A Study to Assess Whether Etrolizumab is a Safe and Efficacious Treatment for Participants With Moderately to Severely Active Crohn's Disease (BERGAMOT)
Crohn Disease
About this trial
This is an interventional treatment trial for Crohn Disease
Eligibility Criteria
Inclusion Criteria:
- Moderately to severely active Crohn's Disease (CD) as determined by the CDAI, patient reported outcomes and endoscopically defined disease activity in the ileum and/or colon
- Intolerance, refractory disease, or no response to corticosteroids (CS), immunosuppressants (IS), or anti-TNF therapy within 5 years from screening. Participants who have not previously demonstrated inadequate response or intolerance to one or more anti-TNF therapies are eligible to participate in the study provided they are intolerant or refractory to CS or IS therapy
- Use of effective contraception as defined by the protocol
Exclusion Criteria:
- A history of, or current conditions affecting the digestive tract, such as ulcerative colitis, indeterminate colitis, fistulizing disease, abdominal or perianal abscess, adenomatous colonic polyps not excised, colonic mucosal dysplasia, and short bowel syndrome
- Planned surgery for CD
- Ileostomy or colostomy
- Has received non-permitted inflammatory bowel disease (IBD) therapies (including natalizumab, vedolizumab, and efalizumab, as stated in the protocol)
- Any prior treatment with ustekinumab within 14 weeks prior to randomization
- Chronic hepatitis B or C infection, human immunodeficiency virus (HIV), active or latent tuberculosis (participants with prior history of Bacillus Calmette-Guérin [BCG] vaccination must pass protocol-defined screening criteria)
- Sinus tract with evidence for infection (e.g., purulent discharge) in the clinical judgment of the investigator. Fistulas related to CD are not exclusionary
- Any prior treatment with anti-adhesion molecules (e.g., anti-mucosal addressin cell adhesion molecule [anti-MAdCAM-1])
- Any major episode of infection requiring treatment with intravenous antibiotics ≤8 weeks prior to screening or oral antibiotics ≤4 weeks prior to screening. Treatment with antibiotics as adjunctive therapy for CD in the absence of documented infection is not exclusionary
- Hospitalization (other than for elective reasons) within 4 weeks prior to randomization
Sites / Locations
- Valley Gastroenterology Consultants
- University of California San Diego Medical Center
- VA Long Beach Healthcare System
- Digestive Care Associates, A Medical Corporation
- SDG Clinical Research
- University of California at San Francisco (PARENT); Gastroenterology, Hepatology & Nutrition
- Peak Gastroenterology Associates; Gastroenterology
- Innovative Medical Research of South Florida
- West Central Gastroenterology d/b/a Gastro Florida
- University of Florida College of Medicine
- Borland-Groover Clinic
- IMIC, Inc
- FQL Research, LLC
- Advanced Research Institute, Inc.
- Shafran Gastroenterology Center
- Emory University Hospital
- Atlanta Gastroenterology Associates
- Gastrointestinal Diseases Research
- Atlanta Center for Gastroenterology, PC
- Gastroenterology Associates of Central Georgia
- Gastrointestinal Specialists of Georgia, PC
- Advanced Clinical Research
- Northwestern University-Feinberg School of Medicine; Division of Gastroenterology and Hepatology
- The University of Chicago Medical Center
- Southwest Gastroenterology; DM Clinical Research
- Carle Foundation Hospital
- Cotton-O'Neil Clinical Research Center, Digestive Health
- Gastroenterology Associates, LLC
- Louisiana Research Center, LLC
- Commonwealth Clinical Studies
- University of Michigan Health System
- Gastroenterology Associates of Western Michigan, P.L.C.
- Center for Digestive Health
- Henry Ford Health System
- Mayo Clinic - Rochester; Gastrology
- University of Mississippi Medical Center; Division of Gastroenterology
- Ehrhardt Clinical Research, LLC
- Concorde Medical Group
- Weill Cornell Medical College (WCMC) - Judith Jaffe Multiple Sclerosis Center (JJMSC)
- Lenox Hill Hospital
- University of North Carolina At Chapel Hill
- Charlotte Gastroenterology and Hepatology, P.L.L.C
- Kinston Medical Specialists
- Consultants for Clinical Research Inc.
- Great Lakes Gastroenterology Research, LLC
- Digestive Disease Specialists, Inc.
- Great Lakes Medical Research, LLC
- Innovative Clinical Research
- Gastroenterology Center of the MidSouth PC
- Vanderbilt University Medical Center
- Texas Digestive Disease Consultants - Dallas
- University of Texas Southwestern Medical Center; Internal Medicne
- Baylor College of Medicine; Gastroenterology
- Methodist Hospital Research Institute
- Wellness Clinical Research Center
- Texas Digestive Disease Consultants - Southlake
- Tyler Research Institute, LLC
- Ericksen Research and Development
- University of Utah School of Medicine
- McGuire Research Institute; Gastroenterology
- Digestive Disease Institute; Virginia Mason Medical Center
- University of Wisconsin
- Hospital Italiano
- The Canberra Hospital
- Bankstown-Lidcombe Hospital
- Concord Repatriation General Hospital
- Royal Brisbane and Women's Hospital
- University of the Sunshine Coast
- Mater Adult Hospital
- Princess Alexandra Hospital
- Flinders Medical Centre
- Monash Medical Centre Clayton
- St Vincent's Hospital Melbourne
- Footscray Hospital; Gastroenterology
- St Frances Xavier Cabrini Hospital
- Alfred Hospital
- Royal Melbourne Hospital; Department of Colorectal Medicine and Genetics
- Fiona Stanley Hospital
- LKH - Universitätsklinikum der PMU Salzburg
- Medizinische Universität Wien
- CHU St Pierre (St Pierre)
- UZ Brussel
- Hospital Erasme
- UZ Antwerpen
- AZ Maria Middelares
- L2IP -Instituto de Pesquisas Clínicas Ltda.
- Instituto Goiano de Gastroenterologia e Endoscopia Digestiva Ltda
- Hospital Felicio Rocho
- Centro Digestivo de Curitiba
- Hospital Universitario Clementino Fraga Filho - UFRJ; Gastroenterologia
- Instituto Brasil de Pesquisa Clínica-IBPCLIN S/A
- Hospital São Vicente de Paulo; Institute of Education and Reseach / Cardiovascular Research Unit
- Hospital das Clinicas - UFRGS
- Hospital Ernesto Dornelles
- UNESP - Faculdade de Medicina da Universidade Estadual Paulista - Campus Botucatu
- Pesquisare Saúde Sociedade Simples
- Praxis Pesquisa Médica
- Hospital Estadual Mario Covas
- Hospital de Base de Sao Jose do Rio Preto
- Hospital Sírio-Libanês
- Hospital Sao Paulo
- Hospital do Servidor Público Estadual/HSPE-SP
- "City Clinic UMHAC" EOOD
- UMHAT "Sv. Ivan Rilski", EAD
- UMHAT Tsaritsa Yoanna - ISUL, EAD
- University of Calgary
- Zeidler Ledcor Centre - University of Alberta; Division of Gasroenterology
- (G.I.R.I.) GI Research Institute
- Winnipeg Regional Health Authority
- Queen Elizabeth II Health Sciences Centre; Gastroenterology Research
- University Hospital - London Health Sciences Centre
- Taunton Health Centre
- The Ottawa Hospital - Riverside Campus; Gastrointestinal Clinical Research Unit
- Mount Sinai Hospital
- Toronto Digestive Disease Associates
- Hôpital Maisonneuve - Rosemont
- McGill University Health Centre - Glen Site
- Royal University Hospital
- Clinical Hospital Centre Osijek
- General Hospital Pula
- Clinical Hospital Center Sestre Milosrdnice
- University Hospital Center Zagreb
- Vojenska nemocnice Brno
- Fakultni nemocnice u sv. Anny v Brne
- Nemocnice Ceske Budejovice a.s.
- Gastroenterologie s.r.o.
- Fakultni nemocnice Hradec Kralove
- Hepato-Gastroenterologie HK, s.r.o.
- PreventaMed, s.r.o.
- Fakultni nemocnice Ostrava
- Klinicke centrum ISCARE Lighthouse
- Fakultni nemocnice Kralovske Vinohrady
- West Tallinn Central Hospital
- North Estonia Medical Centre Foundation
- Tartu University Hospital
- CHU Amiens - Hopital Sud
- CHU de Caen - Hopital Cote de Nacre
- Hôpital Beaujon
- Hopital Claude Huriez - CHU Lille
- CHU NANTES - Hôtel Dieu; Pharmacy
- CHU Nice - Hopital de l'Archet 2
- Hôpital Saint-Louis
- Groupe Hospitalier Sud - Hôpital Haut-Lévêque - USN
- Centre Hospitalier Lyon Sud; Service de Gastro-Enterologie
- CHU du Reims - Hopital Robert Debré
- CHU Rennes - Hopital Pontchaillou
- CHU Saint Etienne - Hôpital Nord
- Höpital Hautepierre; Pediatrie1
- Hôpital de Brabois Adultes
- Charite-Campus Virchow Klinikum; Hepatologie und Gastroenterologie
- Krankenhaus Waldfriede e. V.
- Berufsgenossenschaftliches Universitaetsklinikum Bergmannsheil GmbH
- Klinikum der Johann Wolfgang Goethe-Universitaet
- Universitaetsklinikum Halle (Saale)
- Medizinische Hochschule Hannover; Gastroenterology and Hepatology dept
- Universitätsklinikum Koeln
- Klinikum Mannheim GmbH Universitätsklinikum
- Gemeinschaftspraxis
- Universitaetsklinikum Tuebingen
- Universitaetsklinikum Ulm
- Bekes Megyei Kozponti Korhaz Dr. Rethy Pal Tagkorhaza
- Obudai Egeszsegugyi Centrum Kft.
- Semmelweis Egyetem
- Eszak-Kozep-budai Centrum, Uj Szent Janos Korhaz es Szakrendelo
- Pannonia Maganorvosi Centrum
- Debreceni Egyetem
- Petz Aladar Megyei Oktato Korhaz
- Pest Megyei Flor Ferenc Korhaz
- Pecsi Tudomanyegyetem
- Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz
- Haemek Medical Center
- Soroka University Medical Centre
- Wolfson Medical Center; Obstetrics and Gynecology
- Shaare Zedek Medical Center
- Hadassah University Hospital - Ein Kerem
- Holy Family Hospital
- Rabin Medical Center-Beilinson Campus
- Tel Aviv Sourasky Medical Center; Pharmacy
- A.O.U. Policlinico di Modena
- Azienda Ospedaliera San Camillo Forlanini
- Policlinico Universitario Agostino Gemelli; Farmacia
- Asst Fatebenefratelli Sacco (Fatebenefratelli)
- ASST FATEBENEFRATELLI SACCO (Sacco)
- Azienda Socio Sanitaria Territoriale Niguarda (Grande Ospedale Metropolitano Niguarda)
- Istituto Clinico Humanitas
- I.R.C.C.S Policlinico San Donato
- Ospedale Umberto I di Torino
- Azienda Ospedaliera Universitaria Careggi
- Inje University Busan Paik Hospital
- Dong-A University Hospital
- Pusan National University Hospital
- Kyungpook National University Hospital
- Yeungnam Univ. Hospital
- Hanyang University Guri Hospital
- Korea University Ansan Hospital
- Seoul National University Bundang Hospital
- CHA Bundang Medical Centre; CHA university
- Seoul National University Hospital
- Kangbuk Samsung Hospital
- Severance Hospital, Yonsei University Health System
- Asan Medical Center
- Samsung Medical Center
- Yonsei University Wonju Severance Christian Hospital
- Riga East Clinical University Hospital; Clinic Gailezers
- Pauls Stradins Clinical University Hospital
- Hospital of Lithuanian University of Health. Sciences Kaunas Clinics
- Vilnius University Hospital Santariskiu Clinic, Public Institution; Cardiology
- Clinical Research Institute
- Medical Care & Research SA de CV
- Amsterdam UMC, Locatie VUMC; Neurology
- Amsterdam UMC Location AMC
- Leids Universitair Medisch Centrum
- Maastricht University Medical Center
- Erasmus Medisch Centrum
- Zuyderland Medisch Centrum - Sittard Geleen
- ETZ TweeSteden
- North Shore Hospital
- Christchurch Hospital NZ
- Dunedin Public Hospital
- Waikato Hospital
- Shakespeare Specialist Group
- Tauranga Hospital
- SP ZOZ Wojewodzki Szpital Zespolony im. J. Sniadeckiego
- Nasz Lekarz Osrodek Badan Klinicznych
- Elblaski Szpital Specjalistyczny z Przychodnia SP ZOZ
- ETG Kielce
- Centrum Opieki Zdrowotnej Orkan-Med
- Indywidualna Specjalistyczna Praktyka Lekarska
- Allmedica Badania Kliniczne Sp z o.o. Sp K.
- Centrum Medyczne "MEDYK"
- Gabinet Lekarski, Bartosz Korczowski
- Specjalistyczna Praktyka Lekarska Dr med. Marek Horynski; endoskopia
- Niepubliczny Zaklad Opieki Zdrowotnej SONOMED
- Twoja Przychodnia-Szczecinskie Centrum Medyczne
- Gastromed Kopon Zmudzinski i Wspolnicy Sp.j.Specjalistyczne Centrum Gastrologii i Endoskopii Specj
- Centrum Zdrowia MDM
- Warsaw IBD Point Profesor Kierkus
- Zespó Przychodni Specjalistycznych PRIMA
- LexMedica Osrodek Badan Klinicznych
- EuroMediCare Szpital Specjalistyczny z Przychodnią we Wrocławiu
- PlanetMed sp. z o.o.
- Spitalul Clinic Colentina
- S.C MedLife S.A
- Centrul de Gastroenterologie Dr. Goldis
- Yusupov Hospital
- LLC "Novosibirsk GastroCenter"
- Baltic Medicine
- North-Western Medical University n.a. I.I. Mechnikov; Rheumatology
- SBIH City Clinical Hospital #31
- SBEI HPE Altai StateMedicalUniversityofMoH andSD
- Irkutsk State Medical Academy of Continuing Education
- SBEIHPE Novosibirsk State Medical University
- BHI of Omsk region Clinical Oncology Dispensary
- Evromedservis LCC
- SEIHPE "Rostov SMU of MoH of RF"
- Federal State Military Educational Institution; High Professional Education Military Medical Acad
- Clinical Helth Centre Zvezdara
- Military Medical Academy
- University Hospital Medical Center Bezanijska kosa
- Clinical Center of Vojvodina
- General Hospital Djordje Joanovic
- IBDcentrum s.r.o.
- KM Management spol. s r.o.
- Endomed, s.r.o.
- Accout Center s.r.o.
- Dr D Epstein Practice
- Emmed Research
- Hospital Universitario de Bellvitge
- Hospital Universitario Puerta de Hierro Majadahonda; Hepatology studies
- Hospital Clínic i Provincial; Servicio de Farmacia
- Centro Médico Teknon
- Hospital Reina Sofia; Medical Oncology
- Hospital Juan Ramón Jiménez
- Hospital Universitario de la Princesa
- Hospital Universitario La Paz
- Hospital Universitario de Fuenlabrada
- Complejo Hospitalario de Pontevedra
- Hospital Universitario Virgen Macarena
- Hospital Universitario Virgen del Rocio
- Hospital Universitari i Politecnic La Fe
- Hospital Universitario Miguel Servet
- Inselspital-Universitaetsspital Bern
- Crohn-Colitis Zentrum Bern - Gemeinschaftspraxis Balsiger, Seibold und Partner
- Universitätsspital Zürich
- Ankara University Medical Faculty
- Hacettepe University Medical Faculty; Gastroenterology
- Gazi University Medical Faculty
- Acibadem Fulya Hospital; Neurology
- Haydarpasa Numune Training and Research Hospital; Medical Oncology
- Medeniyet University Goztepe Training and Research Hospital; Chest Diseases
- Ege University Medical Faculty
- Kocaeli Universitesi Tip Fakultesi; Infectious Diseases
- Acibadem Kozyatagi Hospital; Gastroenterology
- CHI Prof.O.O.Shalimov Kharkiv City Clinical Hospital #2
- CI of Healthcare Kharkiv Reg Clin Hosp-Center of Med Emergency & Accident Medicine
- Medical Center of Limited Liability Company Medical Clinic Blagomed
- Med Center of International Institute of Clinical Trials LLC; Medical Center "OK!Clinic+"
- CI of Kyiv RC Regional Clinical Hospital #2
- Lviv Regional Clinical Hospital
- Ivano-Frankivsk Regional Clinical Hospital
- RCNECRCH Dept of Surgery, SHEI Ukr BSMU
- Kremenchuk first city hospital n.a. O.T. Bohaievskyi; Gastroenterology department
- CI City Hospital #1
- GI L.T.Malaya Therapy National Institute of the NAMS of Ukraine
- CHI Kharkiv City Clinical Hospital #13
- Kyiv CCH #18 Dept of Proctology O. O. Bogomolets NMU
- City Hospital #1
- Railway Transport Odesa CH of Healthcare Ctr Branch of PJSC Ukrainian Railway Dept of Therapy #2
- Private Small Enterprise Medical Center Pulse
- M.I. Pyrogov VRCH Dept of Gastroenterology M.I. Pyrogov VNMU
- MCIC MC LLC Health Clinic
- LLC Diaservis
- Royal Victoria Hospital
- Addenbrooke's Hospital
- University Hospital Coventry
- Royal Devon and Exeter Hospital (Wonford)
- Queen Elizabeth Hospital
- St James University Hospital
- Royal Liverpool University Hospital
- Whipps Cross Hospital
- University College London Hospital
- Fairfield General Hospital
- Royal Victoria Infirmary; Stroke unit
- Nottingham University Hospitals Queen's Medical Centre
- Royal Berkshire Hospital
- Southampton General Hospital
- Royal Wolverhampton hospital; McHale Building
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm 9
Arm 10
Arm 11
Experimental
Experimental
Placebo Comparator
Experimental
Experimental
Experimental
Experimental
Placebo Comparator
Placebo Comparator
Placebo Comparator
Experimental
Induction Phase - Cohort 1 (Exploratory): Etrolizumab 210 mg
Induction Phase - Cohort 1 (Exploratory): Etrolizumab 105 mg
Induction Phase - Cohort 1 (Exploratory): Placebo
Induction Phase - Cohort 2 (Open-Label): Etrolizumab 210 mg
Induction Phase - Cohort 2 (Open-Label): Etrolizumab 105 mg
Induction Phase - Cohort 3 (Pivotal): Etrolizumab 210 mg
Induction Phase - Cohort 3 (Pivotal): Etrolizumab 105 mg
Induction Phase - Cohort 3 (Pivotal): Placebo
Maintenance Phase - Placebo Responders: Placebo
Maintenance Phase - Etrolizumab Responders: Placebo
Maintenance Phase - Etrolizumab Responders: Etrolizumab 105 mg
Cohort 1 enrolled participants first before Cohorts 2 and 3 in order to conduct an exploratory analysis on induction data. Participants randomized to this arm will receive one subcutaneous (SC) injection of etrolizumab (210 mg) at Weeks 0, 2, 4, 8, and 12 during the 14-week Induction Phase. In order to preserve the masking, participants will also receive one SC injection of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12.
Cohort 1 enrolled participants first before Cohorts 2 and 3 in order to conduct an exploratory analysis on induction data. Participants randomized to this arm will receive one SC injection of etrolizumab (105 mg) at Weeks 0, 4, 8, 12 and one SC injection of etrolizumab-matching placebo at Week 2 during the 14-week Induction Phase. In order to preserve the masking, participants will also receive one SC injection of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12.
Cohort 1 enrolled participants first before Cohorts 2 and 3 in order to conduct an exploratory analysis on induction data. Participants randomized to this arm will receive two SC injections of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12 (and one SC injection of etrolizumab-matching placebo at Week 2) during the 14-week Induction Phase, in order to preserve the masking.
Cohort 2 is enrolling participants after Cohort 1 and is considered a "feeder" cohort to help achieve the necessary sample size for the Maintenance Phase. Participants randomized to this arm will receive one SC injection of open-label etrolizumab (210 mg) at Weeks 0, 2, 4, 8, and 12 during the 14-week Induction Phase. In order to preserve the masking for the dose of etrolizumab, participants will also receive one SC injection of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12.
Cohort 2 is enrolling participants after Cohort 1 and is considered a "feeder" cohort to help achieve the necessary sample size for the Maintenance Phase. Participants randomized to this arm will receive one SC injection of open-label etrolizumab (105 mg) at Weeks 0, 4, 8, 12 and one SC injection of etrolizumab-matching placebo at Week 2 during the 14-week Induction Phase. In order to preserve the masking of the dose of etrolizumab, participants will also receive one SC injection of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12.
Cohort 3 is the last to enroll participants (after Cohort 2) and will be the pivotal cohort for the Induction Phase. Participants randomized to this arm will receive one SC injection of etrolizumab (210 mg) at Weeks 0, 2, 4, 8, and 12 during the 14-week Induction Phase. In order to preserve the masking, participants will also receive one SC injection of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12.
Cohort 3 is the last to enroll participants (after Cohort 2) and will be the pivotal cohort for the Induction Phase. Participants randomized to this arm will receive one SC injection of etrolizumab (105 mg) at Weeks 0, 4, 8, 12 and one SC injection of etrolizumab-matching placebo at Week 2 during the 14-week Induction Phase. In order to preserve the masking, participants will also receive one SC injection of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12.
Cohort 3 is the last to enroll participants (after Cohort 2) and will be the pivotal cohort for the Induction Phase. Participants randomized to this arm will receive two SC injections of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12 (and one SC injection of etrolizumab-matching placebo at Week 2) during the 14-week Induction Phase, in order to preserve the masking.
Participants who received placebo during the Induction Phase (from Cohorts 1 and 3) and achieved a CDAI-70 response at Week 14 will undergo a sham randomization into the Maintenance Phase. Placebo responders from induction will receive blinded maintenance treatment with an SC injection of placebo once every 4 weeks (q4w) from Week 16 to Week 64.
Participants who received etrolizumab during the Induction Phase (from Cohorts 1-3) and achieved a CDAI-70 response at Week 14 without the use of rescue therapy will be re-randomized into the Maintenance Phase. Etrolizumab responders from induction who are re-randomized to this arm will receive blinded maintenance treatment with an SC injection of placebo q4w from Week 16 to Week 64.
Participants who received etrolizumab during the Induction Phase (from Cohorts 1-3) and achieved a CDAI-70 response at Week 14 without the use of rescue therapy will be re-randomized into the Maintenance Phase. Etrolizumab responders from induction who are re-randomized to this arm will receive blinded maintenance treatment with an SC injection of etrolizumab (105 mg) q4w from Week 16 to Week 64.