NCT02136069

Brief Summary

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.

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network
Enrollment
397

participants targeted

Target at P50-P75 for phase_3

Timeline
Completed

Started Dec 2014

Longer than P75 for phase_3

Geographic Reach
20 countries

119 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 15, 2014

Completed
27 days until next milestone

First Posted

Study publicly available on registry

May 12, 2014

Completed
8 months until next milestone

Study Start

First participant enrolled

December 24, 2014

Completed
5.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 23, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 23, 2020

Completed
1.1 years until next milestone

Results Posted

Study results publicly available

August 13, 2021

Completed
Last Updated

December 3, 2021

Status Verified

December 1, 2021

Enrollment Period

5.5 years

First QC Date

April 15, 2014

Results QC Date

June 18, 2021

Last Update Submit

December 1, 2021

Conditions

Outcome Measures

Primary Outcomes (1)

  • Percentage of Participants With Both Clinical Response at Week 10 and Clinical Remission at Week 54, as Determined by the Mayo Clinic Score (MCS)

    Mayo Clinic Score (MCS) is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease. 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. Clinical Remission is MCS ≤2 with individual subscores ≤1.

    Week 10, Week 54

Secondary Outcomes (21)

  • Percentage of Participants Achieving Clinical Remission at Week 10, Defined as MCS ≤2 With Individual Subscores ≤1

    Week 10

  • Percentage of Participants Achieving Clinical Remission at Week 54, as Determined by the MCS

    Week 54

  • Percentage of Participants Achieving Clinical Remission at Both Week 10 and Week 54, as Determined by the MCS

    Week 10 and Week 54

  • Percentage of Participants Achieving Clinical Remission at Week 54 Among Those With a Clinical Response at Week 10, as Determined by the MCS

    Week 10 and Week 54

  • Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Week 10, Determined by the MCS

    Baseline to Week 10

  • +16 more secondary outcomes

Study Arms (2)

Etrolizumab + Placebo (IV)

EXPERIMENTAL

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

Drug: EtrolizumabOther: Placebo (IV)

Infliximab + Placebo (Injection)

ACTIVE COMPARATOR

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.

Drug: InfliximabOther: Placebo (Injection)

Interventions

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

Also known as: PRO145223, RO5490261, RG7413
Etrolizumab + Placebo (IV)

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.

Infliximab + Placebo (Injection)

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

Etrolizumab + Placebo (IV)

Administered by SC injection Q4W until Week 52

Infliximab + Placebo (Injection)

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (119)

LKH - Universitätsklinikum der PMU Salzburg

Salzburg, 5020, Austria

Location

GZA Ziekenhuizen - Campus Sint-Vincentius

Antwerp, 2018, Belgium

Location

Imeldaziekenhuis

Bonheiden, 2820, Belgium

Location

CHU St Pierre (St Pierre)

Brussels, 1000, Belgium

Location

Universitair Ziekenhuis Brussel; Neurology

Brussels, 1090, Belgium

Location

Cliniques Universitaires Saint-Luc; Pharmacy

Brussels, 1200, Belgium

Location

UZ Gent

Ghent, 9000, Belgium

Location

AZ Sint Elisabeth Herentals

Herentals, 2200, Belgium

Location

University of Calgary; Heritage Medical Research Clinic

Calgary, Alberta, T2N 4Z6, Canada

Location

Zeidler Ledcor Centre - University of Alberta; Division of Gasroenterology

Edmonton, Alberta, T6G 2X8, Canada

Location

Guelph GI & Surgery Clinic

Guelph, Ontario, N1H 3R3, Canada

Location

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

Greenfield Park, Quebec, J4V 2H1, Canada

Location

Hôpital Maisonneuve - Rosemont

Montreal, Quebec, H1T 2M4, Canada

Location

Royal University Hospital

Saskatoon, Saskatchewan, S7N 0W8, Canada

Location

Vojenska nemocnice Brno

Brno, 636 00, Czechia

Location

Fakultni nemocnice Hradec Kralove

Hradec Králové, 500 05, Czechia

Location

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

Kladno, 272 59, Czechia

Location

Mestska Nemocnice Ostrava

Ostrava, 728 80, Czechia

Location

Pardubicka krajska nemocnice, a.s.

Pardubice, 532 03, Czechia

Location

ISCARE a.s.

Prague, 170 04, Czechia

Location

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

Ústí nad Labem, 401 13, Czechia

Location

Krajska nemocnice T. Bati, a.s.

Zlín, 76001, Czechia

Location

CHU de Caen - Hopital Cote de Nacre

Caen, 14033, France

Location

CHU Tours - Hôpital Trousseau

Chambray-lès-Tours, 37170, France

Location

CHU Clermont Ferrand - Hôtel Dieu

Clermont-Ferrand, 63000, France

Location

Hôpital Beaujon

Clichy, 92110, France

Location

CHU Hopital Saint Eloi

Montpellier, 34295, France

Location

CHU Nice - Hopital de l'Archet 2

Nice, 06202, France

Location

Centre Hospitalier Lyon Sud; Service de Gastro-Enterologie

Pierre-Bénite, 69495, France

Location

Hôpital de Brabois Adultes

Vandœuvre-lès-Nancy, 54511, France

Location

Charite Universitaetsmedizin Berlin - Campus Benjamin Franklin

Berlin, 12200, Germany

Location

DRK Kliniken Berlin Westend

Berlin, 14050, Germany

Location

Krankenhaus Waldfriede e. V.

Berlin, 14163, Germany

Location

Universitätsklinikum Koeln

Cologne, 50937, Germany

Location

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

Freiburg im Breisgau, 79106, Germany

Location

Gastroenterologie Eppendorfer Baum

Hamburg, 20249, Germany

Location

Universitaetsklinikum Schleswig-Holstein, Campus Kiel

Kiel, 24116, Germany

Location

Bekes Megyei Kozponti Korhaz Dr. Rethy Pal Tagkorhaza

Békéscsaba, 5600, Hungary

Location

Semmelweis Egyetem

Budapest, 1083, Hungary

Location

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

Budapest, 1125, Hungary

Location

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

Budapest, H-1077, Hungary

Location

Vasutegeszsegugyi Nonprofit KiemeltenKozhasznu Kft

Debrecen, 4025, Hungary

Location

Markhot Ferenc Oktato Korhaz es Rendelointezet

Eger, 3300, Hungary

Location

Petz Aladar Megyei Oktato Korhaz

Győr, 9024, Hungary

Location

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

Miskolc, 3526, Hungary

Location

Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont

Szeged, 6720, Hungary

Location

Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz

Székesfehérvár, 8000, Hungary

Location

Rabin Medical Center-Beilinson Campus

Petah Tikva, 4941492, Israel

Location

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

Tel Litwinsky, 52621, Israel

Location

Azienda Ospedaliero Universitaria di Parma

Parma, Emilia-Romagna, 43100, Italy

Location

Azienda Ospedaliera Universitaria Policlinico Tor Vergata

Rome, Lazio, 00133, Italy

Location

Azienda Ospedaliera San Camillo Forlanini

Rome, Lazio, 00152, Italy

Location

Asst Fatebenefratelli Sacco (Fatebenefratelli)

Milan, Lombardy, 20121, Italy

Location

Azienda Socio Sanitaria Territoriale Niguarda (Grande Ospedale Metropolitano Niguarda)

Milan, Lombardy, 20162, Italy

Location

Azienda Socio Sanitaria Territoriale Fatebenefratelli (Presidio Ospedale Sacco)

Milan, Lombardy, Italy

Location

Istituto Clinico Humanitas

Rozzano (MI), Lombardy, 20089, Italy

Location

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

San Donato Milanese (MI), Lombardy, 20097, Italy

Location

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

San Giovanni Rotondo, Lombardy, 71013, Italy

Location

Ospedale Mauriziano Umberto I

Turin, Piedmont, 10128, Italy

Location

Azienda Ospedaliera Universitaria Careggi

Florence, Tuscany, 50141, Italy

Location

Azienda Ospedaliero Universitaria Pisana

Pisa, Tuscany, 56100, Italy

Location

Azienda Ospedaliera Di Padova

Padua, Veneto, 35128, Italy

Location

Amsterdam UMC Location VUMC

Amsterdam, 1081 HV, Netherlands

Location

Amsterdam UMC Location AMC

Amsterdam, 1105 AZ, Netherlands

Location

Maastricht University Medical Center

Maastricht, 6229 HX, Netherlands

Location

Radboudumc

NL -nijmegen, 6525 GA, Netherlands

Location

Akershus universitetssykehus HF

Lørenskog, 1478, Norway

Location

Hospital de Braga

Braga, 4710-243, Portugal

Location

Hospital da Senhora da Oliveira Guimarães

Guimarães, 4835-044, Portugal

Location

S.C MedLife S.A

Bucharest, 010719, Romania

Location

Institutul Clinic Fundeni Bucuresti

Bucharest, 022328, Romania

Location

Centrul Medical Unirea SRL

Bucharest, 040055, Romania

Location

Spitalul Clinic Colentina

Bucharest, 772202, Romania

Location

Spitalul Clinic Judetean Mures

Târgu Mureş, 540103, Romania

Location

Centrul de Gastroenterologie Dr. Goldis

Timișoara, 300002, Romania

Location

Singapore General Hospital

Singapore, 169608, Singapore

Location

Netcare Universitas Private Hospital

Bloemfontein, 9301, South Africa

Location

Dr MJ Prins Practice

Cape Town, 7500, South Africa

Location

Dr Corne Kruger Inc.

Cape Town, 7550, South Africa

Location

Dong-A University Hospital

Busan, 49201, South Korea

Location

Pusan National University Hospital

Busan, 49241, South Korea

Location

Kyungpook National University Chilgok Hospital

Daegu, 41404, South Korea

Location

Keimyung University Dongsan Medical Center

Daegu, 41931, South Korea

Location

Kyungpook National University Hospital

Daegu, 41944, South Korea

Location

Yeungnam Univ. Hospital

Daegu, 705-717, South Korea

Location

Korea University Ansan Hospital

Gyeonggi-do, 15355, South Korea

Location

CHA Bundang Medical Centre; CHA university

Seongnam, 13520, South Korea

Location

Seoul National University Bundang Hospital

Seongnam-si, 13605, South Korea

Location

Kyung Hee University Hospital

Seoul, 02447, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Kangbuk Samsung Hospital

Seoul, 03181, South Korea

Location

Severance Hospital, Yonsei University

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

The Catholic University of Korea St. Vincent's Hospital

Suwon, 442-723, South Korea

Location

Ajou University Hospital

Suwon, 443-721, South Korea

Location

Yonsei University Wonju Severance Christian Hospital

Wŏnju, 220-701, South Korea

Location

Corporacio Sanitaria Parc Tauli

Sabadell, Barcelona, 08208, Spain

Location

Complejo Hospitalario Universitario de Ferrol

Ferrol, LA Coruña, 15405, Spain

Location

Fundacion Hospital de Alcorcon; Servicio de Digestivo

Alcorcón, Madrid, 28922, Spain

Location

Centro Médico Teknon

Barcelona, Spain

Location

Hospital Universitario de la Princesa

Madrid, 28006, Spain

Location

Hospital Universitario La Paz

Madrid, 280146, Spain

Location

Hospital Universitari i Politecnic La Fe

Valencia, 46026, Spain

Location

Danderyds Sjukhus AB

Stockholm, 18288, Sweden

Location

Inselspital-Universitaetsspital Bern

Bern, 3010, Switzerland

Location

Universitätsspital Zürich

Zurich, 8091, Switzerland

Location

The Royal Bournemouth Hospital

Bournemouth, BH7 7DW, United Kingdom

Location

Addenbrooke's Hospital

Cambridge, CB2 0QQ, United Kingdom

Location

University Hospital Coventry

Coventry, CV2 2DX, United Kingdom

Location

Royal Devon and Exeter Hospital (Wonford)

Exeter, EX2 5DW, United Kingdom

Location

St James University Hospital

Leeds, LS9 7TF, United Kingdom

Location

The Royal London Hospital

London, E1 1FR, United Kingdom

Location

St Thomas Hospital

London, SE1 7EH, United Kingdom

Location

King's College London

London, SE5 9NU, United Kingdom

Location

Fairfield General Hospital

Manchester, M8 5RB, United Kingdom

Location

Royal Victoria Infirmary

Newcastle upon Tyne, NE1 4LP, United Kingdom

Location

Nottingham University Hospitals NHS Trust

Nottingham, NG7 2UH, United Kingdom

Location

Southampton General Hospital

Southampton, SO16 6YD, United Kingdom

Location

Related Publications (2)

  • 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.

  • 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.

MeSH Terms

Conditions

Colitis, Ulcerative

Interventions

etrolizumabInfliximabInjections

Condition Hierarchy (Ancestors)

ColitisGastroenteritisGastrointestinal DiseasesDigestive System DiseasesInflammatory Bowel DiseasesColonic DiseasesIntestinal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsDrug Administration RoutesDrug TherapyTherapeutics

Results Point of Contact

Title
Medical Communications
Organization
Hoffmann-La Roche

Study Officials

  • Clinical Trials

    Hoffmann-La Roche

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

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

Study Record Dates

First Submitted

April 15, 2014

First Posted

May 12, 2014

Study Start

December 24, 2014

Primary Completion

June 23, 2020

Study Completion

June 23, 2020

Last Updated

December 3, 2021

Results First Posted

August 13, 2021

Record last verified: 2021-12

Data Sharing

IPD Sharing
Will share

Qualified researchers may request access to individual patient level data through the request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on Sharing of Clinical Study Information and how to request access to related clinical study documents, see here (https://www.roche.com/research\_and\_development/who\_we\_are\_how\_we\_work/clinical\_trials/our\_commitment\_to\_data\_sharing.htm).

Locations