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

Rheumatoid Arthritis Clinical Trial

— SELECT-EARLY  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02706873
• Other study ID #: M13-545
• Secondary ID: 2015-003334-27
• Status: Completed
• Phase: Phase 3
• Start date: February 23, 2016
• Est. completion date: November 10, 2022

Study information

• Verified date: June 2023
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1002
• Est. completion date: November 10, 2022
• Est. primary completion date: March 15, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Placebo to Upadacitinib
Tablet; Oral
• Methotrexate
Capsule or Tablet; Oral
• Placebo to Methotrexate
Capsule or Tablet; Oral
• Upadacitinib
Tablet; Oral

Locations

Country	Name	City	State
Argentina	Org Medica de Investigacion /ID# 143142	Buenos Aires
Argentina	Aprillus Asistencia e Investig /ID# 149179	Capital Federal	Buenos Aires
Argentina	Consultora Integral de Salud S /ID# 143144	Cordoba
Argentina	Instituto CAICI /ID# 143141	Rosario	Santa FE
Argentina	Iari /Id# 148595	San isidro	Buenos Aires
Argentina	Centro Integral de Reumatologi /ID# 143143	San Miguel de Tucuman
Argentina	Centro Medico Privado/Reuma /ID# 143140	San Miguel de Tucuman
Australia	Emeritus Research /ID# 143146	Camberwell	Victoria
Australia	Royal Prince Alfred Hospital /ID# 143149	Camperdown	New South Wales
Australia	Southern Clinical Research Pty /ID# 143150	Hobart	Tasmania
Australia	Rheumatology Research Unit /ID# 143147	Maroochydore	Queensland
Australia	The Queen Elizabeth Hospital /ID# 143148	Woodville	South Australia
Belarus	City Clinical Hospital #9 /ID# 145650	Minsk
Belarus	First City Clinical Hospital /ID# 159020	Minsk
Belgium	Algemeen Stedelijk Ziekenhuis /ID# 153504	Aalst	Oost-Vlaanderen
Belgium	Rhumaconsult SPRL /ID# 143158	Charleroi	Hainaut
Belgium	ReumaClinic Genk /ID# 143159	Genk
Belgium	UZ Gent /ID# 143157	Gent	Oost-Vlaanderen
Belgium	CHU Ambroise Pare /ID# 152955	Mons
Bosnia and Herzegovina	University Clinical Centre of the Republic of Srpska /ID# 143161	Banja Luka	Republika Srpska
Bosnia and Herzegovina	University Clinical Centre of the Republic of Srpska /ID# 143162	Banja Luka	Republika Srpska
Bosnia and Herzegovina	Clinical Center University of Sarajevo /ID# 143164	Sarajevo
Brazil	Ceti - Centro de Estudos Em Terapias Inovadoras Ltda /Id# 143169	Curitiba	Parana
Brazil	CIP - Centro Internacional de Pesquisa /ID# 143171	Goiânia	Goias
Brazil	Hospital de Clinicas de Porto Alegre /ID# 143168	Porto Alegre	Rio Grande Do Sul
Brazil	LMK Sevicos Medicos S/S /ID# 143167	Porto Alegre	Rio Grande Do Sul
Brazil	CCBR Brasil /ID# 150925	Rio de Janeiro
Brazil	CEPIC - Centro Paulista de Investigação Clínica e Serviços Médicos Ltda /ID# 143166	São Paulo	Sao Paulo
Bulgaria	MHAT Kaspela /ID# 143172	Plovdiv
Bulgaria	MHAT Trimontsium /ID# 143173	Plovdiv
Bulgaria	UMHAT Pulmed OOD /ID# 143176	Plovdiv
Bulgaria	Diagnostic Consultative Center /ID# 143174	Sofia
Bulgaria	UMHAT Sv. Ivan Rilski /ID# 143175	Sofia
Canada	Rheumatology Research Assoc /ID# 143206	Edmonton	Alberta
Canada	Ctr. de Rheum de l'est du QC /ID# 151317	Rimouski	Quebec
Canada	CA Ctr for Clin Trials CCCT /ID# 159080	Thornhill	Ontario
Canada	Ciads /Id# 143205	Winnipeg	Manitoba
Canada	Manitoba Clinic /ID# 143203	Winnipeg	Manitoba
Chile	Someal /Id# 143207	Providencia	Santiago
Chile	Quantum Research LTDA. /ID# 143210	Puerto Varas
Chile	Investigaciones Medicas SSMSO /ID# 151685	Santiago
Chile	Quantum Research Stgo. /ID# 145651	Santiago
Chile	Soc. de Prestaciones medicas y Paramedicas Goecke /ID# 143209	Santiago
Chile	Ctr de Inv Clinica del Sur /ID# 143208	Temuco	Araucania
Chile	Centro de Estudios Clinicos Qu /ID# 152913	Vina Del Mar
China	1st Aff Hosp of Bengbu Med Col /ID# 162974	Bengbu	Anhui
China	1st Aff Hosp of Shantou Univ /ID# 162968	Shantou	Guangdong
China	The 1st Aff Hosp Xiamen Univ /ID# 162076	Xiamen	Fujian
Colombia	Ctr Int de Reum del Caribe SAS /ID# 143211	Barranquilla
Colombia	Centro de Investigacion en Reumatologia y Especialidades Medicas- CIREEM SAS /ID# 143214	Bogota	Cundinamarca
Colombia	Riesgo de Fractura S.A - CAYRE /ID# 143212	Bogota
Colombia	Simedics IPS SAS /ID# 152572	Bogota
Colombia	Fund Inst de Reum F. Chalem /ID# 159544	Bogotá
Colombia	Medicity S.A.S. /ID# 143213	Bucaramanga
Croatia	Klinicki bolnicki centar Split /ID# 143216	Split
Croatia	Clinical Hospital Dubrava /ID# 143217	Zagreb
Croatia	Medical Center Kuna-Peric /ID# 143218	Zagreb
Croatia	Poliklinika Bonifarm /ID# 143215	Zagreb
Czechia	RHEUMA s.r.o. /ID# 143230	Breclav
Czechia	Revmatologie, s.r.o. /ID# 143223	Brno
Czechia	Revmatologie Bruntal, s.r.o /ID# 143220	Bruntál
Czechia	L.K.N. Arthrocentrum, s.r.o /ID# 143224	Hlucín	Moravskoslezsky Kraj
Czechia	CTCenter MaVe, s.r.o. /ID# 143226	Olomouc	Olomoucky Kraj
Czechia	Thomayerova nemocnice /ID# 143228	Prague	Praha 4
Czechia	Nuselská poliklinika, Revmatologie /ID# 143232	Prague 4	Praha 4
Czechia	Nuselská poliklinika, Revmatologie /ID# 143233	Prague 4	Praha 4
Czechia	Nemocnice Slany /ID# 143221	Slany
Czechia	Medical Plus, s.r.o. /ID# 143219	Uherské Hradište
Czechia	PV MEDICAL Services s.r.o. /ID# 143234	Zlín 1	Zlin
Estonia	Paernu Hospital /ID# 143238	Pärnu
Estonia	Center of Clinical and Basic Research /ID# 143239	Tallinn	Harjumaa
Estonia	East Tallinn Central Hospital /ID# 143240	Tallinn
Estonia	North Estonian Medical Centre /ID# 145456	Tallinn
Germany	Rheumaforschungszentrum II /ID# 143247	Hamburg
Germany	Schoen Klinikum Hamburg Eilbek /ID# 143251	Hamburg
Germany	Rheumazentrum Ruhrgebiet /ID# 145652	Herne	Nordrhein-Westfalen
Germany	Uniklinik Koln /ID# 143248	Köln	Nordrhein-Westfalen
Germany	LMU Klinikum der Universität München /ID# 143249	Munich
Germany	Praxis Walter, Rendsburg /ID# 143250	Rendsburg	Schleswig-Holstein
Greece	University General Hospital Attikon /ID# 143252	Athens	Attiki
Guatemala	Clin Especializada Med Interna /ID# 153716	Ciudad de Guatemala
Guatemala	Clinica Medica Reumatologia /ID# 153714	Ciudad de Guatemala
Guatemala	Clinica Medica Reumatologia /ID# 153931	Ciudad de Guatemala
Guatemala	Clinicas Hospital Herrera Ller /ID# 153715	Ciudad de Guatemala
Guatemala	Creer /Id# 153713	Ciudad de Guatemala
Hong Kong	Queen Mary Hospital /ID# 143255	Hong Kong
Hong Kong	Tuen Mun Hospital /ID# 143256	Tuen Mun
Hungary	Qualiclinic Kft. /ID# 143259	Budapest	Pest
Hungary	Hevizgyogyfurdo es Szent Andra /ID# 143257	Heviz
Hungary	Pest Megyei Flor Ferenc Korhaz /ID# 143260	Kistarcsa
Hungary	CRU Hungary Egeszsegugyi és Szolgaltato Kft. /ID# 143258	Miskolc	Borsod-Abauj-Zemplen
Hungary	Fejer Megyei Szent Gyorgy Korh /ID# 144724	Szekesfehervar
Hungary	Markusovszky Egyetemi Oktatókórház /ID# 143261	Szombathely	Vas
Ireland	St Vincent's University Hosp /ID# 143262	Dublin
Israel	Barzilai Medical Center /ID# 144725	Ashkelon
Israel	Rambam Health Care Campus /ID# 143263	Haifa
Israel	Sheba Medical Center /ID# 145975	Ramat Gan
Italy	Azienda Ospedaliera Luigi Sacc /ID# 143270	Milan
Italy	Fondazione IRCCS Policlinico /ID# 143265	Pavia
Italy	Istituto Clinico Humanitas /ID# 147531	Rozzano	Milano
Italy	A.O.U.I. di Verona Policlinico /ID# 143266	Verona
Japan	Katayama Orthopedic Rheumatology Clinic /ID# 148029	Asahikawa	Hokkaido
Japan	National Hospital Organization Asahikawa Medical Center /ID# 148021	Asahikawa	Hokkaido
Japan	National Hospital Organization Beppu Medical Center /ID# 161058	Beppu
Japan	Juntendo University Hospital /ID# 148050	Bunkyo-ku	Tokyo
Japan	NHO Chiba-East-Hospital /ID# 148035	Chiba
Japan	St.Luke's International Hospital /ID# 148041	Chuo-ku	Tokyo
Japan	Sugimoto Rheumatology and Internal Medicine Clinic /ID# 148047	Fukui
Japan	Shono Rheumatism Clinic /ID# 148046	Fukuoka
Japan	NHO Kyushu Medical Center /ID# 148263	Fukuoka-shi	Fukuoka
Japan	NHO Kyushu Medical Center /ID# 148264	Fukuoka-shi	Fukuoka
Japan	Kansai Medical University Hospital /ID# 159622	Hirakata-shi	Osaka
Japan	Teikyo University Chiba Medical Center /ID# 159618	Ichihara	Chiba
Japan	Matsubara Mayflower Hospital /ID# 148033	Kato
Japan	Saitama Medical Center, Saitama Medical University /ID# 148015	Kawagoe-shi	Saitama
Japan	Kobe University Hospital /ID# 153461	Kobe	Hyogo
Japan	Bay Side Misato Medical Center /ID# 148256	Kochi-shi	Kochi
Japan	Center for Arthritis and Clinical Rheumatology Matsubara Clinic /ID# 148254	Kumamoto-shi	Kumamoto
Japan	Kumamoto Orthopaedic Hospital /ID# 148054	Kumamoto-shi	Kumamoto
Japan	Kumamoto Shinto General Hospital /ID# 148266	Kumamoto-shi	Kumamoto
Japan	St. Mary's Hospital /ID# 148038	Kurume
Japan	Kagawa University Hospital /ID# 148016	Kyoto
Japan	Toho University Ohashi Medical Center /ID# 148027	Meguro-ku	Tokyo
Japan	Yu Family Clinic /ID# 148048	Miyagi
Japan	Nagaoka Red Cross Hospital /ID# 148018	Nagaoka-shi	Niigata
Japan	Daido Hospital /ID# 160868	Nagoya
Japan	Kondo Clinic for Ortho & Rheum /ID# 148032	Nagoya
Japan	Nagoya University Hospital /ID# 148031	Nagoya-shi	Aichi
Japan	Shirahama Hamayu Hospital /ID# 148253	Nishimura
Japan	Oribe Clinic of Rheumatology and Internal Medicine /ID# 156035	Oita
Japan	Japanese Red Cross Okayama Hospital /ID# 159619	Okayama-shi	Okayama
Japan	NHO Osaka Minami Med Ctr /ID# 148042	Osaka	Kawachinagano-shi
Japan	Osaka City General Hospital /ID# 159617	Osaka
Japan	National Hospital Organization Sagamihara National Hospital /ID# 148019	Sagamihara-shi	Kanagawa
Japan	Sanuki Municipal Hospital /ID# 158842	Sanuki
Japan	Hokkaido Medical Center for Rheumatic Diseases /ID# 148259	Sapporo
Japan	Hokkaido University Hospital /ID# 148262	Sapporo
Japan	Sagawa Akira Rheumatology Clin /ID# 148043	Sapporo
Japan	Sapporo City General Hospital /ID# 148037	Sapporo
Japan	Sasebo Chuo Hospital /ID# 148261	Sasebo-city	Nagasaki
Japan	Azuma Rheumatology Clinic /ID# 161050	Sayama
Japan	Hikarigaoka Spellman Hospital /ID# 148020	Sendai
Japan	Tokito Clinic Rheumatology and Orthopaedics Surgery /ID# 148052	Shimonoseki-shi	Yamaguchi
Japan	Jichi Medical University Hospital /ID# 159620	Shimotsuke-shi	Tochigi
Japan	Keio University Hospital /ID# 148057	Shinjuku-ku	Tokyo
Japan	Takaoka Rheumatic Orthopedic Clinic /ID# 148022	Takaoka
Japan	Osaka Medical College Hospital /ID# 159624	Takatsuki -shi	Osaka
Japan	National Hospital Organization Tokyo Medical Center /ID# 148040	Tokyo
Japan	NHO Toyohashi Medical Center /ID# 161033	Toyohashi-shi	Aichi
Japan	National Hospital Organization Shimoshizu National Hospital /ID# 148258	Yotsukaido
Kazakhstan	JSC Nat Scientific Med Res Ctr /ID# 143272	Astana
Kazakhstan	Karaganda State Medical Univ /ID# 153431	Karaganda
Kazakhstan	Semey State Medical University /ID# 152661	Semey
Kazakhstan	Regional Clinical Hospital /ID# 147173	Shymkent
Latvia	LTD M+M Centers /ID# 143279	Adazi
Lithuania	Hosp Lithuanian Univ Health Sc /ID# 143582	Kaunas	Kovno
Lithuania	Klaipeda University Hospital /ID# 143583	Klaipeda
Lithuania	Vilnius University Hospital /ID# 143584	Vilnius
Mexico	Invest y Biomed de Chihuahua /ID# 143595	Chihuahua
Mexico	Clinstile, S.A. de C.V. /ID# 143591	Cuauhtemoc	Ciudad De Mexico
Mexico	Centro Especializado en Diabetes, Obesidad y Prevención de Enfermedades Cardiova /ID# 143589	Mexico City
Mexico	CINTRE, Centro de Investigación y Tratamiento Reumatológico SC /ID# 153562	Mexico City	Ciudad De Mexico
Mexico	RM Pharma Specialists, S.A de C.V /ID# 143593	Mexico City
Mexico	Unidad de Investigacion de las Enfermedades Reumatologicas SA de CV /ID# 143592	Mexico City
Mexico	Centro Reumatologico de Queret /ID# 149493	Queretaro
New Zealand	Middlemore Clinical Trials /ID# 143600	Auckland
New Zealand	Waikato Hospital /ID# 143602	Hamilton	Waikato
New Zealand	Porter Rheumatology Ltd /ID# 143601	Nelson
New Zealand	Timaru Medical Specialists Ltd /ID# 143599	Timaru
Poland	NZOZ Centrum Reumatologiczne /ID# 143603	Elblag	Warminsko-mazurskie
Poland	Centrum Medyczne Pratia Gdynia /ID# 143607	Gdynia	Pomorskie
Poland	Silmedic Sp z o.o /ID# 143605	Katowice	Slaskie
Poland	Medyczne Centrum Hetmanska /ID# 144726	Poznan	Wielkopolskie
Poland	Centrum Medyczne AMED /ID# 143604	Warsaw	Mazowieckie
Poland	Centrum Medyczne Pratia Warszawa /ID# 143608	Warsaw	Mazowieckie
Poland	WroMedica I. Bielicka, A. Strzalkowska s.c. /ID# 143606	Wroclaw	Dolnoslaskie
Portugal	Centro Hospitalar Lisboa Norte, EPE /ID# 143613	Lisboa
Portugal	Centro Hospitalar Lisboa Ocidental, EPE /ID# 151009	Lisbon	Lisboa
Portugal	Instituto Portugues De Reumatologia /ID# 148313	Lisbon	Lisboa
Portugal	Centro Hospitalar Baixo Vouga /ID# 153726	Porto
Portugal	Centro Hospitalar de Sao Joao, EPE /ID# 153575	Porto
Portugal	Unidade Local De Saude Do Alto Minho /ID# 143611	Viana Do Castelo
Portugal	Centro Hospitalar De Vila Nova /ID# 143615	Vila Nova De Gaia	Porto
Portugal	Centro Hosp de Tondela-Viseu /ID# 143612	Viseu
Puerto Rico	Ponce School of Medicine /ID# 145657	Ponce
Puerto Rico	GCM Medical Group /ID# 143618	San Juan
Puerto Rico	School of Medicine University of Puerto Rico-Medical Sciences Campus /ID# 143619	San Juan
Romania	Spitalul Clinic Dr. I. Cantacuzino /ID# 143622	Bucharest	Bucuresti
Romania	Spitalul Clinic Sf. Maria /ID# 143623	Bucuresti
Romania	Spitalul Clinic Sf. Maria /ID# 143625	Bucuresti
Romania	Spitalul Clinic Sf. Maria /ID# 143627	Bucuresti
Romania	Spitalul Clinic de Recuperare /ID# 143620	Iasi
Romania	Ecomed SRL /ID# 143629	Oradea
Russian Federation	Kazan State Medical University /ID# 143645	Kazan	Tatarstan, Respublika
Russian Federation	Family Outpatient clinic#4,LLC /ID# 151010	Korolev	Moskva
Russian Federation	Clinical Hospital No.1 n.a. N.I.Pirogov /ID# 143641	Moscow	Moskva
Russian Federation	Russian National Research Medi /ID# 143642	Moscow
Russian Federation	LLC Medical Center /ID# 143647	Novosibirsk	Novosibirskaya Oblast
Russian Federation	Orenburg Regional Clinical Hos /ID# 143630	Orenburg
Russian Federation	Republican Clin Hos n.a. Baran /ID# 143634	Petrozavodsk
Russian Federation	LLC Novaya Klinika /ID# 143631	Pyatigorsk	Stavropol Skiy Kray
Russian Federation	Ryazan State Medical Universit /ID# 143646	Ryazan
Russian Federation	Samara Regional Clinical Hosp /ID# 150928	Samara
Russian Federation	Tver Regional Clinical Hosp. /ID# 143639	Tver	Tverskaya Oblast
Russian Federation	Reg Clin Hosp n.a. Kuvatova G. /ID# 143632	UFA
Russian Federation	Ulyanovsk Regional Clin Hosp /ID# 143644	Ulyanovsk
Russian Federation	Voronezh State Medical Univers /ID# 150926	Voronezh
Serbia	Clinical Center Serbia /ID# 143649	Belgrade	Beograd
Serbia	Clinical Center Serbia /ID# 143650	Belgrade	Beograd
Serbia	Special Hospital for Rheuma /ID# 143648	Novi Sad	Vojvodina
Slovakia	Reuma -MUDr. Maria Palasthyova /ID# 143662	Žiar nad Hronom
Slovakia	MEDMAN s.r.o. /ID# 143661	Martin
Slovakia	Reumatologická ambulancia Reum.hapi s.r.o. /ID# 143657	Nové Mesto Nad Váhom
Slovakia	REUMACENTRUM s.r.o. /ID# 143653	Partizanske
Slovakia	Slovak research center Team Member, Thermium s.r.o. /ID# 143663	Pieštany
Slovakia	Slovak Research Center /ID# 143659	Puchov
Slovakia	TIMMED spol. s r.o. /ID# 143664	Stará Lubovna
Slovakia	Reumatologicka ambulancia, LER /ID# 143660	Topolcany
Slovakia	MEDEOS s.r.o. /ID# 143656	Trencin
Slovakia	REUMA-GLOBAL, s.r.o. /ID# 143655	Trnava
Slovakia	ALBAMED s.r.o. /ID# 143654	Zvolen
Slovenia	Univ Medical Ctr Ljubljana /ID# 143667	Ljubljana
South Africa	Arthritis Clinical Research Tr /ID# 143670	Cape Town	Western Cape
South Africa	Jakaranda Hosp, Emmed Research /ID# 143668	Pretoria	Gauteng
South Africa	Jakaranda Hosp, Emmed Research /ID# 145976	Pretoria	Gauteng
South Africa	Winelands Medical Research Ctr /ID# 143669	Stellenbosch	Western Cape
Spain	Comple Hosp Univ de A Coruna /ID# 143672	A Coruna
Spain	Hospital Univ Vall d'Hebron /ID# 143675	Barcelona
Spain	Hospital Clin Univ San Carlos /ID# 143674	Madrid
Spain	H. Un. Marques de Valdecilla /ID# 143671	Santander	Cantabria
Spain	Clinica Gaias /ID# 143673	Santiago de Compostela
Spain	Hosp Nuestra Senora Esperanza /ID# 143677	Santiago de Compostela
Switzerland	HFR Fribourg - Hopital Canton /ID# 143700	Fribourg
Taiwan	Dalin Tzu Chi General Hospital /ID# 153535	Dalin
Taiwan	China Medical University Hosp /ID# 143703	Taichung City	Taichung
Taiwan	National Taiwan Univ Hosp /ID# 143702	Taipei City	Taipei
Tunisia	Hopital Mongi Slim /ID# 152870	La Marsa
Tunisia	Institut Mohamed Kassab /ID# 152869	Manouba
Tunisia	Hopital Farhat Hached /ID# 152868	Sousse
Tunisia	Charles Nicolle Univ Hosp /ID# 152866	Tunis
Tunisia	Hospital La Rabta /ID# 152867	Tunis
Turkey	Izmir Katip Celebi Ataturk Training & Research Hospital /ID# 143704	Izmir
Turkey	Izmir Tepecik Training and Research Hospital /ID# 157863	Konak	Izmir
Turkey	Uludag Universitesi Ataturk Rehabilitasyon ve Uygulama Merkezi /ID# 143705	Osmangazi	Bursa
Ukraine	Regional Clinical Hospital /ID# 152029	Ivano-frankivsk
Ukraine	NSC-Strazhesko Ist Cardiology /ID# 152026	Kiev
Ukraine	LLC Revmocentr /ID# 143710	Kyiv
Ukraine	Lviv Regional Clinical Hospita /ID# 154449	Lviv	Lvivska Oblast
Ukraine	MNCE "Lviv City Clinical Hospital #4" /ID# 143711	Lviv
Ukraine	Odessa National Medical Univ /ID# 143715	Odesa
Ukraine	Vinnytsia Regional Clinical Hospital n.a. M.I.Pyrogov /ID# 143714	Vinnytsia	Vinnytska Oblast
Ukraine	Zaporizhzhia Regional Clinical /ID# 143712	Zaporizhia
United Kingdom	Western General Hospital /ID# 144431	Edinburgh
United Kingdom	Chapel Allerton Hospital /ID# 143717	Leeds
United Kingdom	Leicester Royal Infirmary /ID# 143718	Leicester	England
United Kingdom	Whipps Cross Univ Hospital /ID# 143721	London	London, City Of
United Kingdom	Queen Alexandra Hospital /ID# 143722	Portsmouth
United Kingdom	Southampton General Hospital /ID# 143716	Southampton
United States	Arthritis Clinic of N. VA, P.C /ID# 143734	Arlington	Virginia
United States	Diagnostic Group Integrated He /ID# 152921	Beaumont	Texas
United States	Adriana Pop-Moody MD Clinic PA /ID# 147626	Corpus Christi	Texas
United States	International Medical Research - Daytona /ID# 143748	Daytona Beach	Florida
United States	Doctor's Hosp at Renaissance /ID# 156407	Edinburg	Texas
United States	MedResearch Inc. /ID# 156409	El Paso	Texas
United States	Accurate Clinical Research /ID# 143749	Houston	Texas
United States	Rheumatic Disease Clin Res Ctr /ID# 151103	Houston	Texas
United States	West Tennessee Research Inst /ID# 143723	Jackson	Tennessee
United States	TriWest Research Associates- La Mesa /ID# 143738	La Mesa	California
United States	Dr. Ramesh Gupta /ID# 143732	Memphis	Tennessee
United States	SW Rheumatology Res. LLC /ID# 143745	Mesquite	Texas
United States	FL Med Ctr and Research, Inc. /ID# 143724	Miami	Florida
United States	Trinity Health Med Arts Clinic /ID# 143727	Minot	North Dakota
United States	Millennium Research /ID# 143736	Ormond Beach	Florida
United States	Four Rivers Clinical Research /ID# 143741	Paducah	Kentucky
United States	Desert Medical Advances /ID# 143730	Palm Desert	California
United States	Arthritis Research of Florida /ID# 143743	Palm Harbor	Florida
United States	Accurate Clinical Management /ID# 159543	San Antonio	Texas
United States	NextGen Clinical Trials LLP /ID# 150930	San Antonio	Texas
United States	Sun Research Institute /ID# 159546	San Antonio	Texas
United States	Arthritis Clinic of Central TX /ID# 159541	San Marcos	Texas
United States	Sarasota Arthritis Center /ID# 145978	Sarasota	Florida
United States	Articularis Healthcare Group, Inc d/b/a Low Country Rheumatology /ID# 145653	Summerville	South Carolina
United States	Ocean Rheumatology, PA /ID# 143737	Toms River	New Jersey
United States	Healthcare Research Consultant /ID# 143747	Tulsa	Oklahoma
United States	STAT Research, Inc. /ID# 143750	Vandalia	Ohio
United States	Deerbrook Medical Associates /ID# 143728	Vernon Hills	Illinois
United States	Arthritis Rheumatic Back Disorder /ID# 143733	Voorhees	New Jersey
United States	Arthritis & Osteoporosis Clinic /ID# 159542	Waco	Texas
United States	Advanced Rheumatology & Arthri /ID# 147947	Wexford	Pennsylvania
United States	FL Med Clinic, PA /ID# 143744	Zephyrhills	Florida

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belarus,  Belgium,  Bosnia and Herzegovina,  Brazil,  Bulgaria,  Canada,  Chile,  China,  Colombia,  Croatia,  Czechia,  Estonia,  Germany,  Greece,  Guatemala,  Hong Kong,  Hungary,  Ireland,  Israel,  Italy,  Japan,  Kazakhstan,  Latvia,  Lithuania,  Mexico,  New Zealand,  Poland,  Portugal,  Puerto Rico,  Romania,  Russian Federation,  Serbia,  Slovakia,  Slovenia,  South Africa,  Spain,  Switzerland,  Taiwan,  Tunisia,  Turkey,  Ukraine,  United Kingdom, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	Baseline and Week 12
Primary	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.	Week 24
Primary	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).	Baseline and Week 12
Primary	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.	Baseline to Week 24
Secondary	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.	Baseline to Week 12
Secondary	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.	Baseline to week 12
Secondary	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.	Week 12
Secondary	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.	Baseline to week 12
Secondary	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.	Baseline to Week 24
Secondary	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.	Baseline to Week 24
Secondary	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).	Baseline and Week 24
Secondary	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.	Week 24
Secondary	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.	Baseline to Week 24
Secondary	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).	Week 24
Secondary	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).	Baseline and Week 12
Secondary	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).	Baseline and Week 24
Secondary	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).	Baseline and Week 24
Secondary	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).	Baseline and Week 12
Secondary	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).	Baseline and Week 12
Secondary	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).	Baseline and Week 12
Secondary	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.	Baseline to Week 12
Secondary	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.	Baseline to week 12
Secondary	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.	Baseline to Week 12
Secondary	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.	Week 12
Secondary	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.	Week 24
Secondary	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.	Baseline to Week 24
Secondary	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).	Week 24

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