A Study Comparing the Efficacy and Safety of Etrolizumab to Infliximab in Participants With Moderate to Severe Ulcerative Colitis Who Are Naïve to Tumor Necrosis Factor (TNF) Inhibitors

NCT ID: NCT02136069

Last Updated: 2021-12-03

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

397 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-12-24

Study Completion Date

2020-06-23

Brief Summary

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This is a multicenter, Phase III, randomized, double-blind, double-dummy, parallel-group study to evaluate the safety, efficacy, and tolerability of etrolizumab compared with infliximab in treating participants with moderate to severe ulcerative colitis (UC) who are naive to tumor necrosis factor (TNF) inhibitors. Participants will be randomized in a 1:1 ratio to receive either etrolizumab 105 milligrams (mg) by subcutaneous (SC) injection once every 4 weeks (Q4W) + placebo (intravenous \[IV\] infusion at Weeks 0, 2, and 6, then once every 8 weeks \[Q8W\]) or infliximab 5 milligrams/kilogram (mg/kg) IV at Weeks 0, 2, and 6, then Q8W) + placebo (SC Q4W). Time on treatment is 54 weeks.

Detailed Description

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Conditions

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Ulcerative Colitis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Etrolizumab + Placebo (IV)

Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.

Group Type EXPERIMENTAL

Etrolizumab

Intervention Type DRUG

105 mg administered by subcutaneous (SC) injection once every 4 weeks (Q4W) until Week 52.

Placebo (IV)

Intervention Type OTHER

Administered by (IV) infusion at Weeks 0, 2, and 6 and then every 8 weeks until Week 46.

Infliximab + Placebo (Injection)

Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.

Group Type ACTIVE_COMPARATOR

Infliximab

Intervention Type DRUG

5 mg/kg of infliximab will be administered by intravenous (IV) infusion at Weeks 0, 2, and 6 and then every 8 weeks until Week 46.

Placebo (Injection)

Intervention Type OTHER

Administered by SC injection Q4W until Week 52

Interventions

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Etrolizumab

105 mg administered by subcutaneous (SC) injection once every 4 weeks (Q4W) until Week 52.

Intervention Type DRUG

Infliximab

5 mg/kg of infliximab will be administered by intravenous (IV) infusion at Weeks 0, 2, and 6 and then every 8 weeks until Week 46.

Intervention Type DRUG

Placebo (IV)

Administered by (IV) infusion at Weeks 0, 2, and 6 and then every 8 weeks until Week 46.

Intervention Type OTHER

Placebo (Injection)

Administered by SC injection Q4W until Week 52

Intervention Type OTHER

Other Intervention Names

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PRO145223 RO5490261 RG7413

Eligibility Criteria

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Inclusion Criteria

* Moderately to severely active UC as determined by the Mayo Clinic Score assessment (MCS)
* Naive to treatment with any anti-TNF inhibitor therapy (including TNF inhibitor biosimilars)
* An inadequate response to or intolerance of prior corticosteroid and/or immunosuppressant treatment
* Background regimen for UC may include oral 5-aminosalicylate (5-ASA), oral corticosteroids, budenoside multi-matrix system (MMX), probiotics, azathioprine (AZA), 6-mercaptopurine (6-MP), or methotrexate (MTX) if doses have been stable during the screening period
* Use of highly effective contraception during and at least 24 weeks after the last dose of study drug

Exclusion Criteria

* A history of or current conditions and diseases affecting the digestive tract, such as indeterminate colitis, suspicion of ischemic, radiation 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
* Have received non-permitted inflammatory bowel disease (IBD) therapies (including natalizumab, vedolizumab, efalizumab, and tofactinib)
* History of moderate or severe allergic or anaphylactic/anaphylactoid reactions to chimeric, human, or humanized antibodies; fusion proteins, or murine proteins; hypersensitivity to etrolizumab or any of its excipients
* Chronic hepatitis B or C infection, Human deficiency virus (HIV) or tuberculosis (active or latent)
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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LKH - Universitätsklinikum der PMU Salzburg

Salzburg, , Austria

Site Status

GZA Ziekenhuizen - Campus Sint-Vincentius

Antwerp, , Belgium

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Imeldaziekenhuis

Bonheiden, , Belgium

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CHU St Pierre (St Pierre)

Brussels, , Belgium

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Universitair Ziekenhuis Brussel; Neurology

Brussels, , Belgium

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Cliniques Universitaires Saint-Luc; Pharmacy

Brussels, , Belgium

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UZ Gent

Ghent, , Belgium

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AZ Sint Elisabeth Herentals

Herentals, , Belgium

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University of Calgary; Heritage Medical Research Clinic

Calgary, Alberta, Canada

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Zeidler Ledcor Centre - University of Alberta; Division of Gasroenterology

Edmonton, Alberta, Canada

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Guelph GI & Surgery Clinic

Guelph, Ontario, Canada

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Centre de santé et de services sociaux Champlain-Charles-Le Moyne

Greenfield Park, Quebec, Canada

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Hôpital Maisonneuve - Rosemont

Montreal, Quebec, Canada

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Royal University Hospital

Saskatoon, Saskatchewan, Canada

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Vojenska nemocnice Brno

Brno, , Czechia

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Fakultni nemocnice Hradec Kralove

Hradec Králové, , Czechia

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Oblastni nemocnice Kladno, a.s., nemocnice Stredoces. kraje; Endoskopicke centrum

Kladno, , Czechia

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Mestska Nemocnice Ostrava

Ostrava, , Czechia

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Pardubicka krajska nemocnice, a.s.

Pardubice, , Czechia

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ISCARE a.s.

Prague, , Czechia

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Krajska zdravotni, a.s. - Masarykova nemocnice v Usti nad Labem, o.z., Ocni oddeleni

Ústí nad Labem, , Czechia

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Krajska nemocnice T. Bati, a.s.

Zlín, , Czechia

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CHU de Caen - Hopital Cote de Nacre

Caen, , France

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CHU Tours - Hôpital Trousseau

Chambray-lès-Tours, , France

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CHU Clermont Ferrand - Hôtel Dieu

Clermont-Ferrand, , France

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Hôpital Beaujon

Clichy, , France

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CHU Hopital Saint Eloi

Montpellier, , France

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CHU Nice - Hopital de l'Archet 2

Nice, , France

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Centre Hospitalier Lyon Sud; Service de Gastro-Enterologie

Pierre-Bénite, , France

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Hôpital de Brabois Adultes

Vandœuvre-lès-Nancy, , France

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Charite Universitaetsmedizin Berlin - Campus Benjamin Franklin

Berlin, , Germany

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DRK Kliniken Berlin Westend

Berlin, , Germany

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Krankenhaus Waldfriede e. V.

Berlin, , Germany

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Universitätsklinikum Koeln

Cologne, , Germany

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Universitätsklinikum Freiburg; Innere Medizin I; Hämatologie, Onkologie und Stammzelltransplantation

Freiburg im Breisgau, , Germany

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Gastroenterologie Eppendorfer Baum

Hamburg, , Germany

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Universitaetsklinikum Schleswig-Holstein, Campus Kiel

Kiel, , Germany

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Bekes Megyei Kozponti Korhaz Dr. Rethy Pal Tagkorhaza

Békéscsaba, , Hungary

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Semmelweis Egyetem

Budapest, , Hungary

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Eszak-Kozep-budai Centrum, Uj Szent Janos Korhaz es Szakrendelo

Budapest, , Hungary

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Magyar Honvedseg Egeszsegugyi Kozpont; Fázis I-es Klinikai Farmakológiai Vizsgálóhely

Budapest, , Hungary

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Vasutegeszsegugyi Nonprofit KiemeltenKozhasznu Kft

Debrecen, , Hungary

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Markhot Ferenc Oktato Korhaz es Rendelointezet

Eger, , Hungary

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Petz Aladar Megyei Oktato Korhaz

Győr, , Hungary

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Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktato Korhaz; II. Belgyogyaszat

Miskolc, , Hungary

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Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont

Szeged, , Hungary

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Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz

Székesfehérvár, , Hungary

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Rabin Medical Center-Beilinson Campus

Petah Tikva, , Israel

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Chaim Sheba Medical Center; Pediatrics B North and Pediatric Endocrinology Unit

Tel Litwinsky, , Israel

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Azienda Ospedaliero Universitaria di Parma

Parma, Emilia-Romagna, Italy

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Azienda Ospedaliera Universitaria Policlinico Tor Vergata

Rome, Lazio, Italy

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Azienda Ospedaliera San Camillo Forlanini

Rome, Lazio, Italy

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Asst Fatebenefratelli Sacco (Fatebenefratelli)

Milan, Lombardy, Italy

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Azienda Socio Sanitaria Territoriale Niguarda (Grande Ospedale Metropolitano Niguarda)

Milan, Lombardy, Italy

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Azienda Socio Sanitaria Territoriale Fatebenefratelli (Presidio Ospedale Sacco)

Milan, Lombardy, Italy

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Istituto Clinico Humanitas

Rozzano (MI), Lombardy, Italy

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I.R.C.C.S Policlinico San Donato

San Donato Milanese (MI), Lombardy, Italy

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IRCCS Ospedale Casa Sollievo della Soffenza; Stru Comp di Gastroenterologia ed Endoscopia digest

San Giovanni Rotondo, Lombardy, Italy

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Ospedale Mauriziano Umberto I

Turin, Piedmont, Italy

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Azienda Ospedaliera Universitaria Careggi

Florence, Tuscany, Italy

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Azienda Ospedaliero Universitaria Pisana

Pisa, Tuscany, Italy

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Azienda Ospedaliera Di Padova

Padua, Veneto, Italy

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Amsterdam UMC Location VUMC

Amsterdam, , Netherlands

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Amsterdam UMC Location AMC

Amsterdam, , Netherlands

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Maastricht University Medical Center

Maastricht, , Netherlands

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Radboudumc

NL -nijmegen, , Netherlands

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Akershus universitetssykehus HF

Lørenskog, , Norway

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Hospital de Braga

Braga, , Portugal

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Hospital da Senhora da Oliveira Guimarães

Guimarães, , Portugal

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S.C MedLife S.A

Bucharest, , Romania

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Institutul Clinic Fundeni Bucuresti

Bucharest, , Romania

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Centrul Medical Unirea SRL

Bucharest, , Romania

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Spitalul Clinic Colentina

Bucharest, , Romania

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Spitalul Clinic Judetean Mures

Târgu Mureş, , Romania

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Centrul de Gastroenterologie Dr. Goldis

Timișoara, , Romania

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Singapore General Hospital

Singapore, , Singapore

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Netcare Universitas Private Hospital

Bloemfontein, , South Africa

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Dr MJ Prins Practice

Cape Town, , South Africa

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Dr Corne Kruger Inc.

Cape Town, , South Africa

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Dong-A University Hospital

Busan, , South Korea

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Pusan National University Hospital

Busan, , South Korea

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Kyungpook National University Chilgok Hospital

Daegu, , South Korea

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Keimyung University Dongsan Medical Center

Daegu, , South Korea

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Kyungpook National University Hospital

Daegu, , South Korea

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Yeungnam Univ. Hospital

Daegu, , South Korea

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Korea University Ansan Hospital

Gyeonggi-do, , South Korea

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CHA Bundang Medical Centre; CHA university

Seongnam, , South Korea

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Seoul National University Bundang Hospital

Seongnam-si, , South Korea

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Kyung Hee University Hospital

Seoul, , South Korea

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Seoul National University Hospital

Seoul, , South Korea

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Kangbuk Samsung Hospital

Seoul, , South Korea

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Severance Hospital, Yonsei University

Seoul, , South Korea

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Asan Medical Center

Seoul, , South Korea

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Samsung Medical Center

Seoul, , South Korea

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The Catholic University of Korea St. Vincent's Hospital

Suwon, , South Korea

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Ajou University Hospital

Suwon, , South Korea

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Yonsei University Wonju Severance Christian Hospital

Wŏnju, , South Korea

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Corporacio Sanitaria Parc Tauli

Sabadell, Barcelona, Spain

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Complejo Hospitalario Universitario de Ferrol

Ferrol, LA Coruña, Spain

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Fundacion Hospital de Alcorcon; Servicio de Digestivo

Alcorcón, Madrid, Spain

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Centro Médico Teknon

Barcelona, , Spain

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Hospital Universitario de la Princesa

Madrid, , Spain

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Hospital Universitario La Paz

Madrid, , Spain

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Hospital Universitari i Politecnic La Fe

Valencia, , Spain

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Danderyds Sjukhus AB

Stockholm, , Sweden

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Inselspital-Universitaetsspital Bern

Bern, , Switzerland

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Universitätsspital Zürich

Zurich, , Switzerland

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The Royal Bournemouth Hospital

Bournemouth, , United Kingdom

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Addenbrooke's Hospital

Cambridge, , United Kingdom

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University Hospital Coventry

Coventry, , United Kingdom

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Royal Devon and Exeter Hospital (Wonford)

Exeter, , United Kingdom

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St James University Hospital

Leeds, , United Kingdom

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The Royal London Hospital

London, , United Kingdom

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St Thomas Hospital

London, , United Kingdom

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King's College London

London, , United Kingdom

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Fairfield General Hospital

Manchester, , United Kingdom

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Royal Victoria Infirmary

Newcastle upon Tyne, , United Kingdom

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Nottingham University Hospitals NHS Trust

Nottingham, , United Kingdom

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Southampton General Hospital

Southampton, , United Kingdom

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Countries

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Philippines Vietnam Austria Belgium Canada Czechia France Germany Hungary Israel Italy Netherlands Norway Portugal Romania Singapore South Africa South Korea Spain Sweden Switzerland United Kingdom

References

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Danese S, Colombel JF, Lukas M, Gisbert JP, D'Haens G, Hayee B, Panaccione R, Kim HS, Reinisch W, Tyrrell H, Oh YS, Tole S, Chai A, Chamberlain-James K, Tang MT, Schreiber S; GARDENIA Study Group. Etrolizumab versus infliximab for the treatment of moderately to severely active ulcerative colitis (GARDENIA): a randomised, double-blind, double-dummy, phase 3 study. Lancet Gastroenterol Hepatol. 2022 Feb;7(2):118-127. doi: 10.1016/S2468-1253(21)00294-6. Epub 2021 Nov 17.

Reference Type DERIVED
PMID: 34798038 (View on PubMed)

Sandborn WJ, Vermeire S, Tyrrell H, Hassanali A, Lacey S, Tole S, Tatro AR; Etrolizumab Global Steering Committee. Etrolizumab for the Treatment of Ulcerative Colitis and Crohn's Disease: An Overview of the Phase 3 Clinical Program. Adv Ther. 2020 Jul;37(7):3417-3431. doi: 10.1007/s12325-020-01366-2. Epub 2020 May 22.

Reference Type DERIVED
PMID: 32445184 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2013-004282-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GA29103

Identifier Type: -

Identifier Source: org_study_id