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

NCT ID: NCT02165215

Last Updated: 2021-08-19

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

359 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-08-12

Study Completion Date

2020-04-06

Brief Summary

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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.

Detailed Description

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Conditions

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Colitis, Ulcerative

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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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.

Group Type EXPERIMENTAL

Etrolizumab

Intervention Type DRUG

Participants will receive 105 mg etrolizumab SC injection Q4W.

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.

Group Type EXPERIMENTAL

Etrolizumab

Intervention Type DRUG

Participants will receive 105 mg etrolizumab SC injection Q4W.

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.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Participants will receive placebo (matched to etrolizumab) SC injection Q4W.

Interventions

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Etrolizumab

Participants will receive 105 mg etrolizumab SC injection Q4W.

Intervention Type DRUG

Placebo

Participants will receive placebo (matched to etrolizumab) SC injection Q4W.

Intervention Type DRUG

Other Intervention Names

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RG7413 RO5490261 PRO145223 rhuMAb Beta7

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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University of California, Irvine Medical Center

Orange, California, United States

Site Status

Clinical Applications Laboratories, Inc.

San Diego, California, United States

Site Status

University of California at San Francisco

San Francisco, California, United States

Site Status

Ventura Clinical Trials

Ventura, California, United States

Site Status

Peak Gastroenterology Associates; Gastroenterology

Colorado Springs, Colorado, United States

Site Status

Clinical Research of the Rockies

Lafayette, Colorado, United States

Site Status

West Central Gastroenterology d/b/a Gastro Florida

Clearwater, Florida, United States

Site Status

Regenerate Clinical Trials

Miami, Florida, United States

Site Status

IMIC, Inc

Miami Beach, Florida, United States

Site Status

Advanced Research Institute, Inc.

Trinity, Florida, United States

Site Status

Shafran Gastroenterology Center

Winter Park, Florida, United States

Site Status

Northwestern University-Feinberg School of Medicine; Division of Gastroenterology and Hepatology

Chicago, Illinois, United States

Site Status

Southwest Gastroenterology

Oak Lawn, Illinois, United States

Site Status

Aquiant Research

New Albany, Indiana, United States

Site Status

Louisiana Research Center, LLC

Shreveport, Louisiana, United States

Site Status

Commonwealth Clinical Studies

Brockton, Massachusetts, United States

Site Status

Henry Ford Health System

Detroit, Michigan, United States

Site Status

Center for Digestive Health

Troy, Michigan, United States

Site Status

University of Minnesota

Minneapolis, Minnesota, United States

Site Status

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status

Ehrhardt Clinical Research, LLC

Belton, Missouri, United States

Site Status

Manhattan Clinical Research

New York, New York, United States

Site Status

Weill Cornell Medical College-New York Presbyterian Hospital

New York, New York, United States

Site Status

Asheville Gastroenterology Associates, P.A.

Asheville, North Carolina, United States

Site Status

UNC at Chapel Hill - Dpt of Family Medicine; Center for Functional GI and Motility Disorders

Chapel Hill, North Carolina, United States

Site Status

Kinston Medical Specialists

Kinston, North Carolina, United States

Site Status

Texas Digestive Disease Consultants - Dallas

Dallas, Texas, United States

Site Status

Texas Digestive Disease Consultants - Southlake

Southlake, Texas, United States

Site Status

Digestive Health Specialists of Tyler

Tyler, Texas, United States

Site Status

Ericksen Research and Development

Clinton, Utah, United States

Site Status

University of Utah School of Medicine

Salt Lake City, Utah, United States

Site Status

McGuire Research Institute; Gastroenterology

Richmond, Virginia, United States

Site Status

Northwest Gastroenterology Associates

Bellevue, Washington, United States

Site Status

Hospital Universitario Walter Cantidio - UFC

Fortaleza, Ceará, Brazil

Site Status

Centro Digestivo de Curitiba

Curitiba, Paraná, Brazil

Site Status

Hospital Moinhos de Vento

Porto Alegre, Rio Grande do Sul, Brazil

Site Status

CECIP - Centro de Estudos Clínicos do Interior Paulista

Jaú, São Paulo, Brazil

Site Status

Pesquisare Saúde Sociedade Simples

Santo André, São Paulo, Brazil

Site Status

Hospital Estadual Mario Covas

Santo André, São Paulo, Brazil

Site Status

Hospital Sírio-Libanês

São Paulo, São Paulo, Brazil

Site Status

Hospital do Servidor Público Estadual/HSPE-SP

São Paulo, São Paulo, Brazil

Site Status

Pacific Gastroenterology Associates

Vancouver, British Columbia, Canada

Site Status

Queen Elizabeth II Health Sciences Centre; Gastroenterology Research

Halifax, Nova Scotia, Canada

Site Status

LHSC - University Hospital; Movement Disorders Program

London, Ontario, Canada

Site Status

London Health Sciences Centre Victoria Hospital; Research Pharmacy

London, Ontario, Canada

Site Status

Mount Sinai Hospital

Toronto, Ontario, Canada

Site Status

Toronto Digestive Disease Associates

Vaughan, Ontario, Canada

Site Status

Fakultni nemocnice u sv. Anny v Brne; I.Interni kardioangiologicka klinika

Brno, , Czechia

Site Status

Hepato-Gastroenterologie HK, s.r.o.

Hradec Králové, , Czechia

Site Status

Nemocnice Na Bulovce

Prague, , Czechia

Site Status

Alborg Universitets Hospital

Aalborg, , Denmark

Site Status

Herlev og Gentofte Hospital

Herlev, , Denmark

Site Status

Charite Universitaetsmedizin Berlin - Campus Charite Mitte

Berlin, , Germany

Site Status

Berufsgenossenschaftliches Universitaetsklinikum Bergmannsheil GmbH

Bochum, , Germany

Site Status

Ärztezentrum Ellwangen; Gemeinschaftspraxis

Ellwangen, , Germany

Site Status

Klinik Johann Wolfgang von Goethe Uni

Frankfurt, , Germany

Site Status

Medizinische Hochschule Hannover; Klinik für Gastroenterologie, Hepatologie und Endokrinologie

Hanover, , Germany

Site Status

Universitaetsklinikum Jena; Apotheke des Uniersitätsklinikums Jena

Jena, , Germany

Site Status

Medizinisches Zentrum Klinikum Lueneburg

Lüneburg, , Germany

Site Status

Klinikum Mannheim GmbH Universitätsklinikum

Mannheim, , Germany

Site Status

DRC Gyogyszervizsgalo Kozpont Kft

Balatonfüred, , Hungary

Site Status

Pannónia Klinika Magánorvosi

Budapest, , Hungary

Site Status

Debreceni Egyetem Klinikai Kozpont

Debrecen, , Hungary

Site Status

Pest Megyei Flor Ferenc Korhaz

Kistarcsa, , Hungary

Site Status

Csongrad Megyei Dr. Bugyi Istvan Korhaz

Szentes, , Hungary

Site Status

Osmania General Hospital

Hyderabad, Andhra Pradesh, India

Site Status

Deccan College of Medical Sciences and Allied Hospitals

Hyderabad, Andhra Pradesh, India

Site Status

Shree Giriraj Multispeciality Hospital

Rajkot, Gujarat, India

Site Status

Nirmal Hospital

Surat, Gujarat, India

Site Status

K.L.E. Society's Dr. Prabhakar Kore Hospital and Medical Research Centre

Belagavi, Karnataka, India

Site Status

M. S. Ramaiah Medical College and Hospital

Bengaluru, Karnataka, India

Site Status

Midas institute of Gastroenterology

Nagpur, Maharashtra, India

Site Status

Pushpawati Singhania Research Institute

New Delhi, National Capital Territory of Delhi, India

Site Status

Dayanand Medical College and Hospital

Ludhiana, Punjab, India

Site Status

S. R. Kalla Memorial General Hospital

Jaipur, , India

Site Status

Kasturba Medical College & Hospital

Mangalore, , India

Site Status

Ruby Hall Clinic

Pune, , India

Site Status

King Edward Memorial Hospital Research Centre

Pune, , India

Site Status

Assaf Harofeh Medical Center

Beer Yaacov, , Israel

Site Status

Bnei Zion Medical Center; Department of Internal Medicine B

Haifa, , Israel

Site Status

Shaare Zedek Medical Center

Jerusalem, , Israel

Site Status

Hadassah University Hospital - Ein Kerem

Jerusalem, , Israel

Site Status

Holy Family Hospital

Nazareth, , Israel

Site Status

Ospedale Sandro Pertini

Rome, Lazio, Italy

Site Status

Fondazione Poliambulanza Istituto Ospedaliero

Brescia, Lombardy, Italy

Site Status

Ospedale di Circolo; Neuropsichiatria Infantile

Rho, Lombardy, Italy

Site Status

Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone

Palermo, Sicily, Italy

Site Status

Centro Regiomontano de Estudios Clínicos Roma S.C.

Monterrey, Nuevo León, Mexico

Site Status

Instituto de Investigaciones Aplicadas a la Neurociencia A.C.

Durango, , Mexico

Site Status

Phylasis Clinicas Research S de RL de CV

Estado de México, , Mexico

Site Status

Zespó Przychodni Specjalistycznych PRIMA

Warsaw, , Poland

Site Status

LexMedica Osrodek Badan Klinicznych

Wroclaw, , Poland

Site Status

Fakultna nemocnica Nitra

Nitra, , Slovakia

Site Status

Endomed, s.r.o.

Vranov nad Topľou, , Slovakia

Site Status

Dr JP Wright Practice

Cape Town, , South Africa

Site Status

Emmed Research

Pretoria, , South Africa

Site Status

CI of SRC Sumy RCH Dept of Rheumatology Sumy SU MI

Sumy, Kharkiv Governorate, Ukraine

Site Status

CI of Kyiv RC Kyiv Regional Clinical Hospital

Kyiv, KIEV Governorate, Ukraine

Site Status

Lviv Regional Clinical Hospital

Lviv, KIEV Governorate, Ukraine

Site Status

A.Novak Transcarpathian Regional Clinical Hospital

Uzhhorod, KIEV Governorate, Ukraine

Site Status

Odessa regional clinical Hospital

Odesa, , Ukraine

Site Status

M.V. Sklifosovskyi Poltava RCH Dept of Gastroenterology HSEIU UMSA

Poltava, , Ukraine

Site Status

SI Divisional Clinical Hospital of Uzhgorod Station of ST&BA LZ Dep of Therapy SHEI Uzhgorod NU

Uzhhorod, , Ukraine

Site Status

M.I. Pyrogov VRCH Dept of Gastroenterology M.I. Pyrogov VNMU

Vinnytsia, , Ukraine

Site Status

Countries

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United States Brazil Canada Czechia Denmark Germany Hungary India Israel Italy Mexico Poland Slovakia South Africa Ukraine

References

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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.

Reference Type DERIVED
PMID: 34798037 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32445184 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2013-004280-31

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GA29102

Identifier Type: -

Identifier Source: org_study_id

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