A Study Comparing the Efficacy and Safety of Etrolizumab to Infliximab in Participants With Moderate to Severe Ulcerative Colitis Who Are Naïve to Tumor Necrosis Factor (TNF) Inhibitors (GARDENIA)

Phase III, Randomized, Multicenter Double-Blind, Double Dummy Study to Evaluate the Efficacy and Safety of Etrolizumab Compared With Infliximab in Patients With Moderate to Severe Active Ulcerative Colitis Who Are Naive to TNF Inhibitors

This is a multicenter, Phase III, randomized, double-blind, double-dummy, parallel-group study to evaluate the safety, efficacy, and tolerability of etrolizumab compared with infliximab in treating participants with moderate to severe ulcerative colitis (UC) who are naive to tumor necrosis factor (TNF) inhibitors. Participants will be randomized in a 1:1 ratio to receive either etrolizumab 105 milligrams (mg) by subcutaneous (SC) injection once every 4 weeks (Q4W) + placebo (intravenous [IV] infusion at Weeks 0, 2, and 6, then once every 8 weeks [Q8W]) or infliximab 5 milligrams/kilogram (mg/kg) IV at Weeks 0, 2, and 6, then Q8W) + placebo (SC Q4W). Time on treatment is 54 weeks.

Study Overview

• Status: Completed
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Drug: Etrolizumab; Other: Placebo (IV); Drug: Infliximab; Other: Placebo (Injection)

• Study Type: Interventional
• Enrollment (Actual): 397
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Salzburg, Austria, 5020
    • LKH - Universitätsklinikum der PMU Salzburg
• Belgium
  • Antwerpen, Belgium, 2018
    • GZA Ziekenhuizen - campus Sint-Vincentius
  • Bonheiden, Belgium, 2820
    • Imeldaziekenhuis
  • Brussels, Belgium, 1000
    • CHU St Pierre (St Pierre)
  • Bruxelles, Belgium, 1200
    • Cliniques Universitaires Saint-Luc; Pharmacy
  • Bruxelles, Belgium, 1090
    • Universitair Ziekenhuis Brussel; Neurology
  • Gent, Belgium, 9000
    • UZ Gent
  • Herentals, Belgium, 2200
    • AZ Sint Elisabeth Herentals
• 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
  • Ontario
    • Guelph, Ontario, Canada, N1H 3R3
      • Guelph GI & Surgery Clinic
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2H1
      • Centre de santé et de services sociaux Champlain-Charles-Le Moyne
    • Montreal, Quebec, Canada, H1T 2M4
      • Hôpital Maisonneuve - Rosemont
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 0W8
      • Royal University Hospital
• Czechia
  • Brno, Czechia, 636 00
    • Vojenska nemocnice Brno
  • Hradec Kralove, Czechia, 500 05
    • Fakultni nemocnice Hradec Kralove
  • Kladno, Czechia, 272 59
    • Oblastni nemocnice Kladno, a.s., nemocnice Stredoces. kraje; Endoskopicke centrum
  • Ostrava, Czechia, 728 80
    • Mestska nemocnice Ostrava
  • Pardubice, Czechia, 532 03
    • Pardubicka krajska nemocnice, a.s.
  • 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
  • Zlin, Czechia, 76001
    • Krajska nemocnice T. Bati, a.s.
• France
  • Caen, France, 14033
    • CHU de Caen - Hopital Cote de Nacre
  • Chambray les Tours, France, 37170
    • CHU Tours - Hôpital Trousseau
  • Clermont-Ferrand, France, 63000
    • CHU Clermont Ferrand - Hôtel Dieu
  • Clichy cedex, France, 92110
    • Hopital Beaujon
  • Montpellier, France, 34295
    • CHU Hopital Saint Eloi
  • Nice, France, 06202
    • CHU Nice - Hopital de l'Archet 2
  • Pierre-Benite, France, 69495
    • Centre Hospitalier Lyon Sud; Service de Gastro-Enterologie
  • Vandoeuvre-les-nancy, France, 54511
    • Hôpital de Brabois Adultes
• Germany
  • Berlin, Germany, 12200
    • Charite Universitaetsmedizin Berlin - Campus Benjamin Franklin
  • Berlin, Germany, 14050
    • DRK Kliniken Berlin Westend
  • Berlin, Germany, 14163
    • Krankenhaus Waldfriede e. V.
  • Freiburg, Germany, 79106
    • Universitätsklinikum Freiburg; Innere Medizin I; Hämatologie, Onkologie und Stammzelltransplantation
  • Hamburg, Germany, 20249
    • Gastroenterologie Eppendorfer Baum
  • Kiel, Germany, 24116
    • Universitaetsklinikum Schleswig-Holstein, Campus Kiel
  • Koeln, Germany, 50937
    • Universitatsklinikum Koeln
• 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, 1125
    • Eszak-Kozep-budai Centrum, Uj Szent Janos Korhaz és Szakrendelo
  • Debrecen, Hungary, 4025
    • Vasutegeszsegugyi Nonprofit KiemeltenKozhasznu Kft
  • 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
  • Szeged, Hungary, 6720
    • Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont
  • Székesfehérvár, Hungary, 8000
    • Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz
• Israel
  • Petach Tikva, Israel, 4941492
    • Rabin Medical Center-Beilinson Campus
  • Tel Hashomer, Israel, 52621
    • Chaim Sheba Medical Center; Pediatrics B North and Pediatric Endocrinology Unit
• Italy
  • Emilia-Romagna
    • Parma, Emilia-Romagna, Italy, 43100
      • Azienda Ospedaliero Universitaria di Parma
  • Lazio
    • Roma, Lazio, Italy, 00152
      • Azienda Ospedaliera San Camillo Forlanini
    • Roma, Lazio, Italy, 00133
      • Azienda Ospedaliera Universitaria Policlinico Tor Vergata
  • Lombardia
    • Milano, Lombardia, Italy, 20121
      • Asst Fatebenefratelli Sacco (Fatebenefratelli)
    • Milano, Lombardia, Italy, 20162
      • Azienda Socio Sanitaria Territoriale Niguarda (Grande Ospedale Metropolitano Niguarda)
    • Milano, Lombardia, Italy
      • Azienda Socio Sanitaria Territoriale Fatebenefratelli (Presidio Ospedale Sacco)
    • Rozzano (MI), Lombardia, Italy, 20089
      • Istituto Clinico Humanitas
    • San Donato Milanese (MI), Lombardia, Italy, 20097
      • I.R.C.C.S Policlinico San Donato
    • San Giovanni Rotondo, Lombardia, Italy, 71013
      • IRCCS Ospedale Casa Sollievo della Soffenza; Stru Comp di Gastroenterologia ed Endoscopia digest
  • Piemonte
    • Torino, Piemonte, Italy, 10128
      • Ospedale Mauriziano Umberto I
  • Toscana
    • Firenze, Toscana, Italy, 50141
      • Azienda Ospedaliera Universitaria Careggi
    • Pisa, Toscana, Italy, 56100
      • Azienda Ospedaliero Universitaria Pisana
  • Veneto
    • Padova, Veneto, Italy, 35128
      • Azienda Ospedaliera di Padova
• Korea, Republic of
  • Busan, Korea, Republic of, 49241
    • Pusan National University Hospital
  • Busan, Korea, Republic of, 49201
    • Dong-A University Hospital
  • Daegu, Korea, Republic of, 41404
    • Kyungpook National University Chilgok Hospital
  • Daegu, Korea, Republic of, 41944
    • Kyungpook National University Hospital
  • Daegu, Korea, Republic of, 41931
    • Keimyung University Dongsan Medical Center
  • Daegu, Korea, Republic of, 705-717
    • Yeungnam Univ. Hospital
  • Gyeonggi-do, Korea, Republic of, 15355
    • Korea University Ansan Hospital
  • Seongnam, Korea, Republic of, 13520
    • CHA Bundang Medical Centre; CHA university
  • Seongnam-si, Korea, Republic of, 13605
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 02447
    • Kyung Hee University Hospital
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 03181
    • Kangbuk Samsung Hospital
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital, Yonsei University
  • Suwon City, Korea, Republic of, 443-721
    • Ajou University Hospital
  • Suwon-si,, Korea, Republic of, 442-723
    • The Catholic University Of Korea St. Vincent's Hospital
  • Wonju-Si, Korea, Republic of, 220-701
    • Yonsei University Wonju Severance Christian Hospital
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Amsterdam UMC location AMC
  • Amsterdam, Netherlands, 1081 HV
    • Amsterdam UMC location VUmc
  • Maastricht, Netherlands, 6229 HX
    • Maastricht University Medical Center
  • NL -nijmegen, Netherlands, 6525 GA
    • Radboudumc
• Norway
  • Lørenskog, Norway, 1478
    • Akershus Universitetssykehus HF
• Portugal
  • Braga, Portugal, 4710-243
    • Hospital de Braga
  • Guimarães, Portugal, 4835-044
    • Hospital Da Senhora Da Oliveira Guimarăes
• Romania
  • Bucharest, Romania, 022328
    • Institutul Clinic Fundeni Bucuresti
  • Bucharest, Romania, 772202
    • Spitalul Clinic Colentina
  • Bucuresti, Romania, 010719
    • S.C MedLife S.A
  • Bucuresti, Romania, 040055
    • Centrul Medical Unirea SRL
  • Targu Mures, Romania, 540103
    • Spitalul Clinic Judetean Mures
  • Timisoara, Romania, 300002
    • Centrul de Gastroenterologie Dr. Goldis
• Singapore
  • Singapore, Singapore, 169608
    • Singapore General Hospital
• South Africa
  • Bloemfontein, South Africa, 9301
    • Netcare Universitas Private Hospital
  • Cape Town, South Africa, 7500
    • Dr MJ Prins Practice
  • Cape Town, South Africa, 7550
    • Dr Corne Kruger Inc.
• Spain
  • Barcelona, Spain
    • Centro Médico Teknon
  • Madrid, Spain, 28006
    • Hospital Universitario de La Princesa
  • Madrid, Spain, 280146
    • Hospital Universitario La Paz
  • Valencia, Spain, 46026
    • Hospital Universitari i Politecnic La Fe
  • Barcelona
    • Sabadell, Barcelona, Spain, 08208
      • Corporacio Sanitaria Parc Tauli
  • LA Coruña
    • Ferrol, LA Coruña, Spain, 15405
      • Complejo Hospitalario Universitario de Ferrol
  • Madrid
    • Alcorcon, Madrid, Spain, 28922
      • Fundacion Hospital de Alcorcon; Servicio de Digestivo
• Sweden
  • Stockholm, Sweden, 18288
    • Danderyds Sjukhus AB
• Switzerland
  • Bern, Switzerland, 3010
    • Inselspital-Universitaetsspital Bern
  • Zürich, Switzerland, 8091
    • UniversitätsSpital Zürich
• United Kingdom
  • Bournemouth, United Kingdom, BH7 7DW
    • The Royal Bournemouth Hospital
  • Cambridge, United Kingdom, CB2 0QQ
    • Addenbrooke's Hospital
  • Coventry, United Kingdom, CV2 2DX
    • University Hospital Coventry
  • Exeter, United Kingdom, EX2 5DW
    • Royal Devon and Exeter Hospital (Wonford)
  • Leeds, United Kingdom, LS9 7TF
    • St James University Hospital
  • London, United Kingdom, E1 1FR
    • The Royal London Hospital
  • London, United Kingdom, SE5 9NU
    • King's College London
  • London, United Kingdom, SE1 7EH
    • St Thomas 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 NHS Trust
  • Southampton, United Kingdom, SO16 6YD
    • Southampton General Hospital

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:

• Moderately to severely active UC as determined by the Mayo Clinic Score assessment (MCS)
• Naive to treatment with any anti-TNF inhibitor therapy (including TNF inhibitor biosimilars)
• An inadequate response to or intolerance of prior corticosteroid and/or immunosuppressant treatment
• Background regimen for UC may include oral 5-aminosalicylate (5-ASA), oral corticosteroids, budenoside multi-matrix system (MMX), probiotics, azathioprine (AZA), 6-mercaptopurine (6-MP), or methotrexate (MTX) if doses have been stable during the screening period
• Use of highly effective contraception during and at least 24 weeks after the last dose of study drug

Exclusion Criteria:

• A history of or current conditions and diseases affecting the digestive tract, such as indeterminate colitis, suspicion of ischemic, radiation 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
• Have received non-permitted inflammatory bowel disease (IBD) therapies (including natalizumab, vedolizumab, efalizumab, and tofactinib)
• History of moderate or severe allergic or anaphylactic/anaphylactoid reactions to chimeric, human, or humanized antibodies; fusion proteins, or murine proteins; hypersensitivity to etrolizumab or any of its excipients
• Chronic hepatitis B or C infection, Human deficiency virus (HIV) or tuberculosis (active or latent)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Etrolizumab + Placebo (IV); Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.	Drug: Etrolizumab; 105 mg administered by subcutaneous (SC) injection once every 4 weeks (Q4W) until Week 52.; Other Names: RO5490261; RG7413; PRO145223; Other: Placebo (IV); Administered by (IV) infusion at Weeks 0, 2, and 6 and then every 8 weeks until Week 46.
Active Comparator: Infliximab + Placebo (Injection); Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.	Drug: Infliximab; 5 mg/kg of infliximab will be administered by intravenous (IV) infusion at Weeks 0, 2, and 6 and then every 8 weeks until Week 46.; Other: Placebo (Injection); Administered by SC injection Q4W until Week 52

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Both Clinical Response at Week 10 and Clinical Remission at Week 54, as Determined by the Mayo Clinic Score (MCS)	Mayo Clinic Score (MCS) is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease. 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. Clinical Remission is MCS ≤2 with individual subscores ≤1.	Week 10, Week 54

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving Clinical Remission at Week 10, Defined as MCS ≤2 With Individual Subscores ≤1	MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease.	Week 10
Percentage of Participants Achieving Clinical Remission at Week 54, as Determined by the MCS	Mayo Clinic Score (MCS) is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease. Clinical Remission is MCS ≤2 with individual subscores ≤1.	Week 54
Percentage of Participants Achieving Clinical Remission at Both Week 10 and Week 54, as Determined by the MCS	MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease. Clinical Remission is MCS ≤2 with individual subscores ≤1.	Week 10 and Week 54
Percentage of Participants Achieving Clinical Remission at Week 54 Among Those With a Clinical Response at Week 10, as Determined by the MCS	MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease. Clinical Remission is MCS ≤2 with individual subscores ≤1. 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 10 and Week 54
Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Week 10, Determined by the MCS	MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease. Improvement in endoscopic appearance of the mucosa is Endoscopy subscore ≤1.	Baseline to Week 10
Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Week 54, as Determined by the MCS	MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease. Improvement in endoscopic appearance of the mucosa is Endoscopy subscore ≤1.	Baseline to Week 54
Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Both Week 10 and Week 54, as Determined by the MCS	MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease. Improvement in endoscopic appearance of the mucosa is Endoscopy subscore ≤1.	Baseline to Week 10, Week 54
Percentage of Participants With Endoscopic Remission at Week 54, as Determined by the MCS	MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease. Endoscopic Remission is Endoscopy subscore = 0.	Week 54
Percentage of Participants Achieving Clinical Response at Week 10, as Determined by the MCS	MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease. 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 10
Percentage of Participants Achieving Clinical Response at Both Weeks 10 and 54, as Determined by the MCS	MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease. 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 10, Week 54
Percentage of Participants That Achieve Clinical Remission Corticosteroid-Free at Week 54 (Off Corticosteroid for at Least 24 Weeks Prior to Week 54) Among Those Who Were Receiving Corticosteroids at Baseline, as Determined by the MCS	MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease. Clinical Remission is MCS ≤2 with individual subscores ≤1.	Week 54
Number of Participants With Adverse Events, Severity Determined According to the 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.	Baseline until the end of study (up to 66 weeks)
Number of Participants With Adverse Events Leading to Study Drug Discontinuation		Baseline until the end of study (up to 66 weeks)
Number of Participants With Infection-Related Adverse Events, Severity Determined According to the NCI CTCAE v4.0	All 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.	Baseline until the end of study (up to 66 weeks)
Number of Participants With Serious Infection-Related Adverse Events		Baseline until the end of study (up to 66 weeks)
Number of Participants With Malignancies		Baseline until the end of study (up to 66 weeks)
Number of Participants With Injection-Site Reactions, Severity Determined According to the 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.	Baseline until the end of study (up to 66 weeks)
Number of Participants With Hypersensitivity Reaction Events, Severity Determined According to the 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.	Baseline until the end of study (up to 66 weeks)
Pharmacokinetics: Etrolizumab Serum Concentration		Weeks 2, 10, 12, 30, and 54
Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Overall Score at Weeks 10, 30, and 54	The IBDQ is used to assess participant's health-related quality of life (QOL). The 32-item questionnaire contains four domains: bowel symptoms (10 items), systemic symptoms (5 items), emotional function (12 items), and social function (5 items). The items are scored on a 7-point Likert scale with a higher score indicating better health-related QOL. IBDQ score is a total score summed up from across all 32 questions on the questionnaire. The score can range from 32-224 and the higher score indicates a better quality of life.	Weeks 10, 30, and 54
Number of Participants With Anti-Therapeutic Antibodies (ATAs) to Etrolizumab		Weeks 0, 4, 10, 12, 30, and 54

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.
• Danese S, Colombel JF, Lukas M, Gisbert JP, D'Haens G, Hayee B, Panaccione R, Kim HS, Reinisch W, Tyrrell H, Oh YS, Tole S, Chai A, Chamberlain-James K, Tang MT, Schreiber S; GARDENIA Study Group. Etrolizumab versus infliximab for the treatment of moderately to severely active ulcerative colitis (GARDENIA): a randomised, double-blind, double-dummy, phase 3 study. Lancet Gastroenterol Hepatol. 2022 Feb;7(2):118-127. doi: 10.1016/S2468-1253(21)00294-6. Epub 2021 Nov 17.

Study record dates

Study Major Dates

• Study Start (Actual): December 24, 2014
• Primary Completion (Actual): June 23, 2020
• Study Completion (Actual): June 23, 2020

Study Registration Dates

• First Submitted: April 15, 2014
• First Submitted That Met QC Criteria: May 8, 2014
• First Posted (Estimate): May 12, 2014

Study Record Updates

• Last Update Posted (Actual): December 3, 2021
• Last Update Submitted That Met QC Criteria: December 1, 2021
• Last Verified: December 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; Antirheumatic Agents; Immunologic Factors; Gastrointestinal Agents; Dermatologic Agents; Infliximab; Etrolizumab
• Other Study ID Numbers: GA29103; 2013-004282-14 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

IPD Plan Description

Qualified researchers may request access to individual patient level data through the request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/).

For further details on Roche's Global Policy on Sharing of Clinical Study Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Drug and device information, study documents

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