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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02165215
Recruitment Status : Active, not recruiting
First Posted : June 17, 2014
Last Update Posted : October 22, 2019
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

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.

Condition or disease Intervention/treatment Phase
Colitis, Ulcerative Drug: Etrolizumab Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 359 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : August 12, 2014
Estimated Primary Completion Date : April 21, 2020
Estimated Study Completion Date : July 21, 2020

Resource links provided by the National Library of Medicine


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:
  • PRO145223
  • RO5490261
  • RG7413

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:
  • PRO145223
  • RO5490261
  • RG7413

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.




Primary Outcome Measures :
  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) [ Time Frame: Week 62 ]

Secondary Outcome Measures :
  1. 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 [ Time Frame: Week 62 ]
  2. Maintenance Phase: Percentage of Participants in Clinical Remission at Week 62, as Determined by the MCS [ Time Frame: Week 62 ]
  3. Maintenance Phase: Percentage of Participants in Remission at Week 62 Among Randomized Participants in Remission at Week 10, as Determined by the MCS [ Time Frame: Week 62 ]
  4. 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 [ Time Frame: Baseline, Week 62 ]
  5. Maintenance Phase: Percentage of Participants with Endoscopic Remission at Week 62, as Determined by the MCS Endoscopic Subscore [ Time Frame: Week 62 ]
  6. Maintenance Phase: Percentage of Participants with Histologic Remission at Week 62, as Determined by the Nancy Histological Index [ Time Frame: Week 62 ]
  7. Induction Phase: Change from Baseline to Week 6 in MCS Rectal Bleed Subscore [ Time Frame: Baseline, Week 6 ]
  8. Induction Phase: Change from Baseline to Week 6 in MCS Stool Frequency Subscore [ Time Frame: Baseline, Week 6 ]
  9. 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 [ Time Frame: Baseline, Week 62 ]
  10. 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 [ Time Frame: Baseline, Week 62 ]
  11. 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 [ Time Frame: Baseline, Week 62 ]
  12. Maintenance Phase: Change from Baseline to Week 62 in UC Abdominal Symptoms, as Assessed by the UC-PRO/SS Questionnaire [ Time Frame: Baseline, Week 62 ]
  13. 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) [ Time Frame: Baseline, Week 62 ]
  14. 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) [ Time Frame: From Baseline up to Week 74 ]
  15. Number of Participants with Adverse Events Leading to Study Drug Discontinuation [ Time Frame: From Baseline up to Week 74 ]
  16. Number of Participants with Serious Infection-Related Adverse Events [ Time Frame: From Baseline up to Week 74 ]
  17. Number of Participants with Infection-Related Adverse Events by Severity, According to NCI-CTCAE v4.0 [ Time Frame: From Baseline up to Week 74 ]
  18. Number of Participants with Injection-Site Reactions by Severity, According to NCI-CTCAE v4.0 [ Time Frame: From Baseline up to Week 74 ]
  19. Number of Participants with Hypersensitivity Reaction Events by Severity, According to NCI-CTCAE v4.0 [ Time Frame: From Baseline up to Week 74 ]
  20. Number of Participants with Malignancies [ Time Frame: From Baseline up to Week 74 ]
  21. Number of Participants with Anti-Therapeutic Antibodies (ATAs) to Etrolizumab [ Time Frame: Baseline, Weeks 4, 12, 24, 44, and 62, and and Early Termination/End of Safety Follow-Up (up to Week 74) ]
  22. Etrolizumab Serum Trough Concentration [ Time Frame: Pre-dose (0 hour) at Baseline and Weeks 12, 24, 44, and 62 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02165215


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Locations
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United States, California
University of California, Irvine Medical Center
Orange, California, United States, 92868
Clinical Applications Laboratories, Inc.
San Diego, California, United States, 92103
Uni. of California at San Francisco; Dept Pediatric, Div. of Gastroenterology, Hepatology & Nutri
San Francisco, California, United States, 94158
Ventura Clinical Trials
Ventura, California, United States, 93003
United States, Colorado
Peak Gastroenterology Associates; Gastroenterology
Colorado Springs, Colorado, United States, 80907
Clinical Research of the Rockies
Lafayette, Colorado, United States, 80026
United States, Florida
West Central Gastroenterology d/b/a Gastro Florida
Clearwater, Florida, United States, 33762
IMIC, Inc
Miami Beach, Florida, United States, 33140
Regenerate Clinical Trials
Miami, Florida, United States, 33155
Advanced Research Institute, Inc.
Trinity, Florida, United States, 34655
Shafran Gastroenterology Center
Winter Park, Florida, United States, 32789
United States, Illinois
Northwestern University Feinberg School Of Medicine
Chicago, Illinois, United States, 60611
Southwest Gastroenterology
Oak Lawn, Illinois, United States, 60453
United States, Indiana
Aquiant Research
New Albany, Indiana, United States, 47150
United States, Louisiana
Louisiana Research Center, LLC
Shreveport, Louisiana, United States
United States, Massachusetts
Commonwealth Clinical Studies
Brockton, Massachusetts, United States, 02302
United States, Michigan
Henry Ford Health System
Detroit, Michigan, United States, 48202
Center for Digestive Health
Troy, Michigan, United States, 48098
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, Mississippi
University of Mississippi Medical Center
Jackson, Mississippi, United States, 39216
United States, Missouri
Ehrhardt Clinical Research, LLC
Belton, Missouri, United States, 64012
United States, New York
Concorde Medical Group
New York, New York, United States, 10016
Weill Cornell Medical College-New York Presbyterian Hospital
New York, New York, United States, 10021
United States, North Carolina
Asheville Gastroenterology Associates, P.A.
Asheville, North Carolina, United States, 28801
UNC at Chapel Hill - Dpt of Family Medicine; Center for Functional GI and Motility Disorders
Chapel Hill, North Carolina, United States, 27599
Kinston Medical Specialists
Kinston, North Carolina, United States, 28501
United States, Texas
Texas Digestive Disease Consultants - Dallas
Dallas, Texas, United States, 75231
Texas Digestive Disease Consultants - Southlake
Southlake, Texas, United States, 76092
Digestive Health Specialists of Tyler
Tyler, Texas, United States, 75701
United States, Utah
Ericksen Research and Development
Clinton, Utah, United States, 84015
University of Utah School of Medicine; Psychiatry
Salt Lake City, Utah, United States, 84132
United States, Virginia
McGuire Research Institute; Gastroenterology
Richmond, Virginia, United States, 23249
United States, Washington
Northwest Gastroenterology Associates
Bellevue, Washington, United States, 98004
University of Washington / Harborview Medical Center; University of Washington
Seattle, Washington, United States, 98104
Brazil
Hospital Universitario Walter Cantidio - UFC
Fortaleza, CE, Brazil, 60430-370
Centro Digestivo de Curitiba
Curitiba, PR, Brazil, 80430-160
Hospital Moinhos de Vento; Instituto de Educação e Pesquisa
Porto Alegre, RS, Brazil, 90560-030
CECIP - Centro de Estudos Clínicos do Interior Paulista
Jaú, SP, Brazil, 17210-190
Pesquisare
Santo Andre, SP, Brazil, 09080-110
Centro Multidisciplinar de Estudos Clínicos - CEMEC
Santo Andre, SP, Brazil, 09190-510
Hospital Sírio-Libanês
Sao Paulo, SP, Brazil, 01308-050
Universidade Federal de Sao Paulo - UNIFESP; Neurologia
Sao Paulo, SP, Brazil, 04024-002
Hospital do Servidor Público Estadual "Francisco Morato de Oliveira" (HSPE)
São Paulo, SP, Brazil, 04039-901
Canada, British Columbia
GI Research Institute
Vancouver, British Columbia, Canada, V6Z 2K5
Canada, Nova Scotia
Queen Elizabeth II Health Sciences Centre; Gastroenterology Research
Halifax, Nova Scotia, Canada, B3H 1V7
Canada, Ontario
Toronto Digestive Disease Associates
Downsview, Ontario, Canada, M3N 2V7
LHSC - University Hospital; Movement Disorders Program
London, Ontario, Canada, N6A 5A5
London Health Sciences Centre · Victoria Hospital; Research Pharmacy
London, Ontario, Canada, N6A 5W9
Mount Sinai Hospital
Toronto, Ontario, Canada, M5G 1Z5
Czechia
Fakultni nemocnice u sv. Anny v Brne; I.Interni kardioangiologicka klinika
Brno, Czechia, 65691
Hepato-Gastroenterologie HK, s.r.o.
Hradec Kralove, Czechia, 500 12
Nemocnice Na Bulovce
Prague, Czechia, 180 01
Denmark
Alborg Universitets Hospital
Aalborg, Denmark, 9100
Herlev Hospital
Herlev, Denmark, 2730
Rigshospitalet; Medicinsk gastroenterologisk klinik
København Ø, Denmark, 2100
Germany
Charite Universitaetsmedizin Berlin - Campus Charite Mitte
Berlin, Germany, 10117
Charite - Campus Virchow-Klinikum; Cardiology
Berlin, Germany, 13353
Berufsgenossenschaftliches Universitaetsklinikum Bergmannsheil GmbH
Bochum, Germany, 44789
Ärztezentrum Ellwangen; Gemeinschaftspraxis
Ellwangen, Germany, 73479
Universitaetsklinikum Erlangen
Erlangen, Germany, 91054
Kliniken Essen-Mitte
Essen, Germany, 45136
Klinik Johann Wolfgang von Goethe Uni
Frankfurt, Germany, 60590
Medizinische Hochschule Hannover
Hannover, Germany, 30625
Universitaetsklinikum Jena; Apotheke des Uniersitätsklinikums Jena
Jena, Germany, 07740
Medizinisches Zentrum Klinikum Lueneburg
Lueneburg, Germany, 21339
Klinikum Mannheim GmbH Universitätsklinikum
Mannheim, Germany, 68167
Hungary
DRC Gyogyszervizsgalo Kozpont Kft
Balatonfured, Hungary, 8230
Pannónia Klinika Magánorvosi
Budapest, Hungary, 1136
Debreceni Egyetem Klinikai Kozpont
Debrecen, Hungary, 4032
Pest Megyei Flor Ferenc Korhaz
Kistarcsa, Hungary, 2084
Csongrad Megyei Dr. Bugyi Istvan Korhaz
Szentes, Hungary, 6600
India
Osmania General Hospital
Hyderabad, Andhra Pradesh, India, 500012
Deccan College of Medical Sciences and Allied Hospitals; Department of Gastroenterology
Hyderabad, Andhra Pradesh, India, 500058
Pushpawati Singhania Research Institute
New Delhi, Delhi, India, 110017
Shree Giriraj Multispeciality Hospital
Rajkot, Gujarat, India, 360005
Nirmal Hospital
Surat, Gujarat, India, 395002
K.L.E. Society's Dr. Prabhakar Kore Hospital and Medical Research Centre
Belgaum, Karnataka, India, 590010
M. S. Ramaiah Medical College and Hospital
Bengaluru, Karnataka, India, 560054
P. D. Hinduja National Hospital & Medical Research Centre
Mumbai, Maharashtra, India, 400016
Midas institute of Gastroenterology
Nagpur, Maharashtra, India, 440012
Dayanand Medical College and Hospital
Ludhiana, Punjab, India, 141001
S. R. Kalla Memorial General Hospital
Jaipur, India, 302001
Kasturba Medical College & Hospital
Mangalore, India, 575001
Ruby Hall Clinic
Pune, India, 411 001
King Edward Memorial Hospital Research Centre
Pune, India, 411011
Israel
Assaf Harofeh Medical Center
Beer Yaacov, Israel, 6093000
Bnai Zion Medical Center
Haifa, Israel, 31048
Shaare Zedek Medical Center
Jerusalem, Israel, 9103102
Hadassah University Hospital - Ein Kerem
Jerusalem, Israel, 9112001
Holy Family Hospital
Nazareth, Israel, 16100
Italy
Ospedale Sandro Pertini
Roma, Lazio, Italy, 00157
Fondazione Poliambulanza Istituto Ospedaliero
Brescia, Lombardia, Italy, 25124
Ospedale di Circolo; Neuropsichiatria Infantile
Rho, Lombardia, Italy, 20017
Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone
Palermo, Sicilia, Italy, 90127
Mexico
Gastro Medical
Mexicali, BAJA California, Mexico, 21100
Centro Regiomontano de Estudios Clínicos Roma S.C.
Monterrey, Nuevo LEON, Mexico, 64610
Instituto de Investigaciones Aplicadas a la Neurociencia A.C.
Durango, Mexico, 34000
Phylasis Clinicas Research S de RL de CV
Estado de México, Mexico, 54769
Poland
Zespó Przychodni Specjalistycznych PRIMA
Warszawa, Poland, 02-018
LexMedica Osrodek Badan Klinicznych
Wroclaw, Poland, 53-114
Slovakia
Univerzitna nemocnica Bratislava, Nemocnica Ruzinov
Bratislava, Slovakia, 826 06
Fakultna nemocnica Nitra
Nitra, Slovakia, 950 01
Endomed, s.r.o.
Vranov N. Toplou, Slovakia, 093 01
South Africa
Dr JP Wright Practice
Cape Town, South Africa, 7708
Emmed Research
Pretoria, South Africa, 0084
Ukraine
CI of SRC Sumy RCH Dept of Rheumatology Sumy SU MI
Sumy, Kharkiv Governorate, Ukraine, 40022
CI of Kyiv RC Kyiv Regional Clinical Hospital
Kyiv, KIEV Governorate, Ukraine, 04107
Lviv Regional Clinical Hospital
Lviv, KIEV Governorate, Ukraine, 79010
A.Novak Transcarpathian Regional Clinical Hospital
Uzhgorod, KIEV Governorate, Ukraine, 88018
Odessa regional clinical Hospital
Odessa, Ukraine, 65117
M.V. Sklifosovskyi Poltava RCH Dept of Gastroenterology HSEIU UMSA
Poltava, Ukraine, 36011
SI Divisional Clinical Hospital of Uzhgorod Station of ST&BA LZ Dep of Therapy SHEI Uzhgorod NU
Uzhgorod, Ukraine, 88009
M.I. Pyrogov VRCH Dept of Gastroenterology M.I. Pyrogov VNMU
Vinnytsia, Ukraine, 21018
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche

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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02165215     History of Changes
Other Study ID Numbers: GA29102
2013-004280-31 ( EudraCT Number )
First Posted: June 17, 2014    Key Record Dates
Last Update Posted: October 22, 2019
Last Verified: October 2019
Additional relevant MeSH terms:
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Colitis
Colitis, Ulcerative
Ulcer
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Pathologic Processes
Inflammatory Bowel Diseases
rhuMAb Beta7
Gastrointestinal Agents
Immunologic Factors
Physiological Effects of Drugs