Clinical trial NCT02165215: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Colitis, Ulcerative
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2014-06-17
Enrollment: 359
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: 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)
timeFrame: Week 62
Secondary outcomes:
measure: 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
timeFrame: Week 62
measure: Maintenance Phase: Percentage of Participants in Clinical Remission at Week 62, as Determined by the MCS
timeFrame: Week 62
measure: Maintenance Phase: Percentage of Participants in Remission at Week 62 Among Randomized Participants in Remission at Week 10, as Determined by the MCS
timeFrame: Week 62
measure: 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
timeFrame: Baseline, Week 62
measure: Maintenance Phase: Percentage of Participants With Endoscopic Remission at Week 62, as Determined by the MCS Endoscopic Subscore
timeFrame: Week 62
measure: Maintenance Phase: Percentage of Participants With Histologic Remission at Week 62, as Determined by the Nancy Histological Index
timeFrame: Week 62
measure: 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
timeFrame: Baseline, Week 62
measure: 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
timeFrame: Baseline, Week 62
measure: 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
timeFrame: Baseline, Week 62
measure: Maintenance Phase: Change From Baseline to Week 62 in UC Functional Symptoms, as Assessed by the UC-PRO/SS Questionnaire
timeFrame: Baseline, Week 62
measure: 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)
timeFrame: Baseline, Week 62
measure: 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)
timeFrame: From Baseline up to Week 74
measure: Number of Participants With Adverse Events Leading to Study Drug Discontinuation
timeFrame: From Baseline up to Week 74
measure: Number of Participants With Serious Infection-Related Adverse Events
timeFrame: From Baseline up to Week 74
measure: Number of Participants With Infection-Related Adverse Events by Severity, According to NCI-CTCAE v4.0
timeFrame: From Baseline up to Week 74
measure: Number of Participants With Injection-Site Reactions by Severity, According to NCI-CTCAE v4.0
timeFrame: From Baseline up to Week 74
measure: Number of Participants With Hypersensitivity Reaction Events by Severity, According to NCI-CTCAE v4.0
timeFrame: From Baseline up to Week 74
measure: Number of Participants With Malignancies
timeFrame: From Baseline up to Week 74
measure: Number of Participants With Anti-Therapeutic Antibodies (ATAs) to Etrolizumab
timeFrame: Baseline, Weeks 4, 12, 24, 44, and 62, and and Early Termination/End of Safety Follow-Up (up to Week 74)
measure: Maintenance Phase: Etrolizumab Serum Trough Concentration (for Arms/Timepoints Above LLOQ)
timeFrame: Pre-dose (0 hour) at Baseline and Weeks 12, 24, 44, and 62
measure: Maintenance Phase: Etrolizumab Serum Trough Concentration (for Arms/Timepoints Below LLOQ)
timeFrame: Pre-dose (0 hour) at Baseline and Weeks 12, 24, 44, and 62
Other outcomes:
Locations:
city: Orange
country: United States
facility: University of California, Irvine Medical Center
state: California
city: San Diego
country: United States
facility: Clinical Applications Laboratories, Inc.
state: California
city: San Francisco
country: United States
facility: University of California at San Francisco
state: California
city: Ventura
country: United States
facility: Ventura Clinical Trials
state: California
city: Colorado Springs
country: United States
facility: Peak Gastroenterology Associates; Gastroenterology
state: Colorado
city: Lafayette
country: United States
facility: Clinical Research of the Rockies
state: Colorado
city: Clearwater
country: United States
facility: West Central Gastroenterology d/b/a Gastro Florida
state: Florida
city: Miami Beach
country: United States
facility: IMIC, Inc
state: Florida
city: Miami
country: United States
facility: Regenerate Clinical Trials
state: Florida
city: Trinity
country: United States
facility: Advanced Research Institute, Inc.
state: Florida
city: Winter Park
country: United States
facility: Shafran Gastroenterology Center
state: Florida
city: Chicago
country: United States
facility: Northwestern University-Feinberg School of Medicine; Division of Gastroenterology and Hepatology
state: Illinois
city: Oak Lawn
country: United States
facility: Southwest Gastroenterology
state: Illinois
city: New Albany
country: United States
facility: Aquiant Research
state: Indiana
city: Shreveport
country: United States
facility: Louisiana Research Center, LLC
state: Louisiana
city: Brockton
country: United States
facility: Commonwealth Clinical Studies
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Troy
country: United States
facility: Center for Digestive Health
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Belton
country: United States
facility: Ehrhardt Clinical Research, LLC
state: Missouri
city: New York
country: United States
facility: Manhattan Clinical Research
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College-New York Presbyterian Hospital
state: New York
city: Asheville
country: United States
facility: Asheville Gastroenterology Associates, P.A.
state: North Carolina
city: Chapel Hill
country: United States
facility: UNC at Chapel Hill - Dpt of Family Medicine; Center for Functional GI and Motility Disorders
state: North Carolina
city: Kinston
country: United States
facility: Kinston Medical Specialists
state: North Carolina
city: Dallas
country: United States
facility: Texas Digestive Disease Consultants - Dallas
state: Texas
city: Southlake
country: United States
facility: Texas Digestive Disease Consultants - Southlake
state: Texas
city: Tyler
country: United States
facility: Digestive Health Specialists of Tyler
state: Texas
city: Clinton
country: United States
facility: Ericksen Research and Development
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah School of Medicine
state: Utah
city: Richmond
country: United States
facility: McGuire Research Institute; Gastroenterology
state: Virginia
city: Bellevue
country: United States
facility: Northwest Gastroenterology Associates
state: Washington
city: Fortaleza
country: Brazil
facility: Hospital Universitario Walter Cantidio - UFC
state: CE
city: Curitiba
country: Brazil
facility: Centro Digestivo de Curitiba
state: PR
city: Porto Alegre
country: Brazil
facility: Hospital Moinhos de Vento
state: RS
city: Jaú
country: Brazil
facility: CECIP - Centro de Estudos Clínicos do Interior Paulista
state: SP
city: Santo Andre
country: Brazil
facility: Pesquisare Saúde Sociedade Simples
state: SP
city: Santo Andre
country: Brazil
facility: Hospital Estadual Mario Covas
state: SP
city: Sao Paulo
country: Brazil
facility: Hospital Sírio-Libanês
state: SP
city: São Paulo
country: Brazil
facility: Hospital do Servidor Público Estadual/HSPE-SP
state: SP
city: Vancouver
country: Canada
facility: Pacific Gastroenterology Associates
state: British Columbia
city: Halifax
country: Canada
facility: Queen Elizabeth II Health Sciences Centre; Gastroenterology Research
state: Nova Scotia
city: London
country: Canada
facility: LHSC - University Hospital; Movement Disorders Program
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre Victoria Hospital; Research Pharmacy
state: Ontario
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
city: Vaughan
country: Canada
facility: Toronto Digestive Disease Associates
state: Ontario
city: Brno
country: Czechia
facility: Fakultni nemocnice u sv. Anny v Brne; I.Interni kardioangiologicka klinika
city: Hradec Kralove
country: Czechia
facility: Hepato-Gastroenterologie HK, s.r.o.
city: Prague
country: Czechia
facility: Nemocnice Na Bulovce
city: Aalborg
country: Denmark
facility: Alborg Universitets Hospital
city: Herlev
country: Denmark
facility: Herlev og Gentofte Hospital
city: Berlin
country: Germany
facility: Charite Universitaetsmedizin Berlin - Campus Charite Mitte
city: Bochum
country: Germany
facility: Berufsgenossenschaftliches Universitaetsklinikum Bergmannsheil GmbH
city: Ellwangen
country: Germany
facility: Ärztezentrum Ellwangen; Gemeinschaftspraxis
city: Frankfurt
country: Germany
facility: Klinik Johann Wolfgang von Goethe Uni
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover; Klinik für Gastroenterologie, Hepatologie und Endokrinologie
city: Jena
country: Germany
facility: Universitaetsklinikum Jena; Apotheke des Uniersitätsklinikums Jena
city: Lueneburg
country: Germany
facility: Medizinisches Zentrum Klinikum Lueneburg
city: Mannheim
country: Germany
facility: Klinikum Mannheim GmbH Universitätsklinikum
city: Balatonfured
country: Hungary
facility: DRC Gyogyszervizsgalo Kozpont Kft
city: Budapest
country: Hungary
facility: Pannónia Klinika Magánorvosi
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont
city: Kistarcsa
country: Hungary
facility: Pest Megyei Flor Ferenc Korhaz
city: Szentes
country: Hungary
facility: Csongrad Megyei Dr. Bugyi Istvan Korhaz
city: Hyderabad
country: India
facility: Osmania General Hospital
state: Andhra Pradesh
city: Hyderabad
country: India
facility: Deccan College of Medical Sciences and Allied Hospitals
state: Andhra Pradesh
city: New Delhi
country: India
facility: Pushpawati Singhania Research Institute
state: Delhi
city: Rajkot
country: India
facility: Shree Giriraj Multispeciality Hospital
state: Gujarat
city: Surat
country: India
facility: Nirmal Hospital
state: Gujarat
city: Belgaum
country: India
facility: K.L.E. Society's Dr. Prabhakar Kore Hospital and Medical Research Centre
state: Karnataka
city: Bengaluru
country: India
facility: M. S. Ramaiah Medical College and Hospital
state: Karnataka
city: Nagpur
country: India
facility: Midas institute of Gastroenterology
state: Maharashtra
city: Ludhiana
country: India
facility: Dayanand Medical College and Hospital
state: Punjab
city: Jaipur
country: India
facility: S. R. Kalla Memorial General Hospital
city: Mangalore
country: India
facility: Kasturba Medical College & Hospital
city: Pune
country: India
facility: Ruby Hall Clinic
city: Pune
country: India
facility: King Edward Memorial Hospital Research Centre
city: Beer Yaacov
country: Israel
facility: Assaf Harofeh Medical Center
city: Haifa
country: Israel
facility: Bnei Zion Medical Center; Department of Internal Medicine B
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
city: Jerusalem
country: Israel
facility: Hadassah University Hospital - Ein Kerem
city: Nazareth
country: Israel
facility: Holy Family Hospital
city: Roma
country: Italy
facility: Ospedale Sandro Pertini
state: Lazio
city: Brescia
country: Italy
facility: Fondazione Poliambulanza Istituto Ospedaliero
state: Lombardia
city: Rho
country: Italy
facility: Ospedale di Circolo; Neuropsichiatria Infantile
state: Lombardia
city: Palermo
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone
state: Sicilia
city: Monterrey
country: Mexico
facility: Centro Regiomontano de Estudios Clínicos Roma S.C.
state: Nuevo LEON
city: Durango
country: Mexico
facility: Instituto de Investigaciones Aplicadas a la Neurociencia A.C.
city: Estado de México
country: Mexico
facility: Phylasis Clinicas Research S de RL de CV
city: Warszawa
country: Poland
facility: Zespó Przychodni Specjalistycznych PRIMA
city: Wroclaw
country: Poland
facility: LexMedica Osrodek Badan Klinicznych
city: Nitra
country: Slovakia
facility: Fakultna nemocnica Nitra
city: Vranov nad Topľou
country: Slovakia
facility: Endomed, s.r.o.
city: Cape Town
country: South Africa
facility: Dr JP Wright Practice
city: Pretoria
country: South Africa
facility: Emmed Research
city: Sumy
country: Ukraine
facility: CI of SRC Sumy RCH Dept of Rheumatology Sumy SU MI
state: Kharkiv Governorate
city: Kyiv
country: Ukraine
facility: CI of Kyiv RC Kyiv Regional Clinical Hospital
state: KIEV Governorate
city: Lviv
country: Ukraine
facility: Lviv Regional Clinical Hospital
state: KIEV Governorate
city: Uzhgorod
country: Ukraine
facility: A.Novak Transcarpathian Regional Clinical Hospital
state: KIEV Governorate
city: Odessa
country: Ukraine
facility: Odessa regional clinical Hospital
city: Poltava
country: Ukraine
facility: M.V. Sklifosovskyi Poltava RCH Dept of Gastroenterology HSEIU UMSA
city: Uzhgorod
country: Ukraine
facility: SI Divisional Clinical Hospital of Uzhgorod Station of ST&BA LZ Dep of Therapy SHEI Uzhgorod NU
city: Vinnytsia
country: Ukraine
facility: M.I. Pyrogov VRCH Dept of Gastroenterology M.I. Pyrogov VNMU
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.