A Study of the Efficacy and Safety of Etrolizumab in Participants With Ulcerative Colitis Who Have Been Previously Exposed to Tumor Necrosis Factor (TNF) Inhibitors (HICKORY)
Ulcerative Colitis
About this trial
This is an interventional treatment trial for Ulcerative Colitis
Eligibility Criteria
Inclusion Criteria:
- Diagnosis of UC established at least 3 months prior to Day 1
- Moderately to severely active UC as determined by the Mayo Clinic Score (MCS) assessment
- Treatment within 5 years prior to screening with one or two induction regimens that contain TNF inhibitors (including TNF inhibitor biosimilars)
- Washout of anti-TNF therapy for at least 8 weeks preceding Day 1
- Background regimen for UC may include oral 5-aminosalicylic acid (5-ASA), oral corticosteroids, budesonide, probiotics, azathioprine (AZA), 6-mercaptopurine (6-MP), or methotrexate (MTX) if doses have been stable during the screening period
- Use of highly effective contraception as defined by the protocol
- Must have received a colonoscopy within the past year or be willing to undergo a colonoscopy in lieu of a flexible sigmoidoscopy at screening
Exclusion Criteria:
- A history of or current conditions and diseases affecting the digestive tract, such as indeterminate colitis, suspicion of ischemic colitis, radiation colitis, or microscopic colitis, Crohn's disease, fistulas or abdominal abscesses, colonic mucosal dysplasia, intestinal obstruction, toxic megacolon, or unremoved adenomatous colonic polyps
- Prior or planned surgery for UC
- Past or present ileostomy or colostomy
- Any prior treatment with etrolizumab or other anti-integrin agents (including natalizumab, vedolizumab, and efalizumab)
- Any prior treatment with anti-adhesion molecules (e.g. anti-MAdCAM-1)
- Any prior treatment with rituximab
- Any treatment with tofacitinib during screening
- Congenital or acquired immune deficiency, chronic hepatitis B or C infection, human immunodeficiency virus (HIV) positive, or history of tuberculosis (active or latent)
- Evidence of or treatment for Clostridium difficile or clinically significant cytomegalovirus (CMV) colitis within 60 days prior to Day 1
- Evidence of or treatment for other intestinal pathogens within 30 days prior to Day 1
- History of recurrent opportunistic infections and/or severe disseminated viral infections
- History of organ transplant
- Any major episode of infection requiring treatment with intravenous (IV) antibiotics within 8 weeks prior to screening or oral antibiotics within 4 weeks prior to screening
- Received a live attenuated vaccine within 4 weeks prior to Day 1
Sites / Locations
- University of Alabama at Birmingham
- University of California San Diego Medical Center
- Clinical Applications Laboratories, Inc.
- Precision Research Institute, LLC
- University of California at San Francisco
- Rocky Mountain Gastroenterology Associates
- Rocky Mountain Gastroenterology Associates, P.L.L.C.; Gastroenterology
- FQL Research, LLC
- Center For Digestive Health
- Internal Medicine Specialists
- Shafran Gastroenterology Center
- Gastroenterology Associates of Central Georgia
- Gastrointestinal Specialists of Georgia, PC
- Atlanta Gastroenterology Specialists, PC
- Northwestern University Feinberg School Of Medicine
- Southwest Gastroenterology
- Cotton-O'Neil Clinical Research Center, Digestive Health
- Gastroenterology Associates, LLC
- Louisiana Research Center, LLC
- Massachusetts General Hospital; Crohn's & Colitis Center
- University of Michigan; Michigan Institute for Clinical and Health Research (MICHR)
- Henry Ford Health System
- Center for Digestive Health
- Kansas City Research Institute, LLC
- Clinica Peruano Americana S.A.
- Weill Cornell Medical College-New York Presbyterian Hospital
- University of North Carolina at Chapel Hill
- Consultants for Clinical Research Inc.
- UC Health, LLC.
- Great Lakes Gastroenterology Research, LLC
- Gastroenterology Center of the Midsouth, P.C.
- Vanderbilt University Medical Center
- Tyler Research Institute, LLC
- Ericksen Research and Development
- University of Utah School of Medicine
- Digestive and Liver Disease Specialists, Ltd.
- McGuire Research Institute; Gastroenterology
- Washington Gastroenterology
- Hospital Provincial del Centenario
- Royal Brisbane and Women's Hospital
- Mater Adult Hospital
- Princess Alexandra Hospital
- Launceston General Hospital; Gastroenterology Research
- St Vincent's Hospital Melbourne
- Footscray Hospital; Gastroenterology
- St Frances Xavier Cabrini Hospital
- Fiona Stanley Hospital
- Klinikum Klagenfurt am Wörtersee; Acute geriatric care
- LKH - Universitätsklinikum der PMU Salzburg
- Medizinische Universität Wien
- Imeldaziekenhuis
- CHU St Pierre (St Pierre)
- UZ Brussel
- UZ Gent
- AZ Sint Elisabeth Herentals
- UZ Leuven; Neurology
- CHU de Liège; Tour de Pathologie
- AZ Delta (Stedelijk Ziekenhuis)
- Instituto Goiano de Gastroenterologia e Endoscopia Digestiva Ltda
- Hospital Felicio Rocho
- Centro Digestivo de Curitiba
- Hospital Universitario Clementino Fraga Filho - UFRJ
- Hospital Moinhos de Vento
- Hospital de Clínicas de Porto Alegre X
- UNESP - Faculdade de Medicina da Universidade Estadual Paulista - Campus Botucatu
- CAEP - Centro Avancado de Estudos e Pesquisas Ltda.
- Hospital Estadual Mario Covas
- University of Calgary; Heritage Medical Research Clinic
- Zeidler Ledcor Centre - University of Alberta; Division of Gasroenterology
- Pacific Gastroenterology Associates
- Queen Elizabeth II Health Sciences Centre; Gastroenterology Research
- Taunton Health Centre
- Mount Sinai Hospital
- Toronto Liver Centre
- Toronto Digestive Disease Associates
- Hotel Dieu de Levis
- Hôpital Maisonneuve - Rosemont
- Fakultni nemocnice Brno; Interni kardiologicka klinika
- Hepato-Gastroenterologie HK, s.r.o.
- Pardubicka krajska nemocnice, a.s.
- Nemocnice Na Bulovce
- ISCARE a.s.
- Krajska zdravotni, a.s. - Masarykova nemocnice v Usti nad Labem, o.z., Ocni oddeleni
- Rigshospitalet; Medicinsk gastroenterologisk klinik
- Ålborg Universitets Hospital; Gastromedicinsk
- CHU Amiens - Hopital Sud; Pharmacie - Secteur des Essais cliniques
- Hôpital Beaujon
- Hopital Claude Huriez - CHU Lille
- Hôpital Nord - CHU Marseille; Gastroenterology and Hepatology
- CHU Nice - Hopital de l'Archet 2
- Hôpital Saint-Louis
- Groupe Hospitalier Sud - Hôpital Haut-Lévêque - USN
- CHU Saint Etienne - Hôpital Nord
- Höpital Hautepierre; Pediatrie1
- CHU de Toulouse - Hôpital Rangueil
- Hôpital de Brabois Adultes
- Charite Universitaetsmedizin Berlin - Campus Charite Mitte
- DRK Kliniken Berlin Westend
- Universitaetsklinikum Erlangen
- Klinikum der Johann Wolfgang Goethe-Universitaet
- Universitätsklinikum Freiburg; Innere Medizin I; Hämatologie, Onkologie und Stammzelltransplantation
- Universitaetsklinikum Halle (Saale)
- Hamburgisches Forschungsinstitut fuer CED
- Universitätsklinikum Hamburg-Eppendorf
- Gastroenterologie Eppendorfer Baum
- Medizinische Hochschule Hannover; Klinik für Gastroenterologie, Hepatologie und Endokrinologie
- Universitaetsklinikum Schleswig-Holstein, Campus Kiel
- Klinikum Mannheim GmbH Universitätsklinikum
- Universitaetsklinikum Muenster
- Universitaetsklinikum Ulm
- Anticancer Hospital of Thessaliniki " Theagenio"
- Bekes Megyei Kozponti Korhaz Dr. Rethy Pal Tagkorhaza
- Obudai Egeszsegugyi Centrum Kft.
- Semmelweis Egyetem
- Eszak-Kozep-budai Centrum, Uj Szent Janos Korhaz es Szakrendelo
- Pannonia Maganorvosi Centrum
- Magyar Honvedseg Egeszsegugyi Kozpont; Fázis I-es Klinikai Farmakológiai Vizsgálóhely
- Debreceni Egyetem
- Markhot Ferenc Oktato Korhaz es Rendelointezet
- Petz Aladar Megyei Oktato Korhaz
- Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktato Korhaz; II. Belgyogyaszat
- Pecsi Tudomanyegyetem
- Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz
- Shaare Zedek Medical Center
- Hadassah University Hospital - Ein Kerem; Neurosurgery
- Rabin Medical Center-Beilinson Campus; Gaucher Clinic, Genetics Institute
- Kaplan Medical Center
- Assaf Harofeh
- Azienda Ospedaliera S. Orsola-Malpighi
- A.O.U. Policlinico di Modena
- Azienda Ospedaliera Universitaria Policlinico Tor Vergata
- Azienda Ospedaliera San Camillo Forlanini
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS
- Azienda Socio Sanitaria Territoriale Fatebenefratelli (Presidio Ospedale Sacco)
- Ospedale di Circolo; Neuropsichiatria Infantile
- Istituto Clinico Humanitas
- I.R.C.C.S Policlinico San Donato
- Azienda Ospedaliera Universitaria Careggi
- Azienda Ospedaliera Di Padova
- Kyungpook National University Hospital; Opthalmology
- Korea University Ansan Hospital
- Seoul National University Bundang Hospital
- Seoul National University Hospital
- Severance Hospital, Yonsei University
- Samsung Medical Center
- Asan Medical Center.
- The Catholic University of Korea St. Vincent's Hospital
- Hospital of Lithuanian University of Health. Sciences Kaunas Clinics
- Vilnius University Hospital Santariskiu Clinic Public Insti
- Centro Regiomontano de Estudios Clínicos Roma S.C.
- Amsterdam UMC, Locatie VUMC; Neurology
- Amsterdam UMC Location AMC
- Rijnstate; Internal Medicine Department
- Radboudumc
- Nasz Lekarz Osrodek Badan Klinicznych
- Nzoz All-Medicus
- Gabinet Lekarski, Bartosz Korczowski
- Niepubliczny Zaklad Opieki Zdrowotnej SONOMED
- Centrum Zdrowia MDM
- Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy
- Nzoz Vivamed
- LexMedica Osrodek Badan Klinicznych
- EuroMediCare Szpital Specjalistyczny z Przychodnią we Wrocławiu
- PlanetMed
- SC Euroclinic Hospital SA
- Fundacion Hospital de Alcorcon; Servicio de Digestivo
- Hospital Universitari de Girona Dr Josep Trueta
- Hospital Universitario de la Princesa
- Hospital Universitario de Fuenlabrada
- Hospital Universitari i Politecnic La Fe
- Hospital Universitario Miguel Servet
- Inselspital-Universitaetsspital Bern; Institut fuer Spitalpharmazie
- Cliniques Universitaires Saint-Luc; Nephrology
- Crohn-Colitis Zentrum Bern - Gemeinschaftspraxis Balsiger, Seibold und Partner
- Addenbrooke's Hospital
- Royal Devon and Exeter Hospital (Wonford)
- The Royal London Hospital
- University College London Hospital
- St Thomas Hospital
- King's College London
- Fairfield General Hospital
- Royal Victoria Infirmary
- Nottingham University Hospitals; QMC Campus
- Southampton General Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Placebo Comparator
Experimental
Cohort 1: Etrolizumab (Open-Label Induction (OLI) Phase)
Cohort 2: Placebo (Double-Blind Induction Phase)
Cohort 2: Etrolizumab (Double-Blind Induction Phase)
Placebo Responders: Placebo (Maintenance Phase)
Etrolizumab Responders: Placebo (Maintenance Phase)
Etrolizumab Responders: Etrolizumab (Maintenance Phase)
Participants assigned to this arm will receive treatment with open-label etrolizumab 105 milligrams (mg) subcutaneous (SC) injection once every 4 weeks (Q4W) for 14 weeks during the induction phase.
Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase.
Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.
Participants who received placebo during the induction phase, Cohort 2: Placebo (Double-Blind Induction Phase), and achieve a clinical response with placebo at Week 14 will continue to receive blinded placebo from Week 16 up to Week 66 during the maintenance phase.
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66.
Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66.