A Study of the Efficacy and Safety of Etrolizumab Treatment in Maintenance of Disease Remission in Ulcerative Colitis (UC) Participants Who Are Naive to Tumor Necrosis Factor (TNF) Inhibitors (LAUREL)

Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy (Maintenance of Remission) and Safety of Etrolizumab Compared With Placebo in Patients With Moderate to Severe Active Ulcerative Colitis Who Are Naive to TNF Inhibitors

This Phase III, randomized, double-blind, parallel-grouped, placebo-controlled, multicenter study will investigate the efficacy and safety of etrolizumab in maintenance of remission in participants with moderately to severely active UC who are naive to TNF inhibitors and refractory to or intolerant of prior immunosuppressant and/or corticosteroid treatment.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 359
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • CE
    • Fortaleza, CE, Brazil, 60430-370
      • Hospital Universitário Walter Cantídio - UFC
  • PR
    • Curitiba, PR, Brazil, 80430-160
      • Centro Digestivo de Curitiba
  • RS
    • Porto Alegre, RS, Brazil, 90035-001
      • Hospital Moinhos de Vento
  • SP
    • Jaú, SP, Brazil, 17210-190
      • CECIP - Centro de Estudos Clínicos do Interior Paulista
    • Santo Andre, SP, Brazil, 09080-000
      • Pesquisare Saúde Sociedade Simples
    • Santo Andre, SP, Brazil, 09190-610
      • Hospital Estadual Mario Covas
    • Sao Paulo, SP, Brazil, 01308-050
      • Hospital Sirio-Libanes
    • São Paulo, SP, Brazil, 04039-901
      • Hospital do Servidor Público Estadual/HSPE-SP
• Canada
  • 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
    • London, Ontario, Canada, N6A 5A5
      • LHSC - University Hospital; Movement Disorders Program
    • London, Ontario, Canada, N6A 5W9
      • London Health Sciences Centre Victoria Hospital; Research Pharmacy
    • Toronto, Ontario, Canada, M5G 1X5
      • Mount Sinai Hospital
    • Vaughan, Ontario, Canada, L4L 4Y7
      • Toronto Digestive Disease Associates
• Czechia
  • Brno, Czechia, 65691
    • Fakultni nemocnice u sv. Anny v Brne; I.Interni kardioangiologicka klinika
  • Hradec Kralove, Czechia, 500 12
    • Hepato-gastroenterologie HK, s.r.o.
  • Prague, Czechia, 180 01
    • Nemocnice Na Bulovce
• Denmark
  • Aalborg, Denmark, 9100
    • Ålborg Universitets Hospital
  • Herlev, Denmark, 2730
    • Herlev og Gentofte Hospital
• Germany
  • Berlin, Germany, 10117
    • Charite Universitaetsmedizin Berlin - Campus Charite Mitte
  • Bochum, Germany, 44789
    • Berufsgenossenschaftliches Universitaetsklinikum Bergmannsheil GmbH
  • Ellwangen, Germany, 73479
    • Ärztezentrum Ellwangen; Gemeinschaftspraxis
  • Frankfurt, Germany, 60590
    • Klinik Johann Wolfgang von Goethe Uni
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover; Klinik für Gastroenterologie, Hepatologie und Endokrinologie
  • Jena, Germany, 07740
    • Universitaetsklinikum Jena; Apotheke des Uniersitätsklinikums Jena
  • Lueneburg, Germany, 21339
    • Medizinisches Zentrum Klinikum Lueneburg
  • Mannheim, Germany, 68167
    • Klinikum Mannheim GmbH Universitätsklinikum
• Hungary
  • Balatonfured, Hungary, 8230
    • DRC Gyogyszervizsgalo Kozpont Kft
  • Budapest, Hungary, 1136
    • Pannónia Klinika Magánorvosi
  • Debrecen, Hungary, 4032
    • Debreceni Egyetem Klinikai Kozpont
  • Kistarcsa, Hungary, 2143
    • Pest Megyei Flor Ferenc Korhaz
  • Szentes, Hungary, 6600
    • Csongrád Megyei Dr. Bugyi István Kórház
• India
  • Jaipur, India, 302001
    • S. R. Kalla Memorial General Hospital
  • Mangalore, India, 575001
    • Kasturba Medical College & Hospital
  • Pune, India, 411 001
    • Ruby Hall Clinic
  • Pune, India, 411011
    • King Edward Memorial Hospital Research Centre
  • Andhra Pradesh
    • Hyderabad, Andhra Pradesh, India, 500012
      • Osmania General Hospital
    • Hyderabad, Andhra Pradesh, India, 500058
      • Deccan College of Medical Sciences and Allied Hospitals
  • Delhi
    • New Delhi, Delhi, India, 110017
      • Pushpawati Singhania Research Institute
  • Gujarat
    • Rajkot, Gujarat, India, 360005
      • Shree Giriraj Multispeciality Hospital
    • Surat, Gujarat, India, 395002
      • Nirmal Hospital
  • Karnataka
    • Belgaum, Karnataka, India, 590010
      • K.L.E. Society's Dr. Prabhakar Kore Hospital and Medical Research Centre
    • Bengaluru, Karnataka, India, 560054
      • M. S. Ramaiah Medical College and Hospital
  • Maharashtra
    • Nagpur, Maharashtra, India, 440012
      • Midas Institute of Gastroenterology
  • Punjab
    • Ludhiana, Punjab, India, 141001
      • Dayanand Medical College and Hospital
• Israel
  • Beer Yaacov, Israel, 6093000
    • Assaf Harofeh Medical Center
  • Haifa, Israel, 31048
    • Bnei Zion Medical Center; Department of Internal Medicine B
  • Jerusalem, Israel, 9103102
    • Shaare Zedek Medical Center
  • Jerusalem, Israel, 9112001
    • Hadassah University Hospital - Ein Kerem
  • Nazareth, Israel, 16100
    • Holy Family Hospital
• Italy
  • Lazio
    • Roma, Lazio, Italy, 00157
      • Ospedale Sandro Pertini
  • Lombardia
    • Brescia, Lombardia, Italy, 25124
      • Fondazione Poliambulanza Istituto Ospedaliero
    • Rho, Lombardia, Italy, 20017
      • Ospedale di Circolo; Neuropsichiatria Infantile
  • Sicilia
    • Palermo, Sicilia, Italy, 90127
      • Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone
• Mexico
  • Durango, Mexico, 34000
    • Instituto de Investigaciones Aplicadas a la Neurociencia A.C.
  • Estado de México, Mexico, 54769
    • Phylasis Clinicas Research S de RL de CV
  • Nuevo LEON
    • Monterrey, Nuevo LEON, Mexico, 64610
      • Centro Regiomontano de Estudios Clínicos Roma S.C.
• Poland
  • Warszawa, Poland, 02-018
    • Zespó Przychodni Specjalistycznych PRIMA
  • Wroclaw, Poland, 53-114
    • LexMedica Osrodek Badan Klinicznych
• Slovakia
  • Nitra, Slovakia, 950 01
    • Fakultna nemocnica Nitra
  • Vranov nad Topľou, Slovakia, 093 01
    • Endomed, s.r.o.
• South Africa
  • Cape Town, South Africa, 7708
    • Dr JP Wright Practice
  • Pretoria, South Africa, 0002
    • Emmed Research
• Ukraine
  • Odessa, Ukraine, 65117
    • Odessa regional clinical Hospital
  • Poltava, Ukraine, 36011
    • M.V. Sklifosovskyi Poltava RCH Dept of Gastroenterology HSEIU UMSA
  • Uzhgorod, Ukraine, 88009
    • SI Divisional Clinical Hospital of Uzhgorod Station of ST&BA LZ Dep of Therapy SHEI Uzhgorod NU
  • Vinnytsia, Ukraine, 21018
    • M.I. Pyrogov VRCH Dept of Gastroenterology M.I. Pyrogov VNMU
  • KIEV Governorate
    • Kyiv, KIEV Governorate, Ukraine, 04107
      • CI of Kyiv RC Kyiv Regional Clinical Hospital
    • Lviv, KIEV Governorate, Ukraine, 79010
      • Lviv Regional Clinical Hospital
    • Uzhgorod, KIEV Governorate, Ukraine, 88018
      • A.Novak Transcarpathian Regional Clinical Hospital
  • Kharkiv Governorate
    • Sumy, Kharkiv Governorate, Ukraine, 40022
      • CI of SRC Sumy RCH Dept of Rheumatology Sumy SU MI
• United States
  • California
    • Orange, California, United States, 92868
      • University of California, Irvine Medical Center
    • San Diego, California, United States, 92103
      • Clinical Applications Laboratories, Inc.
    • San Francisco, California, United States, 94115
      • University of California at San Francisco
    • Ventura, California, United States, 93003
      • Ventura Clinical Trials
  • Colorado
    • Colorado Springs, Colorado, United States, 80907
      • Peak Gastroenterology Associates; Gastroenterology
    • Lafayette, Colorado, United States, 80026
      • Clinical Research of the Rockies
  • Florida
    • Clearwater, Florida, United States, 33762
      • West Central Gastroenterology d/b/a Gastro Florida
    • Miami, Florida, United States, 33155
      • Regenerate Clinical Trials
    • Miami Beach, Florida, United States, 33140
      • IMIC, Inc
    • Trinity, Florida, United States, 34655
      • Advanced Research Institute, Inc.
    • Winter Park, Florida, United States, 32789
      • Shafran Gastroenterology Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University-Feinberg School of Medicine; Division of Gastroenterology and Hepatology
    • Oak Lawn, Illinois, United States, 60453
      • Southwest Gastroenterology
  • Indiana
    • New Albany, Indiana, United States, 47150
      • Aquiant Research
  • Louisiana
    • Shreveport, Louisiana, United States
      • Louisiana Research Center, LLC
  • Massachusetts
    • Brockton, Massachusetts, United States, 02302
      • Commonwealth Clinical Studies
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
    • Troy, Michigan, United States, 48098
      • Center for Digestive Health
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Missouri
    • Belton, Missouri, United States, 64012
      • Ehrhardt Clinical Research, LLC
  • New York
    • New York, New York, United States, 10016
      • Manhattan Clinical Research
    • New York, New York, United States, 10021
      • Weill Cornell Medical College-New York Presbyterian Hospital
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Asheville Gastroenterology Associates, P.A.
    • Chapel Hill, North Carolina, United States, 27599
      • UNC at Chapel Hill - Dpt of Family Medicine; Center for Functional GI and Motility Disorders
    • Kinston, North Carolina, United States, 28501
      • Kinston Medical Specialists
  • Texas
    • Dallas, Texas, United States, 75231
      • Texas Digestive Disease Consultants - Dallas
    • Southlake, Texas, United States, 76092
      • Texas Digestive Disease Consultants - Southlake
    • Tyler, Texas, United States, 75701
      • Digestive Health Specialists of Tyler
  • Utah
    • Clinton, Utah, United States, 84015
      • Ericksen Research and Development
    • Salt Lake City, Utah, United States, 84132
      • University of Utah School of Medicine
  • Virginia
    • Richmond, Virginia, United States, 23249
      • McGuire Research Institute; Gastroenterology
  • Washington
    • Bellevue, Washington, United States, 98004
      • Northwest Gastroenterology Associates

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 ulcerative colitis (UC) established at least 3 months prior to Day 1 by clinical and endoscopic evidence
• Moderately to severely active UC as determined by an MCS of 6-12 with an endoscopic subscore greater than or equal to (≥)2 as determined by the central reading procedure (endoscopy to be performed 4-16 days prior to Day 1), a rectal bleeding subscore ≥1, and a stool frequency subscore ≥1 during the screening period (prior to Day 1)
• Evidence of UC extending a minimum of 20 centimeters (cm) from the anal verge as determined by baseline endoscopy (flexible sigmoidoscopy or colonoscopy) performed during screening, 4-16 days prior to Day 1
• Naive to treatment with any anti-TNF therapy
• Participants must have had an inadequate response, loss of response, or intolerance to prior corticosteroid and/or immunosuppressant treatment
• Background regimen for UC may include oral 5-aminosalicylate (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
• 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) as stated in the protocol
• Any prior treatment with anti-adhesion molecules (such as mucosal addressin cell adhesion molecule [MAdCAM-1])
• Any prior treatment with rituximab
• Any treatment with tofacitinib during screening
• Cogenital 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 within 60 days prior to Day 1 or 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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Open-Label Induction Phase: Etrolizumab; All participants will receive treatment with open-label etrolizumab 105 milligrams (mg) subcutaneous (SC) injection once every 4 weeks (Q4W) up to Week 10.	Drug: Etrolizumab; Participants will receive 105 mg etrolizumab SC injection Q4W.; Other Names: RO5490261; RG7413; PRO145223; rhuMAb Beta7
Experimental: Double-Blind Maintenance Phase: Etrolizumab; Participants who achieved a clinical response at Week 10 during the induction phase and randomized to this arm for the double-blind maintenance phase will receive etrolizumab 105 mg SC injection Q4W from Week 12 up to Week 62.	Drug: Etrolizumab; Participants will receive 105 mg etrolizumab SC injection Q4W.; Other Names: RO5490261; RG7413; PRO145223; rhuMAb Beta7
Placebo Comparator: Double-Blind Maintenance Phase: Placebo; Participants who achieved a clinical response at Week 10 during the induction phase and randomized to this arm for the double-blind maintenance phase will receive placebo (matched to etrolizumab) SC injection Q4W from Week 12 up to Week 62.	Drug: Placebo; Participants will receive placebo (matched to etrolizumab) SC injection Q4W.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maintenance Phase: Percentage of Participants in Remission at Week 62 Among Randomized Participants With a Clinical Response at Week 10, as Determined by the Mayo Clinic Score (MCS)	MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. 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. Remission is MCS ≤2 with individual subscores ≤1 and a rectal bleeding subscore of 0.	Week 62

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maintenance Phase: Percentage of Participants Who Maintained Clinical Remission at Week 62 Among Randomized Participants in Clinical Remission 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. Clinical Remission is MCS ≤2 with individual subscores ≤1.	Week 62
Maintenance Phase: Percentage of Participants in Clinical Remission at Week 62, 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. Clinical Remission is MCS ≤2 with individual subscores ≤1.	Week 62
Maintenance Phase: Percentage of Participants in Remission at Week 62 Among Randomized Participants in Remission 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. Remission is MCS ≤2 with individual subscores ≤1 and a rectal bleeding subscore of 0.	Week 62
Maintenance Phase: Percentage of Participants With Improvement From Baseline in Endoscopic Appearance of the Mucosa at Week 62, as Determined by the MCS Endoscopic Subscore	MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Improvement in endoscopic appearance of the mucosa is Endoscopy subscore ≤1.	Baseline, Week 62
Maintenance Phase: Percentage of Participants With Endoscopic Remission at Week 62, as Determined by the MCS Endoscopic Subscore	MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Endoscopic Remission is Endoscopy subscore = 0.	Week 62
Maintenance Phase: Percentage of Participants With Histologic Remission at Week 62, 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 62
Maintenance Phase: Percentage of Participants With Corticosteroid-Free Clinical Remission at Week 62 Among Participants 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. Clinical Remission is MCS ≤2 with individual subscores ≤1.	Baseline, Week 62
Maintenance Phase: Percentage of Participants With Corticosteroid-Free Remission at Week 62 Among Participants 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. Remission is MCS ≤2 with individual subscores ≤1 and a rectal bleeding subscore of 0.	Baseline, Week 62
Maintenance Phase: Change From Baseline to Week 62 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, Week 62
Maintenance Phase: Change From Baseline to Week 62 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 domain score ranges from 0-12, with a higher score indicating a worse disease state.	Baseline, Week 62
Maintenance Phase: Change From Baseline to Week 62 in Health-Related Quality of Life, as Assessed by the Overall Score of the Inflammatory Bowel Disease Questionnaire (IBDQ)	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.	Baseline, Week 62
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 74
Number of Participants With Adverse Events Leading to Study Drug Discontinuation		From Baseline up to Week 74
Number of Participants With Serious Infection-Related Adverse Events		From Baseline up to Week 74
Number of Participants With Infection-Related Adverse Events by Severity, According to 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 74
Number of Participants With Injection-Site Reactions by Severity, According to 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 74
Number of Participants With Hypersensitivity Reaction Events by Severity, According to 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 74
Number of Participants With Malignancies		From Baseline up to Week 74
Number of Participants With Anti-Therapeutic Antibodies (ATAs) to Etrolizumab		Baseline, Weeks 4, 12, 24, 44, and 62, and and Early Termination/End of Safety Follow-Up (up to Week 74)
Maintenance Phase: 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 quantitation (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 12, 24, 44, and 62
Maintenance Phase: 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.	Pre-dose (0 hour) at Baseline and Weeks 12, 24, 44, and 62

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.
• Vermeire S, Lakatos PL, Ritter T, Hanauer S, Bressler B, Khanna R, Isaacs K, Shah S, Kadva A, Tyrrell H, Oh YS, Tole S, Chai A, Pulley J, Eden C, Zhang W, Feagan BG; LAUREL Study Group. Etrolizumab for maintenance therapy in patients with moderately to severely active ulcerative colitis (LAUREL): a randomised, placebo-controlled, double-blind, phase 3 study. Lancet Gastroenterol Hepatol. 2022 Jan;7(1):28-37. doi: 10.1016/S2468-1253(21)00295-8. Epub 2021 Nov 17.

Study record dates

Study Major Dates

• Study Start (Actual): August 12, 2014
• Primary Completion (Actual): April 6, 2020
• Study Completion (Actual): April 6, 2020

Study Registration Dates

• First Submitted: June 13, 2014
• First Submitted That Met QC Criteria: June 16, 2014
• First Posted (Estimate): June 17, 2014

Study Record Updates

• Last Update Posted (Actual): August 19, 2021
• Last Update Submitted That Met QC Criteria: July 27, 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: GA29102; 2013-004280-31 (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