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

NCT02165215 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: GA291022013-004280-31
• Study Type: interventional
• Target: 359
• Locations: 15 countries
• Sites: 104

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.

Conditions

Colitis, Ulcerative

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (21)

• 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

  Week 62

• Maintenance Phase: Percentage of Participants in Clinical Remission at Week 62, as Determined by the MCS

  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

  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

  Baseline, Week 62

• Maintenance Phase: Percentage of Participants With Endoscopic Remission at Week 62, as Determined by the MCS Endoscopic Subscore

  Week 62

Study Arms (3)

Open-Label Induction Phase: Etrolizumab

EXPERIMENTAL

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

Double-Blind Maintenance Phase: Etrolizumab

EXPERIMENTAL

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

Double-Blind Maintenance Phase: Placebo

PLACEBO COMPARATOR

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

Interventions

Etrolizumab DRUG

Participants will receive 105 mg etrolizumab SC injection Q4W.

Also known as: RG7413, RO5490261, PRO145223, rhuMAb Beta7

Double-Blind Maintenance Phase: Etrolizumab; Open-Label Induction Phase: Etrolizumab

Placebo DRUG

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

Double-Blind Maintenance Phase: Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (104)

University of California, Irvine Medical Center

Orange, California, 92868, United States

Location

Clinical Applications Laboratories, Inc.

San Diego, California, 92103, United States

Location

University of California at San Francisco

San Francisco, California, 94115, United States

Location

Ventura Clinical Trials

Ventura, California, 93003, United States

Location

Peak Gastroenterology Associates; Gastroenterology

Colorado Springs, Colorado, 80907, United States

Location

Clinical Research of the Rockies

Lafayette, Colorado, 80026, United States

Location

West Central Gastroenterology d/b/a Gastro Florida

Clearwater, Florida, 33762, United States

Location

Regenerate Clinical Trials

Miami, Florida, 33155, United States

Location

IMIC, Inc

Miami Beach, Florida, 33140, United States

Location

Advanced Research Institute, Inc.

Trinity, Florida, 34655, United States

Location

Shafran Gastroenterology Center

Winter Park, Florida, 32789, United States

Location

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

Chicago, Illinois, 60611, United States

Location

Southwest Gastroenterology

Oak Lawn, Illinois, 60453, United States

Location

Aquiant Research

New Albany, Indiana, 47150, United States

Location

Louisiana Research Center, LLC

Shreveport, Louisiana, United States

Location

Commonwealth Clinical Studies

Brockton, Massachusetts, 02302, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Center for Digestive Health

Troy, Michigan, 48098, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

Ehrhardt Clinical Research, LLC

Belton, Missouri, 64012, United States

Location

Manhattan Clinical Research

New York, New York, 10016, United States

Location

Weill Cornell Medical College-New York Presbyterian Hospital

New York, New York, 10021, United States

Location

Asheville Gastroenterology Associates, P.A.

Asheville, North Carolina, 28801, United States

Location

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

Chapel Hill, North Carolina, 27599, United States

Location

Kinston Medical Specialists

Kinston, North Carolina, 28501, United States

Location

Texas Digestive Disease Consultants - Dallas

Dallas, Texas, 75231, United States

Location

Texas Digestive Disease Consultants - Southlake

Southlake, Texas, 76092, United States

Location

Digestive Health Specialists of Tyler

Tyler, Texas, 75701, United States

Location

Ericksen Research and Development

Clinton, Utah, 84015, United States

Location

University of Utah School of Medicine

Salt Lake City, Utah, 84132, United States

Location

McGuire Research Institute; Gastroenterology

Richmond, Virginia, 23249, United States

Location

Northwest Gastroenterology Associates

Bellevue, Washington, 98004, United States

Location

Hospital Universitario Walter Cantidio - UFC

Fortaleza, Ceará, 60430-370, Brazil

Location

Centro Digestivo de Curitiba

Curitiba, Paraná, 80430-160, Brazil

Location

Hospital Moinhos de Vento

Porto Alegre, Rio Grande do Sul, 90035-001, Brazil

Location

CECIP - Centro de Estudos Clínicos do Interior Paulista

Jaú, São Paulo, 17210-190, Brazil

Location

Pesquisare Saúde Sociedade Simples

Santo André, São Paulo, 09080-000, Brazil

Location

Hospital Estadual Mario Covas

Santo André, São Paulo, 09190-610, Brazil

Location

Hospital Sírio-Libanês

São Paulo, São Paulo, 01308-050, Brazil

Location

Hospital do Servidor Público Estadual/HSPE-SP

São Paulo, São Paulo, 04039-901, Brazil

Location

Pacific Gastroenterology Associates

Vancouver, British Columbia, V6Z 2K5, Canada

Location

Queen Elizabeth II Health Sciences Centre; Gastroenterology Research

Halifax, Nova Scotia, B3H 1V7, Canada

Location

LHSC - University Hospital; Movement Disorders Program

London, Ontario, N6A 5A5, Canada

Location

London Health Sciences Centre Victoria Hospital; Research Pharmacy

London, Ontario, N6A 5W9, Canada

Location

Mount Sinai Hospital

Toronto, Ontario, M5G 1X5, Canada

Location

Toronto Digestive Disease Associates

Vaughan, Ontario, L4L 4Y7, Canada

Location

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

Brno, 65691, Czechia

Location

Hepato-Gastroenterologie HK, s.r.o.

Hradec Králové, 500 12, Czechia

Location

Nemocnice Na Bulovce

Prague, 180 01, Czechia

Location

Alborg Universitets Hospital

Aalborg, 9100, Denmark

Location

Herlev og Gentofte Hospital

Herlev, 2730, Denmark

Location

Charite Universitaetsmedizin Berlin - Campus Charite Mitte

Berlin, 10117, Germany

Location

Berufsgenossenschaftliches Universitaetsklinikum Bergmannsheil GmbH

Bochum, 44789, Germany

Location

Ärztezentrum Ellwangen; Gemeinschaftspraxis

Ellwangen, 73479, Germany

Location

Klinik Johann Wolfgang von Goethe Uni

Frankfurt, 60590, Germany

Location

Medizinische Hochschule Hannover; Klinik für Gastroenterologie, Hepatologie und Endokrinologie

Hanover, 30625, Germany

Location

Universitaetsklinikum Jena; Apotheke des Uniersitätsklinikums Jena

Jena, 07740, Germany

Location

Medizinisches Zentrum Klinikum Lueneburg

Lüneburg, 21339, Germany

Location

Klinikum Mannheim GmbH Universitätsklinikum

Mannheim, 68167, Germany

Location

DRC Gyogyszervizsgalo Kozpont Kft

Balatonfüred, 8230, Hungary

Location

Pannónia Klinika Magánorvosi

Budapest, 1136, Hungary

Location

Debreceni Egyetem Klinikai Kozpont

Debrecen, 4032, Hungary

Location

Pest Megyei Flor Ferenc Korhaz

Kistarcsa, 2143, Hungary

Location

Csongrad Megyei Dr. Bugyi Istvan Korhaz

Szentes, 6600, Hungary

Location

Osmania General Hospital

Hyderabad, Andhra Pradesh, 500012, India

Location

Deccan College of Medical Sciences and Allied Hospitals

Hyderabad, Andhra Pradesh, 500058, India

Location

Shree Giriraj Multispeciality Hospital

Rajkot, Gujarat, 360005, India

Location

Nirmal Hospital

Surat, Gujarat, 395002, India

Location

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

Belagavi, Karnataka, 590010, India

Location

M. S. Ramaiah Medical College and Hospital

Bengaluru, Karnataka, 560054, India

Location

Midas institute of Gastroenterology

Nagpur, Maharashtra, 440012, India

Location

Pushpawati Singhania Research Institute

New Delhi, National Capital Territory of Delhi, 110017, India

Location

Dayanand Medical College and Hospital

Ludhiana, Punjab, 141001, India

Location

S. R. Kalla Memorial General Hospital

Jaipur, 302001, India

Location

Kasturba Medical College & Hospital

Mangalore, 575001, India

Location

Ruby Hall Clinic

Pune, 411 001, India

Location

King Edward Memorial Hospital Research Centre

Pune, 411011, India

Location

Assaf Harofeh Medical Center

Beer Yaacov, 6093000, Israel

Location

Bnei Zion Medical Center; Department of Internal Medicine B

Haifa, 31048, Israel

Location

Shaare Zedek Medical Center

Jerusalem, 9103102, Israel

Location

Hadassah University Hospital - Ein Kerem

Jerusalem, 9112001, Israel

Location

Holy Family Hospital

Nazareth, 16100, Israel

Location

Ospedale Sandro Pertini

Rome, Lazio, 00157, Italy

Location

Fondazione Poliambulanza Istituto Ospedaliero

Brescia, Lombardy, 25124, Italy

Location

Ospedale di Circolo; Neuropsichiatria Infantile

Rho, Lombardy, 20017, Italy

Location

Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone

Palermo, Sicily, 90127, Italy

Location

Centro Regiomontano de Estudios Clínicos Roma S.C.

Monterrey, Nuevo León, 64610, Mexico

Location

Instituto de Investigaciones Aplicadas a la Neurociencia A.C.

Durango, 34000, Mexico

Location

Phylasis Clinicas Research S de RL de CV

Estado de México, 54769, Mexico

Location

Zespó Przychodni Specjalistycznych PRIMA

Warsaw, 02-018, Poland

Location

LexMedica Osrodek Badan Klinicznych

Wroclaw, 53-114, Poland

Location

Fakultna nemocnica Nitra

Nitra, 950 01, Slovakia

Location

Endomed, s.r.o.

Vranov nad Topľou, 093 01, Slovakia

Location

Dr JP Wright Practice

Cape Town, 7708, South Africa

Location

Emmed Research

Pretoria, 0002, South Africa

Location

CI of SRC Sumy RCH Dept of Rheumatology Sumy SU MI

Sumy, Kharkiv Governorate, 40022, Ukraine

Location

CI of Kyiv RC Kyiv Regional Clinical Hospital

Kyiv, KIEV Governorate, 04107, Ukraine

Location

Lviv Regional Clinical Hospital

Lviv, KIEV Governorate, 79010, Ukraine

Location

A.Novak Transcarpathian Regional Clinical Hospital

Uzhhorod, KIEV Governorate, 88018, Ukraine

Location

Odessa regional clinical Hospital

Odesa, 65117, Ukraine

Location

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

Poltava, 36011, Ukraine

Location

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

Uzhhorod, 88009, Ukraine

Location

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

Vinnytsia, 21018, Ukraine

Location

Related Publications (2)

• 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.

  PMID: 34798037 DERIVED

• 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.

  PMID: 32445184 DERIVED

MeSH Terms

Conditions

Colitis, Ulcerative

Interventions

etrolizumab

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 13, 2014
• First Posted: June 17, 2014
• Study Start: August 12, 2014
• Primary Completion: April 6, 2020
• Study Completion: April 6, 2020
• Last Updated: August 19, 2021
• Results First Posted: June 15, 2021

Record last verified: 2021-07

Locations

ZA (2); IL (5); US (33); CA (6); CZ (3); ME (3); DK (2); IN (13); SL (2); HU (5); UA (8); IT (4); PL (2); BR (8); DE (8)