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)

Phase III, Double-Blind, Placebo-Controlled, Multicenter Study of the Efficacy and Safety of Etrolizumab During Induction and Maintenance in Patients With Moderate to Severe Active Ulcerative Colitis Who Have Been Previously Exposed to TNF Inhibitors

This Phase III, double-blind, placebo-controlled, multicenter study will investigate the efficacy and safety of etrolizumab during induction and maintenance of remission compared with placebo in the treatment of participants with moderately to severely active ulcerative colitis (UC) who have been previously exposed to TNF inhibitors.

Study Overview

• Status: Completed
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Drug: Etrozulimab; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 609
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Rosario, Argentina, 2000
    • Hospital Provincial del Centenario
• Australia
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Royal Brisbane and Women's Hospital
    • South Brisbane, Queensland, Australia, 4101
      • Mater Adult Hospital
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital
  • Tasmania
    • Launceston, Tasmania, Australia, 7250
      • Launceston General Hospital; Gastroenterology Research
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
      • St Vincent's Hospital Melbourne
    • Footscray, Victoria, Australia, 3011
      • Footscray Hospital; Gastroenterology
    • Malvern, Victoria, Australia, 3144
      • St Frances Xavier Cabrini Hospital
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Fiona Stanley Hospital
• Austria
  • Klagenfurt, Austria, 9020
    • Klinikum Klagenfurt am Wörtersee; Acute geriatric care
  • Salzburg, Austria, 5020
    • Lkh - Universitatsklinikum Der Pmu Salzburg
  • Wien, Austria, 1090
    • Medizinische Universität Wien
• Belgium
  • Bonheiden, Belgium, 2820
    • Imeldaziekenhuis
  • Brussel, Belgium, 1090
    • UZ Brussel
  • Brussels, Belgium, 1000
    • CHU St Pierre (St Pierre)
  • Gent, Belgium, 9000
    • UZ Gent
  • Herentals, Belgium, 2200
    • AZ Sint Elisabeth Herentals
  • Leuven, Belgium, 3000
    • UZ Leuven; Neurology
  • Liège, Belgium, 4000
    • CHU de Liège; Tour de Pathologie
  • Roeselare, Belgium, 8800
    • AZ Delta (Stedelijk Ziekenhuis)
• Brazil
  • GO
    • Goiânia, GO, Brazil, 74535-170
      • Instituto Goiano de Gastroenterologia e Endoscopia Digestiva Ltda
  • MG
    • Belo Horizonte, MG, Brazil, 30110-068
      • Hospital Felicio Rocho
  • PR
    • Curitiba, PR, Brazil, 80430-160
      • Centro Digestivo de Curitiba
  • RJ
    • Rio de Janeiro, RJ, Brazil, 21941-913
      • Hospital Universitário Clementino Fraga Filho - UFRJ
  • RS
    • Porto Alegre, RS, Brazil
      • Hospital de Clínicas de Porto Alegre X
    • Porto Alegre, RS, Brazil, 90035-001
      • Hospital Moinhos de Vento
  • SP
    • Botucatu, SP, Brazil, 18618-970
      • UNESP - Faculdade de Medicina da Universidade Estadual Paulista - Campus Botucatu
    • Campinas, SP, Brazil, 13087-567
      • CAEP - Centro Avancado de Estudos e Pesquisas Ltda.
    • Santo Andre, SP, Brazil, 09190-610
      • Hospital Estadual Mario Covas
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
      • University of Calgary; Heritage Medical Research Clinic
    • Edmonton, Alberta, Canada, T6G 2X8
      • Zeidler Ledcor Centre - University of Alberta; Division of Gasroenterology
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 2K5
      • Pacific Gastroenterology Associates
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • Queen Elizabeth II Health Sciences Centre; Gastroenterology Research
  • Ontario
    • Oshawa, Ontario, Canada, L1H 7K4
      • Taunton Health Centre
    • Toronto, Ontario, Canada, M6H 3M1
      • Toronto Liver Centre
    • Toronto, Ontario, Canada, M5G 1X5
      • Mount Sinai Hospital
    • Vaughan, Ontario, Canada, L4L 4Y7
      • Toronto Digestive Disease Associates
  • Quebec
    • Levis, Quebec, Canada, G6V 3Z1
      • Hotel Dieu de Levis
    • Montreal, Quebec, Canada, H1T 2M4
      • Hôpital Maisonneuve - Rosemont
• Czechia
  • Brno, Czechia, 625 00
    • Fakultni nemocnice Brno; Interni kardiologicka klinika
  • Hradec Kralove, Czechia, 500 12
    • Hepato-Gastroenterologie HK, s.r.o.
  • Pardubice, Czechia, 532 03
    • Pardubicka krajska nemocnice, a.s.
  • Prague, Czechia, 180 01
    • Nemocnice Na Bulovce
  • Praha 7, Czechia, 170 04
    • ISCARE a.s.
  • Usti Nad Labem, Czechia, 401 13
    • Krajska zdravotni, a.s. - Masarykova nemocnice v Usti nad Labem, o.z., Ocni oddeleni
• Denmark
  • København Ø, Denmark, 2100
    • Rigshospitalet; Medicinsk gastroenterologisk klinik
  • Ålborg, Denmark, 9000
    • Ålborg Universitets Hospital; Gastromedicinsk
• France
  • Amiens Cedex01, France, 80054
    • CHU Amiens - Hopital Sud; Pharmacie - Secteur des Essais cliniques
  • Clichy cedex, France, 92110
    • Hôpital Beaujon
  • Lille, France, 59037
    • Hopital Claude Huriez - CHU Lille
  • Marseille cedex 20, France, 13915
    • Hôpital Nord - CHU Marseille; Gastroenterology and Hepatology
  • Nice, France, 06202
    • CHU Nice - Hôpital de l'Archet 2
  • Paris, France, 75475
    • Hôpital Saint-Louis
  • Pessac, France, 33604
    • Groupe Hospitalier Sud - Hôpital Haut-Lévêque - USN
  • Saint Etienne, France, 42055
    • CHU Saint Etienne - Hôpital Nord
  • Strasbourg, France, 67098
    • Höpital Hautepierre; Pediatrie1
  • Toulouse Cedex 09, France, 31059
    • CHU de Toulouse - Hôpital Rangueil
  • Vandoeuvre-les-nancy, France, 54511
    • Hôpital de Brabois Adultes
• Germany
  • Berlin, Germany, 14050
    • DRK Kliniken Berlin Westend
  • Berlin, Germany, 10117
    • Charite Universitaetsmedizin Berlin - Campus Charite Mitte
  • Erlangen, Germany, 91054
    • Universitaetsklinikum Erlangen
  • Frankfurt, Germany, 60590
    • Klinikum der Johann Wolfgang Goethe-Universitaet
  • Freiburg, Germany, 79106
    • Universitätsklinikum Freiburg; Innere Medizin I; Hämatologie, Onkologie und Stammzelltransplantation
  • Halle, Germany, 06120
    • Universitaetsklinikum Halle (Saale)
  • Hamburg, Germany, 20246
    • Universitätsklinikum Hamburg-Eppendorf
  • Hamburg, Germany, 20148
    • Hamburgisches Forschungsinstitut fuer CED
  • Hamburg, Germany, 20249
    • Gastroenterologie Eppendorfer Baum
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover; Klinik für Gastroenterologie, Hepatologie und Endokrinologie
  • Kiel, Germany, 24116
    • Universitaetsklinikum Schleswig-Holstein, Campus Kiel
  • Mannheim, Germany, 68167
    • Klinikum Mannheim GmbH Universitätsklinikum
  • Muenster, Germany, 48149
    • Universitaetsklinikum Muenster
  • Ulm, Germany, 89081
    • Universitaetsklinikum Ulm
• Greece
  • Thessaloniki, Greece, 54007
    • Anticancer Hospital of Thessaliniki " Theagenio"
• Hungary
  • Bekescsaba, Hungary, 5600
    • Bekes Megyei Kozponti Korhaz Dr. Rethy Pal Tagkorhaza
  • Budapest, Hungary, 1083
    • Semmelweis Egyetem
  • Budapest, Hungary, H-1077
    • Magyar Honvedseg Egeszsegugyi Kozpont; Fázis I-es Klinikai Farmakológiai Vizsgálóhely
  • Budapest, Hungary, 1036
    • Obudai Egeszsegugyi Centrum Kft.
  • Budapest, Hungary, 1125
    • Eszak-Kozep-budai Centrum, Uj Szent Janos Korhaz és Szakrendelo
  • Budapest, Hungary, 1135
    • Pannonia Maganorvosi Centrum
  • Debrecen, Hungary, 4032
    • Debreceni Egyetem
  • Eger, Hungary, 3300
    • Markhot Ferenc Oktato Korhaz es Rendelointezet
  • Gyor, Hungary, 9024
    • Petz Aladar Megyei Oktato Korhaz
  • Miskolc, Hungary, 3526
    • Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktato Korhaz; II. Belgyogyaszat
  • Pecs, Hungary, 7624
    • Pécsi Tudományegyetem
  • Székesfehérvár, Hungary, 8000
    • Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz
• Israel
  • Jerusalem, Israel, 9103102
    • Shaare Zedek Medical Center
  • Jerusalem, Israel, 9112001
    • Hadassah University Hospital - Ein Kerem; Neurosurgery
  • Petach Tiqwa, Israel, 49100
    • Rabin Medical Center-Beilinson Campus; Gaucher Clinic, Genetics Institute
  • Rehovot, Israel, 7610001
    • Kaplan Medical Center
  • Rishon Lezion, Israel, 7505001
    • Assaf Harofeh
• Italy
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40138
      • Azienda Ospedaliera S. Orsola-Malpighi
    • Modena, Emilia-Romagna, Italy, 40124
      • A.O.U. Policlinico di Modena
  • Lazio
    • Roma, Lazio, Italy, 00168
      • Fondazione Policlinico Universitario Agostino Gemelli IRCCS
    • Roma, Lazio, Italy, 00152
      • Azienda Ospedaliera San Camillo Forlanini
    • Roma, Lazio, Italy, 00133
      • Azienda Ospedaliera Universitaria Policlinico Tor Vergata
  • Lombardia
    • Milano, Lombardia, Italy
      • Azienda Socio Sanitaria Territoriale Fatebenefratelli (Presidio Ospedale Sacco)
    • Rho, Lombardia, Italy, 20017
      • Ospedale di Circolo; Neuropsichiatria Infantile
    • Rozzano (MI), Lombardia, Italy, 20089
      • Istituto Clinico Humanitas
    • San Donato Milanese (MI), Lombardia, Italy, 20097
      • I.R.C.C.S Policlinico San Donato
  • Toscana
    • Firenze, Toscana, Italy, 50141
      • Azienda Ospedaliera Universitaria Careggi
  • Veneto
    • Padova, Veneto, Italy, 35128
      • Azienda Ospedaliera di Padova
• Korea, Republic of
  • Daegu, Korea, Republic of, 700-721
    • Kyungpook National University Hospital; Opthalmology
  • Gyeonggi-do, Korea, Republic of, 15355
    • Korea University Ansan Hospital
  • Seongnam-si, Korea, Republic of, 13605
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital, Yonsei University
  • Seoul, Korea, Republic of, 138-736
    • Asan Medical Center.
  • Seoul, Korea, Republic of, 06531
    • Samsung Medical Center
  • Suwon-si,, Korea, Republic of, 442-723
    • The Catholic University of Korea St. Vincent's Hospital
• Lithuania
  • Kaunas, Lithuania, 50009
    • Hospital of Lithuanian University of Health. Sciences Kaunas Clinics
  • Vilnius, Lithuania, 08661
    • Vilnius University Hospital Santariskiu Clinic Public Insti
• Mexico
  • Nuevo LEON
    • Monterrey, Nuevo LEON, Mexico, 64610
      • Centro Regiomontano de Estudios Clínicos Roma S.C.
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • Amsterdam UMC, Locatie VUMC; Neurology
  • Amsterdam, Netherlands, 1105 AZ
    • Amsterdam UMC location AMC
  • Arnhem, Netherlands, 6815 AD
    • Rijnstate; Internal Medicine Department
  • NL -nijmegen, Netherlands, 6525 GA
    • Radboudumc
• Poland
  • Bydgoszcz, Poland, 85-312
    • Nasz Lekarz Osrodek Badan Klinicznych
  • Katowice, Poland, 40-660
    • Nzoz All-Medicus
  • Rzeszów, Poland, 35-302
    • Gabinet Lekarski, Bartosz Korczowski
  • Szczecin, Poland, 70-351
    • Niepubliczny Zaklad Opieki Zdrowotnej SONOMED
  • Warszawa, Poland, 03-580
    • NZOZ Vivamed
  • Warszawa, Poland, 02-781
    • Narodowy Instytut Onkologii Im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy
  • Warszawa, Poland, 00-631
    • Centrum Zdrowia MDM
  • Wroclaw, Poland, 53-114
    • LexMedica Osrodek Badan Klinicznych
  • Wroclaw, Poland, 54-144
    • EuroMediCare Szpital Specjalistyczny z Przychodnią we Wrocławiu
  • Wrocław, Poland, 52-210
    • Planetmed
• Romania
  • Bucuresti, Romania, 014461
    • SC Euroclinic Hospital SA
• Spain
  • Girona, Spain, 17007
    • Hospital Universitari de Girona Dr Josep Trueta
  • Madrid, Spain, 28006
    • Hospital Universitario de La Princesa
  • Madrid, Spain, 28942
    • Hospital Universitario de Fuenlabrada
  • Valencia, Spain, 46026
    • Hospital Universitari i Politecnic La Fe
  • Zaragoza, Spain, 50009
    • Hospital Universitario Miguel Servet
  • Madrid
    • Alcorcon, Madrid, Spain, 28922
      • Fundacion Hospital de Alcorcon; Servicio de Digestivo
• Switzerland
  • Bern, Switzerland, 3012
    • Crohn-Colitis Zentrum Bern - Gemeinschaftspraxis Balsiger, Seibold und Partner
  • Bern, Switzerland, 3010
    • Inselspital-Universitaetsspital Bern; Institut fuer Spitalpharmazie
  • Bern, Switzerland, 3012
    • Cliniques Universitaires Saint-Luc; Nephrology
• United Kingdom
  • Cambridge, United Kingdom, CB2 0QQ
    • Addenbrooke's Hospital
  • Exeter, United Kingdom, EX2 5DW
    • Royal Devon and Exeter Hospital (Wonford)
  • London, United Kingdom, SE5 9NU
    • King's College London
  • London, United Kingdom, SE1 7EH
    • St Thomas Hospital
  • London, United Kingdom, NW1 - 2PG
    • University College London Hospital
  • London, United Kingdom, E1 2ES
    • The Royal London Hospital
  • Manchester, United Kingdom, M8 5RB
    • Fairfield General Hospital
  • Newcastle upon Tyne, United Kingdom, NE1 4LP
    • Royal Victoria Infirmary
  • Nottingham, United Kingdom, NG7 2UH
    • Nottingham University Hospitals; QMC Campus
  • Southampton, United Kingdom, SO16 6YD
    • Southampton General Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • California
    • La Jolla, California, United States, 92093-5354
      • University of California San Diego Medical Center
    • San Diego, California, United States, 92103
      • Clinical Applications Laboratories, Inc.
    • San Diego, California, United States, 92114
      • Precision Research Institute, LLC
    • San Francisco, California, United States, 94115
      • University of California at San Francisco
  • Colorado
    • Denver, Colorado, United States, 80222
      • Rocky Mountain Gastroenterology Associates
    • Lakewood, Colorado, United States, 80215
      • Rocky Mountain Gastroenterology Associates, P.L.L.C.; Gastroenterology
  • Florida
    • Miramar, Florida, United States, 33025
      • FQL Research, LLC
    • Orlando, Florida, United States, 32803
      • Center for Digestive Health
    • Orlando, Florida, United States, 32806
      • Internal Medicine Specialists
    • Winter Park, Florida, United States, 32789
      • Shafran Gastroenterology Center
  • Georgia
    • Macon, Georgia, United States, 31201
      • Gastroenterology Associates of Central Georgia
    • Marietta, Georgia, United States, 30060
      • Gastrointestinal Specialists of Georgia, PC
    • Suwanee, Georgia, United States, 30024
      • Atlanta Gastroenterology Specialists, PC
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University Feinberg School of Medicine
    • Oak Lawn, Illinois, United States, 60453
      • Southwest Gastroenterology
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Cotton-O'Neil Clinical Research Center, Digestive Health
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Gastroenterology Associates, LLC
    • Shreveport, Louisiana, United States
      • Louisiana Research Center, LLC
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital; Crohn's & Colitis Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan; Michigan Institute for Clinical and Health Research (MICHR)
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
    • Troy, Michigan, United States, 48098
      • Center for Digestive Health
  • Missouri
    • Kansas City, Missouri, United States, 64131
      • Kansas City Research Institute, LLC
  • New York
    • Great Neck, New York, United States, 11021
      • Clinica Peruano Americana S.A.
    • New York, New York, United States, 10021
      • Weill Cornell Medical College-New York Presbyterian Hospital
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina at Chapel Hill
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Consultants for Clinical Research Inc.
    • Cincinnati, Ohio, United States, 45219
      • UC Health, LLC.
    • Mentor, Ohio, United States, 44060
      • Great Lakes Gastroenterology Research, LLC
  • Tennessee
    • Memphis, Tennessee, United States, 38120
      • Gastroenterology Center of the Midsouth, P.C.
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Tyler, Texas, United States, 75701
      • Tyler Research Institute, LLC
  • Utah
    • Clinton, Utah, United States, 84015
      • Ericksen Research and Development
    • Salt Lake City, Utah, United States, 84132
      • University of Utah School of Medicine
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Digestive and Liver Disease Specialists, Ltd.
    • Richmond, Virginia, United States, 23249
      • McGuire Research Institute; Gastroenterology
  • Washington
    • Bellevue, Washington, United States, 98004
      • Washington Gastroenterology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: Etrolizumab (Open-Label Induction (OLI) 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.	Drug: Etrozulimab; Participants will receive 105 mg etrolizumab administered by SC injection Q4W.; Other Names: RO5490261; RG7413; PRO145223
Placebo Comparator: Cohort 2: Placebo (Double-Blind Induction Phase); Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase.	Drug: Placebo; Participants will receive placebo (matched with etrolizumab) administered by SC injection Q4W.
Experimental: Cohort 2: Etrolizumab (Double-Blind 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.	Drug: Etrozulimab; Participants will receive 105 mg etrolizumab administered by SC injection Q4W.; Other Names: RO5490261; RG7413; PRO145223
Placebo Comparator: Placebo Responders: Placebo (Maintenance 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.	Drug: Placebo; Participants will receive placebo (matched with etrolizumab) administered by SC injection Q4W.
Placebo Comparator: Etrolizumab Responders: Placebo (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.	Drug: Placebo; Participants will receive placebo (matched with etrolizumab) administered by SC injection Q4W.
Experimental: Etrolizumab Responders: Etrolizumab (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 etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66.	Drug: Etrozulimab; Participants will receive 105 mg etrolizumab administered by SC injection Q4W.; Other Names: RO5490261; RG7413; PRO145223

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Induction Phase: Percentage of Participants With Remission at Week 14, as Determined by the Mayo Clinic Score (MCS)	The Mayo Clinic Score (MCS) ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Remission was defined as MCS less than or equal to (≤)2 with individual subscores ≤1 and a rectal bleeding subscore of 0.	Week 14
Maintenance Phase: Percentage of Participants With Remission at Week 66 Among Participants Who Had Achieved a Clinical Response at Week 14, as Determined by the MCS	The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Remission was defined as MCS less than or equal to (≤)2 with individual subscores ≤1 and a rectal bleeding subscore of 0. Clinical Response is MCS with ≥3-point decrease and 30% reduction from baseline as well as ≥1-point decrease in rectal bleeding subscore or an absolute rectal bleeding score of 0 or 1.	Week 66

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Induction Phase: Percentage of Participants With Clinical Remission at Week 14, as Determined by the MCS	The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Clinical Remission is MCS ≤2 with individual subscores ≤1.	Week 14
Induction Phase: Percentage of Participants With Clinical Response at Week 14, as Determined by the MCS	The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Remission was defined as MCS less than or equal to (≤)2 with individual subscores ≤1 and a rectal bleeding subscore of 0. Clinical Response is MCS with ≥3-point decrease and 30% reduction from baseline as well as ≥1-point decrease in rectal bleeding subscore or an absolute rectal bleeding score of 0 or 1.	Week 14
Induction Phase: Percentage of Participants With Improvement From Baseline in Endoscopic Appearance of the Mucosa at Week 14, as Determined by the MCS Endoscopic Subscore	The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Improvement in endoscopic appearance of the mucosa is Endoscopy subscore ≤1.	Baseline and Week 14
Induction Phase: Percentage of Participants With Endoscopic Remission at Week 14, as Determined by the MCS Endoscopic Subscore	The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Endoscopic Remission is Endoscopy subscore = 0.	Week 14
Induction Phase: Percentage of Participants With Histologic Remission at Week 14, as Determined by the Nancy Histological Index	Nancy Histological Index (NHI) is a 5-level classification ranging from grade 0 (No histologically significant disease) to grade 4 (severely active disease). Histologic remission is defined as a Nancy Histological Index of 0 or 1.	Week 14
Induction Phase: Change From Baseline to Week 6 in MCS Rectal Bleed Subscore	Rectal bleeding data were collected via the participant's diaries and each day a participant provided a score from 0 to 3 according to the following definitions: 0 = no blood in the stool; 1 = streaks of blood with stool less than half the time; 2 = obvious blood with stool most of the time; 3 = blood alone passed. The Mayo Clinic Score (MCS) rectal bleeding subscore was calculated as the worst value of three days of daily diary scores closest to anchor dates at baseline and post-baseline. The data was considered non-parametric and was reported using RANK analysis of covariance (ANCOVA). Participants were stratified by concomitant treatment with corticosteroids or immunosuppressants at randomization and disease activity measured during screening (MCS ≤9/MCS ≥10); the model adjusted for these stratification factors along with the baseline rectal bleeding (RB) subscore.	Baseline and Week 6
Induction Phase: Change From Baseline to Week 6 in MCS Stool Frequency Subscore	Stool frequency data were collected via the participant's diaries and each day a participant provided a score from 0 to 3 according to the following definitions: 0 = normal number of stools; 1 = 1 to 2 more stools than normal; 2 = 3 to 4 more stools than normal; 3 = 5 or more stools than normal. The Mayo Clinic Score (MCS) stool frequency subscore was calculated as the average of three days daily diary scores closest to anchor dates at baseline and post-baseline. The data was considered non-parametric and was reported using RANK analysis of covariance (ANCOVA). Participants were stratified by concomitant treatment with corticosteroids or immunosuppressants at randomization and disease activity measured during screening (MCS ≤9/MCS ≥10); the model adjusted for these stratification factors along with the baseline stool frequency (SF) subscore.	Baseline and Week 6
Induction Phase: Change From Baseline to Week 14 in UC Bowel Movement Signs and Symptoms, as Assessed by the Ulcerative Colitis Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS) Questionnaire	The UC-PRO questionnaire is collected in the e-diary and completed by participants for at least 9-12 consecutive days prior to a study visit. The UC-PRO is being reported in three domains; two domains are key endpoints and reported as UC-PRO Signs and Symptoms (UC-PRO/SS). The bowel domain score ranges from 0-27, with a higher score indicating a worse disease state.	Baseline and Week 14
Induction Phase: Change From Baseline to Week 14 in UC Functional Symptoms, as Assessed by the UC-PRO/SS Questionnaire	The UC-PRO questionnaire is collected in the e-diary and completed by participants for at least 9-12 consecutive days prior to a study visit. The UC-PRO is being reported in three domains; two domains are key endpoints and reported as UC-PRO Signs and Symptoms (UC-PRO/SS). The functional (abdominal symptoms) domain score ranges from 0-12, with a higher score indicating a worse disease state.	Baseline and Week 14
Induction Phase: Change From Baseline to Week 14 in Health-Related Quality of Life, as Assessed by the Overall Score of the Inflammatory Bowel Disease Questionnaire (IBDQ)	The IBDQ score is a Total Score summed up from across all 32 questions on the questionnaire. The Total Score range is from 32 to 224 with higher scores representing a better quality of life.	Baseline and Week 14
Maintenance Phase: Percentage of Participants With Clinical Remission at Week 66 Among Participants Who Had Achieved Clinical Remission at Week 14, as Determined by the MCS	The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Remission was defined as MCS less than or equal to (≤)2 with individual subscores ≤1 and a rectal bleeding subscore of 0. Clinical Remission is MCS ≤2 with individual subscores ≤1.	Week 66
Maintenance Phase: Percentage of Participants With Clinical Remission at Week 66, as Determined by the MCS	The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Remission was defined as MCS less than or equal to (≤)2 with individual subscores ≤1 and a rectal bleeding subscore of 0. Clinical Remission is MCS ≤2 with individual subscores ≤1.	Week 66
Maintenance Phase: Percentage of Participants With Remission at Week 66 Among Participants Who Had Achieved Remission at Week 14, as Determined by the MCS	The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Remission was defined as MCS less than or equal to (≤)2 with individual subscores ≤1 and a rectal bleeding subscore of 0.	Week 66
Maintenance Phase: Percentage of Participants With Improvement From Baseline in Endoscopic Appearance of the Mucosa at Week 66, as Determined by the MCS Endoscopic Subscore	The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Improvement in endoscopic appearance of the mucosa is Endoscopy subscore ≤1.	Baseline and Week 66
Maintenance Phase: Percentage of Participants With Histologic Remission at Week 66, as Determined by the Nancy Histological Index	Nancy Histological Index (NHI) is a 5-level classification ranging from grade 0 (No histologically significant disease) to grade 4 (severely active disease). Histologic remission is defined as a Nancy Histological Index of 0 or 1.	Week 66
Maintenance Phase: Percentage of Participants With Endoscopic Remission at Week 66, as Determined by the MCS Endoscopic Subscore	The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Endoscopic Remission is Endoscopy subscore = 0.	Week 66
Maintenance Phase: Percentage of Participants With Corticosteroid-Free Clinical Remission at Week 66 Among Participants Who Were Receiving Corticosteroids at Baseline, as Determined by the MCS	The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Corticosteroid-Free analysis was conducted only on a subgroup of participants who were randomized into the maintenance phase and receiving Corticosteroids (CS) at baseline. Participants were defined as being off CS if they had no record of taking CS on the date that was 24 weeks prior to Week 66.	Week 66
Maintenance Phase: Percentage of Participants With Corticosteroid-Free Remission at Week 66 Among Participants Who Were Receiving Corticosteroids at Baseline, as Determined by the MCS	The MCS ranges from 0 to 12 and is a composite of 4 assessments (each rated from 0-3): stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores represent greater disease severity. Corticosteroid-Free analysis was conducted only on a subgroup of participants who were randomized into the maintenance phase and receiving Corticosteroids (CS) at baseline. Participants were defined as being off CS if they had no record of taking CS on the date that was 24 weeks prior to Week 66.	Week 66
Maintenance Phase: Change From Baseline to Week 66 in UC Bowel Movement Signs and Symptoms, as Assessed by the UC-PRO/SS Questionnaire	The UC-PRO questionnaire is collected in the e-diary and completed by participants for at least 9-12 consecutive days prior to a study visit. The UC-PRO is being reported in three domains; two domains are key endpoints and reported as UC-PRO Signs and Symptoms (UC-PRO/SS). The bowel domain score ranges from 0-27, with a higher score indicating a worse disease state.	Baseline and Week 66
Maintenance Phase: Change From Baseline to Week 66 in UC Functional Symptoms, as Assessed by the UC-PRO/SS Questionnaire	The UC-PRO questionnaire is collected in the e-diary and completed by participants for at least 9-12 consecutive days prior to a study visit. The UC-PRO is being reported in three domains; two domains are key endpoints and reported as UC-PRO Signs and Symptoms (UC-PRO/SS). The functional (abdominal symptoms) domain score ranges from 0-12, with a higher score indicating a worse disease state.	Baseline and Week 66
Maintenance Phase: Change From Baseline to Week 66 in Health-Related Quality of Life, as Assessed by the Overall Score of the IBDQ	The IBDQ is used to assess participant's health-related quality of life (QOL). The IBDQ score is a Total Score summed up from across all 32 questions on the questionnaire. The Total Score range is from 32 to 224 with higher scores representing a better quality of life.	Baseline and Week 66
Number of Participants With at Least One Adverse Event by Severity, According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v4.0)	All Adverse Events (AEs) were graded for severity using the NCI-CTCAE v4.0. Any AE not specifically listed was assessed per the following 5 grades: Grade 1 = mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; or intervention not indicated. Grade 2 = moderate; minimal, local, or non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living. Grade 3 = severe or medically significant, but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living. Grade 4 = life-threatening consequences or urgent intervention indicated. Grade 5 = death related to AE. Not all grades are appropriate for all AEs; some AEs have fewer than 5 options. The terms "severe" and "serious" are not synonymous and are independently assessed for each AE. Multiple occurrences of AEs were counted only once per participant at the highest (worst) grade.	From Baseline up to Week 78
Number of Participants With Adverse Events Leading to Study Drug Discontinuation		From Baseline up to Week 78
Number of Participants With Serious Infection-Related Adverse Events		From Baseline up to Week 78
Number of Participants With Infection-Related Adverse Events	All Adverse Events (AEs) were graded for severity using the NCI-CTCAE v4.0. Any AE not specifically listed was assessed per the following 5 grades: Grade 1 = mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; or intervention not indicated. Grade 2 = moderate; minimal, local, or non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living. Grade 3 = severe or medically significant, but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living. Grade 4 = life-threatening consequences or urgent intervention indicated. Not all grades are appropriate for all AEs; some AEs have fewer than 5 options. The terms "severe" and "serious" are not synonymous and are independently assessed for each AE. Multiple occurrences of AEs were counted only once per participant at the highest (worst) grade.	From Baseline up to Week 78
Number of Participants With Injection-Site Reaction-Related Adverse Events		From Baseline up to Week 78
Number of Participants With Hypersensitivity Reaction-Related Adverse Events		From Baseline up to Week 78
Number of Participants With Malignancies		From Baseline up to Week 78
Number of Participants With Anti-Therapeutic Antibodies to Etrolizumab at Baseline and During the Study	A tiered strategy was used to detect and characterize etrolizumab antibodies within this clinical study. When determining post baseline incidence, participants were considered to be ADA positive if they were ADA negative or had missing data at baseline but developed an ADA response following etrolizumab drug exposure (treatment-induced ADA response), or if they were ADA positive at baseline and the titer of one or more post baseline samples was at least 0.60 titer unit greater than the titer of the baseline sample (treatment-enhanced ADA response). Participants were considered to be ADA negative if they were ADA negative or had missing data at baseline and all post baseline samples were negative, or if they were ADA positive at baseline but did not have any post baseline samples with a titer that was at least 0.60 titer unit greater than the titer of the baseline sample (treatment unaffected).	Pre-dose at Baseline, Weeks 4, 14, 24, 44, and 66, and Early Termination/End of Safety Follow-Up (up to Week 78)
Etrolizumab Serum Trough Concentration (for Arms/Timepoints Above LLOQ)	As per Protocol, the timepoints for each arm where more than a third of the samples were above the lower limit of quantification (LLOQ), full summary statistics (Mean and Standard Deviation) were reported. For timepoints below the LLOQ, only the Median and Max were reported as a separate outcome measure below.	Pre-dose (0 hour) at Baseline and Weeks 14, 24, 44 and 66
Etrolizumab Serum Trough Concentration (for Arms/Timepoints Below LLOQ)	As per Protocol, the timepoints for each arm where more than a third of the samples were below the LLOQ only the Median and Max were reported.	Weeks 44 and 66

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Sandborn WJ, Vermeire S, Tyrrell H, Hassanali A, Lacey S, Tole S, Tatro AR; Etrolizumab Global Steering Committee. Etrolizumab for the Treatment of Ulcerative Colitis and Crohn's Disease: An Overview of the Phase 3 Clinical Program. Adv Ther. 2020 Jul;37(7):3417-3431. doi: 10.1007/s12325-020-01366-2. Epub 2020 May 22.
• Peyrin-Biroulet L, Hart A, Bossuyt P, Long M, Allez M, Juillerat P, Armuzzi A, Loftus EV Jr, Ostad-Saffari E, Scalori A, Oh YS, Tole S, Chai A, Pulley J, Lacey S, Sandborn WJ; HICKORY Study Group. Etrolizumab as induction and maintenance therapy for ulcerative colitis in patients previously treated with tumour necrosis factor inhibitors (HICKORY): a phase 3, randomised, controlled trial. Lancet Gastroenterol Hepatol. 2022 Feb;7(2):128-140. doi: 10.1016/S2468-1253(21)00298-3. Epub 2021 Nov 17.

Study record dates

Study Major Dates

• Study Start (Actual): May 21, 2014
• Primary Completion (Actual): April 16, 2020
• Study Completion (Actual): April 16, 2020

Study Registration Dates

• First Submitted: March 27, 2014
• First Submitted That Met QC Criteria: March 27, 2014
• First Posted (Estimate): April 1, 2014

Study Record Updates

• Last Update Posted (Actual): August 13, 2021
• Last Update Submitted That Met QC Criteria: July 22, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative; Physiological Effects of Drugs; Immunologic Factors; Gastrointestinal Agents; Etrolizumab
• Other Study ID Numbers: GA28950; 2013-004278-88 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No