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

Rheumatoid Arthritis Clinical Trial

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Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02629159
• Other study ID #: M14-465
• Secondary ID: 2022-501017-31-0
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 1, 2015
• Est. completion date: September 30, 2027

Study information

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

Clinical Trial Summary

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

Description:

This study consists of a 48-week double-blind treatment period (Period 1) and a long-term extension period (Period 2). Period 1 is a 48-week randomized, double-blind, parallel-group, placebo-controlled and active comparator-controlled period designed to compare the safety and efficacy of upadacitinib versus placebo, and versus adalimumab. Participants will be randomized in a 2:2:1 ratio to one of three treatment groups: - Placebo (up to Week 26) - Upadacitinib 15 mg once daily (QD) - Adalimumab 40 mg every other week (eow) Participants randomized to placebo who do not achieve a ≥ 20% improvement in tender joint count (TJC) and swollen joint count (SJC) at Weeks 14, 18, or 22 compared to Baseline will be switched to blinded upadacitinib treatment. At Week 26, all participants still receiving placebo will be switched to blinded upadacitinib treatment regardless of clinical response. Participants randomized to adalimumab who do not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline will be switched to blinded upadacitinib. Participants still receiving adalimumab at Week 26 who do not achieve low disease activity (LDA) according to Clinical Disease Activity Index (CDAI; LDA is defined as CDAI ≤ 10) will be switched to blinded upadacitinib treatment to Week 48. Participants randomized to upadacitinib who do not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline will be switched to blinded adalimumab; participants still receiving upadacitinib at Week 26 who do not achieve LDA (CDAI ≤ 10) will be switched to blinded adalimumab treatment to Week 48. Participants who complete the Week 48 visit (end of Period 1) will enter the long-term extension phase of the study (Period 2), for up to 5 years. Participants will continue study treatment as assigned at the end of Period 1. Starting at the Week 48 and thereafter, at least 20% improvement in both TJC and SJC compared to Baseline is required to remain on study drug. Anyone who does not fulfill this criterion at 2 consecutive visits (starting at Week 48) will be discontinued.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1629
• Est. completion date: September 30, 2027
• Est. primary completion date: October 27, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

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

Exclusion Criteria:

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

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Placebo for Adalimumab
Administered by subcutaneous injection once every other week
• Adalimumab
Administered by subcutaneous injection once every other week
• Placebo for Upadacitinib
Tablets taken orally once a day
• Upadacitinib
Tablets taken orally once a day

Locations

Country	Name	City	State
Argentina	Cemic /Id# 148404	Buenos Aires
Argentina	Consultorio Reumatologic Pampa /ID# 144853	Buenos Aires
Argentina	Fundacion Sanatorio Guemes /ID# 148405	Buenos Aires
Argentina	Mautalen Salud e Investigacion /ID# 142843	Buenos Aires
Argentina	Org Medica de Investigacion /ID# 144855	Buenos Aires
Argentina	Aprillus Asistencia e Investig /ID# 148406	Capital Federal	Buenos Aires
Argentina	Consultora Integral de Salud S /ID# 144856	Cordoba
Argentina	Inst. Rheumatologic Strusberg /ID# 145601	Cordoba
Argentina	Instituto CAICI /ID# 144854	Rosario, Santa FE
Argentina	Cordis S.A. /Id# 152622	Salta
Argentina	Iari /Id# 151293	San Fernando
Argentina	Centro Integral de Reumatologi /ID# 142845	San Miguel de Tucuman
Argentina	Centro Medico Privado/Reuma /ID# 142842	San Miguel de Tucuman
Argentina	Centro de Enfermedades /ID# 153542	Santa Fe
Australia	Emeritus Research /ID# 142848	Camberwell	Victoria
Australia	Royal Prince Alfred Hospital /ID# 144857	Camperdown	New South Wales
Austria	LKH-Univ. Klinikum Graz /ID# 142851	Graz
Belarus	First City Clinical Hospital /ID# 158011	Minsk
Belgium	Rhumaconsult SPRL /ID# 142860	Charleroi	Hainaut
Belgium	UZ Gent /ID# 142859	Gent	Oost-Vlaanderen
Belgium	CHU de Liege /ID# 148401	Liège	Liege
Belgium	CHU Ambroise Pare /ID# 152953	Mons
Belgium	Cliniques Universitaires Saint Luc /ID# 142858	Woluwe-Saint-Lambert	Bruxelles-Capitale
Bosnia and Herzegovina	University Clinical Centre of the Republic of Srpska /ID# 142862	Banja Luka	Republika Srpska
Bosnia and Herzegovina	University Clinical Centre of the Republic of Srpska /ID# 142863	Banja Luka	Republika Srpska
Bosnia and Herzegovina	Clinical Center University of Sarajevo /ID# 142865	Sarajevo
Brazil	Hc Ufmg /Id# 142868	Belo Horizonte	Minas Gerais
Brazil	Ceti - Centro de Estudos Em Terapias Inovadoras Ltda /Id# 142871	Curitiba	Parana
Brazil	CIP - Centro Internacional de Pesquisa /ID# 142872	Goiânia	Goias
Brazil	Hospital de Clinicas de Porto Alegre /ID# 142870	Porto Alegre	Rio Grande Do Sul
Brazil	LMK Sevicos Medicos S/S /ID# 142869	Porto Alegre	Rio Grande Do Sul
Brazil	CCBR Brasil /ID# 150918	Rio de Janeiro
Brazil	CEPIC - Centro Paulista de Investigação Clínica e Serviços Médicos Ltda /ID# 142867	São Paulo	Sao Paulo
Bulgaria	MHAT Kaspela /ID# 142873	Plovdiv
Bulgaria	MHAT Trimontsium /ID# 142874	Plovdiv
Bulgaria	UMHAT Pulmed OOD /ID# 142877	Plovdiv
Bulgaria	Diagnostic Consultative Center /ID# 142875	Sofia
Bulgaria	UMHAT Sv. Ivan Rilski /ID# 142876	Sofia
Canada	Adachi Medicine Prof. Corp /ID# 154205	Hamilton	Ontario
Canada	Groupe de Recherche en Maladies Osseuses /ID# 142878	Sainte-foy	Quebec
Canada	St. Clare's Mercy Hospital /ID# 142879	St. John's	Newfoundland and Labrador
Canada	CA Ctr for Clin Trials CCCT /ID# 157379	Thornhill	Ontario
Canada	Ciads /Id# 142880	Winnipeg	Manitoba
Canada	Manitoba Clinic /ID# 161434	Winnipeg	Manitoba
Chile	Reg. Clinical Hosptial Concepcion /ID# 151271	Concepcion
Chile	Corp de Beneficencia Osorno /ID# 147941	Osorno
Chile	Someal /Id# 144704	Providencia-santiago
Chile	Quantum Research LTDA. /ID# 142893	Puerto Varas
Chile	Centro Inter Estud Clin CIEC /ID# 144777	Santiago
Chile	Clinica DermaCross /ID# 142892	Santiago
Chile	Investigaciones Medicas SSMSO /ID# 151686	Santiago
Chile	Quantum Research Stgo. /ID# 157933	Santiago
Chile	Soc. de Prestaciones medicas y Paramedicas Goecke /ID# 142890	Santiago
Chile	Centro Medico de Reumatologia /ID# 148402	Temuco
Chile	Ctr de Inv Clinica del Sur /ID# 142888	Temuco	Araucania
Chile	Cinvec /Id# 144705	Vina Del Mar
Colombia	Ctr Int de Reum del Caribe SAS /ID# 142894	Barranquilla
Colombia	Centro de Investigacion en Reumatologia y Especialidades Medicas- CIREEM SAS /ID# 142898	Bogota	Cundinamarca
Colombia	Riesgo de Fractura S.A - CAYRE /ID# 142896	Bogota
Colombia	Fund Inst de Reum F. Chalem /ID# 149847	Bogota DC
Colombia	Medicity S.A.S. /ID# 144860	Bucaramanga
Colombia	Centro Integral de Reumatologi /ID# 142897	Medellín
Croatia	Klinicki bolnicki centar Rijeka /ID# 160232	Rijeka	Primorsko-goranska Zupanija
Croatia	Klinicki bolnicki centar Split /ID# 152530	Split
Croatia	Clinical Hospital Dubrava /ID# 142900	Zagreb
Croatia	Medical Center Kuna-Peric /ID# 142901	Zagreb
Croatia	Poliklinika Bonifarm /ID# 142899	Zagreb
Czechia	REVMACLINIC s.r.o. /ID# 142906	Brno
Czechia	Revmatologie Bruntal, s.r.o /ID# 142903	Bruntál
Czechia	L.K.N. Arthrocentrum, s.r.o /ID# 145961	Hlucín	Moravskoslezsky Kraj
Czechia	Revmatologicka a interni ambul /ID# 142907	Kladno
Czechia	CTCenter MaVe, s.r.o. /ID# 142905	Olomouc	Olomoucky Kraj
Czechia	Revmatologie MUDr. Klara Sirov /ID# 142908	Ostrava
Czechia	Arthromed, s.r.o. /ID# 144706	Pardubice
Czechia	Revmatologicky ustav Praha /ID# 142904	Prague 2	Praha 2
Czechia	Nuselská poliklinika, Revmatologie /ID# 144862	Prague 4	Praha 4
Czechia	Revmatologická ambulance /ID# 145963	Prague 4	Praha 4
Czechia	Thomayerova nemocnice /ID# 145962	Prague 4	Praha 4
Denmark	Aarhus University Hospital /ID# 158838	Aarhus N	Midtjylland
Denmark	Regionhospital Silkeborg /ID# 142914	Silkeborg
Estonia	Paernu Hospital /ID# 142921	Pärnu
Estonia	Center of Clinical and Basic Research /ID# 142922	Tallinn	Harjumaa
Estonia	East Tallinn Central Hospital /ID# 142923	Tallinn
Estonia	North Estonian Medical Centre /ID# 145454	Tallinn
Estonia	MediTrials /ID# 151870	Tartu	Tartumaa
France	CHU Bordeaux-Hopital Pellegrin /ID# 145618	Bordeaux
France	Hopital de la Cote de Nacre /ID# 145616	Caen
France	CHU Gabriel Montpied /ID# 145619	Clermont Ferrand
France	CHRU Lille - Hôpital Claude Huriez /ID# 151312	Lille CEDEX	Hauts-de-France
France	Hopital de la Conception /ID# 142926	Marseille
France	Hopital Saint Eloi /ID# 142925	Montpellier CEDEX 5	Herault
France	Hopital Pitie Salpetriere /ID# 145605	Paris
France	CHU de Rennes - Hospital Sud /ID# 151957	Rennes
France	CHU Strasbourg Hautepierre Hos /ID# 144708	Strasbourg
France	Hopital Universitaire Purpan /ID# 144707	Toulouse	Haute-Garonne
Germany	Med Versorgungszentrum AGILOME /ID# 154975	Chemnitz
Germany	Rheumaforschungszentrum II /ID# 142930	Hamburg
Germany	Rheumazentrum Ruhrgebiet /ID# 145620	Herne	Nordrhein-Westfalen
Germany	Uniklinik Koln /ID# 145964	Köln	Nordrhein-Westfalen
Germany	LMU Klinikum der Universität München /ID# 142931	Munich
Germany	Praxis Walter, Rendsburg /ID# 142932	Rendsburg	Schleswig-Holstein
Greece	General Hospital of Athens Ippokratio /ID# 142935	Athens
Greece	General Hospital of Athens Laiko /ID# 142934	Athens	Attiki
Greece	University General Hospital Attikon /ID# 142933	Athens	Attiki
Hong Kong	Queen Mary Hospital /ID# 142938	Hong Kong
Hong Kong	Tuen Mun Hospital /ID# 142939	Tuen Mun
Hungary	Budai Irgalmasrendi Korhaz /ID# 142952	Budapest
Hungary	Revita Reumatologiai Rendelo /ID# 142950	Budapest
Hungary	Synexus Magyarorszag Kft. /ID# 153061	Budapest
Hungary	Qualiclinic Kft. /ID# 142953	Budapest III	Pest
Hungary	Debreceni Egyetem Kenezy Gyula Egyetemi Korhaz /ID# 142948	Debrecen
Hungary	Hevizgyogyfurdo es Szent Andra /ID# 142949	Heviz
Hungary	Kiskunhalasi Semmelweis Korhaz /ID# 151944	Kiskunhalas
Hungary	Pest Megyei Flor Ferenc Korhaz /ID# 142954	Kistarcsa
Hungary	CRU Hungary Egeszsegugyi és Szolgaltato Kft. /ID# 142951	Miskolc	Borsod-Abauj-Zemplen
Hungary	Markusovszky Egyetemi Oktatókórház /ID# 145621	Szombathely	Vas
Hungary	Vital Medical Center Orvosi es /ID# 145950	Veszprém	Veszprem
Ireland	St Vincent's University Hosp /ID# 142957	Dublin
Israel	Bnai Zion Medical Center /ID# 151958	Haifa
Israel	Rambam Health Care Campus /ID# 152050	Haifa
Israel	The Lady Davis Carmel MC /ID# 142960	Haifa
Israel	Sheba Medical Center /ID# 145965	Ramat Gan
Israel	Tel Aviv Sourasky Medical Ctr /ID# 144709	Tel Aviv-Yafo	Tel-Aviv
Italy	Azienda Ospedaliera Luigi Sacc /ID# 142966	Milan
Italy	Istituto Clinico Humanitas /ID# 147528	Rozzano	Milano
Italy	AOU Citta della Salute Scienza /ID# 150070	Turin	Piemonte
Italy	A.O.U.I. di Verona Policlinico /ID# 142963	Verona
Kazakhstan	JSC Nat Scientific Med Res Ctr /ID# 142971	Astana
Kazakhstan	Karaganda State Medical Univ /ID# 153433	Karaganda
Kazakhstan	Semey State Medical University /ID# 152659	Semey
Kazakhstan	Regional Clinical Hospital /ID# 147168	Shymkent
Korea, Republic of	Daegu Catholic University Med /ID# 142973	Daegu
Korea, Republic of	Kyungpook National Univ Hosp /ID# 162073	Daegu	Daegu Gwang Yeogsi
Korea, Republic of	Chonnam National University Hospital /ID# 142975	Gwangju	Jeonranamdo
Korea, Republic of	Chungnam National University Hospital /ID# 142977	Jung-gu	Daejeon Gwang Yeogsi
Korea, Republic of	Inha University Hospital /ID# 150886	Jung-gu	Incheon Gwang Yeogsi
Korea, Republic of	Hanyang University Seoul Hospi /ID# 142979	Seongdong-gu	Seoul Teugbyeolsi
Korea, Republic of	Asan Medical Center /ID# 142974	Seoul
Korea, Republic of	Cath Univ Seoul St Mary's Hosp /ID# 142976	Seoul	Seoul Teugbyeolsi
Korea, Republic of	Seoul National University Hospital /ID# 142978	Seoul
Latvia	LTD M+M Centers /ID# 142984	Adazi
Latvia	Daugavpils Regional Hospital /ID# 142982	Daugavpils
Latvia	D.Saulites-Kandevicas PP /ID# 142985	Liepaja
Latvia	Clinic ORTO /ID# 142983	Riga
Latvia	Riga East Clinical Univ Hosp /ID# 142981	Riga
Lithuania	Hosp Lithuanian Univ Health Sc /ID# 142986	Kovno	Kaunas
Lithuania	Vilnius University Hospital /ID# 142987	Vilnius
Malaysia	Hospital Selayang /ID# 156756	Batu Caves
Malaysia	Hospital Raja Perempuan Zainab II /ID# 157862	Kota Bharu	Kelantan
Malaysia	Hospital Umum Sarawak /ID# 142990	Kuching
Malaysia	Hospital Putrajaya /ID# 142989	Putrajaya
Malaysia	Hospital Tuanku Ja afar /ID# 142988	Seremban
Mexico	Invest y Biomed de Chihuahua /ID# 142996	Chihuahua
Mexico	Clinstile, S.A. de C.V. /ID# 144866	Cuauhtemoc	Ciudad De Mexico
Mexico	Centro Peninsular de Investiga /ID# 148159	Mérida
Mexico	Hospital de Jesús Nazareno /ID# 142993	Mexico City
Mexico	RM Pharma Specialists, S.A de C.V /ID# 142994	Mexico City
Mexico	Hosp. Univ. Dr. Jose E. Gonz /ID# 142992	Monterrey	Nuevo Leon
New Zealand	Waikato Hospital /ID# 143002	Hamilton	Waikato
New Zealand	Porter Rheumatology Ltd /ID# 143001	Nelson
New Zealand	Timaru Medical Specialists Ltd /ID# 143000	Timaru
Poland	ClinicMed Badurski i wspolnicy SJ /ID# 163300	Bialystok
Poland	Osteo-Medic spolka cywilna /ID# 143006	Bialystok	Podlaskie
Poland	Malopolskie Centrum Kliniczne /ID# 152782	Cracow	Malopolskie
Poland	Synexus Polska Sp. z o.o. Oddz. Poznan /ID# 163293	Gdynia	Pomorskie
Poland	Synexus Polska Sp. z o.o. Oddz. Poznan /ID# 163294	Gdynia	Pomorskie
Poland	Synexus Polska Sp. z o.o. Oddz. Poznan /ID# 163295	Gdynia	Pomorskie
Poland	McBk Sc /Id# 143003	Grodzisk Mazowiecki	Mazowieckie
Poland	Silmedic Sp z o.o /ID# 152914	Katowice	Slaskie
Poland	Pratia MCM Krakow /ID# 143005	Krakow	Malopolskie
Poland	REUMED Sp.z o.o. Filia nr 1 /ID# 148189	Lublin	Lubelskie
Poland	Solumed Sp. zoo Cent Medyczne /ID# 152783	Poznan
Poland	NZOZ Nasz Lekarz /ID# 143004	Torun	Kujawsko-pomorskie
Poland	Rheuma Medicus /ID# 143007	Warsaw
Poland	Centralny Szpital Kliniczny MSWiA w Warszawie /ID# 151960	Warszawa	Mazowieckie
Poland	Centrum Medyczne AMED Warszawa Targowek /ID# 157621	Warszawa	Mazowieckie
Poland	WroMedica I. Bielicka, A. Strzalkowska s.c. /ID# 145622	Wroclaw	Dolnoslaskie
Portugal	CCA Braga - Hospital de Braga /ID# 148317	Braga
Portugal	Hospital CUF Descobertas /ID# 160539	Lisbon
Portugal	Instituto Portugues De Reumatologia /ID# 148316	Lisbon	Lisboa
Portugal	Centro Hospitalar de Sao Joao, EPE /ID# 152871	Porto
Portugal	Unidade Local De Saude Do Alto Minho /ID# 143009	Viana Do Castelo
Portugal	Centro Hospitalar De Vila Nova /ID# 143010	Vila Nova De Gaia	Porto
Puerto Rico	Ponce School of Medicine /ID# 151961	Ponce
Puerto Rico	GCM Medical Group /ID# 143011	San Juan
Romania	Spitalul Clinic Dr. I. Cantacuzino /ID# 143012	Bucharest	Bucuresti
Romania	Spitalul Clinic Dr. I. Cantacuzino /ID# 143017	Bucharest	Bucuresti
Romania	Spitalul Clinic Sf. Maria /ID# 144868	Bucuresti
Romania	Spitalul Clinic Sf. Maria /ID# 144869	Bucuresti
Romania	Spitalul Clinic Sf. Maria /ID# 145966	Bucuresti
Romania	Spitalul Clinic de Recuperare /ID# 144867	Iasi
Romania	Ecomed SRL /ID# 144870	Oradea
Russian Federation	?ity Clinical Hospital #4 /ID# 143023	Ivanovo
Russian Federation	Kazan State Medical University /ID# 144871	Kazan	Tatarstan, Respublika
Russian Federation	Family Outpatient clinic#4,LLC /ID# 148319	Korolev	Moskva
Russian Federation	City Clinical Hospital Botkina /ID# 145628	Moscow
Russian Federation	Clinical Hospital No.1 n.a. N.I.Pirogov /ID# 143138	Moscow	Moskva
Russian Federation	Moscow State Univ Med and Dent /ID# 145623	Moscow
Russian Federation	Russian National Research Medi /ID# 143028	Moscow
Russian Federation	City Clinical Hospital #5 /ID# 148318	Nizhnij Novgorod
Russian Federation	Orenburg State Medical Academy /ID# 143018	Orenburg
Russian Federation	Perm Clinical Center of FMBA /ID# 145627	Perm	Permskiy Kray
Russian Federation	LLC Novaya Klinika /ID# 143019	Pyatigorsk	Stavropol Skiy Kray
Russian Federation	Ryazan State Medical Universit /ID# 143031	Ryazan
Russian Federation	II Dzhan Research Center /ID# 143027	St. Petersburg
Russian Federation	NW State Med Univ NA Mechnikov /ID# 143022	St. Petersburg
Russian Federation	Tver Regional Clinical Hosp. /ID# 143026	Tver	Tverskaya Oblast
Russian Federation	Republican clinical hospital n /ID# 145626	UFA
Russian Federation	Ulyanovsk Regional Clin Hosp /ID# 143030	Ulyanovsk
Serbia	Institute for Rheumatology /ID# 143032	Belgrade	Beograd
Serbia	Institute for Rheumatology /ID# 143035	Belgrade	Beograd
Serbia	Institute for Rheumatology /ID# 143036	Belgrade	Beograd
Serbia	Institute for Rheumatology /ID# 143037	Belgrade	Beograd
Serbia	Clinical Center of Vojvodina /ID# 143033	Novi Sad	Vojvodina
Serbia	Special Hospital for Rheuma /ID# 143034	Novi Sad	Vojvodina
Slovakia	MEDMAN s.r.o. /ID# 143045	Martin
Slovakia	Reumatologická ambulancia Reum.hapi s.r.o. /ID# 147169	Nové Mesto Nad Váhom
Slovakia	REUMACENTRUM s.r.o. /ID# 143041	Partizanske
Slovakia	Slovak research center Team Member, Thermium s.r.o. /ID# 147614	Pieštany
Slovakia	Reumex, s.r.o. /ID# 143043	Rimavska Sobota
Slovakia	Reumatologicka ambulancia /ID# 144873	Sabinov
Slovakia	TIMMED spol. s r.o. /ID# 144872	Stará Lubovna
Slovakia	Reumatologicka ambulancia, LER /ID# 143044	Topolcany
Slovakia	ALBAMED s.r.o. /ID# 143042	Zvolen
South Africa	Arthritis Clinical Research Tr /ID# 144874	Cape Town	Western Cape
South Africa	Synexus Helderberg Clinical Tr /ID# 148322	Cape Town	Western Cape
South Africa	Tiervlei Trial Centre /ID# 153085	Cape Town	Western Cape
South Africa	St. Augustine's Hospital /ID# 143047	Durban	Kwazulu-Natal
South Africa	Wits Clinical Research Site /ID# 148320	Johannesburg	Gauteng
South Africa	Greenacres Hospital /ID# 144710	Port Elizabeth	Eastern Cape
South Africa	Jakaranda Hosp, Emmed Research /ID# 143046	Pretoria	Gauteng
South Africa	Jakaranda Hosp, Emmed Research /ID# 145968	Pretoria	Gauteng
South Africa	University of Pretoria /ID# 148353	Pretoria	Gauteng
South Africa	Winelands Medical Research Ctr /ID# 143048	Stellenbosch	Western Cape
Spain	Comple Hosp Univ de A Coruna /ID# 143051	A Coruna
Spain	Hospital Universitario Reina S /ID# 153566	Cordoba
Spain	H. Un. Marques de Valdecilla /ID# 143050	Santander	Cantabria
Spain	Clinica Gaias /ID# 143052	Santiago de Compostela
Spain	Complejo Hosp Santiago /ID# 153727	Santiago de Compostela
Taiwan	Kaohsiung Chang Gung Memorial Hospital /ID# 143055	Kaohsiung
Taiwan	Kaohsiung Medical University /ID# 143059	Kaohsiung
Taiwan	Far Eastern Memorial Hospital /ID# 143061	New Taipei City
Taiwan	China Medical University Hosp /ID# 143058	Taichung City	Taichung
Taiwan	Chung Shan Medical University /ID# 143060	Taichung City
Taiwan	National Taiwan Univ Hosp /ID# 143056	Taipei City	Taipei
Taiwan	Taipei Veterans General Hosp /ID# 157940	Taipei City
Taiwan	Linkou Chang Gung Memorial Ho /ID# 143057	Taoyuan City
Turkey	Istanbul Universitesi Cerrahpa /ID# 156088	Cerrahpasa
Turkey	Istanbul Fizik Tedavi Rehabilitasyon Egitim ve Arastirma Hastanesi /ID# 143063	Istanbul
Turkey	Izmir Katip Celebi Ataturk Training & Research Hospital /ID# 143062	Izmir
Ukraine	Regional Clinical Hospital /ID# 152025	Ivano-frankivsk
Ukraine	LLC Revmocentr /ID# 143067	Kiev	Kyiv
Ukraine	NSC-Strazhesko Ist Cardiology /ID# 152030	Kiev
Ukraine	Lviv Municipal City Clinical /ID# 143068	Lviv
Ukraine	Lviv Regional Clinical Hospita /ID# 154450	Lviv	Lvivska Oblast
Ukraine	Odessa National Medical Univ /ID# 143072	Odesa
Ukraine	Vinnytsia Regional Clinical Hospital n.a. M.I.Pyrogov /ID# 143071	Vinnytsia	Vinnytska Oblast
Ukraine	Zaporizhzhia Regional Clinical /ID# 143069	Zaporizhia
United Kingdom	The Royal Free Hospital /ID# 143074	London	London, City Of
United Kingdom	Queen Alexandra Hospital /ID# 143077	Portsmouth
United Kingdom	Warrington + Halton Hosp NHS /ID# 143075	Warrington
United States	Albuquerque Clinical Trials, Inc /ID# 143083	Albuquerque	New Mexico
United States	Arthritis Clinic of N. VA, P.C /ID# 143109	Arlington	Virginia
United States	Arthritis and Rheumatology /ID# 155668	Atlanta	Georgia
United States	Austin Regional Clinic /ID# 143084	Austin	Texas
United States	AARDS Research, Inc. /ID# 154190	Aventura	Florida
United States	Diagnostic Group Integrated He /ID# 148356	Beaumont	Texas
United States	Osteoporosis Medical Center /ID# 153935	Beverly Hills	California
United States	Achieve Clinical Research, LLC /ID# 143136	Birmingham	Alabama
United States	ZASA Clinical Research /ID# 143134	Boynton Beach	Florida
United States	DJL Clinical Research, PLLC /ID# 143101	Charlotte	North Carolina
United States	Joint & Muscle Research Instit /ID# 143119	Charlotte	North Carolina
United States	Ctr for Arth and Rheum Disease /ID# 143113	Chesapeake	Virginia
United States	Great Lakes Clinical Trials /ID# 148357	Chicago	Illinois
United States	Clinical Res of West FL, Inc. /ID# 143112	Clearwater	Florida
United States	Arthritis Assoc & Osteo Ctr /ID# 143122	Colorado Springs	Colorado
United States	Columbia Arthritis Center /ID# 153730	Columbia	South Carolina
United States	Arthritis Care and Diagnostic /ID# 150677	Dallas	Texas
United States	Metroplex Clinical Research /ID# 145631	Dallas	Texas
United States	Clinical Research Solutions, LLC /ID# 154619	Dayton	Ohio
United States	International Medical Research /ID# 143132	Daytona Beach	Florida
United States	St. Luke's Hospital /ID# 156750	Duluth	Minnesota
United States	Altoona Ctr Clinical Res /ID# 143110	Duncansville	Pennsylvania
United States	EmergeOrtho, P.A. /ID# 143100	Durham	North Carolina
United States	Doctor's Hosp at Renaissance /ID# 154616	Edinburg	Texas
United States	MedResearch Inc. /ID# 154618	El Paso	Texas
United States	T. Joseph Raoof, MD, Inc. /ID# 144884	Encino	California
United States	Rheumatology Ctr of San Diego /ID# 153747	Escondido	California
United States	Arthritis and Rheum Clin N. CO /ID# 156094	Fort Collins	Colorado
United States	Rheumatology and Immunotherapy Center /ID# 145646	Franklin	Wisconsin
United States	Arthritis Treatment Center /ID# 155260	Frederick	Maryland
United States	Arthritis Center of North GA /ID# 155258	Gainesville	Georgia
United States	Innovative Clinical Research /ID# 145637	Greenville	South Carolina
United States	C.V. Mehta MD, Med Corporation /ID# 143116	Hemet	California
United States	Accurate Clinical Management /ID# 145644	Houston	Texas
United States	Accurate Clinical Research /ID# 145645	Houston	Texas
United States	Houston Institute for Clin Res /ID# 144879	Houston	Texas
United States	Pioneer Research Solutions, Inc. /ID# 145640	Houston	Texas
United States	Rheumatology Clinic of Houston /ID# 150921	Houston	Texas
United States	Arthritis Consultants, P.A. /ID# 144880	Killeen	Texas
United States	Arthritis Associates, PLLC /ID# 155490	Kingsport	Tennessee
United States	Rheumatology Consultants, PLLC /ID# 153731	Knoxville	Tennessee
United States	Allergy and Rheum Med Clin /ID# 146083	La Jolla	California
United States	Kotha and Kotha /ID# 161046	La Mesa	California
United States	TriWest Research Associates- La Mesa /ID# 143115	La Mesa	California
United States	Advanced Rheumatology, PC /ID# 143118	Lansing	Michigan
United States	Arthritis and Osteo Assoc /ID# 143127	Las Cruces	New Mexico
United States	North Georgia Rheumatology Grp /ID# 147170	Lawrenceville	Georgia
United States	Cape Fear Arthritis Care /ID# 148361	Leland	North Carolina
United States	Physician Res. Collaboration /ID# 143087	Lincoln	Nebraska
United States	Valerius Med Grp & Res Ctr /ID# 143120	Los Alamitos	California
United States	Discovery MM Services, Inc /ID# 163504	Los Angeles	California
United States	Arthritis & Osteoporosis Assoc /ID# 147364	Lubbock	Texas
United States	P&I Clinical Research /ID# 161625	Lufkin	Texas
United States	Dr. Ramesh Gupta /ID# 143099	Memphis	Tennessee
United States	Advanced Clinical Research /ID# 153090	Meridian	Idaho
United States	AZ Arthritis and Rheum Assoc /ID# 143130	Mesa	Arizona
United States	SW Rheumatology Res. LLC /ID# 143126	Mesquite	Texas
United States	Ctr Arthritis & Rheumatic Dise /ID# 143135	Miami	Florida
United States	FL Med Ctr and Research, Inc. /ID# 143081	Miami	Florida
United States	Lakes Research, LLC /ID# 145630	Miami	Florida
United States	Precision Research Org, LLC /ID# 143092	Miami Lakes	Florida
United States	Discovery MM Services, Inc. /ID# 162578	Missouri City	Texas
United States	Discovery MM Services, Inc. /ID# 163183	Missouri City	Texas
United States	Discovery MM Services, Inc. /ID# 163184	Missouri City	Texas
United States	Coastal Carolina Health Care /ID# 148359	New Bern	North Carolina
United States	Advanced Clin Res of Orlando /ID# 154617	Ocoee	Florida
United States	Quality Clinical Research Inc. /ID# 156394	Omaha	Nebraska
United States	HMD Research LLC /ID# 163292	Orlando	Florida
United States	Omega Research Consultants /ID# 145635	Orlando	Florida
United States	Rheum Assoc of Central FL /ID# 145632	Orlando	Florida
United States	Desert Medical Advances /ID# 143097	Palm Desert	California
United States	Arthritis Center, Inc. /ID# 145647	Palm Harbor	Florida
United States	Arthritis Research of Florida /ID# 143125	Palm Harbor	Florida
United States	SunValley Arthritis Center, Lt /ID# 143123	Peoria	Arizona
United States	Arizona Research Center, Inc. /ID# 144877	Phoenix	Arizona
United States	AZ Arthritis & Rheuma Research /ID# 143131	Phoenix	Arizona
United States	AZ Arthritis and Rheum Researc /ID# 143080	Phoenix	Arizona
United States	AZ Arthritis and Rheum Researc /ID# 143121	Phoenix	Arizona
United States	Elite Clinical Studies, LLC /ID# 144881	Phoenix	Arizona
United States	St. Lawrence Health System /ID# 161619	Potsdam	New York
United States	Shanahan Rheuma & Immuno /ID# 145643	Raleigh	North Carolina
United States	Sierra Rheumatology /ID# 155672	Roseville	California
United States	Shores Rheumatology, PC /ID# 162977	Saint Clair Shores	Michigan
United States	St. Anthony Comprehsve Res Ins /ID# 143095	Saint Petersburg	Florida
United States	Accurate Clinical Management /ID# 143089	San Antonio	Texas
United States	Arthritis & Osteo Ctr of S. TX /ID# 143103	San Antonio	Texas
United States	Sun Research Institute /ID# 159539	San Antonio	Texas
United States	West Virginia Research Inst /ID# 153088	South Charleston	West Virginia
United States	Arthritis Northwest, PLLC /ID# 143088	Spokane	Washington
United States	Articularis Healthcare Group, Inc d/b/a Low Country Rheumatology /ID# 143091	Summerville	South Carolina
United States	AZ Arthritis & Rheum Research /ID# 156093	Sun City	Arizona
United States	BayCare Medical Group, Inc. /ID# 143085	Tampa	Florida
United States	Clinical Research West FL /ID# 148358	Tampa	Florida
United States	SW FL Clin Res Ctr, Tampa, FL /ID# 143117	Tampa	Florida
United States	Arthritis Assoc of NW Ohio /ID# 143094	Toledo	Ohio
United States	DM Clinical Research /ID# 151357	Tomball	Texas
United States	Atlantic Coast Research /ID# 148355	Toms River	New Jersey
United States	Ocean Rheumatology, PA /ID# 143111	Toms River	New Jersey
United States	University of Arizona Cancer Center - North Campus /ID# 143114	Tucson	Arizona
United States	Healthcare Research Consultant /ID# 143129	Tulsa	Oklahoma
United States	North Mississippi Med Clinics /ID# 145636	Tupelo	Mississippi
United States	Robin K. Dore MD, Inc /ID# 143090	Tustin	California
United States	The Vancouver Clinic, INC. PS /ID# 143107	Vancouver	Washington
United States	Lovelace Scientific Resources /ID# 143106	Venice	Florida
United States	Arthritis Rheumatic Back Disorder /ID# 143102	Voorhees	New Jersey
United States	The Center for Rheumatology & /ID# 151356	Wheaton	Maryland
United States	Medvin Clinical Research /ID# 148362	Whittier	California
United States	Clinical Pharmacology Study Gr /ID# 143082	Worcester	Massachusetts
United States	Clinical Research Ctr Reading /ID# 143133	Wyomissing	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belarus,  Belgium,  Bosnia and Herzegovina,  Brazil,  Bulgaria,  Canada,  Chile,  Colombia,  Croatia,  Czechia,  Denmark,  Estonia,  France,  Germany,  Greece,  Hong Kong,  Hungary,  Ireland,  Israel,  Italy,  Kazakhstan,  Korea, Republic of,  Latvia,  Lithuania,  Malaysia,  Mexico,  New Zealand,  Poland,  Portugal,  Puerto Rico,  Romania,  Russian Federation,  Serbia,  Slovakia,  South Africa,  Spain,  Taiwan,  Turkey,  Ukraine,  United Kingdom, 

References & Publications (1)

Fleischmann R, Pangan AL, Song IH, Mysler E, Bessette L, Peterfy C, Durez P, Ostor AJ, Li Y, Zhou Y, Othman AA, Genovese MC. Upadacitinib Versus Placebo or Adalimumab in Patients With Rheumatoid Arthritis and an Inadequate Response to Methotrexate: Results of a Phase III, Double-Blind, Randomized Controlled Trial. Arthritis Rheumatol. 2019 Nov;71(11):1788-1800. doi: 10.1002/art.41032. Epub 2019 Aug 28. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12	The primary endpoint for United States (US)/Food and Drug Administration (FDA) regulatory purposes was ACR 20% response (ACR20) at Week 12. Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR20 response criteria: = 20% improvement in 68-tender joint count; = 20% improvement in 66-swollen joint count; and; = 20% improvement in at least 3 of the 5 following parameters: Physician global assessment of disease 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 12	The primary endpoint for European Union (EU)/European Medicines Agency (EMA) regulatory purposes was clinical remission, based on a Disease Activity Score 28 (DAS28)-CRP score of < 2.6 at Week 12.; The DAS28 is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity.; A DAS28 score less than 2.6 indicates clinical remission.	Week 12
Secondary	Change From Baseline in DAS28 (CRP) at Week 12	The DAS28 is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity. A negative change from Baseline in DAS28 (CRP) indicates improvement in disease activity.	Baseline and Week 12
Secondary	Change From Baseline in Modified Total Sharp Score (mTSS) at Week 26	The mTSS measures the level of joint damage from radiographs of the hands and feet, assessed by 2 independent, blinded readers. mTSS is calculated as the sum of the total joint erosion score and total joint space narrowing (JSN) score.; Joint erosion severity was assessed in 16 joints in each hand and wrist and 6 joints in each foot. Each joint was scored from 0 (no erosion) to 5 for hands/wrists or to 10 for feet (complete collapse). The total erosion score ranges from 0 to 280 (worst).; JSN was assessed in 15 joints of each hand and wrist, and 6 joints of each foot, including subluxation, from 0 (normal) to 4 (complete loss of joint space, bony ankylosis, or luxation). The total JSN score ranges from 0 to 168 (worst).; The mTSS is the sum of the joint erosion and JSN scores and ranges from 0 (normal) to 448 (worst). A negative change from Baseline in mTSS indicates improvement in joint damage whereas a change from Baseline greater than 0 indicates progression.	Baseline and Week 26
Secondary	Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12	The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire that measures the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and errands and chores) over the past week. Participants assessed their ability to do each task on a scale from 0 (without any difficulty) to 3 (unable to do). Scores were averaged to provide an overall score ranging from 0 to 3, where 0 represents no disability and 3 represents very severe, high-dependency disability.; A negative change from Baseline in the overall score indicates improvement.	Baseline and Week 12
Secondary	Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12	Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR50 response criteria: = 50% improvement in 68-tender joint count; = 50% improvement in 66-swollen joint count; and; = 50% improvement in at least 3 of the 5 following parameters: Physician global assessment of disease 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 Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 12	The Short Form 36-Item Health Survey (SF-36) Version 2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health).; The physical component score is a weighted combination of the 8 subscales with positive weighting for physical functioning, role-physical, bodily pain, and general health. The PCS was calculated using norm-based scoring so that 50 is the average score and the standard deviation equals 10. Higher scores are associated with better functioning/quality of life; a positive change from baseline score indicates an improvement.	Baseline and Week 12
Secondary	Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 12	The DAS28(CRP) is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity.; A DAS28(CRP) score less than or equal to 3.2 indicates low disease activity.	Week 12
Secondary	Percentage of Participants Achieving Low Disease Activity Based on CDAI at Week 12	Low disease activity based on the clinical disease activity index (CDAI) is defined as a CDAI score = 10.; CDAI is a composite index for assessing disease activity based on the summation of the total tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), patient global assessment of disease activity measured on a VAS from 0 to 10 cm, and physician global assessment of disease activity measured on a VAS from 0 to 10 cm. The total CDAI score ranges from 0 to 78 with higher scores indicating higher disease activity.	Week 12
Secondary	Change From Baseline in Duration of Morning Stiffness at Week 12	Participants were asked to indicate the time it took for them to get as limber as possible after awakening with morning stiffness over the past 7 days. A negative change from Baseline indicates improvement.	Baseline and Week 12
Secondary	Change From Baseline in in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F)	The FACIT Fatigue scale is a 13-item tool that measures an individual's level of fatigue during their usual daily activities over the past 7 days. Each of the fatigue and impact of fatigue items are measured on a four point Likert scale. The FACIT Fatigue Scale is the sum of the individual 13 scores and ranges from 0 to 52 where higher scores indicate better the quality of life. A positive change from Baseline indicates improvement.	Baseline and Week 12
Secondary	Change From Baseline in Patient's Assessment of Pain at Week 12	Participants were asked to indicate the severity of their arthritis pain within the previous week on a visual analog scale (VAS) from 0 to 100. A score of 0 indicates "no pain" and a score of 100 indicates "worst possible pain." A negative change from Baseline indicates improvement.	Baseline and Week 12
Secondary	Percentage of Participants With No Radiographic Progression at Week 26	No radiographic progression is defined as a change from Baseline in mTSS = 0. The mTSS measures the level of joint damage from radiographs of the hands and feet, which were assessed by 2 independent, blinded readers. mTSS is calculated as the sum of the total joint erosion score and total joint space narrowing (JSN) score and ranges from 0 (normal) to 448 (worst).; Joint erosion severity was assessed in 16 joints in each hand and wrist and 6 joints in each foot. Each joint was scored from 0 (no erosion) to 5 for hands/wrists or to 10 for feet (complete collapse). The total erosion score ranges from 0 to 280 (worst).; Joint space narrowing (JSN) was assessed in 15 joints of each hand and wrist, and 6 joints of each foot, including subluxation, from 0 (normal) to 4 (complete loss of joint space, bony ankylosis, or luxation). The total JSN score ranges from 0 to 168 (worst).	Baseline and Week 26
Secondary	Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 12	Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR70 response criteria: = 70% improvement in 68-tender joint count; = 70% improvement in 66-swollen joint count; and; = 70% improvement in at least 3 of the 5 following parameters: Physician global assessment of disease 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

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