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

Ulcerative Colitis Clinical Trial

— GARDENIA  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02136069
• Other study ID #: GA29103
• Secondary ID: 2013-004282-14
• Status: Completed
• Phase: Phase 3
• Start date: December 24, 2014
• Est. completion date: June 23, 2020

Study information

• Verified date: December 2021
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 397
• Est. completion date: June 23, 2020
• Est. primary completion date: June 23, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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)

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

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

Other:
• Placebo (IV)
Administered by (IV) infusion at Weeks 0, 2, and 6 and then every 8 weeks until Week 46.
• Placebo (Injection)
Administered by SC injection Q4W until Week 52

Locations

Country	Name	City	State
Austria	LKH - Universitätsklinikum der PMU Salzburg	Salzburg
Belgium	GZA Ziekenhuizen - Campus Sint-Vincentius	Antwerpen
Belgium	Imeldaziekenhuis	Bonheiden
Belgium	CHU St Pierre (St Pierre)	Brussels
Belgium	Cliniques Universitaires Saint-Luc; Pharmacy	Bruxelles
Belgium	Universitair Ziekenhuis Brussel; Neurology	Bruxelles
Belgium	UZ Gent	Gent
Belgium	AZ Sint Elisabeth Herentals	Herentals
Canada	University of Calgary; Heritage Medical Research Clinic	Calgary	Alberta
Canada	Zeidler Ledcor Centre - University of Alberta; Division of Gasroenterology	Edmonton	Alberta
Canada	Centre de santé et de services sociaux Champlain-Charles-Le Moyne	Greenfield Park	Quebec
Canada	Guelph GI & Surgery Clinic	Guelph	Ontario
Canada	Hôpital Maisonneuve - Rosemont	Montreal	Quebec
Canada	Royal University Hospital	Saskatoon	Saskatchewan
Czechia	Vojenska nemocnice Brno	Brno
Czechia	Fakultni nemocnice Hradec Kralove	Hradec Kralove
Czechia	Oblastni nemocnice Kladno, a.s., nemocnice Stredoces. kraje; Endoskopicke centrum	Kladno
Czechia	Mestska Nemocnice Ostrava	Ostrava
Czechia	Pardubicka krajska nemocnice, a.s.	Pardubice
Czechia	ISCARE a.s.	Praha 7
Czechia	Krajska zdravotni, a.s. - Masarykova nemocnice v Usti nad Labem, o.z., Ocni oddeleni	Usti Nad Labem
Czechia	Krajska nemocnice T. Bati, a.s.	Zlin
France	CHU de Caen - Hopital Cote de Nacre	Caen
France	CHU Tours - Hôpital Trousseau	Chambray les Tours
France	CHU Clermont Ferrand - Hôtel Dieu	Clermont-Ferrand
France	Hôpital Beaujon	Clichy cedex
France	CHU Hopital Saint Eloi	Montpellier
France	CHU Nice - Hopital de l'Archet 2	Nice
France	Centre Hospitalier Lyon Sud; Service de Gastro-Enterologie	Pierre-Benite
France	Hôpital de Brabois Adultes	Vandoeuvre-les-nancy
Germany	Charite Universitaetsmedizin Berlin - Campus Benjamin Franklin	Berlin
Germany	DRK Kliniken Berlin Westend	Berlin
Germany	Krankenhaus Waldfriede e. V.	Berlin
Germany	Universitätsklinikum Freiburg; Innere Medizin I; Hämatologie, Onkologie und Stammzelltransplantation	Freiburg
Germany	Gastroenterologie Eppendorfer Baum	Hamburg
Germany	Universitaetsklinikum Schleswig-Holstein, Campus Kiel	Kiel
Germany	Universitätsklinikum Koeln	Koeln
Hungary	Bekes Megyei Kozponti Korhaz Dr. Rethy Pal Tagkorhaza	Bekescsaba
Hungary	Eszak-Kozep-budai Centrum, Uj Szent Janos Korhaz es Szakrendelo	Budapest
Hungary	Magyar Honvedseg Egeszsegugyi Kozpont; Fázis I-es Klinikai Farmakológiai Vizsgálóhely	Budapest
Hungary	Semmelweis Egyetem	Budapest
Hungary	Vasutegeszsegugyi Nonprofit KiemeltenKozhasznu Kft	Debrecen
Hungary	Markhot Ferenc Oktato Korhaz es Rendelointezet	Eger
Hungary	Petz Aladar Megyei Oktato Korhaz	Gyor
Hungary	Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktato Korhaz; II. Belgyogyaszat	Miskolc
Hungary	Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont	Szeged
Hungary	Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz	Székesfehérvár
Israel	Rabin Medical Center-Beilinson Campus	Petach Tikva
Israel	Chaim Sheba Medical Center; Pediatrics B North and Pediatric Endocrinology Unit	Tel Hashomer
Italy	Azienda Ospedaliera Universitaria Careggi	Firenze	Toscana
Italy	Asst Fatebenefratelli Sacco (Fatebenefratelli)	Milano	Lombardia
Italy	Azienda Socio Sanitaria Territoriale Fatebenefratelli (Presidio Ospedale Sacco)	Milano	Lombardia
Italy	Azienda Socio Sanitaria Territoriale Niguarda (Grande Ospedale Metropolitano Niguarda)	Milano	Lombardia
Italy	Azienda Ospedaliera Di Padova	Padova	Veneto
Italy	Azienda Ospedaliero Universitaria di Parma	Parma	Emilia-Romagna
Italy	Azienda Ospedaliero Universitaria Pisana	Pisa	Toscana
Italy	Azienda Ospedaliera San Camillo Forlanini	Roma	Lazio
Italy	Azienda Ospedaliera Universitaria Policlinico Tor Vergata	Roma	Lazio
Italy	Istituto Clinico Humanitas	Rozzano (MI)	Lombardia
Italy	I.R.C.C.S Policlinico San Donato	San Donato Milanese (MI)	Lombardia
Italy	IRCCS Ospedale Casa Sollievo della Soffenza; Stru Comp di Gastroenterologia ed Endoscopia digest	San Giovanni Rotondo	Lombardia
Italy	Ospedale Mauriziano Umberto I	Torino	Piemonte
Korea, Republic of	Dong-A University Hospital	Busan
Korea, Republic of	Pusan National University Hospital	Busan
Korea, Republic of	Keimyung University Dongsan Medical Center	Daegu
Korea, Republic of	Kyungpook National University Chilgok Hospital	Daegu
Korea, Republic of	Kyungpook National University Hospital	Daegu
Korea, Republic of	Yeungnam Univ. Hospital	Daegu
Korea, Republic of	Korea University Ansan Hospital	Gyeonggi-do
Korea, Republic of	CHA Bundang Medical Centre; CHA university	Seongnam
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Kangbuk Samsung Hospital	Seoul
Korea, Republic of	Kyung Hee University Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University	Seoul
Korea, Republic of	Ajou University Hospital	Suwon City
Korea, Republic of	The Catholic University of Korea St. Vincent's Hospital	Suwon-si,
Korea, Republic of	Yonsei University Wonju Severance Christian Hospital	Wonju-Si
Netherlands	Amsterdam UMC Location AMC	Amsterdam
Netherlands	Amsterdam UMC Location VUMC	Amsterdam
Netherlands	Maastricht University Medical Center	Maastricht
Netherlands	Radboudumc	NL -nijmegen
Norway	Akershus universitetssykehus HF	Lørenskog
Portugal	Hospital de Braga	Braga
Portugal	Hospital da Senhora da Oliveira Guimarães	Guimarães
Romania	Institutul Clinic Fundeni Bucuresti	Bucharest
Romania	Spitalul Clinic Colentina	Bucharest
Romania	Centrul Medical Unirea SRL	Bucuresti
Romania	S.C MedLife S.A	Bucuresti
Romania	Spitalul Clinic Judetean Mures	Targu Mures
Romania	Centrul de Gastroenterologie Dr. Goldis	Timisoara
Singapore	Singapore General Hospital	Singapore
South Africa	Netcare Universitas Private Hospital	Bloemfontein
South Africa	Dr Corne Kruger Inc.	Cape Town
South Africa	Dr MJ Prins Practice	Cape Town
Spain	Fundacion Hospital de Alcorcon; Servicio de Digestivo	Alcorcon	Madrid
Spain	Centro Médico Teknon	Barcelona
Spain	Complejo Hospitalario Universitario de Ferrol	Ferrol	LA Coruña
Spain	Hospital Universitario de la Princesa	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Corporacio Sanitaria Parc Tauli	Sabadell	Barcelona
Spain	Hospital Universitari i Politecnic La Fe	Valencia
Sweden	Danderyds Sjukhus AB	Stockholm
Switzerland	Inselspital-Universitaetsspital Bern	Bern
Switzerland	Universitätsspital Zürich	Zürich
United Kingdom	The Royal Bournemouth Hospital	Bournemouth
United Kingdom	Addenbrooke's Hospital	Cambridge
United Kingdom	University Hospital Coventry	Coventry
United Kingdom	Royal Devon and Exeter Hospital (Wonford)	Exeter
United Kingdom	St James University Hospital	Leeds
United Kingdom	King's College London	London
United Kingdom	St Thomas Hospital	London
United Kingdom	The Royal London Hospital	London
United Kingdom	Fairfield General Hospital	Manchester
United Kingdom	Royal Victoria Infirmary	Newcastle upon Tyne
United Kingdom	Nottingham University Hospitals NHS Trust	Nottingham
United Kingdom	Southampton General Hospital	Southampton

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Percentage of Participants Achieving Clinical Remission at Week 10, Defined as MCS =2 With Individual Subscores =1	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.	Week 10
Secondary	Percentage of Participants Achieving Clinical Remission at Week 54, as Determined by the 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 Remission is MCS =2 with individual subscores =1.	Week 54
Secondary	Percentage of Participants Achieving Clinical Remission at Both Week 10 and Week 54, 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. Higher scores indicate more severe disease.; Clinical Remission is MCS =2 with individual subscores =1.	Week 10 and Week 54
Secondary	Percentage of Participants Achieving Clinical Remission at Week 54 Among Those With a Clinical Response 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. Higher scores indicate more severe disease.; Clinical Remission is MCS =2 with individual subscores =1.; 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.	Week 10 and Week 54
Secondary	Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Week 10, 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. Higher scores indicate more severe disease.; Improvement in endoscopic appearance of the mucosa is Endoscopy subscore =1.	Baseline to Week 10
Secondary	Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Week 54, 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. Higher scores indicate more severe disease.; Improvement in endoscopic appearance of the mucosa is Endoscopy subscore =1.	Baseline to Week 54
Secondary	Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Both Week 10 and Week 54, 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. Higher scores indicate more severe disease.; Improvement in endoscopic appearance of the mucosa is Endoscopy subscore =1.	Baseline to Week 10, Week 54
Secondary	Percentage of Participants With Endoscopic Remission at Week 54, 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. Higher scores indicate more severe disease.; Endoscopic Remission is Endoscopy subscore = 0.	Week 54
Secondary	Percentage of Participants Achieving Clinical Response 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. 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.	Week 10
Secondary	Percentage of Participants Achieving Clinical Response at Both Weeks 10 and 54, 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. 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.	Week 10, Week 54
Secondary	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	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 Remission is MCS =2 with individual subscores =1.	Week 54
Secondary	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)	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.	Baseline until the end of study (up to 66 weeks)
Secondary	Number of Participants With Adverse Events Leading to Study Drug Discontinuation		Baseline until the end of study (up to 66 weeks)
Secondary	Number of Participants With Infection-Related Adverse Events, Severity Determined According to the NCI CTCAE v4.0	All 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.	Baseline until the end of study (up to 66 weeks)
Secondary	Number of Participants With Serious Infection-Related Adverse Events		Baseline until the end of study (up to 66 weeks)
Secondary	Number of Participants With Malignancies		Baseline until the end of study (up to 66 weeks)
Secondary	Number of Participants With Injection-Site Reactions, Severity Determined According to the 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.	Baseline until the end of study (up to 66 weeks)
Secondary	Number of Participants With Hypersensitivity Reaction Events, Severity Determined According to the 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.	Baseline until the end of study (up to 66 weeks)
Secondary	Pharmacokinetics: Etrolizumab Serum Concentration		Weeks 2, 10, 12, 30, and 54
Secondary	Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Overall Score at Weeks 10, 30, and 54	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.	Weeks 10, 30, and 54
Secondary	Number of Participants With Anti-Therapeutic Antibodies (ATAs) to Etrolizumab		Weeks 0, 4, 10, 12, 30, and 54