32117
        • International Medical Research - Daytona /ID# 143748
      • Miami, Florida, United States, 33142
        • FL Med Ctr and Research, Inc. /ID# 143724
      • Ormond Beach, Florida, United States, 32174
        • Millennium Research /ID# 143736
      • Palm Harbor, Florida, United States, 34684-2672
        • Arthritis Research of Florida /ID# 143743
      • Sarasota, Florida, United States, 34239
        • Sarasota Arthritis Center /ID# 145978
      • Zephyrhills, Florida, United States, 33542
        • FL Med Clinic, PA /ID# 143744
    • Illinois
      • Vernon Hills, Illinois, United States, 60061
        • Deerbrook Medical Associates /ID# 143728
    • Kentucky
      • Paducah, Kentucky, United States, 42003
        • Four Rivers Clinical Research /ID# 143741
    • New Jersey
      • Toms River, New Jersey, United States, 08755
        • Ocean Rheumatology, PA /ID# 143737
      • Voorhees, New Jersey, United States, 08043
        • Arthritis Rheumatic Back Disorder /ID# 143733
    • North Dakota
      • Minot, North Dakota, United States, 58701
        • Trinity Health Med Arts Clinic /ID# 143727
    • Ohio
      • Vandalia, Ohio, United States, 45377-9464
        • STAT Research, Inc. /ID# 143750
    • Oklahoma
      • Tulsa, Oklahoma, United States, 74135
        • Healthcare Research Consultant /ID# 143747
    • Pennsylvania
      • Wexford, Pennsylvania, United States, 15090
        • Advanced Rheumatology & Arthri /ID# 147947
    • South Carolina
      • Summerville, South Carolina, United States, 29486-7887
        • Articularis Healthcare Group, Inc d/b/a Low Country Rheumatology /ID# 145653
    • Tennessee
      • Jackson, Tennessee, United States, 38305
        • West Tennessee Research Inst /ID# 143723
      • Memphis, Tennessee, United States, 38119
        • Dr. Ramesh Gupta /ID# 143732
    • Texas
      • Beaumont, Texas, United States, 77701
        • Diagnostic Group Integrated He /ID# 152921
      • Corpus Christi, Texas, United States, 78404
        • Adriana Pop-Moody MD Clinic PA /ID# 147626
      • Edinburg, Texas, United States, 78539
        • Doctor's Hosp at Renaissance /ID# 156407
      • El Paso, Texas, United States, 79935
        • MedResearch Inc. /ID# 156409
      • Houston, Texas, United States, 77004
        • Rheumatic Disease Clin Res Ctr /ID# 151103
      • Houston, Texas, United States, 77089
        • Accurate Clinical Research /ID# 143749
      • Mesquite, Texas, United States, 75150
        • SW Rheumatology Res. LLC /ID# 143745
      • San Antonio, Texas, United States, 78215
        • Sun Research Institute /ID# 159546
      • San Antonio, Texas, United States, 78229
        • Accurate Clinical Management /ID# 159543
      • San Antonio, Texas, United States, 78229
        • NextGen Clinical Trials LLP /ID# 150930
      • San Marcos, Texas, United States, 78666
        • Arthritis Clinic of Central TX /ID# 159541
      • Waco, Texas, United States, 76710
        • Arthritis & Osteoporosis Clinic /ID# 159542
    • Virginia
      • Arlington, Virginia, United States, 22205
        • Arthritis Clinic of N. VA, P.C /ID# 143734

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Duration of symptoms consistent with RA for ≥ 6 weeks who also fulfill the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for RA.
  • Naïve to Methotrexate (MTX) or, if already on MTX, have received no more than 3 weekly MTX doses with requirement to complete a 4-week MTX washout before the first dose of study drug.
  • Participants with prior exposure to conventional synthetic disease-modifying anti-rheumatic drugs(csDMARDs) other than MTX may be enrolled if completed the washout period.

  • Participant meets both of the following minimum disease activity criteria:

    -≥ 6 swollen joints (based on 66 joint counts) and ≥ 6 tender joints (based on 68 joint counts) at Screening and Baseline Visits.

  • high sensitivity C reactive protein (hsCRP) ≥ 5 mg/L (central lab, upper limit of normal [ULN] 2.87 mg/L at Screening Visit.
  • Greater than or equal to 1 bone erosion on x-ray (by local reading) OR in the absence of documented bone erosion, both positive rheumatoid factor (RF) and positive anti-cyclic citrullinated peptide (anti CCP) autoantibodies are required at Screening.
  • Stable dose of non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, oral corticosteroids (equivalent to prednisone ≤ 10 mg/day), or inhaled corticosteroids for stable medical conditions are allowed but must have been at a stable dose ≥ 1 week prior to the first dose of study drug.

Exclusion Criteria:

  • Intolerant to Methotrexate (MTX).
  • Prior exposure to any Janus kinase (JAK) inhibitor (including but not limited to tofacitinib, baricitinib, and filgotinib).
  • Prior exposure to any biologic disease-modifying anti-rheumatic drugs (bDMARDs).
  • History of any arthritis with onset prior to age 17 years or current diagnosis, inflammatory joint disease other than RA (including but not limited to gout, systemic lupus erythematosus, psoriatic arthritis, axial spondyloarthritis including ankylosing spondylitis and non-radiographic axial spondyloarthritis, reactive arthritis, overlap connective tissue diseases, scleroderma, polymyositis, dermatomyositis, fibromyalgia [currently with active symptoms]. Current diagnosis of secondary Sjogren's Syndrome is permitted.
  • Has been treated with intra-articular, intramuscular, intravenous, trigger point or tender point, intra-bursa, or intra-tendon sheath corticosteroids in the preceding 8 weeks prior to the first dose of study drug.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Methotrexate

Period 1: Participants will receive placebo to upadacitinib once daily and methotrexate once weekly for 48 weeks.

Period 2: Participants will continue on placebo to upadacitinib once daily and methotrexate once weekly until the study is unblinded, after which participants will receive open-label methotrexate up to Week 260.
Drug: Placebo to Upadacitinib
Tablet; Oral
Drug: Methotrexate
Capsule or Tablet; Oral
Experimental: Upadacitinib 7.5 mg (Japan-only)

Period 1: Participants will receive upadacitinib 7.5 mg once daily and placebo to methotrexate once weekly for 48 weeks.

Period 2: Participants will continue on upadacitinib 7.5 mg once daily and placebo to methotrexate once weekly until the study is unblinded, after which participants will receive open-label upadacitinib 7.5 mg up to Week 260.
Drug: Upadacitinib
Tablet; Oral
Other Names:
  • ABT-494
  • Rinvoq
Drug: Placebo to Methotrexate
Capsule or Tablet; Oral
Experimental: Upadacitinib 15 mg

Period 1: Participants will receive upadacitinib 15 mg once daily and placebo to methotrexate once weekly for 48 weeks.

Period 2: Participants will continue on upadacitinib 15 mg once daily and placebo to methotrexate once weekly until the study is unblinded, after which participants will receive open-label upadacitinib 15 mg up to Week 260.
Drug: Upadacitinib
Tablet; Oral
Other Names:
  • ABT-494
  • Rinvoq
Drug: Placebo to Methotrexate
Capsule or Tablet; Oral
Experimental: Upadacitinib 30 mg

Period 1: Participants will receive upadacitinib 30 mg once daily and placebo to methotrexate once weekly for 48 weeks.

Period 2: Participants will continue on upadacitinib 30 mg once daily and placebo to methotrexate once weekly until the study is unblinded, after which participants will receive open-label upadacitinib 30 mg once daily. After implementation of Protocol Amendment 6 participants will receive upadacitinib 15 mg once daily up to Week 260.
Drug: Upadacitinib
Tablet; Oral
Other Names:
  • ABT-494
  • Rinvoq
Drug: Placebo to Methotrexate
Capsule or Tablet; Oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants Achieving Clinical Remission (CR) Based on DAS28(CRP) at Week 24 - Global Analysis
Time Frame: Week 24

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 24.

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 24
Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12 - Global Analysis
Time Frame: Baseline and Week 12

The primary endpoint for United States (US)/Food and Drug Administration (FDA) regulatory purposes was ACR 50% response (ACR50) at Week 12. Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR50 response criteria:

  1. ≥ 50% improvement in 68-tender joint count;
  2. ≥ 50% improvement in 66-swollen joint count; and

  3. ≥ 50% improvement in at least 3 of the 5 following parameters:

    • Physician global assessment of disease activity
    • Patient global assessment of disease activity
    • Patient assessment of pain
    • Health 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 20% (ACR20) Response at Week 12 - Global Analysis
Time Frame: Baseline and Week 12

The primary endpoint for Japan/Pharmaceuticals and Medical Devices Agency (PMDA) 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:

  1. ≥ 20% improvement in 68-tender joint count;
  2. ≥ 20% improvement in 66-swollen joint count; and

  3. ≥ 20% improvement in at least 3 of the 5 following parameters:

    • Physician global assessment of disease activity
    • Patient global assessment of disease activity
    • Patient assessment of pain
    • Health Assessment Questionnaire - Disability Index (HAQ-DI)
    • High-sensitivity C-reactive protein (hsCRP).
Baseline and Week 12
Change From Baseline in Modified Total Sharp Score (mTSS) at Week 24 - Global Analysis
Time Frame: Baseline to Week 24

The second primary endpoint for Japan/PMDA regulatory purposes was change from baseline in mTSS at Week 24.

The mTSS measures the level of joint damage from radiographs of the hands and feet. Joint erosion and joint space narrowing (JSN) were assessed by two independent, blinded readers.

Joint erosion was assessed in 16 joints in each hand/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 change from Baseline greater than 0 indicates progression.
Baseline to Week 24

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in DAS28 (CRP) at Week 12 - Global Analysis
Time Frame: Baseline to 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 to Week 12
Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 - Global Analysis
Time Frame: Baseline to 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 to week 12
Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 12 - Global Analysis
Time Frame: 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 Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 12 - Global Analysis
Time Frame: Baseline to 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 to week 12
Change From Baseline in DAS28 (CRP) at Week 24 - Global Analysis
Time Frame: Baseline to Week 24
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 to Week 24
Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 24 - Global Analysis
Time Frame: Baseline to Week 24

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 to Week 24
Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 24 - Global Analysis
Time Frame: Week 24

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 24
Change From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 24 - Global Analysis
Time Frame: Baseline to Week 24

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 to Week 24
Change From Baseline in DAS28 (CRP) at Week 12 - Japan Sub-study
Time Frame: Baseline to 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 to Week 12
Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 - Japan Sub-study
Time Frame: Baseline to 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 to week 12
Change From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 12 - Japan Sub-study
Time Frame: Baseline to 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 to Week 12
Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 12 - Japan Sub-study
Time Frame: 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
Percentage of Participants Achieving Clinical Remission (CR) Based on DAS28(CRP) at Week 24 - Japan Sub-study
Time Frame: Week 24

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 score less than 2.6 indicates clinical remission.
Week 24
Percentage of Participants With an ACR50 Response at Week 24 - Global Analysis
Time Frame: Baseline and Week 24

Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR50 response criteria:

  1. ≥ 50% improvement in 68-tender joint count;
  2. ≥ 50% improvement in 66-swollen joint count; and

  3. ≥ 50% improvement in at least 3 of the 5 following parameters:

    • Physician global assessment of disease activity
    • Patient global assessment of disease activity
    • Patient assessment of pain
    • Health Assessment Questionnaire - Disability Index (HAQ-DI)
    • High-sensitivity C-reactive protein (hsCRP).
Baseline and Week 24
Percentage of Participants With No Radiographic Progression at Week 24 - Global Analysis
Time Frame: Week 24

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. Joint erosion and joint space narrowing (JSN) were assessed by two independent, blinded readers.

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).

The mTSS is the sum of the joint erosion and JSN scores and ranges from 0 (normal) to 448 (worst).
Week 24
Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 12 - Global Analysis
Time Frame: Baseline and Week 12

Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR70 response criteria:

  1. ≥ 70% improvement in 68-tender joint count;
  2. ≥ 70% improvement in 66-swollen joint count; and

  3. ≥ 70% improvement in at least 3 of the 5 following parameters:

    • Physician global assessment of disease activity
    • Patient global assessment of disease activity
    • Patient assessment of pain
    • Health Assessment Questionnaire - Disability Index (HAQ-DI)
    • High-sensitivity C-reactive protein (hsCRP).
Baseline and Week 12
Percentage of Participants With an ACR20 Response at Week 24 - Global Analysis
Time Frame: Baseline and Week 24

Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR20 response criteria:

  1. ≥ 20% improvement in 68-tender joint count;
  2. ≥ 20% improvement in 66-swollen joint count; and

  3. ≥ 20% improvement in at least 3 of the 5 following parameters:

    • Physician global assessment of disease activity
    • Patient global assessment of disease activity
    • Patient assessment of pain
    • Health Assessment Questionnaire - Disability Index (HAQ-DI)
    • High-sensitivity C-reactive protein (hsCRP).
Baseline and Week 24
Percentage of Participants With an ACR70 Response at Week 24 - Global Analysis
Time Frame: Baseline and Week 24

Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR70 response criteria:

  1. ≥ 70% improvement in 68-tender joint count;
  2. ≥ 70% improvement in 66-swollen joint count; and

  3. ≥ 70% improvement in at least 3 of the 5 following parameters:

    • Physician global assessment of disease activity
    • Patient global assessment of disease activity
    • Patient assessment of pain
    • Health Assessment Questionnaire - Disability Index (HAQ-DI)
    • High-sensitivity C-reactive protein (hsCRP).
Baseline and Week 24
Percentage of Participants With an ACR20 Response at Week 12 - Japan Sub-study
Time Frame: Baseline and Week 12

Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR20 response criteria:

  1. ≥ 20% improvement in 68-tender joint count;
  2. ≥ 20% improvement in 66-swollen joint count; and

  3. ≥ 20% improvement in at least 3 of the 5 following parameters:

    • Physician global assessment of disease activity
    • Patient global assessment of disease activity
    • Patient assessment of pain
    • Health Assessment Questionnaire - Disability Index (HAQ-DI)
    • High-sensitivity C-reactive protein (hsCRP).
Baseline and Week 12
Percentage of Participants With an ACR50 Response at Week 12 - Japan Sub-study
Time Frame: Baseline and Week 12

Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR50 response criteria:

  1. ≥ 50% improvement in 68-tender joint count;
  2. ≥ 50% improvement in 66-swollen joint count; and

  3. ≥ 50% improvement in at least 3 of the 5 following parameters:

    • Physician global assessment of disease activity
    • Patient global assessment of disease activity
    • Patient assessment of pain
    • Health Assessment Questionnaire - Disability Index (HAQ-DI)
    • High-sensitivity C-reactive protein (hsCRP).
Baseline and Week 12
Percentage of Participants With an ACR70 Response at Week 12 - Japan Sub-study
Time Frame: Baseline and Week 12

Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR70 response criteria:

  1. ≥ 70% improvement in 68-tender joint count;
  2. ≥ 70% improvement in 66-swollen joint count; and

  3. ≥ 70% improvement in at least 3 of the 5 following parameters:

    • Physician global assessment of disease activity
    • Patient global assessment of disease activity
    • Patient assessment of pain
    • Health Assessment Questionnaire - Disability Index (HAQ-DI)
    • High-sensitivity C-reactive protein (hsCRP).
Baseline and Week 12
Change From Baseline in Modified Total Sharp Score (mTSS) at Week 24 - Japan Sub-study
Time Frame: Baseline to Week 24

The mTSS measures the level of joint damage from radiographs of the hands and feet. Joint erosion and joint space narrowing (JSN) were assessed by two independent, blinded readers.

Joint erosion was assessed in 16 joints in each hand/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 change from Baseline greater than 0 indicates progression.
Baseline to Week 24
Percentage of Participants With No Radiographic Progression at Week 24 - Japan Sub-study
Time Frame: Week 24

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. Joint erosion and joint space narrowing (JSN) were assessed by two independent, blinded readers.

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).

The mTSS is the sum of the joint erosion and JSN scores and ranges from 0 (normal) to 448 (worst).
Week 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AbbVie

Investigators

  • Study Director: ABBVIE INC., AbbVie

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 23, 2016

Primary Completion (Actual)

March 15, 2018

Study Completion (Actual)

November 10, 2022

Study Registration Dates

First Submitted

February 18, 2016

First Submitted That Met QC Criteria

March 8, 2016

First Posted (Estimated)

March 11, 2016

Study Record Updates

Last Update Posted (Actual)

July 7, 2023

Last Update Submitted That Met QC Criteria

June 21, 2023

Last Verified

June 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • M13-545
  • 2015-003334-27 (EudraCT Number)

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
  • 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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