Clinical trial NCT03086343: 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
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis (RA)
Keywords: Musculoskeletal Disease
Arthritis
Joint Disease
Anti-inflammatory agents
Antirheumatic agents
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2017-03-22
Enrollment: 657
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change From Baseline in Disease Activity Score (DAS) 28 C-Reactive Protein (CRP) at Week 12 (Non-inferiority)
timeFrame: Baseline and Week 12
Secondary outcomes:
measure: Change From Baseline in Disease Activity Score (DAS) 28 C-Reactive Protein (CRP) at Week 12 (Superiority)
timeFrame: Baseline and Week 12
measure: Percentage of Participants Achieving Clinical Remission (CR) Based on Disease Activity Score (DAS) 28 C-Reactive Protein (CRP) at Week 12 (Superiority)
timeFrame: At Week 12
Other outcomes:
Locations:
city: Peoria
country: United States
facility: SunValley Arthritis Center, Lt /ID# 154558
state: Arizona
city: Sun City
country: United States
facility: AZ Arthritis & Rheum Research /ID# 156539
state: Arizona
city: Tucson
country: United States
facility: AZ Arth & Rheum Res /ID# 167161
state: Arizona
city: Hot Springs
country: United States
facility: CHI St. Vincent Medical Group /ID# 154561
state: Arkansas
city: Fullerton
country: United States
facility: Saint Jude Heritage /ID# 158833
state: California
city: La Mesa
country: United States
facility: Kotha and Kotha /ID# 154573
state: California
city: Denver
country: United States
facility: Denver Arthritis Clinic /ID# 159195
state: Colorado
city: Fort Collins
country: United States
facility: Arthritis and Rheum Clin N. CO /ID# 155673
state: Colorado
city: Lakewood
country: United States
facility: Scientia Medical Research /ID# 159189
state: Colorado
city: Clearwater
country: United States
facility: Clinical Res of West FL, Inc. /ID# 154576
state: Florida
city: Ocoee
country: United States
facility: Advanced Clin Res of Orlando /ID# 154580
state: Florida
city: Pensacola
country: United States
facility: Gulf Region Clinical Res Inst /ID# 154597
state: Florida
city: Tamarac
country: United States
facility: W. Broward Rheum Assoc Inc. /ID# 158835
state: Florida
city: Venice
country: United States
facility: Lovelace Scientific Resources /ID# 154600
state: Florida
city: Decatur
country: United States
facility: Jefrey D. Lieberman, MD, P.C. /ID# 157178
state: Georgia
city: Meridian
country: United States
facility: Advanced Clinical Research /ID# 154603
state: Idaho
city: Champaign
country: United States
facility: PMG Research of Christie Clini /ID# 154569
state: Illinois
city: Lexington
country: United States
facility: Bluegrass Community Research /ID# 154604
state: Kentucky
city: Paducah
country: United States
facility: Four Rivers Clinical Research /ID# 154606
state: Kentucky
city: Baton Rouge
country: United States
facility: Ochsner Clinic Foundation /ID# 154585
state: Louisiana
city: Wheaton
country: United States
facility: The Center for Rheumatology & Bone Research /ID# 158723
state: Maryland
city: Grand Rapids
country: United States
facility: West Michigan Rheumatology /ID# 154551
state: Michigan
city: Lansing
country: United States
facility: Advanced Rheumatology, PC /ID# 154589
state: Michigan
city: Springfield
country: United States
facility: Clinvest Research LLC /ID# 154554
state: Missouri
city: Summit
country: United States
facility: Overlook Medical Center /ID# 154794
state: New Jersey
city: Toms River
country: United States
facility: Atlantic Coast Research /ID# 155234
state: New Jersey
city: Toms River
country: United States
facility: Ocean Rheumatology, PA /ID# 162980
state: New Jersey
city: Las Cruces
country: United States
facility: Arthritis and Osteo Assoc /ID# 154560
state: New Mexico
city: Albany
country: United States
facility: The Center for Rheumatology /ID# 162979
state: New York
city: Lake Success
country: United States
facility: NYU Langone Rheum Assoc /ID# 155236
state: New York
city: New York
country: United States
facility: NYU Langone Medical Center /ID# 158829
state: New York
city: Greenville
country: United States
facility: Physicians East, PA /ID# 154565
state: North Carolina
city: Salisbury
country: United States
facility: PMG Research of Salisbury /ID# 154605
state: North Carolina
city: Wilmington
country: United States
facility: PMG Research of Wilmington LLC /ID# 154584
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Medical Center /ID# 154586
state: North Carolina
city: Portland
country: United States
facility: Oregon Health and Science University /ID# 163822
state: Oregon
city: Bethlehem
country: United States
facility: East Penn Rheumatology Assoc /ID# 159193
state: Pennsylvania
city: Duncansville
country: United States
facility: Altoona Ctr Clinical Res /ID# 154572
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh MC /ID# 157434
state: Pennsylvania
city: Jackson
country: United States
facility: West Tennessee Research Inst /ID# 158721
state: Tennessee
city: Corpus Christi
country: United States
facility: Adriana Pop-Moody MD Clinic PA /ID# 154607
state: Texas
city: Lufkin
country: United States
facility: P&I Clinical Research /ID# 159191
state: Texas
city: Tomball
country: United States
facility: DM Clinical Research /ID# 158722
state: Texas
city: Salt Lake City
country: United States
facility: Care Access Research /ID# 158098
state: Utah
city: Capital Federal
country: Argentina
facility: Aprillus Asistencia e Investig /ID# 159173
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Ctr Privado Med Familiar /ID# 158814
city: Buenos Aires
country: Argentina
facility: Atencion Integral en Reuma /ID# 155696
city: Buenos Aires
country: Argentina
facility: Hospital General de Agudos /ID# 167117
city: Caba
country: Argentina
facility: Inst. de Rehab. Psicofisica /ID# 167768
city: Cordoba
country: Argentina
facility: Inst. Rheumatologic Strusberg /ID# 159021
city: Cordoba
country: Argentina
facility: Instituto Medico DAMIC /ID# 167770
city: Ramos Mejía
country: Argentina
facility: DIM Clinica Privada /ID# 167769
city: Rosario, Santa FE
country: Argentina
facility: Instituto CAICI SRL /ID# 159022
city: Maroochydore
country: Australia
facility: Rheumatology Research Unit /ID# 159174
state: Queensland
city: Woodville
country: Australia
facility: The Queen Elizabeth Hospital /ID# 159175
state: South Australia
city: Footscray
country: Australia
facility: Western Health Footscray Hospi /ID# 157968
state: Victoria
city: Namur
country: Belgium
facility: CHU UCL Namur /ID# 157628
city: Vitoria
country: Brazil
facility: CEDOES-Centro de Diagnóstico e Pesquisa da Osteoporose do Espírito Santo LTDA /ID# 155228
state: Espirito Santo
city: Belo Horizonte
country: Brazil
facility: Santa Casa de Belo Horizonte /ID# 154631
state: Minas Gerais
city: Juiz de Fora
country: Brazil
facility: CMiP - Centro Mineiro de Pesquisa Ltda - ME /ID# 154564
state: Minas Gerais
city: Curitiba
country: Brazil
facility: Ceti - Centro de Estudos Em Terapias Inovadoras Ltda /Id# 154634
state: Parana
city: Porto Alegre
country: Brazil
facility: Hospital de Clinicas de Porto Alegre /ID# 161211
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: LMK Sevicos Medicos S/S /ID# 159176
state: Rio Grande Do Sul
city: Santo André
country: Brazil
facility: CEMEC - Centro Multidisciplinar de Estudos Clínicos /ID# 154632
state: Sao Paulo
city: São Paulo
country: Brazil
facility: CEPIC - Centro Paulista de Investigação Clínica e Serviços Médicos Ltda /ID# 159587
state: Sao Paulo
city: Plovdiv
country: Bulgaria
facility: MHAT Trimontsium /ID# 155226
city: Sofia
country: Bulgaria
facility: Diag Consult Ctr 17 Sofia EOOD /ID# 169298
city: Sofia
country: Bulgaria
facility: UMHAT Sv. Ivan Rilski /ID# 155000
city: Sofia
country: Bulgaria
facility: Medical Centre Synexus Sofia /ID# 201807
city: Barrie
country: Canada
facility: The Waterside Clinic /ID# 159178
state: Ontario
city: Hamilton
country: Canada
facility: Adachi Medicine Prof. Corp /ID# 158024
state: Ontario
city: Montreal
country: Canada
facility: Institut de Rhum. de Montreal /ID# 155001
state: Quebec
city: Sainte-foy
country: Canada
facility: Groupe de Recherche en Maladies Osseuses /ID# 154601
state: Quebec
city: Prague 2
country: Czechia
facility: Revmatologicky ustav Praha /ID# 154612
state: Praha 2
city: Uherské Hradište
country: Czechia
facility: Medical Plus, s.r.o. /ID# 155230
city: Köln
country: Germany
facility: Uniklinik Koln /ID# 156047
state: Nordrhein-Westfalen
city: Berlin
country: Germany
facility: Praxis fuer Rheumatologie /ID# 156156
city: Hamburg
country: Germany
facility: Rheumaforschungszentrum II /ID# 157177
city: Planegg
country: Germany
facility: Welcker, Planegg, DE /ID# 160185
city: Heraklion
country: Greece
facility: University General Hospital of Heraklion "PA.G.N.I" /ID# 163916
city: Budapest
country: Hungary
facility: Budai Irgalmasrendi Korhaz /ID# 154457
city: Budapest
country: Hungary
facility: Obudai Egeszsegugyi Centrum Kft. /ID# 156159
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Kenezy Gyula Egyetemi Korhaz /ID# 159183
city: Eger
country: Hungary
facility: Markhot Ferenc Oktatokorhaz es Rendelointezet /ID# 159689
city: Szolnok
country: Hungary
facility: MAV Korhaz ess Rendelointezet /ID# 154455
city: Manorhamilton
country: Ireland
facility: Our Lady's Hospital /ID# 161149
city: Ashkelon
country: Israel
facility: Barzilai Medical Center /ID# 161685
city: Haifa
country: Israel
facility: The Lady Davis Carmel MC /ID# 161686
city: Kfar Saba
country: Israel
facility: Meir Medical Center /ID# 162774
city: Ramat Gan
country: Israel
facility: Sheba Medical Center /ID# 163154
city: Ancona
country: Italy
facility: A.O. Univ. Ospedali Riuniti /ID# 161707
state: Marche
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas /ID# 154999
state: Milano
city: Turin
country: Italy
facility: AOU Citta della Salute Scienza /ID# 154577
state: Piemonte
city: Rome
country: Italy
facility: Presidio Columbus, Fondazione Policlinico Gemelli Universita Cattolica S. Cuore /ID# 162252
state: Roma
city: Catania
country: Italy
facility: Azienda Ospedaliero Universitaria Policlinico Vittorio Emanuele /ID# 161172
city: Milan
country: Italy
facility: ASST G. Pini /ID# 162223
city: Seoul
country: Korea, Republic of
facility: SMG-SNU Boramae Medical Center /ID# 155788
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Yeouido St. Mary's Hospital /ID# 155231
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center /ID# 154639
city: Liepaja
country: Latvia
facility: D.Saulites-Kandevicas PP /ID# 154578
city: Riga
country: Latvia
facility: Riga East Clinical Univ Hosp /ID# 155024
city: Mexico City
country: Mexico
facility: CINTRE, Centro de Investigación y Tratamiento Reumatológico SC /ID# 154579
state: Ciudad De Mexico
city: Leon
country: Mexico
facility: Morales Vargas Centro de Investigacion S.C. /ID# 200800
state: Guanajuato
city: Guadalajara
country: Mexico
facility: Centro Integral en Reumatología S.A de C.V /ID# 204493
state: Jalisco
city: Mexico City
country: Mexico
facility: RM Pharma Specialists S.A de C.V /ID# 159588
city: Mexico City
country: Mexico
facility: Centro Especializado en Diabetes, Obesidad y Prevención de Enfermedades Cardiova /ID# 160126
city: Sneek
country: Netherlands
facility: Antonius Ziekenhuis /ID# 155737
state: Fryslan
city: Amsterdam
country: Netherlands
facility: Reade /ID# 161002
city: Haarlem
country: Netherlands
facility: Spaarne Gasthuis /ID# 161003
city: Leeuwarden
country: Netherlands
facility: Medisch Centrum Leeuwarden /ID# 156043
city: Timaru
country: New Zealand
facility: Timaru Medical Specialists Ltd /ID# 159184
city: Wellington
country: New Zealand
facility: Wellington Hospital (Capital and Coast District Health Board) /ID# 154591
city: Lodz
country: Poland
facility: Salve Medica Sp. z o.o. S.K. /ID# 202473
state: Lodzkie
city: Cracow
country: Poland
facility: Malopolskie Centrum Kliniczne /ID# 157180
state: Malopolskie
city: Warszawa
country: Poland
facility: Centrum Medyczne AMED Warszawa Targowek /ID# 159589
state: Mazowieckie
city: Białystok
country: Poland
facility: Gabinet Internistyczno Reum. /ID# 157433
state: Podlaskie
city: Białystok
country: Poland
facility: ClinicMed Daniluk, Nowak Sp.j. /ID# 202998
state: Podlaskie
city: Gdynia
country: Poland
facility: Synexus Polska Sp. z o.o. Oddzial w Gdyni /ID# 202472
state: Pomorskie
city: Poznań
country: Poland
facility: Medyczne Centrum Hetmanska /ID# 155746
state: Wielkopolskie
city: Lodz
country: Poland
facility: Centrum Med Amed Oddzial Lodzi /ID# 154458
city: Lisbon
country: Portugal
facility: Instituto Portugues De Reumatologia /ID# 155698
state: Lisboa
city: Lisbon
country: Portugal
facility: Centro Hospitalar Lisboa Ocidental, EPE /ID# 200035
state: Lisboa
city: Almada
country: Portugal
facility: Hospital Garcia de Orta, E.P.E /ID# 164056
state: Setubal
city: Lisboa
country: Portugal
facility: Centro Hospitalar Lisboa Norte, EPE /ID# 200037
city: Viana Do Castelo
country: Portugal
facility: Unidade Local De Saude Do Alto Minho /ID# 200036
city: Viseu
country: Portugal
facility: Centro Hosp de Tondela-Viseu /ID# 155699
city: Carolina
country: Puerto Rico
facility: Dr. Ramon L. Ortega-Colon, MD /ID# 158097
city: San Juan
country: Puerto Rico
facility: GCM Medical Group /ID# 156158
city: Bucharest
country: Romania
facility: Spitalul Clinic Dr. I. Cantacuzino /ID# 155893
state: Bucuresti
city: Bucuresti
country: Romania
facility: Spitalul Clinic Sf. Maria /ID# 167245
city: Korolev
country: Russian Federation
facility: Family Outpatient clinic#4 LLC /ID# 203524
state: Moskva
city: Novosibirsk
country: Russian Federation
facility: LLC Medical Center /ID# 203523
state: Novosibirskaya Oblast
city: Izhevsk
country: Russian Federation
facility: Alliance Biomedical Ural Group /ID# 154609
state: Udmurtskaya Respublika
city: Moscow
country: Russian Federation
facility: State Budget Healthcare Instit /ID# 154593
city: St. Petersburg
country: Russian Federation
facility: Nort-Western State Medical Uni /ID# 154610
city: Banska Bystrica
country: Slovakia
facility: Novamed,spol.s.r.o. /ID# 157928
city: Bratislava
country: Slovakia
facility: Univerzitna Nemocnica Bratislava /ID# 161143
city: Pieštany
country: Slovakia
facility: Narodny ustav reumatickych chorob Piestany /ID# 156864
city: Cordoba
country: Spain
facility: Hospital Universitario Reina S /ID# 155701
city: Elche
country: Spain
facility: Hospital General Univ de Elche /ID# 158825
city: Madrid
country: Spain
facility: Hospital Universitario La Paz /ID# 163636
city: Sabadell, Barcelona
country: Spain
facility: Corp Sanitaria Parc Tauli /ID# 163634
city: Santiago de Compostela
country: Spain
facility: Complejo Hospitalario /ID# 155700
city: Sevilla
country: Spain
facility: Hospital Infanta Luisa /ID# 154641
city: Malmö
country: Sweden
facility: Skanes Universitetssjukhus /ID# 165133
state: Skane Lan
city: Stockholm
country: Sweden
facility: Akademiskt specialistcentrum Centrum for reumatologi /ID# 156046
state: Stockholms Lan
city: Goteborg
country: Sweden
facility: Sahlgrenska University Hosp /ID# 162775
city: Vasteras
country: Sweden
facility: Vastmanlands Sjukhus /ID# 159186
city: Genève
country: Switzerland
facility: Hopitaux Universitaires de Geneve /ID# 159083
state: Geneve
city: St. Gallen
country: Switzerland
facility: Kantonsspital St. Gallen /ID# 155232
state: Sankt Gallen
city: Basel
country: Switzerland
facility: University Hospital of Basel /ID# 160860
city: Fribourg
country: Switzerland
facility: HFR Fribourg - Hopital Canton /ID# 160970
city: Ankara
country: Turkey
facility: Hacettepe University Medical Faculty /ID# 167995
city: Ankara
country: Turkey
facility: Ankara Univ Medical Faculty /ID# 162691
city: Antalya
country: Turkey
facility: Akdeniz University Faculty /ID# 163153
city: Istanbul
country: Turkey
facility: Istanbul Fizik Tedavi Rehabilitasyon Egitim ve Arastırma Hastanesi /ID# 169479
city: London
country: United Kingdom
facility: Whipps Cross Univ Hospital /ID# 205985
state: London, City Of
city: Dundee
country: United Kingdom
facility: Ninewells Hospital /ID# 156050
city: Londonderry
country: United Kingdom
facility: Altnagelvin Area Hospital /ID# 156540
city: Preston
country: United Kingdom
facility: Lancashire Care NHS Foundation /ID# 156042
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospital /ID# 157785
Study officials:
affiliation: AbbVie
name: AbbVie Inc.
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Bergman M, Tundia N, Martin N, Suboticki JL, Patel J, Goldschmidt D, Song Y, Wright GC. Patient-reported outcomes of upadacitinib versus abatacept in patients with rheumatoid arthritis and an inadequate response to biologic disease-modifying antirheumatic drugs: 12- and 24-week results of a phase 3 trial. Arthritis Res Ther. 2022 Jun 24;24(1):155. doi: 10.1186/s13075-022-02813-x.