Rheumatoid ArthritisPhase 3SELECT-EARLYNCT02706873
A Study to Compare Upadacitinib (ABT-494) Monotherapy to Methotrexate (MTX) Monotherapy in Adults With Rheumatoid Arthritis (RA) Who Have Not Previously Taken Methotrexate
A Phase 3 study testing Methotrexate and Upadacitinib in people with Rheumatoid Arthritis, run by AbbVie at 290 sites in 45 countries.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- Methotrexate and Upadacitinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,002 participants
- Where
- 290 sitesin 45 countries
- Study dates
- 23 Feb 2016to 10 Nov 2022
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
290 sites in 45 countries.
290 sites in 45 countries
Japan49 sites
National Hospital Organization Asahikawa Medical Center /ID# 148021
Asahikawa, Hokkaido, 070-8644
Katayama Orthopedic Rheumatology Clinic /ID# 148029
Asahikawa, Hokkaido, 078-8243
National Hospital Organization Beppu Medical Center /ID# 161058
Beppu, 874 - 001
Juntendo University Hospital /ID# 148050
Bunkyo-ku, Tokyo, 113-8431
NHO Chiba-East-Hospital /ID# 148035
Chiba, 260-8712
St.Luke's International Hospital /ID# 148041
Chuo-ku, Tokyo, 104-8560
Sugimoto Rheumatology and Internal Medicine Clinic /ID# 148047
Fukui, 910-0068
NHO Kyushu Medical Center /ID# 148263
Fukuoka, Fukuoka, 810-8563
NHO Kyushu Medical Center /ID# 148264
Fukuoka, Fukuoka, 810-8563
Shono Rheumatism Clinic /ID# 148046
Fukuoka, 814-0002
Kansai Medical University Hospital /ID# 159622
Hirakata-shi, Osaka, 573-1191
Teikyo University Chiba Medical Center /ID# 159618
Ichihara, Chiba, 299-0111
Matsubara Mayflower Hospital /ID# 148033
Katō, 673-1462
Saitama Medical Center, Saitama Medical University /ID# 148015
Kawagoe-shi, Saitama, 350-8550
Kobe University Hospital /ID# 153461
Kobe, Hyōgo, 650-0017
Bay Side Misato Medical Center /ID# 148256
Kochi, Kochi, 781-0112
Center for Arthritis and Clinical Rheumatology Matsubara Clinic /ID# 148254
Kumamoto, Kumamoto, 862-0920
Kumamoto Orthopaedic Hospital /ID# 148054
Kumamoto, Kumamoto, 862-0976
Kumamoto Shinto General Hospital /ID# 148266
Kumamoto, Kumamoto, 8628655
St. Mary's Hospital /ID# 148038
Kurume, 830-8543
Kagawa University Hospital /ID# 148016
Kyoto, 615-8256
Toho University Ohashi Medical Center /ID# 148027
Meguro-ku, Tokyo, 1538515
Yu Family Clinic /ID# 148048
Miyagi, 981-0112
Nagaoka Red Cross Hospital /ID# 148018
Nagaoka-shi, Niigata, 940-2108
Nagoya University Hospital /ID# 148031
Nagoya, Aichi-ken, 466-8560
Daido Hospital /ID# 160868
Nagoya, 457-8511
Kondo Clinic for Ortho & Rheum /ID# 148032
Nagoya, 464-0071
Shirahama Hamayu Hospital /ID# 148253
Nishimura, 649-2211
Oribe Clinic of Rheumatology and Internal Medicine /ID# 156035
Ōita, 870-0823
Japanese Red Cross Okayama Hospital /ID# 159619
Okayama, Okayama-ken, 7008607
NHO Osaka Minami Med Ctr /ID# 148042
Osaka, Kawachinagano-shi, 586-8521
Osaka City General Hospital /ID# 159617
Osaka, 534-0021
National Hospital Organization Sagamihara National Hospital /ID# 148019
Sagamihara-shi, Kanagawa, 252-0315
Sanuki Municipal Hospital /ID# 158842
Sanuki, 769-2321
Sagawa Akira Rheumatology Clin /ID# 148043
Sapporo, 060-0001
Sapporo City General Hospital /ID# 148037
Sapporo, 060-8604
Hokkaido University Hospital /ID# 148262
Sapporo, 060-8648
Hokkaido Medical Center for Rheumatic Diseases /ID# 148259
Sapporo, 063-0811
Sasebo Chuo Hospital /ID# 148261
Sasebo, Nagasaki, 857-1195
Azuma Rheumatology Clinic /ID# 161050
Sayama, 350-1305
Hikarigaoka Spellman Hospital /ID# 148020
Sendai, 983-0833
Tokito Clinic Rheumatology and Orthopaedics Surgery /ID# 148052
Shimonoseki-shi, Yamaguchi, 752-0976
Jichi Medical University Hospital /ID# 159620
Shimotsuke-shi, Tochigi, 329-0498
Keio University Hospital /ID# 148057
Shinjuku-ku, Tokyo, 160-8582
Takaoka Rheumatic Orthopedic Clinic /ID# 148022
Takaoka, 933-0874
Osaka Medical College Hospital /ID# 159624
Takatsuki -shi, Osaka, 569-8686
National Hospital Organization Tokyo Medical Center /ID# 148040
Tokyo, 152-8902
NHO Toyohashi Medical Center /ID# 161033
Toyohashi, Aichi-ken, 440-8510
National Hospital Organization Shimoshizu National Hospital /ID# 148258
Yotsukaidō, 284-0003
United States32 sites
Arthritis Clinic of N. VA, P.C /ID# 143734
Arlington, Virginia, 22205
Diagnostic Group Integrated He /ID# 152921
Beaumont, Texas, 77701
Adriana Pop-Moody MD Clinic PA /ID# 147626
Corpus Christi, Texas, 78404
International Medical Research - Daytona /ID# 143748
Daytona Beach, Florida, 32117
Doctor's Hosp at Renaissance /ID# 156407
Edinburg, Texas, 78539
MedResearch Inc. /ID# 156409
El Paso, Texas, 79935
Rheumatic Disease Clin Res Ctr /ID# 151103
Houston, Texas, 77004
Accurate Clinical Research /ID# 143749
Houston, Texas, 77089
West Tennessee Research Inst /ID# 143723
Jackson, Tennessee, 38305
TriWest Research Associates- La Mesa /ID# 143738
La Mesa, California, 91942
Dr. Ramesh Gupta /ID# 143732
Memphis, Tennessee, 38119
SW Rheumatology Res. LLC /ID# 143745
Mesquite, Texas, 75150
FL Med Ctr and Research, Inc. /ID# 143724
Miami, Florida, 33142
Trinity Health Med Arts Clinic /ID# 143727
Minot, North Dakota, 58701
Millennium Research /ID# 143736
Ormond Beach, Florida, 32174
Four Rivers Clinical Research /ID# 143741
Paducah, Kentucky, 42003
Desert Medical Advances /ID# 143730
Palm Desert, California, 92260
Arthritis Research of Florida /ID# 143743
Palm Harbor, Florida, 34684-2672
Sun Research Institute /ID# 159546
San Antonio, Texas, 78215
Accurate Clinical Management /ID# 159543
San Antonio, Texas, 78229
NextGen Clinical Trials LLP /ID# 150930
San Antonio, Texas, 78229
Arthritis Clinic of Central TX /ID# 159541
San Marcos, Texas, 78666
Sarasota Arthritis Center /ID# 145978
Sarasota, Florida, 34239
Articularis Healthcare Group, Inc d/b/a Low Country Rheumatology /ID# 145653
Summerville, South Carolina, 29486-7887
Ocean Rheumatology, PA /ID# 143737
Toms River, New Jersey, 08755
Healthcare Research Consultant /ID# 143747
Tulsa, Oklahoma, 74135
STAT Research, Inc. /ID# 143750
Vandalia, Ohio, 45377-9464
Deerbrook Medical Associates /ID# 143728
Vernon Hills, Illinois, 60061
Arthritis Rheumatic Back Disorder /ID# 143733
Voorhees Township, New Jersey, 08043
Arthritis & Osteoporosis Clinic /ID# 159542
Waco, Texas, 76710
Advanced Rheumatology & Arthri /ID# 147947
Wexford, Pennsylvania, 15090
FL Med Clinic, PA /ID# 143744
Zephyrhills, Florida, 33542
Russia14 sites
Kazan State Medical University /ID# 143645
Kazan', Tatarstan, Respublika, 420012
Family Outpatient clinic#4,LLC /ID# 151010
Korolev, Moscow, 141060
Clinical Hospital No.1 n.a. N.I.Pirogov /ID# 143641
Moscow, Moscow, 119049
Russian National Research Medi /ID# 143642
Moscow, 117997
LLC Medical Center /ID# 143647
Novosibirsk, Novosibirsk Oblast, 630099
Orenburg Regional Clinical Hos /ID# 143630
Orenburg, 460018
Republican Clin Hos n.a. Baran /ID# 143634
Petrozavodsk, 185019
LLC Novaya Klinika /ID# 143631
Pyatigorsk, Stavropol Kray, 357500
Ryazan State Medical Universit /ID# 143646
Ryazan, 390026
Samara Regional Clinical Hosp /ID# 150928
Samara, 443095
Tver Regional Clinical Hosp. /ID# 143639
Tver', Tver Oblast, 170036
Reg Clin Hosp n.a. Kuvatova G. /ID# 143632
Ufa, 450005
Ulyanovsk Regional Clin Hosp /ID# 143644
Ulyanovsk, 432018
Voronezh State Medical Univers /ID# 150926
Voronezh, 394036
Czechia11 sites
RHEUMA s.r.o. /ID# 143230
Břeclav, 690 02
Revmatologie, s.r.o. /ID# 143223
Brno, 638 00
Revmatologie Bruntal, s.r.o /ID# 143220
Bruntál, 79201
L.K.N. Arthrocentrum, s.r.o /ID# 143224
Hlučín, Moravian-Silesian Region, 748 01
CTCenter MaVe, s.r.o. /ID# 143226
Olomouc, Olomouc Region, 779 00
Nuselská poliklinika, Revmatologie /ID# 143232
Prague, Praha 4, 140 00
Nuselská poliklinika, Revmatologie /ID# 143233
Prague, Praha 4, 140 00
Thomayerova nemocnice /ID# 143228
Prague, Praha 4, 140 59
Nemocnice Slany /ID# 143221
Slaný, 274 01
Medical Plus, s.r.o. /ID# 143219
Uherské Hradište, 686 01
PV MEDICAL Services s.r.o. /ID# 143234
Zlín, Zlín, 760 01
Slovakia11 sites
MEDMAN s.r.o. /ID# 143661
Martin, 036 01
Reumatologická ambulancia Reum.hapi s.r.o. /ID# 143657
Nové Mesto nad Váhom, 915 01
REUMACENTRUM s.r.o. /ID# 143653
Partizánske, 958 01
Slovak research center Team Member, Thermium s.r.o. /ID# 143663
Pieštany, 921 01
Slovak Research Center /ID# 143659
Púchov, 02001
TIMMED spol. s r.o. /ID# 143664
Stará Lubovna, 06401
Reumatologicka ambulancia, LER /ID# 143660
Topoľčany, 955 01
MEDEOS s.r.o. /ID# 143656
Trenčín, 91101
REUMA-GLOBAL, s.r.o. /ID# 143655
Trnava, 91701
Reuma -MUDr. Maria Palasthyova /ID# 143662
Žiar nad Hronom, 965 01
ALBAMED s.r.o. /ID# 143654
Zvolen, 960 01
Portugal8 sites
Instituto Portugues De Reumatologia /ID# 148313
Lisbon, Lisbon District, 1050-034
Centro Hospitalar Lisboa Ocidental, EPE /ID# 151009
Lisbon, Lisbon District, 1349-019
Centro Hospitalar Lisboa Norte, EPE /ID# 143613
Lisbon, 1649-035
Centro Hospitalar Baixo Vouga /ID# 153726
Porto, 4050-111
Centro Hospitalar de Sao Joao, EPE /ID# 153575
Porto, 4200-319
Unidade Local De Saude Do Alto Minho /ID# 143611
Viana do Castelo, 4901-858
Centro Hospitalar De Vila Nova /ID# 143615
Vila Nova de Gaia, Porto District, 4434-502
Centro Hosp de Tondela-Viseu /ID# 143612
Viseu, 3504-509
Ukraine8 sites
Regional Clinical Hospital /ID# 152029
Ivano-Frankivsk, 76018
NSC-Strazhesko Ist Cardiology /ID# 152026
Kiev, 03680
LLC Revmocentr /ID# 143710
Kyiv, 04070
Lviv Regional Clinical Hospita /ID# 154449
Lviv, Lviv Oblast, 79013
MNCE "Lviv City Clinical Hospital #4" /ID# 143711
Lviv, 79007
Odessa National Medical Univ /ID# 143715
Odesa, 65026
Vinnytsia Regional Clinical Hospital n.a. M.I.Pyrogov /ID# 143714
Vinnytsia, Vinnytsia Oblast, 21018
Zaporizhzhia Regional Clinical /ID# 143712
Zaporizhia, 69600
Argentina7 sites
Org Medica de Investigacion /ID# 143142
Buenos Aires, C1015ABO
Aprillus Asistencia e Investig /ID# 149179
Capital Federal, Buenos Aires, 1046
Consultora Integral de Salud S /ID# 143144
Córdoba, 5900
Instituto CAICI /ID# 143141
Rosario, Santa Fe Province, 2000
Iari /Id# 148595
San Isidro, Buenos Aires, 1646
Centro Integral de Reumatologi /ID# 143143
San Miguel de Tucumán, 4000
Centro Medico Privado/Reuma /ID# 143140
San Miguel de Tucumán, 4000
Chile7 sites
Someal /Id# 143207
Providencia, Santiago Metropolitan, 7510186
Quantum Research LTDA. /ID# 143210
Puerto Varas, 5550170
Quantum Research Stgo. /ID# 145651
Santiago, 7500588
Soc. de Prestaciones medicas y Paramedicas Goecke /ID# 143209
Santiago, 7510047
Investigaciones Medicas SSMSO /ID# 151685
Santiago, 8207257
Ctr de Inv Clinica del Sur /ID# 143208
Temuco, Araucania, 4781156
Centro de Estudios Clinicos Qu /ID# 152913
Viña del Mar
Mexico7 sites
Invest y Biomed de Chihuahua /ID# 143595
Chihuahua City, 31000
Clinstile, S.A. de C.V. /ID# 143591
Cuauhtémoc, Mexico City, 06700
CINTRE, Centro de Investigación y Tratamiento Reumatológico SC /ID# 153562
Mexico City, Mexico City, 11850
RM Pharma Specialists, S.A de C.V /ID# 143593
Mexico City, 03100
Unidad de Investigacion de las Enfermedades Reumatologicas SA de CV /ID# 143592
Mexico City, 06090
Centro Especializado en Diabetes, Obesidad y Prevención de Enfermedades Cardiova /ID# 143589
Mexico City, 11650
Centro Reumatologico de Queret /ID# 149493
Querétaro, 76178
Poland7 sites
NZOZ Centrum Reumatologiczne /ID# 143603
Elblag, Warmian-Masurian Voivodeship, 82-300
Centrum Medyczne Pratia Gdynia /ID# 143607
Gdynia, Pomeranian Voivodeship, 81-338
Silmedic Sp z o.o /ID# 143605
Katowice, Silesian Voivodeship, 40-282
Medyczne Centrum Hetmanska /ID# 144726
Poznan, Greater Poland Voivodeship, 60-218
Centrum Medyczne AMED /ID# 143604
Warsaw, Masovian Voivodeship, 01-518
Centrum Medyczne Pratia Warszawa /ID# 143608
Warsaw, Masovian Voivodeship, 01-869
WroMedica I. Bielicka, A. Strzalkowska s.c. /ID# 143606
Wroclaw, Lower Silesian Voivodeship, 51-685
Brazil6 sites
Ceti - Centro de Estudos Em Terapias Inovadoras Ltda /Id# 143169
Curitiba, Paraná, 80030-110
CIP - Centro Internacional de Pesquisa /ID# 143171
Goiânia, Goiás, 74110-120
Hospital de Clinicas de Porto Alegre /ID# 143168
Porto Alegre, Rio Grande do Sul, 90035-903
LMK Sevicos Medicos S/S /ID# 143167
Porto Alegre, Rio Grande do Sul, 90480-000
CCBR Brasil /ID# 150925
Rio de Janeiro, 22271-100
CEPIC - Centro Paulista de Investigação Clínica e Serviços Médicos Ltda /ID# 143166
São Paulo, São Paulo, 04266-010
Colombia6 sites
Ctr Int de Reum del Caribe SAS /ID# 143211
Barranquilla, 80002
Centro de Investigacion en Reumatologia y Especialidades Medicas- CIREEM SAS /ID# 143214
Bogota, Cundinamarca, 110221
Riesgo de Fractura S.A - CAYRE /ID# 143212
Bogotá, 110221
Simedics IPS SAS /ID# 152572
Bogotá, 110221
Fund Inst de Reum F. Chalem /ID# 159544
Bogotá
Medicity S.A.S. /ID# 143213
Bucaramanga, 680003
Germany6 sites
Uniklinik Koln /ID# 143248
Cologne, North Rhine-Westphalia, 50937
Rheumaforschungszentrum II /ID# 143247
Hamburg, 20095
Schoen Klinikum Hamburg Eilbek /ID# 143251
Hamburg, 22081
Rheumazentrum Ruhrgebiet /ID# 145652
Herne, North Rhine-Westphalia, 44649
LMU Klinikum der Universität München /ID# 143249
Munich, 80337
Praxis Walter, Rendsburg /ID# 143250
Rendsburg, Schleswig-Holstein, 24768
Hungary6 sites
Qualiclinic Kft. /ID# 143259
Budapest, Pest County, 1036
Hevizgyogyfurdo es Szent Andra /ID# 143257
Hévíz, 8380
Pest Megyei Flor Ferenc Korhaz /ID# 143260
Kistarcsa, 2143
CRU Hungary Egeszsegugyi és Szolgaltato Kft. /ID# 143258
Miskolc, Borsod-Abauj Zemplen county, 3529
Fejer Megyei Szent Gyorgy Korh /ID# 144724
Székesfehérvár, 8000
Markusovszky Egyetemi Oktatókórház /ID# 143261
Szombathely, Vas County, 9700
Romania6 sites
Spitalul Clinic Dr. I. Cantacuzino /ID# 143622
Bucharest, Bucharest, 020475
Spitalul Clinic Sf. Maria /ID# 143623
Bucharest, 011172
Spitalul Clinic Sf. Maria /ID# 143625
Bucharest, 011172
Spitalul Clinic Sf. Maria /ID# 143627
Bucharest, 011172
Spitalul Clinic de Recuperare /ID# 143620
Iași, 700656
Ecomed SRL /ID# 143629
Oradea, 410028
Spain6 sites
Comple Hosp Univ de A Coruna /ID# 143672
A Coruña, 15006
Hospital Univ Vall d'Hebron /ID# 143675
Barcelona, 08035
Hospital Clin Univ San Carlos /ID# 143674
Madrid, 28040
H. Un. Marques de Valdecilla /ID# 143671
Santander, Cantabria, 39008
Clinica Gaias /ID# 143673
Santiago de Compostela, 15702
Hosp Nuestra Senora Esperanza /ID# 143677
Santiago de Compostela, 15705
United Kingdom6 sites
Western General Hospital /ID# 144431
Edinburgh, EH4 2XU
Chapel Allerton Hospital /ID# 143717
Leeds, LS7 4SA
Leicester Royal Infirmary /ID# 143718
Leicester, England, LE1 5WW
Whipps Cross Univ Hospital /ID# 143721
London, London, City of, E11 1NR
Queen Alexandra Hospital /ID# 143722
Portsmouth, PO6 3LY
Southampton General Hospital /ID# 143716
Southampton, SO16 6YD
Australia5 sites
Emeritus Research /ID# 143146
Camberwell, Victoria, 3124
Royal Prince Alfred Hospital /ID# 143149
Camperdown, New South Wales, 2050
Southern Clinical Research Pty /ID# 143150
Hobart, Tasmania, 7000
Rheumatology Research Unit /ID# 143147
Maroochydore, Queensland, 4558
The Queen Elizabeth Hospital /ID# 143148
Woodville, South Australia, 5011
Belgium5 sites
Algemeen Stedelijk Ziekenhuis /ID# 153504
Aalst, Oost-Vlaanderen, 9300
Rhumaconsult SPRL /ID# 143158
Charleroi, Hainaut, 6000
ReumaClinic Genk /ID# 143159
Genk, 3600
UZ Gent /ID# 143157
Ghent, Oost-Vlaanderen, 9000
CHU Ambroise Pare /ID# 152955
Mons, 7000
Bulgaria5 sites
MHAT Trimontsium /ID# 143173
Plovdiv, 4000
UMHAT Pulmed OOD /ID# 143176
Plovdiv, 4000
MHAT Kaspela /ID# 143172
Plovdiv, 4001
Diagnostic Consultative Center /ID# 143174
Sofia, 1612
UMHAT Sv. Ivan Rilski /ID# 143175
Sofia, 1612
Canada5 sites
Rheumatology Research Assoc /ID# 143206
Edmonton, Alberta, T5M 0H4
Ctr. de Rheum de l'est du QC /ID# 151317
Rimouski, Quebec, G5L 8W1
CA Ctr for Clin Trials CCCT /ID# 159080
Thornhill, Ontario, L4J 1W3
Manitoba Clinic /ID# 143203
Winnipeg, Manitoba, R3A IM3
Ciads /Id# 143205
Winnipeg, Manitoba, R3N 0K6
Guatemala5 sites
Clinicas Hospital Herrera Ller /ID# 153715
Guatemala City, 01010
Creer /Id# 153713
Guatemala City, 10010
Clin Especializada Med Interna /ID# 153716
Guatemala City, 1011
Clinica Medica Reumatologia /ID# 153714
Guatemala City, 1021
Clinica Medica Reumatologia /ID# 153931
Guatemala City, 1021
Tunisia5 sites
Hopital Mongi Slim /ID# 152870
La Marsa, 2046
Institut Mohamed Kassab /ID# 152869
Manouba, 2010
Hopital Farhat Hached /ID# 152868
Sousse, 4000
Charles Nicolle Univ Hosp /ID# 152866
Tunis, 1006
Hospital La Rabta /ID# 152867
Tunis, 1007
Croatia4 sites
Klinicki bolnicki centar Split /ID# 143216
Split, 21000
Clinical Hospital Dubrava /ID# 143217
Zagreb, 10000
Medical Center Kuna-Peric /ID# 143218
Zagreb, 10000
Poliklinika Bonifarm /ID# 143215
Zagreb, 10000
Estonia4 sites
Paernu Hospital /ID# 143238
Pärnu, 80010
Center of Clinical and Basic Research /ID# 143239
Tallinn, Harju, 10128
East Tallinn Central Hospital /ID# 143240
Tallinn, 10138
North Estonian Medical Centre /ID# 145456
Tallinn, 13419
Italy4 sites
Azienda Ospedaliera Luigi Sacc /ID# 143270
Milan, 20157
Fondazione IRCCS Policlinico /ID# 143265
Pavia, 27100
Istituto Clinico Humanitas /ID# 147531
Rozzano, Milano, 20089
A.O.U.I. di Verona Policlinico /ID# 143266
Verona, 37134
Kazakhstan4 sites
JSC Nat Scientific Med Res Ctr /ID# 143272
Astana, 010009
Karaganda State Medical Univ /ID# 153431
Karaganda, 100008
Semey State Medical University /ID# 152661
Semey, 071403
Regional Clinical Hospital /ID# 147173
Shymkent, 160000
New Zealand4 sites
Middlemore Clinical Trials /ID# 143600
Auckland, 2025
Waikato Hospital /ID# 143602
Hamilton, Waikato Region, 3204
Porter Rheumatology Ltd /ID# 143601
Nelson, 7010
Timaru Medical Specialists Ltd /ID# 143599
Timaru, 7910
South Africa4 sites
Arthritis Clinical Research Tr /ID# 143670
Cape Town, Western Cape, 7405
Jakaranda Hosp, Emmed Research /ID# 143668
Pretoria, Gauteng, 0132
Jakaranda Hosp, Emmed Research /ID# 145976
Pretoria, Gauteng, 0132
Winelands Medical Research Ctr /ID# 143669
Stellenbosch, Western Cape, 7600
Bosnia and Herzegovina3 sites
University Clinical Centre of the Republic of Srpska /ID# 143161
Banja Luka, Republika Srpska, 78000
University Clinical Centre of the Republic of Srpska /ID# 143162
Banja Luka, Republika Srpska, 78000
Clinical Center University of Sarajevo /ID# 143164
Sarajevo, 71000
China3 sites
1st Aff Hosp of Bengbu Med Col /ID# 162974
Bengbu, Anhui, 233099
1st Aff Hosp of Shantou Univ /ID# 162968
Shantou, Guangdong, 515041
The 1st Aff Hosp Xiamen Univ /ID# 162076
Xiamen, Fujian, 361003
Israel3 sites
Barzilai Medical Center /ID# 144725
Ashkelon, 78278
Rambam Health Care Campus /ID# 143263
Haifa, 3109601
Sheba Medical Center /ID# 145975
Ramat Gan, 5262100
Lithuania3 sites
Hosp Lithuanian Univ Health Sc /ID# 143582
Kaunas, Kovno, 50009
Klaipeda University Hospital /ID# 143583
Klaipėda, 92288
Vilnius University Hospital /ID# 143584
Vilnius, LT-08661
Puerto Rico3 sites
Ponce School of Medicine /ID# 145657
Ponce, 00716
GCM Medical Group /ID# 143618
San Juan, 00909
School of Medicine University of Puerto Rico-Medical Sciences Campus /ID# 143619
San Juan, 00935
Serbia3 sites
Clinical Center Serbia /ID# 143649
Belgrade, Beograd, 11000
Clinical Center Serbia /ID# 143650
Belgrade, Beograd, 11000
Special Hospital for Rheuma /ID# 143648
Novi Sad, Vojvodina, 21000
Taiwan3 sites
Dalin Tzu Chi General Hospital /ID# 153535
Dalin, 622
China Medical University Hosp /ID# 143703
Taichung, Taichung, 40447
National Taiwan Univ Hosp /ID# 143702
Taipei City, Taipei, 10002
Turkey (Türkiye)3 sites
Izmir Katip Celebi Ataturk Training & Research Hospital /ID# 143704
Izmir, 35360
Izmir Tepecik Training and Research Hospital /ID# 157863
Konak, İzmir, 35180
Uludag Universitesi Ataturk Rehabilitasyon ve Uygulama Merkezi /ID# 143705
Osmangazi, Bursa, 16080
Belarus2 sites
First City Clinical Hospital /ID# 159020
Minsk, 220013
City Clinical Hospital #9 /ID# 145650
Minsk, 220116
Hong Kong2 sites
Queen Mary Hospital /ID# 143255
Hong Kong, 999077
Tuen Mun Hospital /ID# 143256
Tuenmen, 999077
Greece1 site
University General Hospital Attikon /ID# 143252
Athens, Attica, 12462
Switzerland1 site
HFR Fribourg - Hopital Canton /ID# 143700
Fribourg, 1708
About this study
Official title: 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.
Read the 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.
- Conditions
- Rheumatoid Arthritis
- Being tested
- Placebo to Upadacitinib, Methotrexate, Placebo to Methotrexate, Upadacitinib
- Keywords
- Musculoskeletal disease, Arthritis, Joint disease, Anti-inflammatory agents, Antirheumatic agents, ABT-494, Upadacitinib
- Medical subject headings
- Arthritis, Rheumatoid, Musculoskeletal Diseases, Arthritis, Joint Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Placebo to UpadacitinibDrug
Tablet; Oral
MethotrexateDrug
Capsule or Tablet; Oral
Placebo to MethotrexateDrug
Capsule or Tablet; Oral
UpadacitinibDrug
Also called ABT-494, Rinvoq
Tablet; Oral
| Study group | Role | What they receive |
|---|---|---|
| Methotrexate | Active comparator | 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. Receives: Drug: Placebo to Upadacitinib; Drug: Methotrexate |
| Upadacitinib 7.5 mg (Japan-only) | Experimental | 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. Receives: Drug: Placebo to Methotrexate; Drug: Upadacitinib |
| Upadacitinib 15 mg | Experimental | 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. Receives: Drug: Placebo to Methotrexate; Drug: Upadacitinib |
| Upadacitinib 30 mg | Experimental | 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. Receives: Drug: Placebo to Methotrexate; Drug: Upadacitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12 - Global Analysis
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:
- ≥ 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 activity
- Patient global assessment of disease activity
- Patient assessment of pain
- Health Assessment Questionnaire - Disability Index (HAQ-DI)
- High-sensitivity C-reactive protein (hsCRP).
Measured: Baseline and Week 12
Percentage of Participants Achieving Clinical Remission (CR) Based on DAS28(CRP) at Week 24 - Global Analysis
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.
Measured: Week 24
Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12 - Global Analysis
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:
- ≥ 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 activity
- Patient global assessment of disease activity
- Patient assessment of pain
- Health Assessment Questionnaire - Disability Index (HAQ-DI)
- High-sensitivity C-reactive protein (hsCRP).
Measured: Baseline and Week 12
Change From Baseline in Modified Total Sharp Score (mTSS) at Week 24 - Global Analysis
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.
Measured: Baseline to Week 24
Secondary outcomes (23)
Change From Baseline in DAS28 (CRP) at Week 12 - Global Analysis
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.
Measured: Baseline to Week 12
Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 - Global Analysis
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.
Measured: Baseline to week 12
Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 12 - Global Analysis
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.
Measured: Week 12
Change From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 12 - Global Analysis
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.
Measured: Baseline to week 12
Change From Baseline in DAS28 (CRP) at Week 24 - Global Analysis
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.
Measured: Baseline to Week 24
Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 24 - Global Analysis
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.
Measured: Baseline to Week 24
Percentage of Participants With an ACR50 Response at Week 24 - Global Analysis
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 activity
- Patient global assessment of disease activity
- Patient assessment of pain
- Health Assessment Questionnaire - Disability Index (HAQ-DI)
- High-sensitivity C-reactive protein (hsCRP).
Measured: Baseline and Week 24
Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 24 - Global Analysis
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.
Measured: Week 24
Change From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 24 - Global Analysis
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.
Measured: Baseline to Week 24
Percentage of Participants With No Radiographic Progression at Week 24 - Global Analysis
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).
Measured: Week 24
Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 12 - Global Analysis
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 activity
- Patient global assessment of disease activity
- Patient assessment of pain
- Health Assessment Questionnaire - Disability Index (HAQ-DI)
- High-sensitivity C-reactive protein (hsCRP).
Measured: Baseline and Week 12
Percentage of Participants With an ACR20 Response at Week 24 - Global Analysis
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 activity
- Patient global assessment of disease activity
- Patient assessment of pain
- Health Assessment Questionnaire - Disability Index (HAQ-DI)
- High-sensitivity C-reactive protein (hsCRP).
Measured: Baseline and Week 24
Percentage of Participants With an ACR70 Response at Week 24 - Global Analysis
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 activity
- Patient global assessment of disease activity
- Patient assessment of pain
- Health Assessment Questionnaire - Disability Index (HAQ-DI)
- High-sensitivity C-reactive protein (hsCRP).
Measured: Baseline and Week 24
Percentage of Participants With an ACR20 Response at Week 12 - Japan Sub-study
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 activity
- Patient global assessment of disease activity
- Patient assessment of pain
- Health Assessment Questionnaire - Disability Index (HAQ-DI)
- High-sensitivity C-reactive protein (hsCRP).
Measured: Baseline and Week 12
Percentage of Participants With an ACR50 Response at Week 12 - Japan Sub-study
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 activity
- Patient global assessment of disease activity
- Patient assessment of pain
- Health Assessment Questionnaire - Disability Index (HAQ-DI)
- High-sensitivity C-reactive protein (hsCRP).
Measured: Baseline and Week 12
Percentage of Participants With an ACR70 Response at Week 12 - Japan Sub-study
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 activity
- Patient global assessment of disease activity
- Patient assessment of pain
- Health Assessment Questionnaire - Disability Index (HAQ-DI)
- High-sensitivity C-reactive protein (hsCRP).
Measured: Baseline and Week 12
Change From Baseline in DAS28 (CRP) at Week 12 - Japan Sub-study
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.
Measured: Baseline to Week 12
Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 - Japan Sub-study
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.
Measured: Baseline to week 12
Change From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 12 - Japan Sub-study
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.
Measured: Baseline to Week 12
Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 12 - Japan Sub-study
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.
Measured: Week 12
Percentage of Participants Achieving Clinical Remission (CR) Based on DAS28(CRP) at Week 24 - Japan Sub-study
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.
Measured: Week 24
Change From Baseline in Modified Total Sharp Score (mTSS) at Week 24 - Japan Sub-study
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.
Measured: Baseline to Week 24
Percentage of Participants With No Radiographic Progression at Week 24 - Japan Sub-study
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).
Measured: Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Mar 2016 (estimated)
- Study start23 Feb 2016
- Primary completion15 Mar 2018
- Study completion10 Nov 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (14)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- More trials run by AbbVieThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants were to be randomized in a 1:1:1 ratio to treatment Groups 2, 3, and 4 below, except for participants from Japan, who were to be randomized in a 2:1:1:1 ratio to Groups 1, 2, 3, and 4: Group 1: Upadacitinib 7.5 mg QD monotherapy (Japan only) Group 2: Upadacitinib 15 mg QD monotherapy (43 countries, including Japan) Group 3: Upadacitinib 30 mg QD monotherapy (43 countries, including Japan) Group 4: MTX monotherapy (43 countries, including Japan)
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,002 participants (actual)
Sponsor and investigators
- Lead sponsor
- AbbVie
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- AbbVie Inc., Study director, AbbVie
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02706873
- Sponsor's protocol ID
- M13-545
- Other IDs
- 2015-003334-27, 2015
- Acronym
- SELECT-EARLY
- Status last verified
- Jun 2023
- First submitted
- 18 Feb 2016
- Last updated
- 7 Jul 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
van Vollenhoven R, Takeuchi T, Pangan AL, Friedman A, Mohamed MF, Chen S, Rischmueller M, Blanco R, Xavier RM, Strand V. Efficacy and Safety of Upadacitinib Monotherapy in Methotrexate-Naive Patients With Moderately-to-Severely Active Rheumatoid Arthritis (SELECT-EARLY): A Multicenter, Multi-Country, Randomized, Double-Blind, Active Comparator-Controlled Trial. Arthritis Rheumatol. 2020 Oct;72(10):1607-1620. doi: 10.1002/art.41384. Epub 2020 Sep 8.
PubMed 32638504Burmester GR, Deodhar A, Irvine AD, Panaccione R, Winthrop KL, Vleugels RA, Levy G, Suravaram S, Palac H, Wegrzyn L, Ford S, Meerwein S, Guttman-Yassky E. Safety Profile of Upadacitinib: Descriptive Analysis in Over 27,000 Patient-Years Across Rheumatoid Arthritis, Psoriatic Arthritis, Axial Spondyloarthritis, Atopic Dermatitis, and Inflammatory Bowel Disease. Adv Ther. 2025 Oct;42(10):5215-5237. doi: 10.1007/s12325-025-03328-y. Epub 2025 Aug 28.
PubMed 40875187van Vollenhoven R, Strand V, Takeuchi T, Chavez N, Walter PM, Singhal A, Swierkot J, Khan N, Bu X, Li Y, Penn SK, Camp HS, Aelion J. Upadacitinib monotherapy versus methotrexate monotherapy in patients with rheumatoid arthritis: efficacy and safety through 5 years in the SELECT-EARLY randomized controlled trial. Arthritis Res Ther. 2024 Jul 29;26(1):143. doi: 10.1186/s13075-024-03358-x.
PubMed 39075620Rubbert-Roth A, Kakehasi AM, Takeuchi T, Schmalzing M, Palac H, Coombs D, Liu J, Anyanwu SI, Lippe R, Curtis JR. Malignancy in the Upadacitinib Clinical Trials for Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis, and Non-radiographic Axial Spondyloarthritis. Rheumatol Ther. 2024 Feb;11(1):97-112. doi: 10.1007/s40744-023-00621-6. Epub 2023 Nov 20.
PubMed 37982966Charles-Schoeman C, Choy E, McInnes IB, Mysler E, Nash P, Yamaoka K, Lippe R, Khan N, Shmagel AK, Palac H, Suboticki J, Curtis JR. MACE and VTE across upadacitinib clinical trial programmes in rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. RMD Open. 2023 Nov;9(4):e003392. doi: 10.1136/rmdopen-2023-003392.
PubMed 37945286Fleischmann R, Curtis JR, Charles-Schoeman C, Mysler E, Yamaoka K, Richez C, Palac H, Dilley D, Liu J, Strengholt S, Burmester G. Safety profile of upadacitinib in patients at risk of cardiovascular disease: integrated post hoc analysis of the SELECT phase III rheumatoid arthritis clinical programme. Ann Rheum Dis. 2023 Sep;82(9):1130-1141. doi: 10.1136/ard-2023-223916. Epub 2023 Jun 12.
PubMed 37308218Burmester GR, Cohen SB, Winthrop KL, Nash P, Irvine AD, Deodhar A, Mysler E, Tanaka Y, Liu J, Lacerda AP, Palac H, Shaw T, Mease PJ, Guttman-Yassky E. Safety profile of upadacitinib over 15 000 patient-years across rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and atopic dermatitis. RMD Open. 2023 Feb;9(1):e002735. doi: 10.1136/rmdopen-2022-002735.
PubMed 36754548Kakehasi AM, Radominski SC, Baravalle MD, Palazuelos FCI, Garcia-Garcia C, Arruda MS, Curi M, Liu J, Qiao M, Velez-Sanchez P, Vargas JI. Safety of upadacitinib in Latin American patients with rheumatoid arthritis: an integrated safety analysis of the SELECT phase 3 clinical program. Clin Rheumatol. 2023 May;42(5):1249-1258. doi: 10.1007/s10067-023-06513-y. Epub 2023 Jan 30.
PubMed 36715850Bergman 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.
PubMed 36125701Peterfy 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.
PubMed 34897366Yamaoka 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.
PubMed 34041702Strand V, Tundia N, Wells A, Buch MH, Radominski SC, Camp HS, Friedman A, Suboticki JL, Dunlap K, Goldschmidt D, Bergman M. Upadacitinib monotherapy improves patient-reported outcomes in rheumatoid arthritis: results from SELECT-EARLY and SELECT-MONOTHERAPY. Rheumatology (Oxford). 2021 Jul 1;60(7):3209-3221. doi: 10.1093/rheumatology/keaa770.
PubMed 33313898Cohen 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.
PubMed 33115760Nader 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.
PubMed 31610021