Colitis, UlcerativePhase 3LAURELNCT02165215
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
A Phase 3 study testing Etrolizumab in people with Colitis, Ulcerative, run by Hoffmann-La Roche at 104 sites in 15 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Colitis, Ulcerative
- What is being tested?
- Etrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 359 participants
- Where
- 104 sitesin 15 countries
- Study dates
- 12 Aug 2014to 6 Apr 2020
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
104 sites in 15 countries.
104 sites in 15 countries
United States33 sites
Asheville Gastroenterology Associates, P.A.
Asheville, North Carolina, 28801
Northwest Gastroenterology Associates
Bellevue, Washington, 98004
Ehrhardt Clinical Research, LLC
Belton, Missouri, 64012
Commonwealth Clinical Studies
Brockton, Massachusetts, 02302
UNC at Chapel Hill - Dpt of Family Medicine; Center for Functional GI and Motility Disorders
Chapel Hill, North Carolina, 27599
Northwestern University-Feinberg School of Medicine; Division of Gastroenterology and Hepatology
Chicago, Illinois, 60611
West Central Gastroenterology d/b/a Gastro Florida
Clearwater, Florida, 33762
Ericksen Research and Development
Clinton, Utah, 84015
Peak Gastroenterology Associates; Gastroenterology
Colorado Springs, Colorado, 80907
Texas Digestive Disease Consultants - Dallas
Dallas, Texas, 75231
Henry Ford Health System
Detroit, Michigan, 48202
University of Mississippi Medical Center
Jackson, Mississippi, 39216
Kinston Medical Specialists
Kinston, North Carolina, 28501
Clinical Research of the Rockies
Lafayette, Colorado, 80026
Regenerate Clinical Trials
Miami, Florida, 33155
IMIC, Inc
Miami Beach, Florida, 33140
University of Minnesota
Minneapolis, Minnesota, 55455
Aquiant Research
New Albany, Indiana, 47150
Manhattan Clinical Research
New York, New York, 10016
Weill Cornell Medical College-New York Presbyterian Hospital
New York, New York, 10021
Southwest Gastroenterology
Oak Lawn, Illinois, 60453
University of California, Irvine Medical Center
Orange, California, 92868
McGuire Research Institute; Gastroenterology
Richmond, Virginia, 23249
University of Utah School of Medicine
Salt Lake City, Utah, 84132
Clinical Applications Laboratories, Inc.
San Diego, California, 92103
University of California at San Francisco
San Francisco, California, 94115
Louisiana Research Center, LLC
Shreveport, Louisiana
Texas Digestive Disease Consultants - Southlake
Southlake, Texas, 76092
Advanced Research Institute, Inc.
Trinity, Florida, 34655
Center for Digestive Health
Troy, Michigan, 48098
Digestive Health Specialists of Tyler
Tyler, Texas, 75701
Ventura Clinical Trials
Ventura, California, 93003
Shafran Gastroenterology Center
Winter Park, Florida, 32789
India13 sites
K.L.E. Society's Dr. Prabhakar Kore Hospital and Medical Research Centre
Belagavi, Karnataka, 590010
M. S. Ramaiah Medical College and Hospital
Bengaluru, Karnataka, 560054
Osmania General Hospital
Hyderabad, Andhra Pradesh, 500012
Deccan College of Medical Sciences and Allied Hospitals
Hyderabad, Andhra Pradesh, 500058
S. R. Kalla Memorial General Hospital
Jaipur, 302001
Dayanand Medical College and Hospital
Ludhiana, Punjab, 141001
Kasturba Medical College & Hospital
Mangalore, 575001
Midas institute of Gastroenterology
Nagpur, Maharashtra, 440012
Pushpawati Singhania Research Institute
New Delhi, National Capital Territory of Delhi, 110017
Ruby Hall Clinic
Pune, 411 001
King Edward Memorial Hospital Research Centre
Pune, 411011
Shree Giriraj Multispeciality Hospital
Rajkot, Gujarat, 360005
Nirmal Hospital
Surat, Gujarat, 395002
Brazil8 sites
Centro Digestivo de Curitiba
Curitiba, Paraná, 80430-160
Hospital Universitario Walter Cantidio - UFC
Fortaleza, Ceará, 60430-370
CECIP - Centro de Estudos Clínicos do Interior Paulista
Jaú, São Paulo, 17210-190
Hospital Moinhos de Vento
Porto Alegre, Rio Grande do Sul, 90035-001
Pesquisare Saúde Sociedade Simples
Santo André, São Paulo, 09080-000
Hospital Estadual Mario Covas
Santo André, São Paulo, 09190-610
Hospital Sírio-Libanês
São Paulo, São Paulo, 01308-050
Hospital do Servidor Público Estadual/HSPE-SP
São Paulo, São Paulo, 04039-901
Germany8 sites
Charite Universitaetsmedizin Berlin - Campus Charite Mitte
Berlin, 10117
Berufsgenossenschaftliches Universitaetsklinikum Bergmannsheil GmbH
Bochum, 44789
Ärztezentrum Ellwangen; Gemeinschaftspraxis
Ellwangen, 73479
Klinik Johann Wolfgang von Goethe Uni
Frankfurt, 60590
Medizinische Hochschule Hannover; Klinik für Gastroenterologie, Hepatologie und Endokrinologie
Hanover, 30625
Universitaetsklinikum Jena; Apotheke des Uniersitätsklinikums Jena
Jena, 07740
Medizinisches Zentrum Klinikum Lueneburg
Lüneburg, 21339
Klinikum Mannheim GmbH Universitätsklinikum
Mannheim, 68167
Ukraine8 sites
CI of Kyiv RC Kyiv Regional Clinical Hospital
Kyiv, KIEV Governorate, 04107
Lviv Regional Clinical Hospital
Lviv, KIEV Governorate, 79010
Odessa regional clinical Hospital
Odesa, 65117
M.V. Sklifosovskyi Poltava RCH Dept of Gastroenterology HSEIU UMSA
Poltava, 36011
CI of SRC Sumy RCH Dept of Rheumatology Sumy SU MI
Sumy, Kharkiv Governorate, 40022
A.Novak Transcarpathian Regional Clinical Hospital
Uzhhorod, KIEV Governorate, 88018
SI Divisional Clinical Hospital of Uzhgorod Station of ST&BA LZ Dep of Therapy SHEI Uzhgorod NU
Uzhhorod, 88009
M.I. Pyrogov VRCH Dept of Gastroenterology M.I. Pyrogov VNMU
Vinnytsia, 21018
Canada6 sites
Queen Elizabeth II Health Sciences Centre; Gastroenterology Research
Halifax, Nova Scotia, B3H 1V7
LHSC - University Hospital; Movement Disorders Program
London, Ontario, N6A 5A5
London Health Sciences Centre Victoria Hospital; Research Pharmacy
London, Ontario, N6A 5W9
Mount Sinai Hospital
Toronto, Ontario, M5G 1X5
Pacific Gastroenterology Associates
Vancouver, British Columbia, V6Z 2K5
Toronto Digestive Disease Associates
Vaughan, Ontario, L4L 4Y7
Hungary5 sites
DRC Gyogyszervizsgalo Kozpont Kft
Balatonfüred, 8230
Pannónia Klinika Magánorvosi
Budapest, 1136
Debreceni Egyetem Klinikai Kozpont
Debrecen, 4032
Pest Megyei Flor Ferenc Korhaz
Kistarcsa, 2143
Csongrad Megyei Dr. Bugyi Istvan Korhaz
Szentes, 6600
Israel5 sites
Assaf Harofeh Medical Center
Beer Yaacov, 6093000
Bnei Zion Medical Center; Department of Internal Medicine B
Haifa, 31048
Shaare Zedek Medical Center
Jerusalem, 9103102
Hadassah University Hospital - Ein Kerem
Jerusalem, 9112001
Holy Family Hospital
Nazareth, 16100
Italy4 sites
Fondazione Poliambulanza Istituto Ospedaliero
Brescia, Lombardy, 25124
Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone
Palermo, Sicily, 90127
Ospedale di Circolo; Neuropsichiatria Infantile
Rho, Lombardy, 20017
Ospedale Sandro Pertini
Rome, Lazio, 00157
Czechia3 sites
Fakultni nemocnice u sv. Anny v Brne; I.Interni kardioangiologicka klinika
Brno, 65691
Hepato-Gastroenterologie HK, s.r.o.
Hradec Králové, 500 12
Nemocnice Na Bulovce
Prague, 180 01
Mexico3 sites
Instituto de Investigaciones Aplicadas a la Neurociencia A.C.
Durango, 34000
Phylasis Clinicas Research S de RL de CV
Estado de México, 54769
Centro Regiomontano de Estudios Clínicos Roma S.C.
Monterrey, Nuevo León, 64610
Denmark2 sites
Alborg Universitets Hospital
Aalborg, 9100
Herlev og Gentofte Hospital
Herlev, 2730
Poland2 sites
Zespó Przychodni Specjalistycznych PRIMA
Warsaw, 02-018
LexMedica Osrodek Badan Klinicznych
Wroclaw, 53-114
Slovakia2 sites
Fakultna nemocnica Nitra
Nitra, 950 01
Endomed, s.r.o.
Vranov nad Topľou, 093 01
South Africa2 sites
Dr JP Wright Practice
Cape Town, 7708
Emmed Research
Pretoria, 0002
About this study
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
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
- Being tested
- Etrolizumab, Placebo
- Medical subject headings
- Colitis, Ulcerative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EtrolizumabDrug
Also called RG7413, RO5490261, PRO145223, rhuMAb Beta7
Participants will receive 105 mg etrolizumab SC injection Q4W.
PlaceboDrug
Participants will receive placebo (matched to etrolizumab) SC injection Q4W.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: From Baseline up to Week 74
Number of Participants With Adverse Events Leading to Study Drug Discontinuation
Measured: From Baseline up to Week 74
Number of Participants With Serious Infection-Related Adverse Events
Measured: 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.
Measured: 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.
Measured: 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.
Measured: From Baseline up to Week 74
Number of Participants With Malignancies
Measured: From Baseline up to Week 74
Number of Participants With Anti-Therapeutic Antibodies (ATAs) to Etrolizumab
Measured: 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.
Measured: 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.
Measured: Pre-dose (0 hour) at Baseline and Weeks 12, 24, 44, and 62
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jun 2014 (estimated)
- Study start12 Aug 2014
- Primary completion6 Apr 2020
- Study completion6 Apr 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Colitis, UlcerativeStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 359 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02165215
- Sponsor's protocol ID
- GA29102
- Other IDs
- 2013-004280-31
- Acronym
- LAUREL
- Status last verified
- Jul 2021
- First submitted
- 13 Jun 2014
- Last updated
- 19 Aug 2021
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Li Y, Li J, Rothenberg ME, Rhee H, Zhang J, Lin S, Park KT. Impact of missing patient report outcomes in clinical trials for ulcerative colitis: Should we always assume treatment failure? Crohns Colitis 360. 2026 Feb 26;8(1):otag015. doi: 10.1093/crocol/otag015. eCollection 2026 Jan.
PubMed 41841037Vermeire 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.
PubMed 34798037Sandborn 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.
PubMed 32445184
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02165215
- Acronym / sponsor ID
- LAUREL / GA29102
- Conditions
- Colitis, Ulcerative
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 359 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 12 Aug 2014 (actual)
- Primary completion
- 6 Apr 2020 (actual)
- Study completion
- 6 Apr 2020 (actual)
- First posted
- 17 Jun 2014 (estimated)
- Results
- Posted 15 Jun 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Open-Label Induction Phase: Etrolizumab | Experimental | Drug: EtrolizumabAll participants will receive treatment with open-label etrolizumab 105 milligrams (mg) subcutaneous (SC) injection once every 4 weeks (Q4W) up to Week 10. |
| Double-Blind Maintenance Phase: Etrolizumab | Experimental | Drug: EtrolizumabParticipants 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. |
| Double-Blind Maintenance Phase: Placebo | Placebo comparator | Drug: PlaceboParticipants 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (13 listed)
- 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])
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EtrolizumabAlso: RG7413, RO5490261, PRO145223, rhuMAb Beta7Participants will receive 105 mg etrolizumab SC injection Q4W. | Drug | Double-Blind Maintenance Phase: Etrolizumab, Open-Label Induction Phase: Etrolizumab |
| PlaceboParticipants will receive placebo (matched to etrolizumab) SC injection Q4W. | Drug | Double-Blind Maintenance Phase: Placebo |
Primary outcome
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
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.
21 secondary outcomes
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
Maintenance Phase: Percentage of Participants in Clinical Remission at Week 62, as Determined by the MCS
Time frame: 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
Time frame: 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
Time frame: Baseline, Week 62
Maintenance Phase: Percentage of Participants With Endoscopic Remission at Week 62, as Determined by the MCS Endoscopic Subscore
Time frame: Week 62
Maintenance Phase: Percentage of Participants With Histologic Remission at Week 62, as Determined by the Nancy Histological Index
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Baseline, Week 62
Maintenance Phase: Change From Baseline to Week 62 in UC Functional Symptoms, as Assessed by the UC-PRO/SS Questionnaire
Time frame: 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)
Time frame: 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)
Time frame: From Baseline up to Week 74
Number of Participants With Adverse Events Leading to Study Drug Discontinuation
Time frame: From Baseline up to Week 74
Number of Participants With Serious Infection-Related Adverse Events
Time frame: From Baseline up to Week 74
Number of Participants With Infection-Related Adverse Events by Severity, According to NCI-CTCAE v4.0
Time frame: From Baseline up to Week 74
Number of Participants With Injection-Site Reactions by Severity, According to NCI-CTCAE v4.0
Time frame: From Baseline up to Week 74
Number of Participants With Hypersensitivity Reaction Events by Severity, According to NCI-CTCAE v4.0
Time frame: From Baseline up to Week 74
Number of Participants With Malignancies
Time frame: From Baseline up to Week 74
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)
Maintenance Phase: Etrolizumab Serum Trough Concentration (for Arms/Timepoints Above LLOQ)
Time frame: Pre-dose (0 hour) at Baseline and Weeks 12, 24, 44, and 62
Maintenance Phase: Etrolizumab Serum Trough Concentration (for Arms/Timepoints Below LLOQ)
Time frame: Pre-dose (0 hour) at Baseline and Weeks 12, 24, 44, and 62
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41841037Li Y, Li J, Rothenberg ME, Rhee H, Zhang J, Lin S, Park KT. Impact of missing patient report outcomes in clinical trials for ulcerative colitis: Should we always assume treatment failure? Crohns Colitis 360. 2026 Feb 26;8(1):otag015. doi: 10.1093/crocol/otag015. eCollection 2026 Jan.
- Derived from this study: PubMed 34798037Vermeire 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.
- Derived from this study: PubMed 32445184Sandborn 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.
Related trials for Colitis, Ulcerative
Not yet recruitingPhase 1
An Open-label, DDI Study to Investigate the Effects of Duvakitug on the PK of Selected Cytochrome P450 Substrates
Ulcerative Colitis, Crohn's Disease
RecruitingObservational study
Longitudinal Immunophenotyping of Patients With Inflammatory Bowel Disease
Inflammatory Bowel Disease, Crohn's Disease
RecruitingObservational study
Ibd CAncer and seRious Infections in France (I-CARE 2)
IBD, Ulcerative Colitis
RecruitingObservational study
Characterization of Colorectal Dysplasic Lesions and Stratification of Their Evolving Risk in Inflammatory Bowel Disease Patients: a Prospective, Observational and Multicenter Study
Crohn Disease (CD), Colitis Ulcerative
Enrolling by invitationPhase 4
MOdel-Informed Precision Dosing of Ustekinumab and VEdolizumab in Inflammatory Bowel Disease
Inflammatory Bowel Diseases, Crohn Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
104 sites in 15 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Etrolizumab in people with Colitis, Ulcerative, run by Hoffmann-La Roche at 104 sites in 15 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 104 sites in United States, India, Brazil, Germany, Ukraine and 10 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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) (time frame: Week 62). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02165215, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Aug 2021.