Clinical trial NCT02136069: 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
Official title: Phase III, Randomized, Multicenter Double-Blind, Double Dummy Study to Evaluate the Efficacy and Safety of Etrolizumab Compared With Infliximab in Patients With Moderate to Severe Active Ulcerative Colitis Who Are Naive to TNF Inhibitors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Ulcerative Colitis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2014-05-12
Enrollment: 397
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Percentage of Participants With Both Clinical Response at Week 10 and Clinical Remission at Week 54, as Determined by the Mayo Clinic Score (MCS)
timeFrame: Week 10, Week 54
Secondary outcomes:
measure: Percentage of Participants Achieving Clinical Remission at Week 10, Defined as MCS ≤2 With Individual Subscores ≤1
timeFrame: Week 10
measure: Percentage of Participants Achieving Clinical Remission at Week 54, as Determined by the MCS
timeFrame: Week 54
measure: Percentage of Participants Achieving Clinical Remission at Both Week 10 and Week 54, as Determined by the MCS
timeFrame: Week 10 and Week 54
measure: Percentage of Participants Achieving Clinical Remission at Week 54 Among Those With a Clinical Response at Week 10, as Determined by the MCS
timeFrame: Week 10 and Week 54
measure: Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Week 10, Determined by the MCS
timeFrame: Baseline to Week 10
measure: Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Week 54, as Determined by the MCS
timeFrame: Baseline to Week 54
measure: Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Both Week 10 and Week 54, as Determined by the MCS
timeFrame: Baseline to Week 10, Week 54
measure: Percentage of Participants With Endoscopic Remission at Week 54, as Determined by the MCS
timeFrame: Week 54
measure: Percentage of Participants Achieving Clinical Response at Week 10, as Determined by the MCS
timeFrame: Week 10
measure: Percentage of Participants Achieving Clinical Response at Both Weeks 10 and 54, as Determined by the MCS
timeFrame: Week 10, Week 54
measure: Percentage of Participants That Achieve Clinical Remission Corticosteroid-Free at Week 54 (Off Corticosteroid for at Least 24 Weeks Prior to Week 54) Among Those Who Were Receiving Corticosteroids at Baseline, as Determined by the MCS
timeFrame: Week 54
measure: Number of Participants With Adverse Events, Severity Determined According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0)
timeFrame: Baseline until the end of study (up to 66 weeks)
measure: Number of Participants With Adverse Events Leading to Study Drug Discontinuation
timeFrame: Baseline until the end of study (up to 66 weeks)
measure: Number of Participants With Infection-Related Adverse Events, Severity Determined According to the NCI CTCAE v4.0
timeFrame: Baseline until the end of study (up to 66 weeks)
measure: Number of Participants With Serious Infection-Related Adverse Events
timeFrame: Baseline until the end of study (up to 66 weeks)
measure: Number of Participants With Malignancies
timeFrame: Baseline until the end of study (up to 66 weeks)
measure: Number of Participants With Injection-Site Reactions, Severity Determined According to the NCI CTCAE v4.0
timeFrame: Baseline until the end of study (up to 66 weeks)
measure: Number of Participants With Hypersensitivity Reaction Events, Severity Determined According to the NCI CTCAE v4.0
timeFrame: Baseline until the end of study (up to 66 weeks)
measure: Pharmacokinetics: Etrolizumab Serum Concentration
timeFrame: Weeks 2, 10, 12, 30, and 54
measure: Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Overall Score at Weeks 10, 30, and 54
timeFrame: Weeks 10, 30, and 54
measure: Number of Participants With Anti-Therapeutic Antibodies (ATAs) to Etrolizumab
timeFrame: Weeks 0, 4, 10, 12, 30, and 54
Other outcomes:
Locations:
city: Salzburg
country: Austria
facility: LKH - Universitätsklinikum der PMU Salzburg
city: Antwerpen
country: Belgium
facility: GZA Ziekenhuizen - Campus Sint-Vincentius
city: Bonheiden
country: Belgium
facility: Imeldaziekenhuis
city: Brussels
country: Belgium
facility: CHU St Pierre (St Pierre)
city: Bruxelles
country: Belgium
facility: Universitair Ziekenhuis Brussel; Neurology
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint-Luc; Pharmacy
city: Gent
country: Belgium
facility: UZ Gent
city: Herentals
country: Belgium
facility: AZ Sint Elisabeth Herentals
city: Calgary
country: Canada
facility: University of Calgary; Heritage Medical Research Clinic
state: Alberta
city: Edmonton
country: Canada
facility: Zeidler Ledcor Centre - University of Alberta; Division of Gasroenterology
state: Alberta
city: Guelph
country: Canada
facility: Guelph GI & Surgery Clinic
state: Ontario
city: Greenfield Park
country: Canada
facility: Centre de santé et de services sociaux Champlain-Charles-Le Moyne
state: Quebec
city: Montreal
country: Canada
facility: Hôpital Maisonneuve - Rosemont
state: Quebec
city: Saskatoon
country: Canada
facility: Royal University Hospital
state: Saskatchewan
city: Brno
country: Czechia
facility: Vojenska nemocnice Brno
city: Hradec Kralove
country: Czechia
facility: Fakultni nemocnice Hradec Kralove
city: Kladno
country: Czechia
facility: Oblastni nemocnice Kladno, a.s., nemocnice Stredoces. kraje; Endoskopicke centrum
city: Ostrava
country: Czechia
facility: Mestska Nemocnice Ostrava
city: Pardubice
country: Czechia
facility: Pardubicka krajska nemocnice, a.s.
city: Praha 7
country: Czechia
facility: ISCARE a.s.
city: Usti Nad Labem
country: Czechia
facility: Krajska zdravotni, a.s. - Masarykova nemocnice v Usti nad Labem, o.z., Ocni oddeleni
city: Zlin
country: Czechia
facility: Krajska nemocnice T. Bati, a.s.
city: Caen
country: France
facility: CHU de Caen - Hopital Cote de Nacre
city: Chambray les Tours
country: France
facility: CHU Tours - Hôpital Trousseau
city: Clermont-Ferrand
country: France
facility: CHU Clermont Ferrand - Hôtel Dieu
city: Clichy cedex
country: France
facility: Hôpital Beaujon
city: Montpellier
country: France
facility: CHU Hopital Saint Eloi
city: Nice
country: France
facility: CHU Nice - Hopital de l'Archet 2
city: Pierre-Benite
country: France
facility: Centre Hospitalier Lyon Sud; Service de Gastro-Enterologie
city: Vandoeuvre-les-nancy
country: France
facility: Hôpital de Brabois Adultes
city: Berlin
country: Germany
facility: Charite Universitaetsmedizin Berlin - Campus Benjamin Franklin
city: Berlin
country: Germany
facility: DRK Kliniken Berlin Westend
city: Berlin
country: Germany
facility: Krankenhaus Waldfriede e. V.
city: Freiburg
country: Germany
facility: Universitätsklinikum Freiburg; Innere Medizin I; Hämatologie, Onkologie und Stammzelltransplantation
city: Hamburg
country: Germany
facility: Gastroenterologie Eppendorfer Baum
city: Kiel
country: Germany
facility: Universitaetsklinikum Schleswig-Holstein, Campus Kiel
city: Koeln
country: Germany
facility: Universitätsklinikum Koeln
city: Bekescsaba
country: Hungary
facility: Bekes Megyei Kozponti Korhaz Dr. Rethy Pal Tagkorhaza
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Budapest
country: Hungary
facility: Eszak-Kozep-budai Centrum, Uj Szent Janos Korhaz es Szakrendelo
city: Budapest
country: Hungary
facility: Magyar Honvedseg Egeszsegugyi Kozpont; Fázis I-es Klinikai Farmakológiai Vizsgálóhely
city: Debrecen
country: Hungary
facility: Vasutegeszsegugyi Nonprofit KiemeltenKozhasznu Kft
city: Eger
country: Hungary
facility: Markhot Ferenc Oktato Korhaz es Rendelointezet
city: Gyor
country: Hungary
facility: Petz Aladar Megyei Oktato Korhaz
city: Miskolc
country: Hungary
facility: Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktato Korhaz; II. Belgyogyaszat
city: Szeged
country: Hungary
facility: Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont
city: Székesfehérvár
country: Hungary
facility: Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz
city: Petach Tikva
country: Israel
facility: Rabin Medical Center-Beilinson Campus
city: Tel Hashomer
country: Israel
facility: Chaim Sheba Medical Center; Pediatrics B North and Pediatric Endocrinology Unit
city: Parma
country: Italy
facility: Azienda Ospedaliero Universitaria di Parma
state: Emilia-Romagna
city: Roma
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Tor Vergata
state: Lazio
city: Roma
country: Italy
facility: Azienda Ospedaliera San Camillo Forlanini
state: Lazio
city: Milano
country: Italy
facility: Asst Fatebenefratelli Sacco (Fatebenefratelli)
state: Lombardia
city: Milano
country: Italy
facility: Azienda Socio Sanitaria Territoriale Niguarda (Grande Ospedale Metropolitano Niguarda)
state: Lombardia
city: Milano
country: Italy
facility: Azienda Socio Sanitaria Territoriale Fatebenefratelli (Presidio Ospedale Sacco)
state: Lombardia
city: Rozzano (MI)
country: Italy
facility: Istituto Clinico Humanitas
state: Lombardia
city: San Donato Milanese (MI)
country: Italy
facility: I.R.C.C.S Policlinico San Donato
state: Lombardia
city: San Giovanni Rotondo
country: Italy
facility: IRCCS Ospedale Casa Sollievo della Soffenza; Stru Comp di Gastroenterologia ed Endoscopia digest
state: Lombardia
city: Torino
country: Italy
facility: Ospedale Mauriziano Umberto I
state: Piemonte
city: Firenze
country: Italy
facility: Azienda Ospedaliera Universitaria Careggi
state: Toscana
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
state: Toscana
city: Padova
country: Italy
facility: Azienda Ospedaliera Di Padova
state: Veneto
city: Busan
country: Korea, Republic of
facility: Dong-A University Hospital
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Chilgok Hospital
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Medical Center
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Hospital
city: Daegu
country: Korea, Republic of
facility: Yeungnam Univ. Hospital
city: Gyeonggi-do
country: Korea, Republic of
facility: Korea University Ansan Hospital
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seongnam
country: Korea, Republic of
facility: CHA Bundang Medical Centre; CHA university
city: Seoul
country: Korea, Republic of
facility: Kyung Hee University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Kangbuk Samsung Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Suwon City
country: Korea, Republic of
facility: Ajou University Hospital
city: Suwon-si,
country: Korea, Republic of
facility: The Catholic University of Korea St. Vincent's Hospital
city: Wonju-Si
country: Korea, Republic of
facility: Yonsei University Wonju Severance Christian Hospital
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC Location VUMC
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC Location AMC
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
city: NL -nijmegen
country: Netherlands
facility: Radboudumc
city: Lørenskog
country: Norway
facility: Akershus universitetssykehus HF
city: Braga
country: Portugal
facility: Hospital de Braga
city: Guimarães
country: Portugal
facility: Hospital da Senhora da Oliveira Guimarães
city: Bucharest
country: Romania
facility: Institutul Clinic Fundeni Bucuresti
city: Bucharest
country: Romania
facility: Spitalul Clinic Colentina
city: Bucuresti
country: Romania
facility: S.C MedLife S.A
city: Bucuresti
country: Romania
facility: Centrul Medical Unirea SRL
city: Targu Mures
country: Romania
facility: Spitalul Clinic Judetean Mures
city: Timisoara
country: Romania
facility: Centrul de Gastroenterologie Dr. Goldis
city: Singapore
country: Singapore
facility: Singapore General Hospital
city: Bloemfontein
country: South Africa
facility: Netcare Universitas Private Hospital
city: Cape Town
country: South Africa
facility: Dr MJ Prins Practice
city: Cape Town
country: South Africa
facility: Dr Corne Kruger Inc.
city: Sabadell
country: Spain
facility: Corporacio Sanitaria Parc Tauli
state: Barcelona
city: Ferrol
country: Spain
facility: Complejo Hospitalario Universitario de Ferrol
state: LA Coruña
city: Alcorcon
country: Spain
facility: Fundacion Hospital de Alcorcon; Servicio de Digestivo
state: Madrid
city: Barcelona
country: Spain
facility: Centro Médico Teknon
city: Madrid
country: Spain
facility: Hospital Universitario de la Princesa
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe
city: Stockholm
country: Sweden
facility: Danderyds Sjukhus AB
city: Bern
country: Switzerland
facility: Inselspital-Universitaetsspital Bern
city: Zürich
country: Switzerland
facility: Universitätsspital Zürich
city: Bournemouth
country: United Kingdom
facility: The Royal Bournemouth Hospital
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
city: Coventry
country: United Kingdom
facility: University Hospital Coventry
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Hospital (Wonford)
city: Leeds
country: United Kingdom
facility: St James University Hospital
city: London
country: United Kingdom
facility: The Royal London Hospital
city: London
country: United Kingdom
facility: St Thomas Hospital
city: London
country: United Kingdom
facility: King's College London
city: Manchester
country: United Kingdom
facility: Fairfield General Hospital
city: Newcastle upon Tyne
country: United Kingdom
facility: Royal Victoria Infirmary
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.