Clinical trial NCT02706873: A Study to Compare Upadacitinib (ABT-494) Monotherapy to Methotrexate (MTX) Monotherapy in Adults With Rheumatoid Arthritis (RA) Who Have Not Previously Taken Methotrexate
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Keywords: Musculoskeletal disease
Arthritis
Joint disease
Anti-inflammatory agents
Antirheumatic agents
ABT-494
Upadacitinib
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2016-03-11
Enrollment: 1002
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants were to be randomized in a 1:1:1 ratio to treatment Groups 2, 3, and 4 below, except for participants from Japan, who were to be randomized in a 2:1:1:1 ratio to Groups 1, 2, 3, and 4:

Group 1: Upadacitinib 7.5 mg QD monotherapy (Japan only)

Group 2: Upadacitinib 15 mg QD monotherapy (43 countries, including Japan)

Group 3: Upadacitinib 30 mg QD monotherapy (43 countries, including Japan)

Group 4: MTX monotherapy (43 countries, including Japan)
Primary purpose: TREATMENT

Brief 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.

Detailed description: This study includes 2 periods (a 48-week double-blind treatment period and a long-term extension period) and a Japan substudy. In Period 1 participants will be randomized in a 1:1:1 ratio to treatment Groups 2, 3, and 4 below, except for participants from Japan, who will be randomized in a 2:1:1:1 ratio to Groups 1, 2, 3, and 4:

* Group 1: Upadacitinib 7.5 mg once daily (QD) monotherapy (participants in Japan only)
* Group 2: Upadacitinib 15 mg QD monotherapy
* Group 3: Upadacitinib 30 mg QD monotherapy
* Group 4: Methotrexate monotherapy

Rescue therapy is defined for Weeks 12 through 24, Week 26, and Weeks 36 through 40. Starting at Week 12 through Week 24, participants who do not achieve ≥ 20% improvement in both tender joint count (TJC) and swollen joint count (SJC) compared with baseline at two consecutive visits will continue on their blinded therapy and the Investigator should optimize (initiate or increase) background RA medications: non-steroidal anti-inflammatory drug(s) (NSAIDs), corticosteroids (oral ≤ 10 mg/day prednisone equivalent or prednisone equivalent ≤ 0.5 mg/kg/day for 3 consecutive days) and/or low-potency analgesics.

Rescue therapy for participants who meet the following criteria at Week 26 are as follows:

Participants who do not achieve clinical remission (CR) based on Clinical Disease Activity Index (CDAI) (defined as a CDAI score ≤ 2.8):

* but achieve ≥ 20% improvement in both TJC and SJC compared with baseline will continue on blinded study drug and the Investigator should optimize (initiate or increase) background RA medications: NSAIDs, corticosteroids (oral ≤ 10 mg/day prednisone equivalent and up to 2 local injections), low-potency analgesics and conventional synthetic disease-modifying anti-rheumatic drug(s) (csDMARDs) (only 1 of the following: sulfasalazine, hydroxychloroquine or chloroquine) throughout the remainder of Period 1 and until the study is unblinded.
* and do not achieve ≥ 20% improvement in both TJC and SJC compared with baseline and originally assigned to methotrexate will be re-randomized in a 1:1 ratio to receive blinded upadacitinib 15 mg QD or upadacitinib 30 mg QD (participants in Japan will be randomized 1:1:1 to receive upadacitinib 7.5 mg QD, 15 mg QD, or 30 mg QD) while continuing methotrexate treatment in a blinded manner until the study is unblinded. Participants originally assigned to upadacitinib will add methotrexate 10 mg/week (7.5 mg for Japan) to upadacitinib in a blinded manner and will remain on upadacitinib plus methotrexate 10 mg/week (7.5 mg for Japan) until the study is unblinded.

Starting at Week 36 through Week 40, participants who do not achieve ≥ 20% improvement in both TJC and SJC compared with baseline at two consecutive visits will continue on their blinded therapy and the Investigator should optimize (initiate or increase) background RA medications: NSAIDs, corticosteroids (oral ≤ 10 mg/day prednisone equivalent or prednisone equivalent ≤ 0.5 mg/kg/day for 3 consecutive days and up to 2 local injections), low-potency analgesics and csDMARDs (only 1 of the following: sulfasalazine, hydroxychloroquine or chloroquine).

Participants who complete the Week 48 visit (end of Period 1) will enter the long-term extension, Period 2 (212 weeks) and continue study treatment per assignment at the end of Period 1 in a blinded fashion. When the last participant completes the last visit of Period 1 (Week 48), study drug assignment in both periods may be unblinded, and participants will be dispensed study drug in an open-label fashion until the completion of Period 2. Starting with Protocol Amendment 6, participants receiving upadacitinib 15 mg and 30 mg QD will receive open-label upadacitinib 15 mg QD, and participants receiving methotrexate will receive open-label methotrexate.

A global analysis will be conducted for the comparisons of the primary and secondary efficacy endpoints between the upadacitinib 15 mg QD and 30 mg QD treatment groups versus the methotrexate treatment group for all participants (excluding the Japan specific upadacitinib 7.5 mg treatment group). Analyses will be conducted separately for United States (US)/Food and Drug Administration (FDA), European Union (EU)/European Medicines Agency (EMA), and Japan/Pharmaceuticals and Medical Devices Agency (PMDA) regulatory purposes, each according to a pre-specified sequence of primary and ranked secondary endpoints.

A separate Japan sub-study analysis will be conducted for the comparisons of the efficacy endpoints between the upadacitinib 7.5 mg QD, 15 mg QD, and 30 mg QD treatment groups versus the methotrexate treatment group for participants enrolled in Japan only.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12 - Global Analysis
timeFrame: Baseline and Week 12
measure: Percentage of Participants Achieving Clinical Remission (CR) Based on DAS28(CRP) at Week 24 - Global Analysis
timeFrame: Week 24
measure: Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12 - Global Analysis
timeFrame: Baseline and Week 12
measure: Change From Baseline in Modified Total Sharp Score (mTSS) at Week 24 - Global Analysis
timeFrame: Baseline to Week 24
Secondary outcomes:
measure: Change From Baseline in DAS28 (CRP) at Week 12 - Global Analysis
timeFrame: Baseline to Week 12
measure: Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 - Global Analysis
timeFrame: Baseline to week 12
measure: Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 12 - Global Analysis
timeFrame: Week 12
measure: Change From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 12 - Global Analysis
timeFrame: Baseline to week 12
measure: Change From Baseline in DAS28 (CRP) at Week 24 - Global Analysis
timeFrame: Baseline to Week 24
measure: Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 24 - Global Analysis
timeFrame: Baseline to Week 24
measure: Percentage of Participants With an ACR50 Response at Week 24 - Global Analysis
timeFrame: Baseline and Week 24
measure: Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 24 - Global Analysis
timeFrame: Week 24
measure: Change From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 24 - Global Analysis
timeFrame: Baseline to Week 24
measure: Percentage of Participants With No Radiographic Progression at Week 24 - Global Analysis
timeFrame: Week 24
measure: Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 12 - Global Analysis
timeFrame: Baseline and Week 12
measure: Percentage of Participants With an ACR20 Response at Week 24 - Global Analysis
timeFrame: Baseline and Week 24
measure: Percentage of Participants With an ACR70 Response at Week 24 - Global Analysis
timeFrame: Baseline and Week 24
measure: Percentage of Participants With an ACR20 Response at Week 12 - Japan Sub-study
timeFrame: Baseline and Week 12
measure: Percentage of Participants With an ACR50 Response at Week 12 - Japan Sub-study
timeFrame: Baseline and Week 12
measure: Percentage of Participants With an ACR70 Response at Week 12 - Japan Sub-study
timeFrame: Baseline and Week 12
measure: Change From Baseline in DAS28 (CRP) at Week 12 - Japan Sub-study
timeFrame: Baseline to Week 12
measure: Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 - Japan Sub-study
timeFrame: Baseline to week 12
measure: Change From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 12 - Japan Sub-study
timeFrame: Baseline to Week 12
measure: Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 12 - Japan Sub-study
timeFrame: Week 12
measure: Percentage of Participants Achieving Clinical Remission (CR) Based on DAS28(CRP) at Week 24 - Japan Sub-study
timeFrame: Week 24
measure: Change From Baseline in Modified Total Sharp Score (mTSS) at Week 24 - Japan Sub-study
timeFrame: Baseline to Week 24
measure: Percentage of Participants With No Radiographic Progression at Week 24 - Japan Sub-study
timeFrame: Week 24
Other outcomes:
Locations:
city: La Mesa
country: United States
facility: TriWest Research Associates- La Mesa /ID# 143738
state: California
city: Palm Desert
country: United States
facility: Desert Medical Advances /ID# 143730
state: California
city: Daytona Beach
country: United States
facility: International Medical Research - Daytona /ID# 143748
state: Florida
city: Miami
country: United States
facility: FL Med Ctr and Research, Inc. /ID# 143724
state: Florida
city: Ormond Beach
country: United States
facility: Millennium Research /ID# 143736
state: Florida
city: Palm Harbor
country: United States
facility: Arthritis Research of Florida /ID# 143743
state: Florida
city: Sarasota
country: United States
facility: Sarasota Arthritis Center /ID# 145978
state: Florida
city: Zephyrhills
country: United States
facility: FL Med Clinic, PA /ID# 143744
state: Florida
city: Vernon Hills
country: United States
facility: Deerbrook Medical Associates /ID# 143728
state: Illinois
city: Paducah
country: United States
facility: Four Rivers Clinical Research /ID# 143741
state: Kentucky
city: Toms River
country: United States
facility: Ocean Rheumatology, PA /ID# 143737
state: New Jersey
city: Voorhees
country: United States
facility: Arthritis Rheumatic Back Disorder /ID# 143733
state: New Jersey
city: Minot
country: United States
facility: Trinity Health Med Arts Clinic /ID# 143727
state: North Dakota
city: Vandalia
country: United States
facility: STAT Research, Inc. /ID# 143750
state: Ohio
city: Tulsa
country: United States
facility: Healthcare Research Consultant /ID# 143747
state: Oklahoma
city: Wexford
country: United States
facility: Advanced Rheumatology & Arthri /ID# 147947
state: Pennsylvania
city: Summerville
country: United States
facility: Articularis Healthcare Group, Inc d/b/a Low Country Rheumatology /ID# 145653
state: South Carolina
city: Jackson
country: United States
facility: West Tennessee Research Inst /ID# 143723
state: Tennessee
city: Memphis
country: United States
facility: Dr. Ramesh Gupta /ID# 143732
state: Tennessee
city: Beaumont
country: United States
facility: Diagnostic Group Integrated He /ID# 152921
state: Texas
city: Corpus Christi
country: United States
facility: Adriana Pop-Moody MD Clinic PA /ID# 147626
state: Texas
city: Edinburg
country: United States
facility: Doctor's Hosp at Renaissance /ID# 156407
state: Texas
city: El Paso
country: United States
facility: MedResearch Inc. /ID# 156409
state: Texas
city: Houston
country: United States
facility: Rheumatic Disease Clin Res Ctr /ID# 151103
state: Texas
city: Houston
country: United States
facility: Accurate Clinical Research /ID# 143749
state: Texas
city: Mesquite
country: United States
facility: SW Rheumatology Res. LLC /ID# 143745
state: Texas
city: San Antonio
country: United States
facility: Sun Research Institute /ID# 159546
state: Texas
city: San Antonio
country: United States
facility: Accurate Clinical Management /ID# 159543
state: Texas
city: San Antonio
country: United States
facility: NextGen Clinical Trials LLP /ID# 150930
state: Texas
city: San Marcos
country: United States
facility: Arthritis Clinic of Central TX /ID# 159541
state: Texas
city: Waco
country: United States
facility: Arthritis & Osteoporosis Clinic /ID# 159542
state: Texas
city: Arlington
country: United States
facility: Arthritis Clinic of N. VA, P.C /ID# 143734
state: Virginia
city: Capital Federal
country: Argentina
facility: Aprillus Asistencia e Investig /ID# 149179
state: Buenos Aires
city: San isidro
country: Argentina
facility: Iari /Id# 148595
state: Buenos Aires
city: Rosario
country: Argentina
facility: Instituto CAICI /ID# 143141
state: Santa FE
city: Buenos Aires
country: Argentina
facility: Org Medica de Investigacion /ID# 143142
city: Cordoba
country: Argentina
facility: Consultora Integral de Salud S /ID# 143144
city: San Miguel de Tucuman
country: Argentina
facility: Centro Integral de Reumatologi /ID# 143143
city: San Miguel de Tucuman
country: Argentina
facility: Centro Medico Privado/Reuma /ID# 143140
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital /ID# 143149
state: New South Wales
city: Maroochydore
country: Australia
facility: Rheumatology Research Unit /ID# 143147
state: Queensland
city: Woodville
country: Australia
facility: The Queen Elizabeth Hospital /ID# 143148
state: South Australia
city: Hobart
country: Australia
facility: Southern Clinical Research Pty /ID# 143150
state: Tasmania
city: Camberwell
country: Australia
facility: Emeritus Research /ID# 143146
state: Victoria
city: Minsk
country: Belarus
facility: First City Clinical Hospital /ID# 159020
city: Minsk
country: Belarus
facility: City Clinical Hospital #9 /ID# 145650
city: Charleroi
country: Belgium
facility: Rhumaconsult SPRL /ID# 143158
state: Hainaut
city: Aalst
country: Belgium
facility: Algemeen Stedelijk Ziekenhuis /ID# 153504
state: Oost-Vlaanderen
city: Gent
country: Belgium
facility: UZ Gent /ID# 143157
state: Oost-Vlaanderen
city: Genk
country: Belgium
facility: ReumaClinic Genk /ID# 143159
city: Mons
country: Belgium
facility: CHU Ambroise Pare /ID# 152955
city: Banja Luka
country: Bosnia and Herzegovina
facility: University Clinical Centre of the Republic of Srpska /ID# 143161
state: Republika Srpska
city: Banja Luka
country: Bosnia and Herzegovina
facility: University Clinical Centre of the Republic of Srpska /ID# 143162
state: Republika Srpska
city: Sarajevo
country: Bosnia and Herzegovina
facility: Clinical Center University of Sarajevo /ID# 143164
city: Goiânia
country: Brazil
facility: CIP - Centro Internacional de Pesquisa /ID# 143171
state: Goias
city: Curitiba
country: Brazil
facility: Ceti - Centro de Estudos Em Terapias Inovadoras Ltda /Id# 143169
state: Parana
city: Porto Alegre
country: Brazil
facility: Hospital de Clinicas de Porto Alegre /ID# 143168
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: LMK Sevicos Medicos S/S /ID# 143167
state: Rio Grande Do Sul
city: São Paulo
country: Brazil
facility: CEPIC - Centro Paulista de Investigação Clínica e Serviços Médicos Ltda /ID# 143166
state: Sao Paulo
city: Rio de Janeiro
country: Brazil
facility: CCBR Brasil /ID# 150925
city: Plovdiv
country: Bulgaria
facility: MHAT Trimontsium /ID# 143173
city: Plovdiv
country: Bulgaria
facility: UMHAT Pulmed OOD /ID# 143176
city: Plovdiv
country: Bulgaria
facility: MHAT Kaspela /ID# 143172
city: Sofia
country: Bulgaria
facility: Diagnostic Consultative Center /ID# 143174
city: Sofia
country: Bulgaria
facility: UMHAT Sv. Ivan Rilski /ID# 143175
city: Edmonton
country: Canada
facility: Rheumatology Research Assoc /ID# 143206
state: Alberta
city: Winnipeg
country: Canada
facility: Manitoba Clinic /ID# 143203
state: Manitoba
city: Winnipeg
country: Canada
facility: Ciads /Id# 143205
state: Manitoba
city: Thornhill
country: Canada
facility: CA Ctr for Clin Trials CCCT /ID# 159080
state: Ontario
city: Rimouski
country: Canada
facility: Ctr. de Rheum de l'est du QC /ID# 151317
state: Quebec
city: Temuco
country: Chile
facility: Ctr de Inv Clinica del Sur /ID# 143208
state: Araucania
city: Providencia
country: Chile
facility: Someal /Id# 143207
state: Santiago
city: Puerto Varas
country: Chile
facility: Quantum Research LTDA. /ID# 143210
city: Santiago
country: Chile
facility: Quantum Research Stgo. /ID# 145651
city: Santiago
country: Chile
facility: Soc. de Prestaciones medicas y Paramedicas Goecke /ID# 143209
city: Santiago
country: Chile
facility: Investigaciones Medicas SSMSO /ID# 151685
city: Vina Del Mar
country: Chile
facility: Centro de Estudios Clinicos Qu /ID# 152913
city: Bengbu
country: China
facility: 1st Aff Hosp of Bengbu Med Col /ID# 162974
state: Anhui
city: Xiamen
country: China
facility: The 1st Aff Hosp Xiamen Univ /ID# 162076
state: Fujian
city: Shantou
country: China
facility: 1st Aff Hosp of Shantou Univ /ID# 162968
state: Guangdong
city: Bogota
country: Colombia
facility: Centro de Investigacion en Reumatologia y Especialidades Medicas- CIREEM SAS /ID# 143214
state: Cundinamarca
city: Barranquilla
country: Colombia
facility: Ctr Int de Reum del Caribe SAS /ID# 143211
city: Bogota
country: Colombia
facility: Riesgo de Fractura S.A - CAYRE /ID# 143212
city: Bogota
country: Colombia
facility: Simedics IPS SAS /ID# 152572
city: Bogotá
country: Colombia
facility: Fund Inst de Reum F. Chalem /ID# 159544
city: Bucaramanga
country: Colombia
facility: Medicity S.A.S. /ID# 143213
city: Split
country: Croatia
facility: Klinicki bolnicki centar Split /ID# 143216
city: Zagreb
country: Croatia
facility: Clinical Hospital Dubrava /ID# 143217
city: Zagreb
country: Croatia
facility: Medical Center Kuna-Peric /ID# 143218
city: Zagreb
country: Croatia
facility: Poliklinika Bonifarm /ID# 143215
city: Hlučín
country: Czechia
facility: L.K.N. Arthrocentrum, s.r.o /ID# 143224
state: Moravskoslezsky Kraj
city: Olomouc
country: Czechia
facility: CTCenter MaVe, s.r.o. /ID# 143226
state: Olomoucky Kraj
city: Prague 4
country: Czechia
facility: Nuselská poliklinika, Revmatologie /ID# 143232
state: Praha 4
city: Prague 4
country: Czechia
facility: Nuselská poliklinika, Revmatologie /ID# 143233
state: Praha 4
city: Prague
country: Czechia
facility: Thomayerova nemocnice /ID# 143228
state: Praha 4
city: Zlín 1
country: Czechia
facility: PV MEDICAL Services s.r.o. /ID# 143234
state: Zlin
city: Breclav
country: Czechia
facility: RHEUMA s.r.o. /ID# 143230
city: Brno
country: Czechia
facility: Revmatologie, s.r.o. /ID# 143223
city: Bruntál
country: Czechia
facility: Revmatologie Bruntal, s.r.o /ID# 143220
city: Slany
country: Czechia
facility: Nemocnice Slany /ID# 143221
city: Uherské Hradište
country: Czechia
facility: Medical Plus, s.r.o. /ID# 143219
city: Tallinn
country: Estonia
facility: Center of Clinical and Basic Research /ID# 143239
state: Harjumaa
city: Pärnu
country: Estonia
facility: Paernu Hospital /ID# 143238
city: Tallinn
country: Estonia
facility: East Tallinn Central Hospital /ID# 143240
city: Tallinn
country: Estonia
facility: North Estonian Medical Centre /ID# 145456
city: Herne
country: Germany
facility: Rheumazentrum Ruhrgebiet /ID# 145652
state: Nordrhein-Westfalen
city: Köln
country: Germany
facility: Uniklinik Koln /ID# 143248
state: Nordrhein-Westfalen
city: Rendsburg
country: Germany
facility: Praxis Walter, Rendsburg /ID# 143250
state: Schleswig-Holstein
city: Hamburg
country: Germany
facility: Rheumaforschungszentrum II /ID# 143247
city: Hamburg
country: Germany
facility: Schoen Klinikum Hamburg Eilbek /ID# 143251
city: Munich
country: Germany
facility: LMU Klinikum der Universität München /ID# 143249
city: Athens
country: Greece
facility: University General Hospital Attikon /ID# 143252
state: Attiki
city: Ciudad de Guatemala
country: Guatemala
facility: Clinicas Hospital Herrera Ller /ID# 153715
city: Ciudad de Guatemala
country: Guatemala
facility: Creer /Id# 153713
city: Ciudad de Guatemala
country: Guatemala
facility: Clin Especializada Med Interna /ID# 153716
city: Ciudad de Guatemala
country: Guatemala
facility: Clinica Medica Reumatologia /ID# 153714
city: Ciudad de Guatemala
country: Guatemala
facility: Clinica Medica Reumatologia /ID# 153931
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital /ID# 143255
city: Tuen Mun
country: Hong Kong
facility: Tuen Mun Hospital /ID# 143256
city: Miskolc
country: Hungary
facility: CRU Hungary Egeszsegugyi és Szolgaltato Kft. /ID# 143258
state: Borsod-Abauj-Zemplen
city: Budapest
country: Hungary
facility: Qualiclinic Kft. /ID# 143259
state: Pest
city: Szombathely
country: Hungary
facility: Markusovszky Egyetemi Oktatókórház /ID# 143261
state: Vas
city: Heviz
country: Hungary
facility: Hevizgyogyfurdo es Szent Andra /ID# 143257
city: Kistarcsa
country: Hungary
facility: Pest Megyei Flor Ferenc Korhaz /ID# 143260
city: Szekesfehervar
country: Hungary
facility: Fejer Megyei Szent Gyorgy Korh /ID# 144724
city: Dublin
country: Ireland
facility: St Vincent's University Hosp /ID# 143262
city: Ashkelon
country: Israel
facility: Barzilai Medical Center /ID# 144725
city: Haifa
country: Israel
facility: Rambam Health Care Campus /ID# 143263
city: Ramat Gan
country: Israel
facility: Sheba Medical Center /ID# 145975
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas /ID# 147531
state: Milano
city: Milan
country: Italy
facility: Azienda Ospedaliera Luigi Sacc /ID# 143270
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico /ID# 143265
city: Verona
country: Italy
facility: A.O.U.I. di Verona Policlinico /ID# 143266
city: Nagoya-shi
country: Japan
facility: Nagoya University Hospital /ID# 148031
state: Aichi
city: Toyohashi-shi
country: Japan
facility: NHO Toyohashi Medical Center /ID# 161033
state: Aichi
city: Ichihara
country: Japan
facility: Teikyo University Chiba Medical Center /ID# 159618
state: Chiba
city: Fukuoka-shi
country: Japan
facility: NHO Kyushu Medical Center /ID# 148263
state: Fukuoka
city: Fukuoka-shi
country: Japan
facility: NHO Kyushu Medical Center /ID# 148264
state: Fukuoka
city: Asahikawa
country: Japan
facility: National Hospital Organization Asahikawa Medical Center /ID# 148021
state: Hokkaido
city: Asahikawa
country: Japan
facility: Katayama Orthopedic Rheumatology Clinic /ID# 148029
state: Hokkaido
city: Kobe
country: Japan
facility: Kobe University Hospital /ID# 153461
state: Hyogo
city: Sagamihara-shi
country: Japan
facility: National Hospital Organization Sagamihara National Hospital /ID# 148019
state: Kanagawa
city: Osaka
country: Japan
facility: NHO Osaka Minami Med Ctr /ID# 148042
state: Kawachinagano-shi
city: Kochi-shi
country: Japan
facility: Bay Side Misato Medical Center /ID# 148256
state: Kochi
city: Kumamoto-shi
country: Japan
facility: Center for Arthritis and Clinical Rheumatology Matsubara Clinic /ID# 148254
state: Kumamoto
city: Kumamoto-shi
country: Japan
facility: Kumamoto Orthopaedic Hospital /ID# 148054
state: Kumamoto
city: Kumamoto-shi
country: Japan
facility: Kumamoto Shinto General Hospital /ID# 148266
state: Kumamoto
city: Sasebo-city
country: Japan
facility: Sasebo Chuo Hospital /ID# 148261
state: Nagasaki
city: Nagaoka-shi
country: Japan
facility: Nagaoka Red Cross Hospital /ID# 148018
state: Niigata
city: Okayama-shi
country: Japan
facility: Japanese Red Cross Okayama Hospital /ID# 159619
state: Okayama
city: Hirakata-shi
country: Japan
facility: Kansai Medical University Hospital /ID# 159622
state: Osaka
city: Takatsuki -shi
country: Japan
facility: Osaka Medical College Hospital /ID# 159624
state: Osaka
city: Kawagoe-shi
country: Japan
facility: Saitama Medical Center, Saitama Medical University /ID# 148015
state: Saitama
city: Shimotsuke-shi
country: Japan
facility: Jichi Medical University Hospital /ID# 159620
state: Tochigi
city: Bunkyo-ku
country: Japan
facility: Juntendo University Hospital /ID# 148050
state: Tokyo
city: Chuo-ku
country: Japan
facility: St.Luke's International Hospital /ID# 148041
state: Tokyo
city: Meguro-ku
country: Japan
facility: Toho University Ohashi Medical Center /ID# 148027
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Keio University Hospital /ID# 148057
state: Tokyo
city: Shimonoseki-shi
country: Japan
facility: Tokito Clinic Rheumatology and Orthopaedics Surgery /ID# 148052
state: Yamaguchi
city: Beppu
country: Japan
facility: National Hospital Organization Beppu Medical Center /ID# 161058
city: Chiba
country: Japan
facility: NHO Chiba-East-Hospital /ID# 148035
city: Fukui
country: Japan
facility: Sugimoto Rheumatology and Internal Medicine Clinic /ID# 148047
city: Fukuoka
country: Japan
facility: Shono Rheumatism Clinic /ID# 148046
city: Kato
country: Japan
facility: Matsubara Mayflower Hospital /ID# 148033
city: Kurume
country: Japan
facility: St. Mary's Hospital /ID# 148038
city: Kyoto
country: Japan
facility: Kagawa University Hospital /ID# 148016
city: Miyagi
country: Japan
facility: Yu Family Clinic /ID# 148048
city: Nagoya
country: Japan
facility: Daido Hospital /ID# 160868
city: Nagoya
country: Japan
facility: Kondo Clinic for Ortho & Rheum /ID# 148032
city: Nishimura
country: Japan
facility: Shirahama Hamayu Hospital /ID# 148253
city: Oita
country: Japan
facility: Oribe Clinic of Rheumatology and Internal Medicine /ID# 156035
city: Osaka
country: Japan
facility: Osaka City General Hospital /ID# 159617
city: Sanuki
country: Japan
facility: Sanuki Municipal Hospital /ID# 158842
city: Sapporo
country: Japan
facility: Sagawa Akira Rheumatology Clin /ID# 148043
city: Sapporo
country: Japan
facility: Sapporo City General Hospital /ID# 148037
city: Sapporo
country: Japan
facility: Hokkaido University Hospital /ID# 148262
city: Sapporo
country: Japan
facility: Hokkaido Medical Center for Rheumatic Diseases /ID# 148259
city: Sayama
country: Japan
facility: Azuma Rheumatology Clinic /ID# 161050
city: Sendai
country: Japan
facility: Hikarigaoka Spellman Hospital /ID# 148020
city: Takaoka
country: Japan
facility: Takaoka Rheumatic Orthopedic Clinic /ID# 148022
city: Tokyo
country: Japan
facility: National Hospital Organization Tokyo Medical Center /ID# 148040
city: Yotsukaido
country: Japan
facility: National Hospital Organization Shimoshizu National Hospital /ID# 148258
city: Astana
country: Kazakhstan
facility: JSC Nat Scientific Med Res Ctr /ID# 143272
city: Karaganda
country: Kazakhstan
facility: Karaganda State Medical Univ /ID# 153431
city: Semey
country: Kazakhstan
facility: Semey State Medical University /ID# 152661
city: Shymkent
country: Kazakhstan
facility: Regional Clinical Hospital /ID# 147173
city: Adazi
country: Latvia
facility: LTD M+M Centers /ID# 143279
city: Kaunas
country: Lithuania
facility: Hosp Lithuanian Univ Health Sc /ID# 143582
state: Kovno
city: Klaipeda
country: Lithuania
facility: Klaipeda University Hospital /ID# 143583
city: Vilnius
country: Lithuania
facility: Vilnius University Hospital /ID# 143584
city: Cuauhtemoc
country: Mexico
facility: Clinstile, S.A. de C.V. /ID# 143591
state: Ciudad De Mexico
city: Mexico City
country: Mexico
facility: CINTRE, Centro de Investigación y Tratamiento Reumatológico SC /ID# 153562
state: Ciudad De Mexico
city: Chihuahua
country: Mexico
facility: Invest y Biomed de Chihuahua /ID# 143595
city: Mexico City
country: Mexico
facility: RM Pharma Specialists, S.A de C.V /ID# 143593
city: Mexico City
country: Mexico
facility: Unidad de Investigacion de las Enfermedades Reumatologicas SA de CV /ID# 143592
city: Mexico City
country: Mexico
facility: Centro Especializado en Diabetes, Obesidad y Prevención de Enfermedades Cardiova /ID# 143589
city: Queretaro
country: Mexico
facility: Centro Reumatologico de Queret /ID# 149493
city: Hamilton
country: New Zealand
facility: Waikato Hospital /ID# 143602
state: Waikato
city: Auckland
country: New Zealand
facility: Middlemore Clinical Trials /ID# 143600
city: Nelson
country: New Zealand
facility: Porter Rheumatology Ltd /ID# 143601
city: Timaru
country: New Zealand
facility: Timaru Medical Specialists Ltd /ID# 143599
city: Wrocław
country: Poland
facility: WroMedica I. Bielicka, A. Strzalkowska s.c. /ID# 143606
state: Dolnoslaskie
city: Warsaw
country: Poland
facility: Centrum Medyczne AMED /ID# 143604
state: Mazowieckie
city: Warsaw
country: Poland
facility: Centrum Medyczne Pratia Warszawa /ID# 143608
state: Mazowieckie
city: Gdynia
country: Poland
facility: Centrum Medyczne Pratia Gdynia /ID# 143607
state: Pomorskie
city: Katowice
country: Poland
facility: Silmedic Sp z o.o /ID# 143605
state: Slaskie
city: Elblag
country: Poland
facility: NZOZ Centrum Reumatologiczne /ID# 143603
state: Warminsko-mazurskie
city: Poznań
country: Poland
facility: Medyczne Centrum Hetmanska /ID# 144726
state: Wielkopolskie
city: Lisbon
country: Portugal
facility: Instituto Portugues De Reumatologia /ID# 148313
state: Lisboa
city: Lisbon
country: Portugal
facility: Centro Hospitalar Lisboa Ocidental, EPE /ID# 151009
state: Lisboa
city: Vila Nova De Gaia
country: Portugal
facility: Centro Hospitalar De Vila Nova /ID# 143615
state: Porto
city: Lisboa
country: Portugal
facility: Centro Hospitalar Lisboa Norte, EPE /ID# 143613
city: Porto
country: Portugal
facility: Centro Hospitalar Baixo Vouga /ID# 153726
city: Porto
country: Portugal
facility: Centro Hospitalar de Sao Joao, EPE /ID# 153575
city: Viana Do Castelo
country: Portugal
facility: Unidade Local De Saude Do Alto Minho /ID# 143611
city: Viseu
country: Portugal
facility: Centro Hosp de Tondela-Viseu /ID# 143612
city: Ponce
country: Puerto Rico
facility: Ponce School of Medicine /ID# 145657
city: San Juan
country: Puerto Rico
facility: GCM Medical Group /ID# 143618
city: San Juan
country: Puerto Rico
facility: School of Medicine University of Puerto Rico-Medical Sciences Campus /ID# 143619
city: Bucharest
country: Romania
facility: Spitalul Clinic Dr. I. Cantacuzino /ID# 143622
state: Bucuresti
city: Bucuresti
country: Romania
facility: Spitalul Clinic Sf. Maria /ID# 143623
city: Bucuresti
country: Romania
facility: Spitalul Clinic Sf. Maria /ID# 143625
city: Bucuresti
country: Romania
facility: Spitalul Clinic Sf. Maria /ID# 143627
city: Iasi
country: Romania
facility: Spitalul Clinic de Recuperare /ID# 143620
city: Oradea
country: Romania
facility: Ecomed SRL /ID# 143629
city: Korolev
country: Russian Federation
facility: Family Outpatient clinic#4,LLC /ID# 151010
state: Moskva
city: Moscow
country: Russian Federation
facility: Clinical Hospital No.1 n.a. N.I.Pirogov /ID# 143641
state: Moskva
city: Novosibirsk
country: Russian Federation
facility: LLC Medical Center /ID# 143647
state: Novosibirskaya Oblast
city: Pyatigorsk
country: Russian Federation
facility: LLC Novaya Klinika /ID# 143631
state: Stavropol Skiy Kray
city: Kazan
country: Russian Federation
facility: Kazan State Medical University /ID# 143645
state: Tatarstan, Respublika
city: Tver
country: Russian Federation
facility: Tver Regional Clinical Hosp. /ID# 143639
state: Tverskaya Oblast
city: Moscow
country: Russian Federation
facility: Russian National Research Medi /ID# 143642
city: Orenburg
country: Russian Federation
facility: Orenburg Regional Clinical Hos /ID# 143630
city: Petrozavodsk
country: Russian Federation
facility: Republican Clin Hos n.a. Baran /ID# 143634
city: Ryazan
country: Russian Federation
facility: Ryazan State Medical Universit /ID# 143646
city: Samara
country: Russian Federation
facility: Samara Regional Clinical Hosp /ID# 150928
city: UFA
country: Russian Federation
facility: Reg Clin Hosp n.a. Kuvatova G. /ID# 143632
city: Ulyanovsk
country: Russian Federation
facility: Ulyanovsk Regional Clin Hosp /ID# 143644
city: Voronezh
country: Russian Federation
facility: Voronezh State Medical Univers /ID# 150926
city: Belgrade
country: Serbia
facility: Clinical Center Serbia /ID# 143649
state: Beograd
city: Belgrade
country: Serbia
facility: Clinical Center Serbia /ID# 143650
state: Beograd
city: Novi Sad
country: Serbia
facility: Special Hospital for Rheuma /ID# 143648
state: Vojvodina
city: Martin
country: Slovakia
facility: MEDMAN s.r.o. /ID# 143661
city: Nové Mesto Nad Váhom
country: Slovakia
facility: Reumatologická ambulancia Reum.hapi s.r.o. /ID# 143657
city: Partizanske
country: Slovakia
facility: REUMACENTRUM s.r.o. /ID# 143653
city: Pieštany
country: Slovakia
facility: Slovak research center Team Member, Thermium s.r.o. /ID# 143663
city: Puchov
country: Slovakia
facility: Slovak Research Center /ID# 143659
city: Stará Lubovna
country: Slovakia
facility: TIMMED spol. s r.o. /ID# 143664
city: Topolcany
country: Slovakia
facility: Reumatologicka ambulancia, LER /ID# 143660
city: Trencin
country: Slovakia
facility: MEDEOS s.r.o. /ID# 143656
city: Trnava
country: Slovakia
facility: REUMA-GLOBAL, s.r.o. /ID# 143655
city: Zvolen
country: Slovakia
facility: ALBAMED s.r.o. /ID# 143654
city: Žiar nad Hronom
country: Slovakia
facility: Reuma -MUDr. Maria Palasthyova /ID# 143662
city: Ljubljana
country: Slovenia
facility: Univ Medical Ctr Ljubljana /ID# 143667
city: Pretoria
country: South Africa
facility: Jakaranda Hosp, Emmed Research /ID# 143668
state: Gauteng
city: Pretoria
country: South Africa
facility: Jakaranda Hosp, Emmed Research /ID# 145976
state: Gauteng
city: Cape Town
country: South Africa
facility: Arthritis Clinical Research Tr /ID# 143670
state: Western Cape
city: Stellenbosch
country: South Africa
facility: Winelands Medical Research Ctr /ID# 143669
state: Western Cape
city: Santander
country: Spain
facility: H. Un. Marques de Valdecilla /ID# 143671
state: Cantabria
city: A Coruna
country: Spain
facility: Comple Hosp Univ de A Coruna /ID# 143672
city: Barcelona
country: Spain
facility: Hospital Univ Vall d'Hebron /ID# 143675
city: Madrid
country: Spain
facility: Hospital Clin Univ San Carlos /ID# 143674
city: Santiago de Compostela
country: Spain
facility: Clinica Gaias /ID# 143673
city: Santiago de Compostela
country: Spain
facility: Hosp Nuestra Senora Esperanza /ID# 143677
city: Fribourg
country: Switzerland
facility: HFR Fribourg - Hopital Canton /ID# 143700
city: Taichung City
country: Taiwan
facility: China Medical University Hosp /ID# 143703
state: Taichung
city: Taipei City
country: Taiwan
facility: National Taiwan Univ Hosp /ID# 143702
state: Taipei
city: Dalin
country: Taiwan
facility: Dalin Tzu Chi General Hospital /ID# 153535
city: La Marsa
country: Tunisia
facility: Hopital Mongi Slim /ID# 152870
city: Manouba
country: Tunisia
facility: Institut Mohamed Kassab /ID# 152869
city: Sousse
country: Tunisia
facility: Hopital Farhat Hached /ID# 152868
city: Tunis
country: Tunisia
facility: Charles Nicolle Univ Hosp /ID# 152866
city: Tunis
country: Tunisia
facility: Hospital La Rabta /ID# 152867
city: Osmangazi
country: Turkey
facility: Uludag Universitesi Ataturk Rehabilitasyon ve Uygulama Merkezi /ID# 143705
state: Bursa
city: Konak
country: Turkey
facility: Izmir Tepecik Training and Research Hospital /ID# 157863
state: Izmir
city: Izmir
country: Turkey
facility: Izmir Katip Celebi Ataturk Training & Research Hospital /ID# 143704
city: Lviv
country: Ukraine
facility: Lviv Regional Clinical Hospita /ID# 154449
state: Lvivska Oblast
city: Vinnytsia
country: Ukraine
facility: Vinnytsia Regional Clinical Hospital n.a. M.I.Pyrogov /ID# 143714
state: Vinnytska Oblast
city: Ivano-frankivsk
country: Ukraine
facility: Regional Clinical Hospital /ID# 152029
city: Kiev
country: Ukraine
facility: NSC-Strazhesko Ist Cardiology /ID# 152026
city: Kyiv
country: Ukraine
facility: LLC Revmocentr /ID# 143710
city: Lviv
country: Ukraine
facility: MNCE "Lviv City Clinical Hospital #4" /ID# 143711
city: Odesa
country: Ukraine
facility: Odessa National Medical Univ /ID# 143715
city: Zaporizhia
country: Ukraine
facility: Zaporizhzhia Regional Clinical /ID# 143712
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary /ID# 143718
state: England
city: London
country: United Kingdom
facility: Whipps Cross Univ Hospital /ID# 143721
state: London, City Of
city: Edinburgh
country: United Kingdom
facility: Western General Hospital /ID# 144431
city: Leeds
country: United Kingdom
facility: Chapel Allerton Hospital /ID# 143717
city: Portsmouth
country: United Kingdom
facility: Queen Alexandra Hospital /ID# 143722
city: Southampton
country: United Kingdom
facility: Southampton General Hospital /ID# 143716
Study officials:
affiliation: AbbVie
name: AbbVie Inc.
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Bergman M, Buch MH, Tanaka Y, Citera G, Bahlas S, Wong E, Song Y, Zueger P, Ali M, Strand V. Routine Assessment of Patient Index Data 3 (RAPID3) in Patients with Rheumatoid Arthritis Treated with Long-Term Upadacitinib Therapy in Five Randomized Controlled Trials. Rheumatol Ther. 2022 Dec;9(6):1517-1529. doi: 10.1007/s40744-022-00483-4. Epub 2022 Sep 20.
citation: Peterfy CG, Strand V, Friedman A, Hall S, Mysler E, Durez P, Baraliakos X, Enejosa JV, Shaw T, Li Y, Chen S, Song IH. Inhibition of structural joint damage progression with upadacitinib in rheumatoid arthritis: 1-year outcomes from the SELECT phase 3 program. Rheumatology (Oxford). 2022 Aug 3;61(8):3246-3256. doi: 10.1093/rheumatology/keab861.
citation: Yamaoka K, Tanaka Y, Kameda H, Khan N, Sasaki N, Harigai M, Song Y, Zhang Y, Takeuchi T. The Safety Profile of Upadacitinib in Patients with Rheumatoid Arthritis in Japan. Drug Saf. 2021 Jun;44(6):711-722. doi: 10.1007/s40264-021-01067-x. Epub 2021 May 27.
citation: Strand V, Tundia N, Wells A, Buch MH, Radominski SC, Camp HS, Friedman A, Suboticki JL, Dunlap K, Goldschmidt D, Bergman M. Upadacitinib monotherapy improves patient-reported outcomes in rheumatoid arthritis: results from SELECT-EARLY and SELECT-MONOTHERAPY. Rheumatology (Oxford). 2021 Jul 1;60(7):3209-3221. doi: 10.1093/rheumatology/keaa770.
citation: Cohen SB, van Vollenhoven RF, Winthrop KL, Zerbini CAF, Tanaka Y, Bessette L, Zhang Y, Khan N, Hendrickson B, Enejosa JV, Burmester GR. Safety profile of upadacitinib in rheumatoid arthritis: integrated analysis from the SELECT phase III clinical programme. Ann Rheum Dis. 2021 Mar;80(3):304-311. doi: 10.1136/annrheumdis-2020-218510. Epub 2020 Oct 28.
citation: Nader A, Mohamed MF, Winzenborg I, Doelger E, Noertersheuser P, Pangan AL, Othman AA. Exposure-Response Analyses of Upadacitinib Efficacy and Safety in Phase II and III Studies to Support Benefit-Risk Assessment in Rheumatoid Arthritis. Clin Pharmacol Ther. 2020 Apr;107(4):994-1003. doi: 10.1002/cpt.1671. Epub 2019 Nov 30.