A Phase 3 Study to Compare Upadacitinib to Abatacept in Subjects With Rheumatoid Arthritis on Stable Dose of Conventional Synthetic Disease- Modifying Antirheumatic Drugs (csDMARDs) Who Have an Inadequate Response or Intolerance to Biologic DMARDs

Rheumatoid Arthritis (RA) Clinical Trial

Official title:

A Phase 3, Randomized, Active-Controlled, Double-Blind Study Comparing Upadacitinib (ABT-494) to Abatacept in Subjects With Moderately to Severely Active Rheumatoid Arthritis With Inadequate Response or Intolerance to Biologic DMARDs (bDMARDs) on Stable Conventional Synthetic Disease Modifying Anti-Rheumatic Drugs (csDMARDs)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03086343
• Other study ID #: M15-925
• Secondary ID: 2016-000933-37
• Status: Completed
• Phase: Phase 3
• Start date: May 9, 2017
• Est. completion date: June 6, 2023

Study information

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

Clinical Trial Summary

The study objective of Period 1 was to compare the safety and efficacy of upadacitinib 15 mg once daily (QD) to abatacept on a background of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) for the treatment of signs and symptoms of rheumatoid arthritis (RA) in biologic disease-modifying antirheumatic drug (bDMARD)-inadequate response or bDMARD-intolerant participants with moderately to severely active RA. The study objective of Period 2 is to evaluate the long-term safety, tolerability, and efficacy of upadacitinib 15 mg QD in participants with RA who had completed Period 1.

Description:

This is a Phase 3 multicenter study with 2 periods. Period 1 was a 24-week, randomized, double-blind, parallel-group, active-controlled period designed to compare the safety and efficacy of upadacitinib 15 mg and abatacept for the treatment of signs and symptoms of participants with moderately to severely active rheumatoid RA who had an inadequate response to or intolerance to bDMARD therapy and were currently on a stable dose of csDMARD(s) and had never received abatacept. Period 2 is an open-label, long-term extension study to evaluate the long-term safety, tolerability, and efficacy of upadacitinib 15 mg once a day (QD) in participants with RA who had completed Period 1.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 613
• Est. completion date: June 6, 2023
• Est. primary completion date: June 13, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Main Inclusion Criteria:

• Diagnosis of rheumatoid arthritis (RA) for = 3 months who also fulfill the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for RA
• Participants have been treated for = 3 months prior to the screening visit with = 1 bDMARD therapy, but continue to exhibit active RA or had to discontinue due to intolerability or toxicity, irrespective of treatment duration and have never received abatacept prior to the first dose of study drug
• Participants have been receiving csDMARD therapy = 3 months and on a stable dose for = 4 weeks prior to the first dose of study drug. The following csDMARDs are allowed: methotrexate (MTX), sulfasalazine, hydroxychloroquine, chloroquine, and leflunomide. A combination of up to two background csDMARDs is allowed except the combination of MTX and leflunomide
• Meets the following criteria: = 6 swollen joints (based on 66 joint counts) and = 6 tender joints (based on 68 joint counts) at Screening and Baseline Visits and high-sensitivity C-reactive protein (hsCRP) = 3 mg/L at Screening

Main Exclusion Criteria:

• Prior exposure to any Janus kinase (JAK) inhibitor (including but not limited to upadacitinib, tofacitinib, baricitinib and filgotinib)
• Prior exposure to abatacept
• History of any arthritis with onset prior to age 17 years or current diagnosis of inflammatory joint disease other than RA. Current diagnosis of secondary Sjogren's Syndrome is permitted
• Laboratory values meeting the following criteria within the Screening period prior to the first dose of study drug: serum aspartate transaminase > 2 × upper limit of normal (ULN); serum alanine transaminase > 2 × ULN; estimated glomerular filtration rate by simplified 4-variable Modification of Diet in Renal Disease formula < 40 mL/minute/1.73 meter (m)^2; total white blood cell count < 2,500/ µL; absolute neutrophil count < 1,500/µL; platelet count < 100,000/µL; absolute lymphocyte count < 800/µL; and hemoglobin < 10 g/dL

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis (RA)

Intervention

Drug:
• Abatacept
IV infusion
• Placebo for abatacept
IV infusion
• Upadacitinib
15 mg extended release tablet
• Placebo for upadacitinib
Film-coated tablet

Locations

Country	Name	City	State
Argentina	Atencion Integral en Reuma /ID# 155696	Buenos Aires
Argentina	Ctr Privado Med Familiar /ID# 158814	Buenos Aires
Argentina	Hospital General de Agudos /ID# 167117	Buenos Aires
Argentina	Inst. de Rehab. Psicofisica /ID# 167768	Caba
Argentina	Aprillus Asistencia e Investig /ID# 159173	Capital Federal	Buenos Aires
Argentina	Inst. Rheumatologic Strusberg /ID# 159021	Cordoba
Argentina	Instituto Medico DAMIC /ID# 167770	Cordoba
Argentina	DIM Clinica Privada /ID# 167769	Ramos Mejía
Argentina	Instituto CAICI SRL /ID# 159022	Rosario, Santa FE
Australia	Western Health Footscray Hospi /ID# 157968	Footscray	Victoria
Australia	Rheumatology Research Unit /ID# 159174	Maroochydore	Queensland
Australia	The Queen Elizabeth Hospital /ID# 159175	Woodville	South Australia
Belgium	CHU UCL Namur /ID# 157628	Namur
Brazil	Santa Casa de Belo Horizonte /ID# 154631	Belo Horizonte	Minas Gerais
Brazil	Ceti - Centro de Estudos Em Terapias Inovadoras Ltda /Id# 154634	Curitiba	Parana
Brazil	CMiP - Centro Mineiro de Pesquisa Ltda - ME /ID# 154564	Juiz de Fora	Minas Gerais
Brazil	Hospital de Clinicas de Porto Alegre /ID# 161211	Porto Alegre	Rio Grande Do Sul
Brazil	LMK Sevicos Medicos S/S /ID# 159176	Porto Alegre	Rio Grande Do Sul
Brazil	CEMEC - Centro Multidisciplinar de Estudos Clínicos /ID# 154632	Santo André	Sao Paulo
Brazil	CEPIC - Centro Paulista de Investigação Clínica e Serviços Médicos Ltda /ID# 159587	São Paulo	Sao Paulo
Brazil	CEDOES-Centro de Diagnóstico e Pesquisa da Osteoporose do Espírito Santo LTDA /ID# 155228	Vitoria	Espirito Santo
Bulgaria	MHAT Trimontsium /ID# 155226	Plovdiv
Bulgaria	Diag Consult Ctr 17 Sofia EOOD /ID# 169298	Sofia
Bulgaria	Medical Centre Synexus Sofia /ID# 201807	Sofia
Bulgaria	UMHAT Sv. Ivan Rilski /ID# 155000	Sofia
Canada	The Waterside Clinic /ID# 159178	Barrie	Ontario
Canada	Adachi Medicine Prof. Corp /ID# 158024	Hamilton	Ontario
Canada	Institut de Rhum. de Montreal /ID# 155001	Montreal	Quebec
Canada	Groupe de Recherche en Maladies Osseuses /ID# 154601	Sainte-foy	Quebec
Czechia	Revmatologicky ustav Praha /ID# 154612	Prague 2	Praha 2
Czechia	Medical Plus, s.r.o. /ID# 155230	Uherské Hradište
Germany	Praxis fuer Rheumatologie /ID# 156156	Berlin
Germany	Rheumaforschungszentrum II /ID# 157177	Hamburg
Germany	Uniklinik Koln /ID# 156047	Köln	Nordrhein-Westfalen
Germany	Welcker, Planegg, DE /ID# 160185	Planegg
Greece	University General Hospital of Heraklion "PA.G.N.I" /ID# 163916	Heraklion
Hungary	Budai Irgalmasrendi Korhaz /ID# 154457	Budapest
Hungary	Obudai Egeszsegugyi Centrum Kft. /ID# 156159	Budapest
Hungary	Debreceni Egyetem Kenezy Gyula Egyetemi Korhaz /ID# 159183	Debrecen
Hungary	Markhot Ferenc Oktatokorhaz es Rendelointezet /ID# 159689	Eger
Hungary	MAV Korhaz ess Rendelointezet /ID# 154455	Szolnok
Ireland	Our Lady's Hospital /ID# 161149	Manorhamilton
Israel	Barzilai Medical Center /ID# 161685	Ashkelon
Israel	The Lady Davis Carmel MC /ID# 161686	Haifa
Israel	Meir Medical Center /ID# 162774	Kfar Saba
Israel	Sheba Medical Center /ID# 163154	Ramat Gan
Italy	A.O. Univ. Ospedali Riuniti /ID# 161707	Ancona	Marche
Italy	Azienda Ospedaliero Universitaria Policlinico Vittorio Emanuele /ID# 161172	Catania
Italy	ASST G. Pini /ID# 162223	Milan
Italy	Presidio Columbus, Fondazione Policlinico Gemelli Universita Cattolica S. Cuore /ID# 162252	Rome	Roma
Italy	Istituto Clinico Humanitas /ID# 154999	Rozzano	Milano
Italy	AOU Citta della Salute Scienza /ID# 154577	Turin	Piemonte
Korea, Republic of	Asan Medical Center /ID# 154639	Seoul
Korea, Republic of	SMG-SNU Boramae Medical Center /ID# 155788	Seoul	Seoul Teugbyeolsi
Korea, Republic of	The Catholic University of Korea, Yeouido St. Mary's Hospital /ID# 155231	Seoul	Seoul Teugbyeolsi
Latvia	D.Saulites-Kandevicas PP /ID# 154578	Liepaja
Latvia	Riga East Clinical Univ Hosp /ID# 155024	Riga
Mexico	Centro Integral en Reumatología S.A de C.V /ID# 204493	Guadalajara	Jalisco
Mexico	Morales Vargas Centro de Investigacion S.C. /ID# 200800	Leon	Guanajuato
Mexico	Centro Especializado en Diabetes, Obesidad y Prevención de Enfermedades Cardiova /ID# 160126	Mexico City
Mexico	CINTRE, Centro de Investigación y Tratamiento Reumatológico SC /ID# 154579	Mexico City	Ciudad De Mexico
Mexico	RM Pharma Specialists S.A de C.V /ID# 159588	Mexico City
Netherlands	Reade /ID# 161002	Amsterdam
Netherlands	Spaarne Gasthuis /ID# 161003	Haarlem
Netherlands	Medisch Centrum Leeuwarden /ID# 156043	Leeuwarden
Netherlands	Antonius Ziekenhuis /ID# 155737	Sneek	Fryslan
New Zealand	Timaru Medical Specialists Ltd /ID# 159184	Timaru
New Zealand	Wellington Hospital (Capital and Coast District Health Board) /ID# 154591	Wellington
Poland	ClinicMed Daniluk, Nowak Sp.j. /ID# 202998	Bialystok	Podlaskie
Poland	Gabinet Internistyczno Reum. /ID# 157433	Bialystok	Podlaskie
Poland	Malopolskie Centrum Kliniczne /ID# 157180	Cracow	Malopolskie
Poland	Synexus Polska Sp. z o.o. Oddzial w Gdyni /ID# 202472	Gdynia	Pomorskie
Poland	Centrum Med Amed Oddzial Lodzi /ID# 154458	Lodz
Poland	Salve Medica Sp. z o.o. S.K. /ID# 202473	Lodz	Lodzkie
Poland	Medyczne Centrum Hetmanska /ID# 155746	Poznan	Wielkopolskie
Poland	Centrum Medyczne AMED Warszawa Targowek /ID# 159589	Warszawa	Mazowieckie
Portugal	Hospital Garcia de Orta, E.P.E /ID# 164056	Almada	Setubal
Portugal	Centro Hospitalar Lisboa Norte, EPE /ID# 200037	Lisboa
Portugal	Centro Hospitalar Lisboa Ocidental, EPE /ID# 200035	Lisbon	Lisboa
Portugal	Instituto Portugues De Reumatologia /ID# 155698	Lisbon	Lisboa
Portugal	Unidade Local De Saude Do Alto Minho /ID# 200036	Viana Do Castelo
Portugal	Centro Hosp de Tondela-Viseu /ID# 155699	Viseu
Puerto Rico	Dr. Ramon L. Ortega-Colon, MD /ID# 158097	Carolina
Puerto Rico	GCM Medical Group /ID# 156158	San Juan
Romania	Spitalul Clinic Dr. I. Cantacuzino /ID# 155893	Bucharest	Bucuresti
Romania	Spitalul Clinic Sf. Maria /ID# 167245	Bucuresti
Russian Federation	Alliance Biomedical Ural Group /ID# 154609	Izhevsk	Udmurtskaya Respublika
Russian Federation	Family Outpatient clinic#4 LLC /ID# 203524	Korolev	Moskva
Russian Federation	State Budget Healthcare Instit /ID# 154593	Moscow
Russian Federation	LLC Medical Center /ID# 203523	Novosibirsk	Novosibirskaya Oblast
Russian Federation	Nort-Western State Medical Uni /ID# 154610	St. Petersburg
Slovakia	Novamed,spol.s.r.o. /ID# 157928	Banska Bystrica
Slovakia	Univerzitna Nemocnica Bratislava /ID# 161143	Bratislava
Slovakia	Narodny ustav reumatickych chorob Piestany /ID# 156864	Pieštany
Spain	Hospital Universitario Reina S /ID# 155701	Cordoba
Spain	Hospital General Univ de Elche /ID# 158825	Elche
Spain	Hospital Universitario La Paz /ID# 163636	Madrid
Spain	Corp Sanitaria Parc Tauli /ID# 163634	Sabadell, Barcelona
Spain	Complejo Hospitalario /ID# 155700	Santiago de Compostela
Spain	Hospital Infanta Luisa /ID# 154641	Sevilla
Sweden	Sahlgrenska University Hosp /ID# 162775	Goteborg
Sweden	Skanes Universitetssjukhus /ID# 165133	Malmö	Skane Lan
Sweden	Akademiskt specialistcentrum Centrum for reumatologi /ID# 156046	Stockholm	Stockholms Lan
Sweden	Vastmanlands Sjukhus /ID# 159186	Vasteras
Switzerland	University Hospital of Basel /ID# 160860	Basel
Switzerland	HFR Fribourg - Hopital Canton /ID# 160970	Fribourg
Switzerland	Hopitaux Universitaires de Geneve /ID# 159083	Genève	Geneve
Switzerland	Kantonsspital St. Gallen /ID# 155232	St. Gallen	Sankt Gallen
Turkey	Ankara Univ Medical Faculty /ID# 162691	Ankara
Turkey	Hacettepe University Medical Faculty /ID# 167995	Ankara
Turkey	Akdeniz University Faculty /ID# 163153	Antalya
Turkey	Istanbul Fizik Tedavi Rehabilitasyon Egitim ve Arastirma Hastanesi /ID# 169479	Istanbul
United Kingdom	Ninewells Hospital /ID# 156050	Dundee
United Kingdom	Whipps Cross Univ Hospital /ID# 205985	London	London, City Of
United Kingdom	Altnagelvin Area Hospital /ID# 156540	Londonderry
United Kingdom	Lancashire Care NHS Foundation /ID# 156042	Preston
United Kingdom	Royal Cornwall Hospital /ID# 157785	Truro
United States	The Center for Rheumatology /ID# 162979	Albany	New York
United States	Ochsner Clinic Foundation /ID# 154585	Baton Rouge	Louisiana
United States	East Penn Rheumatology Assoc /ID# 159193	Bethlehem	Pennsylvania
United States	PMG Research of Christie Clini /ID# 154569	Champaign	Illinois
United States	Clinical Res of West FL, Inc. /ID# 154576	Clearwater	Florida
United States	Adriana Pop-Moody MD Clinic PA /ID# 154607	Corpus Christi	Texas
United States	Jefrey D. Lieberman, MD, P.C. /ID# 157178	Decatur	Georgia
United States	Denver Arthritis Clinic /ID# 159195	Denver	Colorado
United States	Altoona Ctr Clinical Res /ID# 154572	Duncansville	Pennsylvania
United States	Arthritis and Rheum Clin N. CO /ID# 155673	Fort Collins	Colorado
United States	Saint Jude Heritage /ID# 158833	Fullerton	California
United States	West Michigan Rheumatology /ID# 154551	Grand Rapids	Michigan
United States	Physicians East, PA /ID# 154565	Greenville	North Carolina
United States	CHI St. Vincent Medical Group /ID# 154561	Hot Springs	Arkansas
United States	West Tennessee Research Inst /ID# 158721	Jackson	Tennessee
United States	Kotha and Kotha /ID# 154573	La Mesa	California
United States	NYU Langone Rheum Assoc /ID# 155236	Lake Success	New York
United States	Scientia Medical Research /ID# 159189	Lakewood	Colorado
United States	Advanced Rheumatology, PC /ID# 154589	Lansing	Michigan
United States	Arthritis and Osteo Assoc /ID# 154560	Las Cruces	New Mexico
United States	Bluegrass Community Research /ID# 154604	Lexington	Kentucky
United States	P&I Clinical Research /ID# 159191	Lufkin	Texas
United States	Advanced Clinical Research /ID# 154603	Meridian	Idaho
United States	NYU Langone Medical Center /ID# 158829	New York	New York
United States	Advanced Clin Res of Orlando /ID# 154580	Ocoee	Florida
United States	Four Rivers Clinical Research /ID# 154606	Paducah	Kentucky
United States	Gulf Region Clinical Res Inst /ID# 154597	Pensacola	Florida
United States	SunValley Arthritis Center, Lt /ID# 154558	Peoria	Arizona
United States	University of Pittsburgh MC /ID# 157434	Pittsburgh	Pennsylvania
United States	Oregon Health and Science University /ID# 163822	Portland	Oregon
United States	PMG Research of Salisbury /ID# 154605	Salisbury	North Carolina
United States	Care Access Research /ID# 158098	Salt Lake City	Utah
United States	Clinvest Research LLC /ID# 154554	Springfield	Missouri
United States	Overlook Medical Center /ID# 154794	Summit	New Jersey
United States	AZ Arthritis & Rheum Research /ID# 156539	Sun City	Arizona
United States	W. Broward Rheum Assoc Inc. /ID# 158835	Tamarac	Florida
United States	DM Clinical Research /ID# 158722	Tomball	Texas
United States	Atlantic Coast Research /ID# 155234	Toms River	New Jersey
United States	Ocean Rheumatology, PA /ID# 162980	Toms River	New Jersey
United States	AZ Arth & Rheum Res /ID# 167161	Tucson	Arizona
United States	Lovelace Scientific Resources /ID# 154600	Venice	Florida
United States	The Center for Rheumatology & Bone Research /ID# 158723	Wheaton	Maryland
United States	PMG Research of Wilmington LLC /ID# 154584	Wilmington	North Carolina
United States	Wake Forest Baptist Medical Center /ID# 154586	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Bulgaria,  Canada,  Czechia,  Germany,  Greece,  Hungary,  Ireland,  Israel,  Italy,  Korea, Republic of,  Latvia,  Mexico,  Netherlands,  New Zealand,  Poland,  Portugal,  Puerto Rico,  Romania,  Russian Federation,  Slovakia,  Spain,  Sweden,  Switzerland,  Turkey,  United Kingdom, 

References & Publications (1)

Rubbert-Roth A, Enejosa J, Pangan AL, Haraoui B, Rischmueller M, Khan N, Zhang Y, Martin N, Xavier RM. Trial of Upadacitinib or Abatacept in Rheumatoid Arthritis. N Engl J Med. 2020 Oct 15;383(16):1511-1521. doi: 10.1056/NEJMoa2008250. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Disease Activity Score (DAS) 28 C-Reactive Protein (CRP) at Week 12 (Non-inferiority)	The Disease Activity Score (DAS) 28 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 high-sensitivity C-reactive protein (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 indicates improvement in disease activity.	Baseline and Week 12
Secondary	Change From Baseline in Disease Activity Score (DAS) 28 C-Reactive Protein (CRP) at Week 12 (Superiority)	The Disease Activity Score (DAS) 28 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 high-sensitivity C-reactive protein (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 indicates improvement in disease activity.	Baseline and Week 12
Secondary	Percentage of Participants Achieving Clinical Remission (CR) Based on Disease Activity Score (DAS) 28 C-Reactive Protein (CRP) at Week 12 (Superiority)	The Disease Activity Score (DAS) 28 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 high-sensitivity C-reactive protein (hsCRP; in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity. A DAS 28 score less than 2.6 indicates clinical remission.	At Week 12