A Study to Evaluate the Safety and Efficacy of Upadacitinib (ABT-494) for Induction and Maintenance Therapy in Participants With Moderately to Severely Active Ulcerative Colitis (UC)

June 3, 2022 updated by: AbbVie

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Upadacitinib (ABT-494) for Induction and Maintenance Therapy in Subjects With Moderately to Severely Active Ulcerative Colitis

This study was comprised of three substudies. The objective of Substudy 1 was to characterize the dose-response, efficacy, and safety of upadacitinib compared to placebo in inducing clinical remission to identify the induction dose of upadacitinib for further evaluation in Substudy 2. The objective of Substudy 2 was to evaluate the efficacy and safety of upadacitinib compared to placebo in inducing clinical remission in participants. The objective of Substudy 3 was to evaluate the efficacy and safety of upadacitinib compared to placebo in achieving clinical remission in participants who had a response following induction with upadacitinib.

Study Overview

Status

Completed

Intervention / Treatment

Detailed Description

Substudy 1 was a Phase 2b dose-ranging study designed to evaluate the efficacy and safety of different oral doses of upadacitinib compared to placebo as 8-week induction therapy in participants with moderately to severely active UC. Approximately 250 participants were planned to be randomized 1:1:1:1:1 to the placebo group and 4 upadacitinib doses (7.5, 15, 30, and 45 mg). Randomization was stratified by previous biologic therapy use (yes/no), Baseline corticosteroid use (yes/no), and Baseline Adapted Mayo score (≤ 7 or > 7). The study duration included a Screening Period of up to 5 weeks and an 8-week double-blind (DB) Induction Period. After all randomized participants completed the 8-week induction, a dose-selection analysis of efficacy and safety (selected laboratory parameters) of upadacitinib versus placebo was performed. Based on this dose-selection analysis, one induction dose (upadacitinib 45 mg) was identified for further evaluation in two Phase 3 induction studies, M14-234 Substudy 2 and M14-675 (NCT03653026). During the analysis period, 132 additional participants were randomized into Groups 3 and 4 of Substudy 1 (upadacitinib 30 mg and 45 mg dose groups; approximately 66 participants per dose group). The objectives of enrolling these additional participants were to avoid interrupting the study activities during the analysis period and to support a sufficient number of participants with clinical response to be re-randomized into the maintenance portion in Substudy 3. Substudy 1 main participants are defined as those first 250 randomized 250, and additional participants are defined as those who were randomized after the main participants.

Substudy 2 was a two-part Phase 3 dose-confirming study designed to evaluate the efficacy and safety of oral administration of upadacitinib 45 mg compared to placebo as induction therapy for up to 16 weeks in participants with moderately to severely active UC. Substudy 2 included a Screening Period of up to 5 weeks, Part 1, and Part 2. Part 1 was a randomized, DB, placebo-controlled 8-week induction period. Part 2 was an open-label, 8-week extended treatment period for clinical non-responders from Part 1 of Substudy 2. Part 1 was planned to enroll 462 subjects; actual enrollment was 474 subjects. Eligible participants were randomized in a 2:1 ratio to one of the two treatment groups (DB upadacitinib 45 mg or matching placebo) for 8 weeks. The randomization was stratified by bio-IR status (Biologic inadequate responders [bio-IR] vs Non-biologic-inadequate responders [non-bio-IR], corticosteroid use (yes or no), and Adapted Mayo score (≤ 7 or > 7) at Baseline. Within bio-IR, the randomization was further stratified by number of prior biologic treatments (≤ 1 or > 1). Within non-bio-IR, the randomization was further stratified by previous biologic use (yes or no). Part 2 was an open label, 8-week Extended Treatment Period for those who did not achieve clinical response per Adapted Mayo score at Week 8 in Part 1. All participants received upadacitinib 45 mg.

Substudy 3 was a Phase 3 maintenance study designed to evaluate the efficacy and safety of upadacitinib 15 and 30 mg once daily (QD) compared to placebo in achieving clinical remission per Adapted Mayo score in participants with moderately to severely active UC who achieved clinical response per Adapted Mayo score following induction therapy from Substudy 1, Substudy 2, or Study M14-675. A total of 1,046 subjects who achieved clinical response per Adapted Mayo score after completion of induction treatment or Extended Treatment Period in Study M14-234 Substudy 1, Substudy 2, or Study M14-675 entered Substudy 3, and 1,044 were treated with a blinded treatment assignment for up to 52 weeks. Substudy 3 included 4 cohorts. Cohort 1: 847 participants who achieved clinical response in Substudy 1, Substudy 2, or Study M14-675 at either Week 8 or Week 16, and received upadacitinib 15, 30, or 45 mg QD. The treatment groups in Cohort 1 were Group 1: upadacitinib 15 mg QD; Group 2: upadacitinib 30 mg QD; and Group 3: placebo QD. Those who achieved clinical response and received upadacitinib 15 mg QD in Substudy 1 were re-randomized 1:1 to only receive upadacitinib 15 mg QD or placebo QD (treatment Group 1 or 3). Cohort 2: 104 participants who received double-blind placebo QD treatment for 8 weeks during Substudy 1, Substudy 2 Part 1, or Study M14-675 Part 1 and achieved clinical response at Week 8 continued to receive blinded placebo QD in Substudy 3. Cohort 3: 75 participants who received upadacitinib 45 mg QD in Induction Phase and did not achieve clinical response and received upadacitinib 45 mg QD in Extended Treatment in Substudy 2 Part 2 or in Study M14-675 Part 2 and achieved clinical response at Week 16 were re-randomized 1:1 and received blinded upadacitinib 30 mg QD or upadacitinib 15 mg QD in Substudy 3. Cohort 4: 20 participants who received double-blinded treatment of upadacitinib 7.5 mg QD for 8 weeks during Substudy 1 and achieved clinical response at Week 8 continued to receive blinded treatment of upadacitinib 7.5 mg QD in Substudy 3.

Study Type

Interventional

Enrollment (Actual)

1302

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Cordoba, Argentina, 5016
        • Hospital Privado Univesitario /ID# 164185
    • Buenos Aires
      • San Isidro, Buenos Aires, Argentina, 1642
        • Cardio Alem /ID# 211280
    • Ciuadad Autonoma De Buenos Aires
      • Ciudad Autonoma de Buenos Aire, Ciuadad Autonoma De Buenos Aires, Argentina, 1115
        • Gedyt /ID# 210015
      • Ciudad Autonoma de Buenos Aire, Ciuadad Autonoma De Buenos Aires, Argentina, 1128
        • Mautalen Salud e Investigacion /ID# 171173
      • Ciudad Autonoma de Buenos Aire, Ciuadad Autonoma De Buenos Aires, Argentina, 1280
        • Hospital Britanico de Buenos Aires /ID# 209495
    • Tucuman
      • San Miguel de Tucuman, Tucuman, Argentina, 4000
        • Sanatorio 9 de Julio /ID# 150189
    • New South Wales
      • Macquarie University, New South Wales, Australia, 2109
        • Macquarie University Hospital /ID# 211951
    • Queensland
      • South Brisbane, Queensland, Australia, 4101
        • Mater Misericordiae Limited /ID# 212685
      • Southport, Queensland, Australia, 4222
        • Griffith University /ID# 211952
    • Victoria
      • Clayton, Victoria, Australia, 3168
        • Monash Medical Centre /ID# 150206
      • Fitzroy Melbourne, Victoria, Australia, 3065
        • St Vincent's Hospital Melbourne /ID# 152472
    • Western Australia
      • Murdoch, Western Australia, Australia, 6150
        • Fiona Stanley Hospital /ID# 211640
      • Salzburg, Austria, 5020
        • Landeskrankenhaus Salzburg-Universitätsklinikum der PMU (LKH) /ID# 150306
    • Oberoesterreich
      • Linz, Oberoesterreich, Austria, 4010
        • Ordensklinikum Linz GmbH Barmherzige Schwestern /ID# 150305
    • Wien
      • Vienna, Wien, Austria, 1030
        • Klinik Landstrasse /ID# 162866
      • Vienna, Wien, Austria, 1090
        • Medizinische Universitaet Wien /ID# 150614
      • Витебск, Belarus, 210001
        • Vitebsk Regional Advanced Clin /ID# 169612
      • Gent, Belgium, 9000
        • AZ Maria Middelares /ID# 150331
      • Roeselare, Belgium, 8800
        • AZ-Delta /ID# 150330
    • Vlaams-Brabant
      • Leuven, Vlaams-Brabant, Belgium, 3000
        • Universitair Ziekenhuis Leuven /ID# 150332
      • Mostar, Bosnia and Herzegovina, 88000
        • University Clinical Hospital Mostar /ID# 150705
      • Sarajevo, Bosnia and Herzegovina, 71000
        • Clinical Center University of Sarajevo /ID# 150208
    • Republika Srpska
      • Banja Luka, Republika Srpska, Bosnia and Herzegovina, 78000
        • University Clinical Centre of the Republic of Srpska /ID# 150209
      • Banja Luka, Republika Srpska, Bosnia and Herzegovina, 78000
        • University Clinical Centre of the Republic of Srpska /ID# 150706
    • Tuzlanski
      • Tuzla, Tuzlanski, Bosnia and Herzegovina, 75000
        • University Clinical Center Tuzla /ID# 150211
    • Goias
      • Goiânia, Goias, Brazil, 74535-170
        • Instituto Goiano de Gastroenterologia e Endoscopia Digestiva /ID# 153742
    • Parana
      • Curitiba, Parana, Brazil, 80810-040
        • Hospital Nossa Senhora das Graças /ID# 152480
    • Rio Grande Do Sul
      • Porto Alegre, Rio Grande Do Sul, Brazil, 90035-903
        • Hospital de Clinicas de Porto Alegre /ID# 153743
    • Sao Paulo
      • Botucatu, Sao Paulo, Brazil, 18618-686
        • Upeclin Fmb - Unesp /Id# 152485
      • Ribeirão Preto, Sao Paulo, Brazil, 14051-140
        • Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto - USP /ID# 152484
      • Santo André, Sao Paulo, Brazil, 09060-870
        • Faculdade de Medicina do ABC /ID# 152481
      • Sao Jose Do Rio Preto, Sao Paulo, Brazil, 15015-110
        • Kaiser Clinica e Hospital Dia /ID# 152483
    • Alberta
      • Calgary, Alberta, Canada, T2N 4Z6
        • University of Calgary /ID# 151821
      • Edmonton, Alberta, Canada, T5R 1W2
        • Allen Whey Khye Lim Professional Corporation /ID# 211168
      • Edmonton, Alberta, Canada, T6G 2X8
        • University of Alberta - Zeidler Ledcor Centre /ID# 151100
      • Edmonton, Alberta, Canada, T6K 4B2
        • Covenant Health /ID# 158930
    • British Columbia
      • Kelowna, British Columbia, Canada, V1Y 1Z9
        • Okanagan Clinical Trials /ID# 153178
      • Victoria, British Columbia, Canada, V8V 3M9
        • Percuro Clinical Research, Ltd /ID# 150367
    • Ontario
      • Hamilton, Ontario, Canada, L8S 4K1
        • Hamilton Health Sciences - McMaster University Medical Centre /ID# 150365
      • Ottawa, Ontario, Canada, K1H 8L6
        • Ottawa Hospital Research Institute /ID# 151820
      • Sudbury, Ontario, Canada, P3A 1W8
        • Medicor Research Inc /ID# 151101
      • Vaughan, Ontario, Canada, L4L 4Y7
        • Toronto Digestive Disease Asso /ID# 150363
    • Quebec
      • Greenfield Park, Quebec, Canada, J4V 2H1
        • CISSS de la Monteregie /ID# 159215
      • Levis, Quebec, Canada, G6V 3Z1
        • CISSS de Chaudière-Appalaches, Hôpital Hotel-Dieu de Lévis /ID# 150361
      • Montreal, Quebec, Canada, H1M 1B1
        • Recherche GCP Research /ID# 151822
      • Montreal, Quebec, Canada, H2X 0A9
        • Centre Hospitalier de l'Universite de Montreal - CRCHUM /ID# 167169
      • Montréal, Quebec, Canada, H3G 1A4
        • Montreal General Hospital - McGill University Health Centre /ID# 170012
      • Sherbrooke, Quebec, Canada, J1G 2E8
        • CIUSSS de l'Estrie - CHUS /ID# 150366
      • Concepción, Chile, 4070038
        • Hospital Guillermo Grant Benavente de Concepción /ID# 212424
      • Providencia, Chile, 7500571
        • CTR Estudios Clinicos /ID# 200110
      • Santiago, Chile, 7501504
        • Hospital Clinico Universidad De Los Andes /ID# 207422
    • Region Metropolitana De Santiago
      • Santiago, Region Metropolitana De Santiago, Chile, 2540364
        • Research Group /ID# 203176
    • Region Metropolitana Santiago
      • Santiago, Region Metropolitana Santiago, Chile, 7750495
        • M y F Estudios Clínicos /ID# 200107
    • Valparaíso
      • Viña del Mar, Valparaíso, Chile, 2540488
        • Centro de Investigaciones Clínicas Viña del Mar /ID# 150212
      • Changsha, China, 410008
        • Xiangya Hospital Central South University /ID# 167229
      • Chengdu, China, 610041
        • West China Hospital, Sichuan University /ID# 167040
      • Shenyang, China, 110022
        • Shengjing Hospital of China Medical University /ID# 166920
      • Tianjin, China, 300052
        • Tianjin Medical University General Hospital /ID# 170604
    • Guangdong
      • Guangzhou, Guangdong, China, 510080
        • The First Affiliated Hospital, Sun Yat-sen University /ID# 150455
      • Guangzhou, Guangdong, China, 510655
        • The Sixth Affiliated Hosp Sun /ID# 150456
    • Hubei
      • Shiyan, Hubei, China, 442700
        • Affiliated Taihe Hospital of Hubei University of Medicine /ID# 216405
      • Wuhan, Hubei, China, 430022
        • Tongji Hospital Tongji Medical College Huazhong University of Science and Techno /ID# 167088
      • Wuhan, Hubei, China, 430022
        • Union Hospital Tongji Medical College Huazhong University of Science and Technol /ID# 167078
    • Jiangxi
      • Nanchang, Jiangxi, China, 330006
        • The First Affiliated Hospital of Nanchang University /ID# 211750
    • Jilin
      • Changchun, Jilin, China, 130021
        • The First Hospital of Jilin University /ID# 209986
    • Shanghai
      • Shanghai, Shanghai, China, 200065
        • Ruijin Hospital, Shanghai Jiaotong University School of Medicine /ID# 150461
      • Shanghai, Shanghai, China, 200072
        • Shanghai Tenth People's Hospital /ID# 150460
      • Shanghai, Shanghai, China, 200127
        • Renji Hospital, Shanghai Jiaotong University School of Medicine /ID# 165815
    • Zhejiang
      • Hangzhou, Zhejiang, China, 310009
        • The second Affiliated hospital of Zhejiang University school of Medicine /ID# 165807
      • Hangzhou, Zhejiang, China, 310018
        • Sir Run Run Shaw Hospital,Meical School Zhejiang University /ID# 150454
      • Medellin, Colombia
        • Hospital Universitario de San /ID# 155387
    • Cordoba
      • Monteria, Cordoba, Colombia, 230002
        • Instituto Medico de Alta Tecnologia Oncomédica S.A /ID# 207042
    • Cundinamarca
      • Bogota DC, Cundinamarca, Colombia, 111221
        • Corporacion Hospitalaria Juan Cuidad Sede Denominada Hospital Universitario Mayo /ID# 151564
      • Zadar, Croatia, 23000
        • Zadar General Hospital /ID# 150221
    • Grad Zagreb
      • Zagreb, Grad Zagreb, Croatia, 10000
        • Clinical Hospital Dubrava /ID# 150213
      • Zagreb, Grad Zagreb, Croatia, 10000
        • Klinicki bolnicki centar Zagreb /ID# 150225
      • Zagreb, Grad Zagreb, Croatia, 10000
        • Klinicki bolnicki centar Zagreb /ID# 150709
      • Zagreb, Grad Zagreb, Croatia, 10000
        • Poliklinika Solmed /ID# 211483
    • Osjecko-baranjska Zupanija
      • Osijek, Osjecko-baranjska Zupanija, Croatia, 31000
        • Duplicate_Klinicki bolnicki centar Osijek /ID# 150216
    • Primorsko-goranska Zupanija
      • Rijeka, Primorsko-goranska Zupanija, Croatia, 51000
        • Klinicki bolnicki centar Rijeka /ID# 150708
    • Splitsko-dalmatinska Zupanija
      • Split, Splitsko-dalmatinska Zupanija, Croatia, 21000
        • Klinicki bolnicki centar Split /ID# 213988
      • Hradec Kralove, Czechia, 500 12
        • Hepato-Gastroenterologie HK, s.r.o. /ID# 150912
      • Olomouc, Czechia, 779 00
        • CTCenter MaVe s.r.o. /ID# 150904
      • Ostrava, Czechia, 722 00
        • ARTROSCAN s.r.o. /ID# 150401
      • Pardubice, Czechia, 530 03
        • Nemocnice Pardubickeho kraje, a.s. /ID# 213539
      • Praha, Czechia, 118 33
        • Nemocnice Milosrdnych sester sv. Karla Boromejskeho v Praze /ID# 216221
      • Praha, Czechia, 140 00
        • Axon Clinical, s.r.o. /ID# 152479
      • Praha, Czechia, 190 00
        • ISCARE a.s. /ID# 209278
      • Tallinn, Estonia, 10617
        • West Tallinn Central Hospital /ID# 150419
    • Harjumaa
      • Kesklinna Linnaosa, Harjumaa, Estonia, 10138
        • East Tallinn Central Hospital /ID# 150417
      • Mustamäe Linnaosa, Harjumaa, Estonia, 13419
        • North Estonia Medical Centre /ID# 160870
    • Tartumaa
      • Tartu Linn, Tartumaa, Estonia, 50406
        • Tartu University Hospital /ID# 150418
      • Helsinki, Finland, 00290
        • Duplicate_Helsinki Univ Central Hospital /ID# 150407
      • Jyvaskyla, Finland, 40620
        • Keski-Suomen Sairaala Nova /ID# 155666
      • Mikkeli, Finland, 50100
        • Laakarikeskus Ikioma /ID# 150121
      • Turku, Finland, 20520
        • Turku University Hospital /ID# 168301
    • Pirkanmaa
      • Tampere, Pirkanmaa, Finland, 33520
        • Tampere University Hospital /ID# 150114
      • La Roche Sur Yon, France, 85000
        • CHD Vendée- La Roche-sur-Yon - Les Oudairies /ID# 154452
      • SAINT-ETIENNE Cedex 1, France, 42270
        • CHU de Saint-Etienne, Hopital Nord /ID# 154453
    • Alpes-Maritimes
      • Nice, Alpes-Maritimes, France, 06200
        • Chu de Nice-Hopital L'Archet Ii /Id# 152606
    • Auvergne-Rhone-Alpes
      • Pierre Benite CEDEX, Auvergne-Rhone-Alpes, France, 69495
        • HCL - Hôpital Lyon Sud /ID# 152539
    • Bouches-du-Rhone
      • Marseille, Bouches-du-Rhone, France, 13915
        • CHU Hopital Nord /ID# 163508
    • Hauts-de-France
      • Lille, Hauts-de-France, France, 59037
        • CHRU Lille - Hopital Claude Huriez /ID# 152607
    • Herault
      • Montpellier Cedex 5, Herault, France, 34295
        • CHU Montpellier - Hôpital Saint Eloi /ID# 200006
    • Somme
      • Amiens CEDEX 1, Somme, France, 80054
        • CHU Amiens-Picardie Site Sud /ID# 163456
      • Berlin, Germany, 10825
        • MVZ fuer Gastroenterlogie am Bayerischen Platz /ID# 150766
      • Frankfurt am Main, Germany, 60431
        • Agaplesion Markus Krankenhaus /ID# 161982
      • Muenster, Germany, 48155
        • Medizinisches Versorgungszentrum Portal 10 /ID# 207135
      • Wiesbaden, Germany, 65189
        • Praxis medicum /ID# 150166
    • Baden-Wuerttemberg
      • Mannheim, Baden-Wuerttemberg, Germany, 68167
        • Universitatsklinikum Mannheim /ID# 150173
      • Tubingen, Baden-Wuerttemberg, Germany, 72076
        • Universitaetsklinimum Tuebingen /ID# 150767
    • Niedersachsen
      • Munster, Niedersachsen, Germany, 48149
        • Universitatsklinikum Munster /ID# 150158
    • Nordrhein-Westfalen
      • Herne, Nordrhein-Westfalen, Germany, 44623
        • Gastroenterologische Gemeinschaftspraxis Herne /ID# 214574
    • Saarland
      • Saarbrücken, Saarland, Germany, 66111
        • Zentrum für Gastroenterologie Saar MVZ GmbH /ID# 215811
    • Schleswig-Holstein
      • Kiel, Schleswig-Holstein, Germany, 24105
        • Universitaetsklinikum Schleswig-Holstein Campus Kiel /ID# 161981
      • Athens, Greece, 10676
        • General Hospital of Athens Evaggelismos and Ophthalmiatrio of Athens Polyclinic /ID# 150309
      • Ioannina, Greece, 45500
        • University General Hospital of Ioannina /ID# 164248
      • Thessaloniki, Greece, 54639
        • Theageneio Anticancer Hospital /ID# 163896
      • Thessaloniki, Greece, 54642
        • General Hospital of Thessaloniki Hippokrateio /ID# 209521
    • Attiki
      • Athens, Attiki, Greece, 11527
        • General Hospital of Athens Laiko /ID# 208669
      • Athens, Attiki, Greece, 11527
        • General Hospital of Chest Diseases of Athens SOTIRIA /ID# 202100
    • Kriti
      • Heraklion, Kriti, Greece, 71500
        • University General Hospital of Heraklion PA.G.N.I /ID# 150250
      • Bekescsaba, Hungary, 5600
        • Bekes Megyei Kozponti Korhaz /ID# 151572
      • Budapest, Hungary, 1085
        • Semmelweis Egyetem /ID# 150312
      • Kecskemet, Hungary, 6000
        • Meditres Kft. /ID# 151521
      • Sopron, Hungary, 9400
        • Soproni Erzsebet Oktato Korhaz es Rehabilitacios Intezet /ID# 151523
      • Szekesfehervar, Hungary, 8000
        • Mentahaz Maganorvosi Kozpont /ID# 205884
    • Vas
      • Szombathely, Vas, Hungary, 9700
        • Markusovszky Egyetemi Oktatokorhaz /ID# 150313
      • Cork, Ireland, T12 WE28
        • Mercy University Hospital /ID# 151529
      • Galway, Ireland, H91 YR71
        • University Hospital Galway /ID# 150319
    • Dublin
      • Beaumont, Dublin, Ireland, D09 XR63
        • Beaumont Hospital /ID# 150321
      • Dublin 8, Dublin, Ireland, D08 NHY1
        • St James Hospital /ID# 150320
      • Elm Park, Dublin, Ireland, D04 T6F4
        • St Vincent's University Hospital /ID# 150318
      • Haifa, Israel, 3109601
        • Rambam Health Care Campus /ID# 150325
      • Jerusalem, Israel, 91031
        • Shaare Zedek Medical Center /ID# 161677
      • Jerusalem, Israel, 91120
        • Hadassah Medical Center-Hebrew University /ID# 165118
    • HaDarom
      • Be'er Sheva, HaDarom, Israel, 8443901
        • Soroka University Medical Center /ID# 156561
      • Bologna, Italy, 40138
        • IRCCS Azienda Ospedaliero-Universitaria di Bologna /ID# 150337
      • Milan, Italy, 20122
        • Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico /ID# 150334
      • Milano, Italy, 20121
        • ASST Fatebenefratelli Sacco - Ospedale Fatebenefratelli e Oftalmico /ID# 150602
      • Palermo, Italy, 90146
        • A.O. Ospedali Riuniti Villa Sofia - Cervello /ID# 150253
    • Lazio
      • Rome, Lazio, Italy, 00152
        • Azienda Ospedaliera San Camillo Forlanini /ID# 151360
    • Milano
      • Rho, Milano, Italy, 20017
        • ASST Rhodense/Presidio Ospedaliero di Rho /ID# 216610
      • Rozzano, Milano, Italy, 20089
        • Istituto Clinico Humanitas /ID# 151361
    • Roma
      • Rome, Roma, Italy, 00133
        • Fondazione PTV Policlinico Tor Vergata /ID# 150338
      • Rome, Roma, Italy, 00168
        • Presidio Columbus-Fondazione Policlinico Universitario Agostino Gemelli IRCCS-Un /ID# 150333
    • Verona
      • Negrar, Verona, Italy, 37024
        • IRCCS Ospedale Sacro Cuore Don Calabria /ID# 201725
      • Takatsuki-shi, Japan, 569-0086
        • Shoyukai Fujita Gastroenterological Hospital /ID# 216492
    • Aichi
      • Nagakute-shi, Aichi, Japan, 480-1195
        • Aichi Medical University Hospital /ID# 151993
      • Nagoya shi, Aichi, Japan, 467-8602
        • Nagoya City University Hospital /ID# 151950
      • Nagoyashi, Aichi, Japan, 4668560
        • Nagoya University Hospital /ID# 152709
      • Toyohashi-shi, Aichi, Japan, 441-8570
        • Toyohashi Municipal Hospital /ID# 171457
      • Toyota-shi, Aichi, Japan, 470-1219
        • Ieda Hospital /ID# 157781
    • Aomori
      • Hirosaki-shi, Aomori, Japan, 036-8545
        • Hirosaki National Hospital /ID# 152763
    • Chiba
      • Abiko-shi, Chiba, Japan, 270-1168
        • Tokatsu Tsujinaka Hospital /ID# 214962
      • Kashiwa-shi, Chiba, Japan, 277-0871
        • Tsujinaka Hospital Kashiwanoha /ID# 209130
      • Sakura-shi, Chiba, Japan, 285-8741
        • Toho University Sakura Medical Center /ID# 151936
      • Urayasu-shi, Chiba, Japan, 279-0021
        • Juntendo University Urayasu Hospital /ID# 208781
    • Fukui
      • Fukui-shi, Fukui, Japan, 910-8526
        • Fukui Prefectural Hospital /ID# 210448
    • Fukuoka
      • Chikushino-shi, Fukuoka, Japan, 818-8502
        • Fukuoka University Chikushi Hospital /ID# 152628
      • Fukuoka-shi, Fukuoka, Japan, 810-0001
        • Saiseikai Fukuoka Genaral Hospital /ID# 209479
      • Fukuoka-shi, Fukuoka, Japan, 812-8582
        • Kyushu University Hospital /ID# 152526
      • Kitakyushu, Fukuoka, Japan, 8020077
        • Kitakyushu Municipal Med Ctr /ID# 152588
      • Kurume-shi, Fukuoka, Japan, 830-0011
        • Kurume University Hospital /ID# 151976
    • Gifu
      • Ogaki-shi, Gifu, Japan, 503-8502
        • Ogaki Municipal Hospital /ID# 208225
    • Hiroshima
      • Fukuyama-shi, Hiroshima, Japan, 720-8520
        • NHO Fukuyama Medical Center /ID# 206293
      • Hiroshima-shi, Hiroshima, Japan, 734-8551
        • Hiroshima University Hospital /ID# 151951
    • Hokkaido
      • Asahikawa-shi, Hokkaido, Japan, 078-8510
        • Asahikawa Medical University Hospital /ID# 170289
      • Obihiro-shi, Hokkaido, Japan, 080-0024
        • Obihiro kosei Hospital /ID# 210412
      • Sapporo-shi, Hokkaido, Japan, 004-0041
        • Sapporo Tokushukai Hospital /ID# 209397
      • Sapporo-shi, Hokkaido, Japan, 060-0033
        • Hokkaido P.W.F.A.C. Sapporo-Kosei General Hospital /ID# 151506
      • Sapporo-shi, Hokkaido, Japan, 060-8543
        • Sapporo Medical University Hospital /ID# 206492
      • Sapporo-shi, Hokkaido, Japan, 065-0033
        • Sapporo Higashi Tokushukai Hospital /ID# 208487
    • Hyogo
      • Kobe-shi, Hyogo, Japan, 650-0015
        • Aoyama Clinic /ID# 152049
      • Nishinomiya-shi, Hyogo, Japan, 663-8501
        • Hyogo College of Medicine College Hospital /Id# 152434
    • Ibaraki
      • Higashi Ibaraki-gun, Ibaraki, Japan, 311-3193
        • National Hospital Organization Mito Medical Center /ID# 152631
    • Ishikawa
      • Kanazawa-shi, Ishikawa, Japan, 920-8641
        • Kanazawa University Hospital /ID# 205099
    • Iwate
      • Morioka-shi, Iwate, Japan, 020-8505
        • Iwate Medical University Uchimaru Medical Center /ID# 203411
    • Kagoshima
      • Kagoshima-shi, Kagoshima, Japan, 890-0064
        • Imamura General Hospital /ID# 227134
      • Kagoshima-shi, Kagoshima, Japan, 892-0824
        • Idzuro Imamura Hospital /ID# 206024
      • Kagoshima-shi, Kagoshima, Japan, 892-0846
        • Sameshima Hospital /ID# 206672
    • Kanagawa
      • Kawasaki-shi, Kanagawa, Japan, 216-8511
        • St. Marianna University School of Medicine Hospital /ID# 208654
      • Yokohama shi, Kanagawa, Japan, 232-0024
        • Yokohama City University Medical Center /ID# 169899
      • Yokohama-shi, Kanagawa, Japan, 227-8501
        • Showa University Fujigaoka Hospital /ID# 208222
    • Kyoto
      • Kyoto-shi, Kyoto, Japan, 605-0981
        • Japanese Red Cross Kyoto Daiichi Hosital /ID# 152359
      • Kyoto-shi, Kyoto, Japan, 606-8507
        • Kyoto University Hospital /ID# 211758
    • Mie
      • Tsu-shi, Mie, Japan, 514-8507
        • Mie University Hospital /ID# 205362
      • Yokkaichi-shi, Mie, Japan, 510-0016
        • Yokkaichi Hazu Medical Center /ID# 214347
    • Miyagi
      • Sendai-shi, Miyagi, Japan, 983-8520
        • National Hospital Organization Sendai Medical Center /ID# 209527
    • Nagasaki
      • Omura-shi, Nagasaki, Japan, 856-8562
        • NHO Nagasaki Medical Center /ID# 209531
    • Nara
      • Yamatotakada-shi, Nara, Japan, 635-0022
        • Kenseikai Dongo Hospital /ID# 208100
    • Niigata
      • Niigata-shi, Niigata, Japan, 950-1104
        • Saiseikai Niigata Hospital /ID# 209916
      • Niigata-shi, Niigata, Japan, 951-8520
        • Niigata University Medical & Dental Hospital /ID# 218048
    • Oita
      • Oita-shi, Oita, Japan, 870-0823
        • Ishida Clinic of IBD and Gastroenterology /ID# 210117
    • Okayama
      • Kurashiki-shi, Okayama, Japan, 710-0142
        • Chikuba Hospital for Proctological and Gastrointestinal Diseases /ID# 157821
      • Okayama-shi, Okayama, Japan, 700-8558
        • Okayama University Hospital /ID# 217923
    • Osaka
      • Osaka-shi, Osaka, Japan, 530-0011
        • Kinshukai Infusion Clinic /ID# 207864
      • Osaka-shi, Osaka, Japan, 530-8480
        • Kitano Hospital /ID# 210395
      • Osaka-shi, Osaka, Japan, 534-0021
        • Osaka City General Hospital /ID# 152704
      • Osaka-shi, Osaka, Japan, 543-8555
        • Japanese Red Cross Osaka Hospital /ID# 209476
      • Osaka-shi, Osaka, Japan, 545-8586
        • Osaka City University Hospital /ID# 152682
      • Toyonaka-shi, Osaka, Japan, 560-0055
        • Toyonaka Municipal Hospital /ID# 217079
    • Saga
      • Saga-shi, Saga, Japan, 849-8501
        • Saga University Hospital /ID# 209268
    • Saitama
      • Kawagoe-shi, Saitama, Japan, 350-8550
        • Saitama Medical Center /ID# 152031
      • Saitama-shi, Saitama, Japan, 336-0963
        • Tokitokai Tokito clinic /ID# 152677
    • Shiga
      • Higashi-ohmi-shi, Shiga, Japan, 527-8505
        • National Hospital Organization Higashi-Ohmi General Medical Center /ID# 210709
    • Shimane
      • Izumo-shi, Shimane, Japan, 693-8501
        • Shimane University Hospital /ID# 208899
    • Shizuoka
      • Hamamatsu-shi, Shizuoka, Japan, 431-3192
        • Hamamatsu University Hospital /ID# 205708
      • Sunto-gun, Shizuoka, Japan, 411-8611
        • NHO Shizuoka Medical Center /ID# 163572
    • Tokyo
      • Bunkyo-ku, Tokyo, Japan, 113-8519
        • Tokyo Medical And Dental University Hospital /ID# 152016
      • Chuo-ku, Tokyo, Japan, 104-8560
        • St.Luke's International Hospital /ID# 208074
      • Hachioji-shi, Tokyo, Japan, 192-0032
        • Tokai University Hachioji Hospital /ID# 152587
      • Itabashi-ku, Tokyo, Japan, 173-8606
        • Teikyo University Hospital /ID# 208897
      • Minato-ku, Tokyo, Japan, 108-8642
        • Kitasato University Kitasato Institute Hospital /ID# 152686
      • Mitaka-shi, Tokyo, Japan, 181-8611
        • Kyorin University Hospital /ID# 153194
      • Shinjuku-ku, Tokyo, Japan, 162-8655
        • Center Hospital of the National Center for Global Health and Medicine /ID# 209267
      • Shinjuku-ku, Tokyo, Japan, 162-8666
        • Tokyo Women's Medical University Hospital /ID# 205977
    • Yamagata
      • Yamagata-shi, Yamagata, Japan, 990-9585
        • Yamagata University Hospital /ID# 171454
    • Yamaguchi
      • Shunan-shi, Yamaguchi, Japan, 745-8522
        • Tokuyama Central Hospital /ID# 216993
    • Yamanashi
      • Kofu-shi, Yamanashi, Japan, 400-8506
        • Yamanashi Prefectural Central Hospital /ID# 151908
      • Busan, Korea, Republic of, 49201
        • Dong-A University Hospital /ID# 159480
      • Busan, Korea, Republic of, 49241
        • Pusan National University Hospital /ID# 159481
      • Daegu, Korea, Republic of, 42415
        • Yeungnam University Medical Center /ID# 150345
      • Seoul, Korea, Republic of, 05505
        • Asan Medical Center /ID# 150900
      • Seoul, Korea, Republic of, 06351
        • Samsung Medical Center /ID# 150346
    • Gyeonggido
      • Guri, Gyeonggido, Korea, Republic of, 11923
        • Hayang University GuriHospital /ID# 150344
      • Seongnam si, Gyeonggido, Korea, Republic of, 13496
        • CHA University Bundang Medical Center /ID# 159479
      • Suwon, Gyeonggido, Korea, Republic of, 16247
        • The Catholic University of Korea, ST. Vincent's Hospital /ID# 150347
    • Seoul Teugbyeolsi
      • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 03181
        • Kangbuk Samsung Hospital /ID# 150348
      • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 03722
        • Yonsei University Health System Severance Hospital /ID# 159478
      • Riga, Latvia, 1002
        • Pauls Stradins Clinical University Hospital /ID# 151409
      • Riga, Latvia, LV-1079
        • Riga East Clinical University Hospital /ID# 150354
      • Kaunas, Lithuania, 50161
        • Hospital of Lithuanian University of Health Sciences Kaunas Clinics /ID# 150357
      • Klaipeda, Lithuania, 92288
        • Klaipeda Seamens Hospital /ID# 154319
      • Klaipeda, Lithuania, 92288
        • Klaipeda University Hospital /ID# 158862
      • Vilnius, Lithuania, LT-08661
        • Vilnius University Hospital /ID# 154318
      • Ampang, Malaysia, 68000
        • Hospital Ampang /ID# 151298
      • Kuala Lumpur, Malaysia, 59100
        • Uni Malaya MC /ID# 150359
    • Kedah
      • Alor Setar, Kedah, Malaysia, 05460
        • Hospital Sultanah Bahiyah /ID# 151687
    • Selangor
      • Kuala Lumpur, Selangor, Malaysia, 56000
        • Universiti Kebangsaan Malaysia (UKM) Medical Centre /ID# 151689
    • Guanajuato
      • Leon, Guanajuato, Mexico, 37000
        • Morales Vargas Centro de Investigacion S.C. /ID# 211325
    • Jalisco
      • Guadalajara, Jalisco, Mexico, 44650
        • Clinica de Investigacion en Reumatologia y Obesidad S.C. /ID# 150710
    • Nuevo Leon
      • Monterrey, Nuevo Leon, Mexico, 64610
        • Centro Regiomontano de Estudios Clínicos ROMA S.C /ID# 150256
      • Amsterdam, Netherlands, 1105 AZ
        • Academisch Medisch Centrum /ID# 150647
      • Leiden, Netherlands, 2333 ZA
        • Leids Universitair Medisch Centrum /ID# 152624
      • Utrecht, Netherlands, 3584 CX
        • Universitair Medisch Centrum Utrecht /ID# 152775
    • Gelderland
      • Nijmegen, Gelderland, Netherlands, 6525 GA
        • Radboud Universitair Medisch Centrum /ID# 151700
    • Zuid-Holland
      • Rotterdam, Zuid-Holland, Netherlands, 3015 GD
        • Erasmus Medisch Centrum /ID# 150308
    • Akershus
      • Nordbyhagen, Akershus, Norway, 1474
        • Akershus universitetssykehus /ID# 150317
    • Troms
      • Tromsø, Troms, Norway, 9019
        • Universitetssykehuset Nord-Norge /ID# 152835
    • Kujawsko-pomorskie
      • Torun, Kujawsko-pomorskie, Poland, 87-100
        • Gastromed /Id# 216197
    • Mazowieckie
      • Warszawa, Mazowieckie, Poland, 00-635
        • Centrum Zdrowia MDM /ID# 150351
      • Warszawa, Mazowieckie, Poland, 02-507
        • Centralny Szpital Kliniczny MSWiA w Warszawie /ID# 150580
      • Warszawa, Mazowieckie, Poland, 02-665
        • Centrum Medyczne Reuma Park /ID# 150349
      • Warszawa, Mazowieckie, Poland, 03-580
        • NZOZ Vivamed /ID# 216742
      • Warszawa, Mazowieckie, Poland, 04-730
        • Instytut Pomnik - Centrum Zdrowia Dziecka /ID# 215732
    • Pomorskie
      • Sopot, Pomorskie, Poland, 81-756
        • Endoskopia Sp. z o.o. /ID# 150765
      • Almada, Portugal, 2805-267
        • Hospital Garcia de Orta, EPE /ID# 151613
      • Braga, Portugal, 4710-243
        • CCA Braga - Hospital de Braga /ID# 151608
      • Lisboa, Portugal, 1169-050
        • Centro Hospitalar Universitario Lisboa Central, EPE - Hospital dos Capuchos /ID# 151611
      • Lisboa, Portugal, 1649-035
        • Centro Hospitalar Universitário de Lisboa Norte, EPE - Hospital de Santa Maria /ID# 151606
      • Porto, Portugal, 4200-319
        • Centro Hospitalar Universitario de Sao Joao, EPE /ID# 151610
    • Braga
      • Guimaraes, Braga, Portugal, 4835-044
        • Hospital da Senhora da Oliveira Guimaraes, EPE /ID# 151607
    • Porto
      • Santa Maria Da Feira, Porto, Portugal, 4520-211
        • Centro Hospitalar de Entre Douro e Vouga /ID# 152335
    • Viana Do Castelo
      • Ponte de Lima, Viana Do Castelo, Portugal, 4990-041
        • Unidade Local de Saúde do Alto Minho, EPE - Hospital Conde de Bertiandos /ID# 151609
      • San Juan, Puerto Rico, 00935
        • School of Medicine University of Puerto Rico-Medical Science Campus /ID# 150358
      • Moscow, Russian Federation, 105554
        • Olla-Med Clinic /ID# 215332
      • Moscow, Russian Federation, 127015
        • City Clinical Hospital #24 /ID# 150395
      • Petrozavodsk, Russian Federation, 185019
        • Republican hospital named after V.A. Baranov /ID# 206506
      • Pushkin, Russian Federation, 196603
        • Euromedservice /ID# 203800
      • Stavropol, Russian Federation, 355017
        • Duplicate_Stavropol State Medical Univ /ID# 150387
    • Kaliningradskaya Oblast
      • Kaliningrad, Kaliningradskaya Oblast, Russian Federation, 236016
        • Immanuel Kant Baltic Federal University /ID# 200719
    • Leningradskaya Oblast
      • St. Petersburg, Leningradskaya Oblast, Russian Federation, 191015
        • NW State Medical Univ na Mechn /ID# 169322
    • Permskiy Kray
      • Perm, Permskiy Kray, Russian Federation, 614109
        • Perm Clinical Center of the Federal Medical and Biological Agency /ID# 150386
    • Samarskaya Oblast
      • Samara, Samarskaya Oblast, Russian Federation, 443063
        • Medical Company Hepatolog /ID# 200197
    • Stavropol Skiy Kray
      • Pyatigorsk, Stavropol Skiy Kray, Russian Federation, 357500
        • LLC Novaya Klinika /ID# 208107
    • Tatarstan, Respublika
      • Kazan, Tatarstan, Respublika, Russian Federation, 420012
        • Kazan State Medical University /ID# 166042
      • Leskovac, Serbia, 16000
        • General Hospital Leskovac /ID# 217880
    • Beograd
      • Belgrade, Beograd, Serbia, 11000
        • Clinical Hosp Center Zvezdara /ID# 150427
      • Belgrade, Beograd, Serbia, 11000
        • Military Medical Academy /ID# 150429
      • Belgrade, Beograd, Serbia, 11000
        • University Clinical Center Serbia /ID# 150428
      • Belgrade, Beograd, Serbia, 11080
        • Clin Hosp Ctr Bezanijska Kosa /ID# 150426
    • Nisavski Okrug
      • NIS, Nisavski Okrug, Serbia, 18000
        • University Clinical Center of Nis /ID# 151903
    • Sumadijski Okrug
      • Kragujevac, Sumadijski Okrug, Serbia, 34000
        • University Clinical Center Kragujevac /ID# 150430
    • Vojvodina
      • Novi Sad, Vojvodina, Serbia, 21000
        • Clinical Center Vojvodina /ID# 150764
      • Singapore, Singapore, 119074
        • National University Hospital /ID# 150453
      • Singapore, Singapore, 258499
        • Gleneagles Medical Centre /ID# 206018
      • Singapore, Singapore, 308433
        • Tan Tock Seng Hospital /ID# 150443
      • Banska Bystrica, Slovakia, 975 17
        • Fakultna nemocnica s poliklinikou F.D. Roosevelta Banska Bystrica /ID# 150868
      • Bratislava, Slovakia, 851 01
        • Medak s.r.o. /ID# 150480
      • Ilava, Slovakia, 019 01
        • Slovak Research Center Team Me /ID# 150257
      • Kosice, Slovakia, 040 01
        • B+B MED, s.r.o. /ID# 150471
      • Nove Zamky, Slovakia, 940 34
        • Fakultna nemocnica s poliklinikou Nove Zamky /ID# 211370
      • Presov, Slovakia, 080 01
        • GASTRO I., s.r.o. /ID# 150472
    • Gauteng
      • Boksburg North, Gauteng, South Africa, 1460
        • MD Search /ID# 167293
      • Johannesburg, Gauteng, South Africa, 1619
        • Clinresco Centers /ID# 163622
      • Johannesburg, Gauteng, South Africa, 1820
        • Lenasia Clinical Trial Centre /ID# 214344
      • Johannesburg, Gauteng, South Africa, 2193
        • Wits Clinical Research , Wits Health Consortium (PTY) Ltd /ID# 150785
      • Johannesburg, Gauteng, South Africa, 2193
        • Wits Clinical Research Site /ID# 150496
    • Western Cape
      • CAPE TOWN Milnerton, Western Cape, South Africa, 7441
        • Spoke Research Inc /ID# 162202
      • Cape Town, Western Cape, South Africa, 7708
        • Kingsbury Hospital /ID# 150497
      • Cape Town, Western Cape, South Africa, 7800
        • Private Practice Dr MN Rajabally /ID# 155144
      • A Coruna, Spain, 15006
        • Hospital Universitario A Coruna - CHUAC /ID# 203911
      • Barcelona, Spain, 08036
        • Hospital Clinic de Barcelona /ID# 150612
      • Cordoba, Spain, 14004
        • Hospital Universitario Reina Sofia /ID# 151066
      • Madrid, Spain, 28034
        • Hospital Universitario Ramon y Cajal /ID# 151067
      • Madrid, Spain, 28046
        • Hospital Universitario La Paz /ID# 214539
      • Salamanca, Spain, 37711
        • Hospital Universitario de Salamanca /ID# 150509
      • Valencia, Spain, 46026
        • Hospital Universitario y Politecnico La Fe /ID# 150611
    • A Coruna
      • Santiago de Compostela, A Coruna, Spain, 15706
        • Hospital Clínico Universitario de Santiago-CHUS /ID# 151065
    • Cantabria
      • Santander, Cantabria, Spain, 39008
        • Hospital Unversitario Marques de Valdecilla /ID# 216620
    • Las Palmas
      • Las Palmas de Gran Canaria, Las Palmas, Spain, 35019
        • Hospital Universitario Dr. Negrin /ID# 203937
    • Vastra Gotalands Lan
      • Gothenburg, Vastra Gotalands Lan, Sweden, 413 45
        • Sahlgrenska University Hospital /ID# 151496
      • Bern, Switzerland, 3010
        • Inselspital, Universitätsspital Bern /ID# 152590
    • Basel-Stadt
      • Basel, Basel-Stadt, Switzerland, 4031
        • Universitätsspital Basel /ID# 161731
    • Sankt Gallen
      • St. Gallen, Sankt Gallen, Switzerland, 9007
        • Kantonsspital St. Gallen /ID# 152599
    • Zuerich
      • Zürich, Zuerich, Switzerland, 8091
        • Universitätsspital Zürich /ID# 152591
      • Kaohsiung, Taiwan, 807
        • Kaohsiung Medical University Chung-Ho Memorial Hospital /ID# 150575
      • Taichung, Taiwan, 40201
        • Chung Shan Medical University Hospital /ID# 150573
      • Taichung City, Taiwan, 40447
        • China Medical University Hospital /ID# 150571
      • Tainan, Taiwan, 704
        • National Cheng Kung University Hospital /ID# 151749
      • Taipei City, Taiwan, 100
        • National Taiwan University Hospital /ID# 150574
      • Taipei City, Taiwan, 11217
        • Taipei Veterans General Hosp /ID# 151748
      • Istanbul, Turkey, 34098
        • Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty /ID# 150125
      • Istanbul, Turkey, 34764
        • Umraniye Training and Res Hosp /ID# 162659
      • Istanbul, Turkey, 34899
        • Marmara University Medical Fac /ID# 213969
      • Mersin, Turkey, 33343
        • Mersin University Medical /ID# 157849
      • Yenimahalle, Turkey, 06560
        • Gazi Universitesi Tip Fakultes /ID# 150127
    • Kayseri
      • Melikgazi, Kayseri, Turkey, 38030
        • Erciyes University Medical Fac /ID# 150129
      • Dnipro, Ukraine, 49005
        • Municipal Enterprise "I.I. Mechnikov Dnipropetrovsk Regional Clinical Hospital" /ID# 207723
      • Kharkiv, Ukraine, 61058
        • CNCE of Kharkiv Regional Council Regional Clinical Hospital /ID# 206940
      • Kropyvnytskyi, Ukraine, 25006
        • PE PMC Acinus, Medical and Diagnostic Center /ID# 217216
      • Kyiv, Ukraine, 01030
        • Kyiv Municipal Clinical Hospital #18 /ID# 150372
      • Kyiv, Ukraine, 04050
        • Medical Center CONSILIUM MEDICAL /ID# 217446
      • Kyiv, Ukraine, 04073
        • CNPE of Kyiv Regional Council Kyiv Regional Hospital /ID# 217372
      • Lviv, Ukraine, 79010
        • Lviv Regional Clinical Hospital /ID# 150375
      • Odesa, Ukraine, 65025
        • Municipal Non-Commercial Enterprise Odesa Regional Clinical Hospital of the Od /ID# 151275
      • Vinnytsia, Ukraine, 21028
        • CNE Vinnytsya Regional Clinical Hospital named after N.I.Pirogov /ID# 216297
    • Vinnytska Oblast
      • Vinnytsya, Vinnytska Oblast, Ukraine, 21009
        • Medical Center of the "Health /ID# 151274
      • Bath, United Kingdom, BA1 3NG
        • Royal United Hospitals Bath /ID# 151532
      • Birmingham, United Kingdom, B15 2TH
        • University Hospitals Birmingham NHS Foundation Trust /ID# 150382
      • Huddersfield, United Kingdom, HX3 0PW
        • Calderdale and Huddersfield NHS Foundation Trust /ID# 217658
      • Tooting, United Kingdom, SW17 0QT
        • St George's University Hospitals NHS Foundation Trust /ID# 208374
    • Devon
      • Exeter, Devon, United Kingdom, EX2 5DW
        • Royal Devon and Exeter NHS Trust Hospital /ID# 150379
    • Essex
      • Basingstoke, Essex, United Kingdom, RG24 9NA
        • Hampshire Hospitals NHS Foundation Trust /ID# 150380
    • London, City Of
      • London, London, City Of, United Kingdom, E1 2ES
        • Barts Health NHS Trust /ID# 150384
    • Scotland
      • Glasgow, Scotland, United Kingdom, G12 0XH
        • NHS Greater Glasgow and Clyde /ID# 163787
    • Alabama
      • Birmingham, Alabama, United States, 35209
        • Birmingham Gastroenterology Associates P.C /ID# 151276
      • Mobile, Alabama, United States, 36606
        • East View Medical Research, LLC /ID# 171183
      • Mobile, Alabama, United States, 36608
        • CB Flock Research Corporation /ID# 165980
    • Arizona
      • Chandler, Arizona, United States, 85224
        • Delsol Research Management, Ll /Id# 170131
      • Mesa, Arizona, United States, 85206
        • Digestive Disease Consultants, A Division of Arizona Digestive Health, P.C /ID# 211885
      • Sun City, Arizona, United States, 85306
        • Arizona Arthritis & Rheumatology Research, PLLC /ID# 169822
      • Tucson, Arizona, United States, 85712
        • Adobe Clinical Research LLC /ID# 155250
      • Tucson, Arizona, United States, 85724
        • University of Arizona /ID# 150553
    • California
      • Covina, California, United States, 91722-3797
        • Citrus Valley Gastroenterology /ID# 151914
      • Huntington Beach, California, United States, 92648-5994
        • Newport Huntington Medical Group /ID# 217005
      • La Jolla, California, United States, 92093
        • UC San Diego Health System /ID# 155185
      • Los Alamitos, California, United States, 90720-3309
        • United Medical Doctors /ID# 207464
      • Los Angeles, California, United States, 90048
        • TLC Clinical Research Inc /ID# 216829
      • Los Angeles, California, United States, 90067-2001
        • Gastrointestinal Biosciences Clinical Trials, LLC /ID# 157080
      • Mission Hills, California, United States, 91345
        • Facey Medical Foundation /ID# 203133
      • Murrieta, California, United States, 92563
        • United Medical Doctors - Murrieta /ID# 151211
      • Oxnard, California, United States, 93030
        • InSite Digestive Health Care - Oxnard /ID# 163414
      • Rialto, California, United States, 92377
        • Inland Empire Clinical Trials, LLC /ID# 216038
      • San Diego, California, United States, 92120
        • San Diego Clinical Trials /ID# 212120
      • San Diego, California, United States, 92123
        • Medical Assoc Research Grp /ID# 169148
      • San Francisco, California, United States, 94158
        • Univ of California San Francis /ID# 164581
    • Colorado
      • Colorado Springs, Colorado, United States, 80918
        • Delta Waves, Inc. /ID# 151721
      • Lone Tree, Colorado, United States, 80124
        • South Denver Gastroenterology /ID# 151223
      • Wheat Ridge, Colorado, United States, 80033-2896
        • Western States Clinical Res /ID# 158076
    • Connecticut
      • Danbury, Connecticut, United States, 06810
        • Western Connecticut Medical Group /ID# 169210
      • Hamden, Connecticut, United States, 06518
        • Medical Research Center of CT /ID# 150482
    • Florida
      • Clearwater, Florida, United States, 33756
        • Gastro Florida /ID# 155245
      • Doral, Florida, United States, 33166
        • Moonshine Research Center, Inc /ID# 152533
      • Doral, Florida, United States, 33166
        • Universal Axon Clinical Research /ID# 213461
      • Hialeah, Florida, United States, 33016
        • Palmetto Research, LLC /ID# 151716
      • Inverness, Florida, United States, 34452-4717
        • Nature Coast Clinical Research - Inverness /ID# 154064
      • Jacksonville, Florida, United States, 32256
        • Encore Borland-Groover Clinical Research /Id# 170912
      • Kissimmee, Florida, United States, 34741-4161
        • SIH Research Mumtaz, Inc /ID# 163319
      • Maitland, Florida, United States, 32751-6108
        • Cfagi Llc /Id# 202017
      • Miami, Florida, United States, 33136
        • University of Miami /ID# 215441
      • Miami, Florida, United States, 33147
        • Advanced Pharma /ID# 151719
      • Miami, Florida, United States, 33165-3372
        • New Horizon Research Center /ID# 152474
      • Miami, Florida, United States, 33165
        • Crystal Pharmacology Research /ID# 151841
      • Miami, Florida, United States, 33186-4643
        • Coral Research Clinic /ID# 150444
      • New Port Richey, Florida, United States, 34653
        • Advanced Research Institute, Inc /ID# 163098
      • Orlando, Florida, United States, 32803
        • Endoscopic Research, Inc. /ID# 151720
      • Orlando, Florida, United States, 32808
        • Omega Research Maitland, LLC /ID# 200269
      • Tampa, Florida, United States, 33607
        • Clinical Research Trials of Florida, Inc. /ID# 201790
      • Tampa, Florida, United States, 33612
        • University of South Florida /ID# 214493
      • Tampa, Florida, United States, 33613-4680
        • AdventHealth Tampa /ID# 200272
    • Georgia
      • Macon, Georgia, United States, 31201
        • Gastroenterology Associates of Central Georgia, LLC /ID# 165782
      • Riverdale, Georgia, United States, 30274
        • Infinite Clinical Trials /ID# 215340
      • Suwanee, Georgia, United States, 30024
        • Atlanta Gastroenterology Spec /ID# 150548
    • Illinois
      • Chicago, Illinois, United States, 60605-2168
        • Next Innovative Clinical Research - Chicago /ID# 216060
      • Chicago, Illinois, United States, 60637
        • The University of Chicago DCAM /ID# 150547
      • Evanston, Illinois, United States, 60201
        • NorthShore University HealthSystem /ID# 150555
      • Hoffman Estates, Illinois, United States, 60169
        • Northwest Health Care Associates /ID# 151590
      • Urbana, Illinois, United States, 61801
        • Carle Foundation Hospital /ID# 151137
    • Indiana
      • Evansville, Indiana, United States, 47714-8011
        • MediSphere Medical Research Center /ID# 152064
      • Indianapolis, Indiana, United States, 46237
        • Indianapolis Gastroenterology /ID# 162901
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa Hospitals and Clinics /ID# 157058
    • Kansas
      • Topeka, Kansas, United States, 66606
        • Cotton-O'Neil Clinical Res Ctr /ID# 167182
    • Kentucky
      • Crestview Hills, Kentucky, United States, 41017
        • Tri-State Gastroenterology /ID# 169811
    • Louisiana
      • Houma, Louisiana, United States, 70360
        • Houma Digestive Health Special /ID# 151844
      • New Orleans, Louisiana, United States, 70115
        • Nola Research Works, LLC /ID# 153356
      • Shreveport, Louisiana, United States, 71105-6800
        • Louisana Research Center, LLC /ID# 150446
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • University of Maryland Med Ctr /ID# 150449
      • Columbia, Maryland, United States, 21045
        • Gastro Center of Maryland /ID# 200022
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital /ID# 165676
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan Comprehensive Cancer Center Michigan Medicine /ID# 151140
      • Ann Arbor, Michigan, United States, 48197
        • Huron Gastroenterology Assoc /ID# 152710
      • Chesterfield, Michigan, United States, 48047
        • Clin Res Inst of Michigan, LLC /ID# 153027
      • Southfield, Michigan, United States, 48034-1659
        • Revival Research Institute, LLC /ID# 207280
      • Troy, Michigan, United States, 48098-6363
        • Center for Digestive Health /ID# 161984
      • Wyoming, Michigan, United States, 49519
        • Gastroenterology Associates of Western Michigan, PLC d.b.a. West Michigan Clinic /ID# 157484
    • Minnesota
      • Rochester, Minnesota, United States, 55905-0001
        • Mayo Clinic - Rochester /ID# 151677
      • Saint Paul, Minnesota, United States, 55114
        • Minnesota Gastroenterology PA /ID# 151678
    • Mississippi
      • Jackson, Mississippi, United States, 39216-4500
        • University of Mississippi Medical Center /ID# 213139
      • Jackson, Mississippi, United States, 39216
        • Southern Therapy and Advanced Research (STAR) LLC /ID# 170712
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University-School of Medicine /ID# 150485
    • Nevada
      • Las Vegas, Nevada, United States, 89113
        • Las Vegas Medical Research /ID# 153044
    • New Hampshire
      • Lebanon, New Hampshire, United States, 03756
        • Dartmouth-Hitchcock Medical Center /ID# 150549
    • New Jersey
      • Egg Harbor Township, New Jersey, United States, 08234
        • AGA Clinical Research Associates, LLC /ID# 153040
      • Morristown, New Jersey, United States, 07960
        • Atlantic Digestive Health Inst /ID# 150447
      • New Brunswick, New Jersey, United States, 08901
        • Rutgers Robert Wood Johnson /ID# 155248
    • New Mexico
      • Albuquerque, New Mexico, United States, 87131
        • Duplicate_University of New Mexico Department of Internal Medicine /ID# 214396
    • New York
      • Bronx, New York, United States, 10467
        • Montefiore Medical Center - Moses Campus /ID# 150543
      • Bronx, New York, United States, 10468
        • Advantage Clinical Trials /ID# 163938
      • Brooklyn, New York, United States, 11235
        • NY Scientific /ID# 152707
      • Great Neck, New York, United States, 11021
        • NYU Langone Long Island Clinical Research Association /ID# 155272
      • New York, New York, United States, 10032-3725
        • Columbia Univ Medical Center /ID# 163410
      • North Massapequa, New York, United States, 11758
        • DiGiovanna Institute for Medical Education & Research /ID# 201533
      • Poughkeepsie, New York, United States, 12601
        • Premier Medical Group - GI Division /ID# 153357
      • Rochester, New York, United States, 14618-5703
        • Gastoenterology Group of Rochester /ID# 151079
      • Staten Island, New York, United States, 10310-1664
        • Richmond University Medical Center /ID# 201859
    • North Carolina
      • Asheville, North Carolina, United States, 28801
        • Digestive Health Partners, P.A /ID# 167237
      • Charlotte, North Carolina, United States, 28203
        • Atrium Health Carolinas Medical Center /ID# 156971
      • Charlotte, North Carolina, United States, 28207
        • Charlotte Gastroenterology and Hepatology, PLLC /ID# 150545
      • Greenville, North Carolina, United States, 27834
        • Atlantic Gastroenterology Clinical Research /ID# 151899
      • Winston-Salem, North Carolina, United States, 27103
        • Clinical Trials of America /ID# 153448
      • Winston-Salem, North Carolina, United States, 27157-0001
        • Wake Forest Baptist Medical Center /ID# 150448
    • North Dakota
      • Fargo, North Dakota, United States, 58104-5925
        • Plains Clinical Research Center, LLC /ID# 170290
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • Consultants for Clinical Research /ID# 151679
      • Cincinnati, Ohio, United States, 45267-0585
        • University of Cincinnati /ID# 164582
      • Columbus, Ohio, United States, 43210
        • The Ohio State University /ID# 169416
      • Columbus, Ohio, United States, 43235
        • Optimed Research, Ltd. /ID# 169696
      • Dayton, Ohio, United States, 45424
        • Hometown Urgent Care and Resea /ID# 200065
      • Englewood, Ohio, United States, 45415
        • Dayton Gastroenterology, Inc. /ID# 167631
      • Mentor, Ohio, United States, 44060-6211
        • Great Lakes Medical Research, LLC /ID# 201772
      • Mentor, Ohio, United States, 44060
        • Ohio Clinical Research Partner /ID# 154068
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73102
        • Hightower Clinical /ID# 216337
      • Oklahoma City, Oklahoma, United States, 73112
        • Digestive Disease Specialists /ID# 201056
      • Tulsa, Oklahoma, United States, 74104
        • Options Health Research, LLC /ID# 150554
      • Tulsa, Oklahoma, United States, 74135
        • Healthcare Research Consultant /ID# 163100
    • Oregon
      • Portland, Oregon, United States, 97210
        • Northwest Gastroenterology Clinic /ID# 152527
    • Pennsylvania
      • Sayre, Pennsylvania, United States, 18840
        • Guthrie Medical Group, PC /ID# 150481
      • State College, Pennsylvania, United States, 16803-2309
        • Penn State Health Colonnade /ID# 150259
    • South Carolina
      • Charleston, South Carolina, United States, 29412
        • Pharmacorp Clinical Trials /ID# 153354
      • Greenville, South Carolina, United States, 29615-3593
        • Gastroenterology Associates, P.A. of Greenville /ID# 150541
    • Tennessee
      • Germantown, Tennessee, United States, 38138
        • Gastro One /ID# 151144
      • Johnson City, Tennessee, United States, 37604
        • East Tennessee Research Institute /ID# 203610
      • Nashville, Tennessee, United States, 37211
        • Quality Medical Research /ID# 203426
      • Nashville, Tennessee, United States, 37232-0011
        • Vanderbilt University Medical Center /ID# 153355
    • Texas
      • Arlington, Texas, United States, 76012
        • TX Clinical Research Institute /ID# 151526
      • Baytown, Texas, United States, 77521-2415
        • Inquest Clinical Research /ID# 164635
      • Cedar Park, Texas, United States, 78613-5028
        • Texas Digestive Disease Consultants /ID# 209947
      • Cedar Park, Texas, United States, 78613
        • Texas Digestive Disease Consultants /ID# 209804
      • Dallas, Texas, United States, 75246
        • Baylor Scott & White Center for Inflammatory Bowel Diseases /ID# 200770
      • Garland, Texas, United States, 75044-2208
        • DHAT Research Institute /ID# 151218
      • Houston, Texas, United States, 77017-2337
        • Vilo Research Group Inc /ID# 212624
      • Houston, Texas, United States, 77027-6812
        • CliniCore International, LLC /ID# 152062
      • Houston, Texas, United States, 77030-3411
        • Baylor College of Medicine - Baylor Medical Center /ID# 150486
      • Houston, Texas, United States, 77058
        • Centex Studies, Inc. - Houston /ID# 201216
      • Houston, Texas, United States, 77070-4347
        • GI Specialists of Houston /ID# 202327
      • Lubbock, Texas, United States, 79424-3017
        • Caprock Gastro Research, LLC /ID# 214754
      • San Antonio, Texas, United States, 78212
        • Clinical Associates in Research Therapeutics of America, LLC /ID# 201260
      • San Antonio, Texas, United States, 78229-5390
        • Southern Star Research Institute, LLC /ID# 169396
      • Sugar Land, Texas, United States, 77478
        • Carl R. Meisner Medical Clinic /ID# 171061
      • Temple, Texas, United States, 76508
        • Baylor Scott & White Center for Diagnostic Medicine /ID# 204499
      • Tyler, Texas, United States, 75701-4464
        • Tyler Research Institute, LLC /ID# 169146
      • Victoria, Texas, United States, 77904
        • Gastro Health & Nutrition - Victoria /ID# 167761
    • Utah
      • Bountiful, Utah, United States, 84010
        • HP Clinical Research /ID# 163939
      • Ogden, Utah, United States, 84403
        • Advanced Research Institute /ID# 162624
      • Salt Lake City, Utah, United States, 84124
        • Utah Gastroenternology - St. Mark's Office /ID# 163101
      • West Jordan, Utah, United States, 84088
        • Velocity Clinical Research - Salt Lake City /ID# 163181
    • Virginia
      • Franklin, Virginia, United States, 23851
        • Ctr for Gastrointestinal Healt /ID# 153360
      • Leesburg, Virginia, United States, 20176
        • Emeritas Research Group, LLC /ID# 150258
    • Washington
      • Bellevue, Washington, United States, 98004
        • Washington Gastroenterology /ID# 163629
      • Seattle, Washington, United States, 98101
        • Virginia Mason Medical Center /ID# 153026
      • Seattle, Washington, United States, 98122-4201
        • The Polyclinic /ID# 164369
      • Vancouver, Washington, United States, 98664
        • The Vancouver Clinic, INC. PS /ID# 162333
    • Wisconsin
      • Grafton, Wisconsin, United States, 53024
        • Aurora Medical Center - Grafto /ID# 151717
      • Milwaukee, Wisconsin, United States, 53215
        • Wisconsin Center for Advanced Research, a division of GI Associates, LLC /ID# 151838
      • Milwaukee, Wisconsin, United States, 53226-3522
        • Medical College of Wisconsin /ID# 151843

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 75 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Note: Adolescent participants who are 16 or 17 years old will be eligible to participate if approved by the country or regulatory/health authority. If approval has not been granted, only participants ≥18 years old will be enrolled. Adolescents must weigh ≥ 40 kilograms and meet the definition of Tanner Stage 5 at Screening Visit.

  • Diagnosis of ulcerative colitis for 90 days or greater prior to Baseline, confirmed by colonoscopy during the Screening Period, with exclusion of current infection, colonic dysplasia and/or malignancy. Appropriate documentation of biopsy results consistent with the diagnosis of UC, in the assessment of the Investigator, must be available.
  • Active ulcerative colitis with an Adapted Mayo score of 5 to 9 points and endoscopic sub score of 2 to 3 (confirmed by central reader).
  • Demonstrated an inadequate response to, loss of response to, or intolerance to at least one of the following treatments including: oral aminosalicylates, corticosteroids, immunosuppressants, and/or biologic therapies in the opinion of the investigator.

Note: Participants who have had inadequate response, loss of response to conventional therapy, but have not failed biologic therapy (Non-bio-IR) and have received a prior biologic for up to 1 year may be enrolled, however they must have discontinued the biologic for reasons other than inadequate response or intolerance (e.g., change of insurance, well controlled disease) and must meet criteria for inadequate response, loss of response or intolerance to aminosalicylates, corticosteroids, and/or immunosuppressants as defined above.

  • If female, participant must meet the criteria for Contraception Recommendations
  • Female participants of childbearing potential must have a negative serum pregnancy test at the Screening Visit and a negative urine pregnancy test at the Baseline Visit prior to study drug dosing.

Exclusion Criteria:

  • Participant with current diagnosis of Crohn's disease (CD) or diagnosis of indeterminate colitis (IC)
  • Current diagnosis of fulminant colitis and/or toxic megacolon
  • Participant with disease limited to the rectum (ulcerative proctitis) during the screening endoscopy
  • Received cyclosporine, tacrolimus, mycophenolate mofetil, or thalidomide within 30 days prior to Baseline
  • Participant on azathioprine or 6-mercaptopurine within 10 days of Baseline
  • Received intravenous corticosteroids within 14 days prior to Screening or during the Screening Period.
  • Participant with previous exposure to Janus Activated Kinase (JAK) inhibitor (e.g., tofacitinib, baricitinib, filgotinib, upadacitinib).
  • Screening laboratory and other analyses show any abnormal results meeting the exclusion criteria

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: SS1: Placebo
During the 8-week induction phase in Substudy 1, participants received placebo for upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks.
Film-coated tablet for oral administration
Experimental: SS1: Upadacitinib 7.5 mg
During the 8-week induction phase in Substudy 1, participants received 7.5 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks.
Film-coated tablet for oral administration
Other Names:
  • RINVOQ
  • ABT-494
Experimental: SS1: Upadacitinib 15 mg
During the 8-week induction phase in Substudy 1, participants received 15 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks.
Film-coated tablet for oral administration
Other Names:
  • RINVOQ
  • ABT-494
Experimental: SS1: Upadacitinib 30 mg
During the 8-week induction phase in Substudy 1, participants received 30 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. Additional participants were enrolled during the Substudy 1 analysis period and received 30 mg upadacitinib film-coated tablets once daily by mouth (QD) for 4 weeks.
Film-coated tablet for oral administration
Other Names:
  • RINVOQ
  • ABT-494
Experimental: SS1: Upadacitinib 45 mg
During the 8-week induction phase in Substudy 1, participants received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. Additional participants were enrolled during the Substudy 1 analysis period and received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for 4 weeks.
Film-coated tablet for oral administration
Other Names:
  • RINVOQ
  • ABT-494
Experimental: SS2: Placebo/Upadacitinib 45 mg
During the Substudy 2 Part 1 induction period, participants received placebo for upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. Participants who did not achieve clinical response at Week 8 of Part 1 were enrolled in an open-label extended treatment period and received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for an additional 8 weeks.
Film-coated tablet for oral administration
Film-coated tablet for oral administration
Other Names:
  • RINVOQ
  • ABT-494
Experimental: SS2: Upadacitinib 45 mg/Upadacitinib 45 mg
During the Substudy 2 Part 1 induction period, participants received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. Participants who did not achieve clinical response at Week 8 of Part 1 were enrolled in an open-label expended treatment period and received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for an additional 8 weeks.
Film-coated tablet for oral administration
Other Names:
  • RINVOQ
  • ABT-494
Experimental: SS3: M14-675 clinical responders
Participants in Study M14-675 (NCT03653026) who achieved clinical response defined by Adapted Mayo Score at Week 8 or Week 16 in that study and did not meet any study discontinuation criteria were eligible to enroll into Substudy 3. Participants were re-randomized and treated with a blinded treatment assignment (15 mg upadacitinib film-coated tablets once daily by mouth [QD], or 30 mg upadacitinib film-coated tablets QD, or placebo for upadacitinib film-coated tablets QD) for up to 52 weeks.
Film-coated tablet for oral administration
Film-coated tablet for oral administration
Other Names:
  • RINVOQ
  • ABT-494

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Substudy 1: Percentage Of Participants Who Achieved Clinical Remission Per Adapted Mayo Score at Week 8
Time Frame: At Week 8

The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores:

  1. Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal)
  2. Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed)
  3. Endoscopic subscore, scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration)

The overall Adapted Mayo score ranges from 0 to 9 where higher scores represent more severe disease.

For Substudy 1, clinical remission is defined as SFS ≤ 1, RBS of 0, and endoscopic subscore ≤ 1.

At Week 8
Substudy 2: Percentage Of Participants Who Achieved Clinical Remission Per Adapted Mayo Score at Week 8
Time Frame: At Week 8

The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores:

  1. Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal)
  2. Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed)
  3. Endoscopic subscore, scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration)

The overall Adapted Mayo score ranges from 0 to 9 where higher scores represent more severe disease.

For Substudy 2, clinical remission is defined as SFS ≤ 1 and not greater than Baseline, RBS of 0, and endoscopic subscore ≤ 1. In Substudy 2, evidence of friability during endoscopy in participants with otherwise "mild" endoscopic activity conferred an endoscopic subscore of 2.

At Week 8
Substudy 3: Percentage Of Participants Who Achieved Clinical Remission Per Adapted Mayo Score at Week 52
Time Frame: At Week 52

The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores:

  1. Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal).
  2. Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed).
  3. Endoscopic subscore, scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration).

The overall Adapted Mayo score ranges from 0 to 9 where higher scores represent more severe disease.

For Substudy 3, clinical remission is defined as SFS ≤ 1 and not greater than Baseline, RBS of 0, and endoscopic subscore ≤ 1. In addition, evidence of friability during endoscopy in participants with otherwise "mild" endoscopic activity conferred an endoscopic subscore of 2.

At Week 52

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Substudy 1: Percentage Of Participants With Endoscopic Improvement at Week 8
Time Frame: At Week 8
Endoscopic improvement is defined as an endoscopic subscore of 0 or 1. Endoscopies were assessed by a blinded central reader and scored according to the following scale: 0 = Normal or inactive disease; 1 = Mild disease (erythema, decreased vascular pattern); 2 = Moderate disease (marked erythema, lack of vascular pattern, any friability, erosions); 3 = Severe disease (spontaneous bleeding, ulceration).
At Week 8
Substudy 1: Percentage Of Participants Achieving Clinical Remission Per Full Mayo Score at Week 8
Time Frame: At Week 8
The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The Full Mayo score (FMS) ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy [confirmed by a central reader], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Clinical remission per FMS is defined as Mayo Score ≤ 2 and no individual subscore > 1.
At Week 8
Substudy 1: Percentage Of Participants Achieving Clinical Response Per Adapted Mayo Score at Week 8
Time Frame: At Week 8

The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores:

  1. Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal).
  2. Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed).
  3. Endoscopic subscore, scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration).

The overall Adapted Mayo score ranges from 0 to 9 where higher scores represent more severe disease. Clinical response is defined as a decrease from baseline in the Adapted Mayo score ≥ 2 points and ≥ 30% from baseline, and a decrease in RBS ≥ 1 or an absolute RBS ≤ 1).

At Week 8
Substudy 1: Percentage Of Participants Achieving Clinical Response Per Partial Mayo Score at Week 2
Time Frame: At Week 2

The Partial Mayo Score is a composite score of UC disease activity based on the following 2 subscores:

  1. Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal).
  2. Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed).

The overall Partial Mayo score ranges from 0 to 6 with higher scores representing more severe disease.

Clinical response per Partial Mayo Score is defined as a decrease in Partial Adapted Mayo score ≥ 2 points and ≥ 30% from Baseline, plus a decrease in RBS ≥ 1 or an absolute RBS ≤ 1.

At Week 2
Substudy 1: Change in Full Mayo Score From Baseline to Week 8
Time Frame: Baseline (Week 0), Week 8
The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The Full Mayo score (FMS) ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy [confirmed by a central reader], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Clinical remission per FMS is defined as Mayo Score ≤ 2 and no individual subscore > 1.
Baseline (Week 0), Week 8
Substudy 1: Percentage Of Participants With Endoscopic Remission at Week 8
Time Frame: At Week 8
Endoscopic remission is defined as an endoscopic subscore of 0. Endoscopies were assessed by a blinded central reader and scored according to the following scale: 0 = Normal or inactive disease; 1 = Mild disease (erythema, decreased vascular pattern); 2 = Moderate disease (marked erythema, lack of vascular pattern, any friability, erosions); 3 = Severe disease (spontaneous bleeding, ulceration).
At Week 8
Substudy 1: Percentage Of Participants Who Achieved Histologic Improvement at Week 8
Time Frame: At Week 8

The Geboes histologic index includes seven histological features (architectural change, chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in epithelium, crypt destruction and erosion or ulcers). The Geboes score has 6 grades, each with 3-5 subgrades: Grade 0, structural change only; Grade 1, chronic inflammation; Grade 2, lamina propria neutrophils and eosinophils; Grade 3, neutrophils in epithelium; Grade 4, crypt destruction; and Grade 5, erosions or ulceration.

Histologic improvement was defined as decrease from baseline in Geboes score.

At Week 8
Substudy 2: Percentage Of Participants With Endoscopic Improvement at Week 8
Time Frame: At Week 8
Endoscopic improvement is defined as an endoscopic subscore of 0 or 1. Endoscopies were assessed by a blinded central reader and scored according to the following scale: 0 = Normal or inactive disease; 1 = Mild disease (erythema, decreased vascular pattern); 2 = Moderate disease (marked erythema, lack of vascular pattern, any friability, erosions); 3 = Severe disease (spontaneous bleeding, ulceration).
At Week 8
Substudy 2: Percentage Of Participants With Endoscopic Remission at Week 8
Time Frame: At Week 8
Endoscopic remission is defined as an endoscopic subscore of 0. Endoscopies were assessed by a blinded central reader and scored according to the following scale: 0 = Normal or inactive disease; 1 = Mild disease (erythema, decreased vascular pattern); 2 = Moderate disease (marked erythema, lack of vascular pattern, any friability, erosions); 3 = Severe disease (spontaneous bleeding, ulceration).
At Week 8
Substudy 2: Percentage Of Participants Achieving Clinical Response Per Adapted Mayo Score at Week 8
Time Frame: At Week 8

The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores:

  1. Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal).
  2. Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed).
  3. Endoscopic subscore, scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration).

The overall Adapted Mayo score ranges from 0 to 9 where higher scores represent more severe disease. Clinical response is defined as a decrease from baseline in the Adapted Mayo score ≥ 2 points and ≥ 30% from baseline, and a decrease in RBS ≥ 1 or an absolute RBS ≤ 1).

At Week 8
Substudy 2: Percentage Of Participants Achieving Clinical Response Per Partial Mayo Score at Week 2
Time Frame: At Week 2

The Partial Mayo Score is a composite score of UC disease activity based on the following 2 subscores:

  1. Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal).
  2. Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed).

The overall Partial Mayo score ranges from 0 to 6 with higher scores representing more severe disease.

Clinical response per Partial Mayo Score is defined as a decrease from Baseline ≥ 1 point and ≥ 30% from Baseline, plus a decrease in RBS ≥ 1 or an absolute RBS ≤ 1.

At Week 2
Substudy 2: Percentage Of Participants Who Achieved Histologic-Endoscopic Mucosal Improvement at Week 8
Time Frame: At Week 8

Histologic-endoscopic mucosal improvement is defined as an endoscopic subscore of 0 or 1 and a Geboes score ≤ 3.1.

The endoscopic subscore ranges from 0 (normal or inactive disease) to 3 (severe disease with spontaneous bleeding, ulceration).

The Geboes histologic index includes seven histological features (architectural change, chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in epithelium, crypt destruction and erosion or ulcers). The Geboes score has 6 grades, each with 3-5 subgrades: Grade 0, structural change only; Grade 1, chronic inflammation; Grade 2, lamina propria neutrophils and eosinophils; Grade 3, neutrophils in epithelium; Grade 4, crypt destruction; and Grade 5, erosions or ulceration.

At Week 8
Substudy 2: Percentage Of Participants Who Report No Bowel Urgency at Week 8
Time Frame: At Week 8
Bowel urgency was assessed by participants in a subject diary completed once a day.
At Week 8
Substudy 2: Percentage Of Participants Who Reported No Abdominal Pain at Week 8
Time Frame: At Week 8
Abdominal pain was assessed by participants in a subject diary completed once a day.
At Week 8
Substudy 2: Percentage Of Participants Who Achieved Histologic Improvement at Week 8
Time Frame: At Week 8
The Geboes histologic index includes seven histological features (architectural change, chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in epithelium, crypt destruction and erosion or ulcers). The Geboes score has 6 grades, each with 3-5 subgrades: Grade 0, structural change only; Grade 1, chronic inflammation; Grade 2, lamina propria neutrophils and eosinophils; Grade 3, neutrophils in epithelium; Grade 4, crypt destruction; and Grade 5, erosions or ulceration. Histologic improvement was defined as decrease from baseline in Geboes score.
At Week 8
Substudy 2: Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Week 8
Time Frame: Baseline (Week 0), Week 8
The Inflammatory Bowel Disease Questionnaire (IBDQ) is used to assess health-related quality of life (HRQoL) in patients with ulcerative colitis. It consists of 32 questions evaluating bowel and systemic symptoms, as well as emotional and social functions. Each question is answered on a scale from 1 (worst) to 7 (best). The total score ranges from 32 to 224 with higher scores indicating better health-related quality of life. A positive change from Baseline indicates improvement.
Baseline (Week 0), Week 8
Substudy 2: Percentage Of Participants With Mucosal Healing at Week 8
Time Frame: At Week 8

Mucosal healing is defined as an endoscopic score of 0 and Geboes score < 2.0. The endoscopic subscore ranges from 0 (normal or inactive disease) to 3 (severe disease with spontaneous bleeding, ulceration).

The Geboes histologic index includes seven histological features (architectural change, chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in epithelium, crypt destruction and erosion or ulcers). The Geboes score has 6 grades, each with 3-5 subgrades: Grade 0, structural change only; Grade 1, chronic inflammation; Grade 2, lamina propria neutrophils and eosinophils; Grade 3, neutrophils in epithelium; Grade 4, crypt destruction; and Grade 5, erosions or ulceration.

At Week 8
Substudy 2: Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 8
Time Frame: Baseline (Week 0), Week 8
The FACIT fatigue questionnaire was developed to assess fatigue associated with anemia. It consists of 13 fatigue-related questions. Each question is answered on a 5-point Likert scale: 0 (not at all); 1 (a little bit); 2 (somewhat); 3 (quite a bit); and 4 (very much). The total score ranges from 0 to 52, where higher scores represent less fatigue, and a positive change from Baseline indicates improvement.
Baseline (Week 0), Week 8
Substudy 3: Percentage Of Participants With Endoscopic Improvement at Week 52
Time Frame: At Week 52
Endoscopic improvement is defined as an endoscopic subscore of 0 or 1. Endoscopies were assessed by a blinded central reader and scored according to the following scale: 0 = Normal or inactive disease; 1 = Mild disease (erythema, decreased vascular pattern); 2 = Moderate disease (marked erythema, lack of vascular pattern, any friability, erosions); 3 = Severe disease (spontaneous bleeding, ulceration).
At Week 52
Substudy 3: Percentage of Participants With Clinical Remission Per Adapted Mayo Score at Week 52 Among Those Who Achieved Clinical Remission at the End of the Induction Treatment
Time Frame: At Week 52

The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores:

  1. Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal).
  2. Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed).
  3. Endoscopic subscore, scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration).

The overall Adapted Mayo score ranges from 0 to 9 where higher scores represent more severe disease.

For Substudy 3, clinical remission is defined as SFS ≤ 1 and not greater than Baseline, RBS of 0, and endoscopic subscore ≤ 1. In addition, evidence of friability during endoscopy in participants with otherwise "mild" endoscopic activity conferred an endoscopic subscore of 2.

At Week 52
Substudy 3: Percentage of Participants Who Achieved Clinical Remission Per Adapted Mayo Score at Wk 52 and Were Corticosteroid Free for ≥ 90 Days Immediately Preceding Wk 52 Among Those Who Achieved Clinical Remission at the End of the Induction Treatment
Time Frame: At Week 52

The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores:

  1. Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal).
  2. Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed).
  3. Endoscopic subscore, scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration).

The overall Adapted Mayo score ranges from 0 to 9 where higher scores represent more severe disease.

For Substudy 3, clinical remission is defined as SFS ≤ 1 and not greater than Baseline, RBS of 0, and endoscopic subscore ≤ 1. In addition, evidence of friability during endoscopy in participants with otherwise "mild" endoscopic activity conferred an endoscopic subscore of 2.

At Week 52
Substudy 3: Percentage of Participants With Endoscopic Improvement at Wk 52 Among Those Who Achieved Endoscopic Improvement at the End of the Induction Treatment
Time Frame: At Week 52
Endoscopic improvement is defined as an endoscopic subscore of 0 or 1. Endoscopies were assessed by a blinded central reader and scored according to the following scale: 0 = Normal or inactive disease; 1 = Mild disease (erythema, decreased vascular pattern); 2 = Moderate disease (marked erythema, lack of vascular pattern, any friability, erosions); 3 = Severe disease (spontaneous bleeding, ulceration).
At Week 52
Substudy 3: Percentage Of Participants With Endoscopic Remission At Week 52
Time Frame: At Week 52
Endoscopic remission is defined as an endoscopic subscore of 0. Endoscopies were assessed by a blinded central reader and scored according to the following scale: 0 = Normal or inactive disease; 1 = Mild disease (erythema, decreased vascular pattern); 2 = Moderate disease (marked erythema, lack of vascular pattern, any friability, erosions); 3 = Severe disease (spontaneous bleeding, ulceration).
At Week 52
Substudy 3: Percentage Of Participants Who Maintained Clinical Response Per Adapted Mayo Score at Wk 52 Among Those Who Achieved Clinical Response at the End of the Induction Treatment
Time Frame: At Week 52

The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores:

  1. Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal).
  2. Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed).
  3. Endoscopic subscore, scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration).

The overall Adapted Mayo score ranges from 0 to 9 where higher scores represent more severe disease. Clinical response is defined as a decrease from baseline in the Adapted Mayo score ≥ 2 points and ≥ 30% from baseline, and a decrease in RBS ≥ 1 or an absolute RBS ≤ 1).

At Week 52
Substudy 3: Percentage Of Participants Who Achieved Histologic-Endoscopic Mucosal Improvement at Week 52
Time Frame: At Week 52

Histologic-endoscopic mucosal improvement is defined as an endoscopic subscore of 0 or 1 and a Geboes score ≤ 3.1.

The endoscopic subscore ranges from 0 (normal or inactive disease) to 3 (severe disease with spontaneous bleeding, ulceration).

The Geboes histologic index includes seven histological features (architectural change, chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in epithelium, crypt destruction and erosion or ulcers). The Geboes score has 6 grades, each with 3-5 subgrades: Grade 0, structural change only; Grade 1, chronic inflammation; Grade 2, lamina propria neutrophils and eosinophils; Grade 3, neutrophils in epithelium; Grade 4, crypt destruction; and Grade 5, erosions or ulceration.

At Week 52
Substudy 3: Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Week 52
Time Frame: Baseline (Week 0), Week 52
The Inflammatory Bowel Disease Questionnaire (IBDQ) is used to assess health-related quality of life (HRQoL) in patients with ulcerative colitis. It consists of 32 questions evaluating bowel and systemic symptoms, as well as emotional and social functions. Each question is answered on a scale from 1 (worst) to 7 (best). The total score ranges from 32 to 224 with higher scores indicating better health-related quality of life. A positive change from Baseline indicates improvement.
Baseline (Week 0), Week 52
Substudy 3: Percentage Of Participants With Mucosal Healing at Week 52
Time Frame: At Week 52

Mucosal healing is defined as an endoscopic score of 0 and Geboes score < 2.0. The endoscopic subscore ranges from 0 (normal or inactive disease) to 3 (severe disease with spontaneous bleeding, ulceration).

The Geboes histologic index includes seven histological features (architectural change, chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in epithelium, crypt destruction and erosion or ulcers). The Geboes score has 6 grades, each with 3-5 subgrades: Grade 0, structural change only; Grade 1, chronic inflammation; Grade 2, lamina propria neutrophils and eosinophils; Grade 3, neutrophils in epithelium; Grade 4, crypt destruction; and Grade 5, erosions or ulceration.

At Week 52
Substudy 3: Percentage Of Participants Who Reported No Bowel Urgency at Week 52
Time Frame: At Week 52
Bowel urgency was assessed by participants in a subject diary completed once a day.
At Week 52
Substudy 3: Percentage Of Participants Who Reported No Abdominal Pain at Week 52
Time Frame: At Week 52
Abdominal pain was assessed by participants in a subject diary completed once a day.
At Week 52
Substudy 3: Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 52
Time Frame: Baseline (Week 0), Week 52
The FACIT fatigue questionnaire was developed to assess fatigue associated with anemia. It consists of 13 fatigue-related questions. Each question is answered on a 5-point Likert scale: 0 (not at all); 1 (a little bit); 2 (somewhat); 3 (quite a bit); and 4 (very much). The total score ranges from 0 to 52, where higher scores represent less fatigue, and a positive change from Baseline indicates improvement.
Baseline (Week 0), Week 52

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 26, 2016

Primary Completion (Actual)

December 13, 2021

Study Completion (Actual)

December 13, 2021

Study Registration Dates

First Submitted

June 28, 2016

First Submitted That Met QC Criteria

June 28, 2016

First Posted (Estimate)

June 30, 2016

Study Record Updates

Last Update Posted (Actual)

June 30, 2022

Last Update Submitted That Met QC Criteria

June 3, 2022

Last Verified

June 1, 2022

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.

IPD Sharing Time Frame

For details on when studies are available for sharing, please refer to the link below.

IPD Sharing Access Criteria

Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Use Agreement (DUA). For more information on the process, or to submit a request, visit the following link.

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)
  • Clinical Study Report (CSR)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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