Ulcerative ColitisPhase 3GARDENIANCT02136069
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
A Phase 3 study testing Etrolizumab and Infliximab in people with Ulcerative Colitis, run by Hoffmann-La Roche at 119 sites in 20 countries.
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Ulcerative Colitis
- What is being tested?
- Etrolizumab and Infliximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 397 participants
- Where
- 119 sitesin 20 countries
- Study dates
- 24 Dec 2014to 23 Jun 2020
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Trial locations and contacts
119 sites in 20 countries.
119 sites in 20 countries
South Korea18 sites
Dong-A University Hospital
Busan, 49201
Pusan National University Hospital
Busan, 49241
Kyungpook National University Chilgok Hospital
Daegu, 41404
Keimyung University Dongsan Medical Center
Daegu, 41931
Kyungpook National University Hospital
Daegu, 41944
Yeungnam Univ. Hospital
Daegu, 705-717
Korea University Ansan Hospital
Gyeonggi-do, 15355
CHA Bundang Medical Centre; CHA university
Seongnam, 13520
Seoul National University Bundang Hospital
Seongnam-si, 13605
Kyung Hee University Hospital
Seoul, 02447
Seoul National University Hospital
Seoul, 03080
Kangbuk Samsung Hospital
Seoul, 03181
Severance Hospital, Yonsei University
Seoul, 03722
Asan Medical Center
Seoul, 05505
Samsung Medical Center
Seoul, 06351
The Catholic University of Korea St. Vincent's Hospital
Suwon, 442-723
Ajou University Hospital
Suwon, 443-721
Yonsei University Wonju Severance Christian Hospital
Wŏnju, 220-701
Italy13 sites
Azienda Ospedaliera Universitaria Careggi
Florence, Tuscany, 50141
Asst Fatebenefratelli Sacco (Fatebenefratelli)
Milan, Lombardy, 20121
Azienda Socio Sanitaria Territoriale Niguarda (Grande Ospedale Metropolitano Niguarda)
Milan, Lombardy, 20162
Azienda Socio Sanitaria Territoriale Fatebenefratelli (Presidio Ospedale Sacco)
Milan, Lombardy
Azienda Ospedaliera Di Padova
Padova, Veneto, 35128
Azienda Ospedaliero Universitaria di Parma
Parma, Emilia-Romagna, 43100
Azienda Ospedaliero Universitaria Pisana
Pisa, Tuscany, 56100
Azienda Ospedaliera Universitaria Policlinico Tor Vergata
Rome, Lazio, 00133
Azienda Ospedaliera San Camillo Forlanini
Rome, Lazio, 00152
Istituto Clinico Humanitas
Rozzano (MI), Lombardy, 20089
I.R.C.C.S Policlinico San Donato
San Donato Milanese (MI), Lombardy, 20097
IRCCS Ospedale Casa Sollievo della Soffenza; Stru Comp di Gastroenterologia ed Endoscopia digest
San Giovanni Rotondo, Lombardy, 71013
Ospedale Mauriziano Umberto I
Turin, Piedmont, 10128
United Kingdom12 sites
The Royal Bournemouth Hospital
Bournemouth, BH7 7DW
Addenbrooke's Hospital
Cambridge, CB2 0QQ
University Hospital Coventry
Coventry, CV2 2DX
Royal Devon and Exeter Hospital (Wonford)
Exeter, EX2 5DW
St James University Hospital
Leeds, LS9 7TF
The Royal London Hospital
London, E1 1FR
St Thomas Hospital
London, SE1 7EH
King's College London
London, SE5 9NU
Fairfield General Hospital
Manchester, M8 5RB
Royal Victoria Infirmary
Newcastle upon Tyne, NE1 4LP
Nottingham University Hospitals NHS Trust
Nottingham, NG7 2UH
Southampton General Hospital
Southampton, SO16 6YD
Hungary10 sites
Bekes Megyei Kozponti Korhaz Dr. Rethy Pal Tagkorhaza
Békéscsaba, 5600
Semmelweis Egyetem
Budapest, 1083
Eszak-Kozep-budai Centrum, Uj Szent Janos Korhaz es Szakrendelo
Budapest, 1125
Magyar Honvedseg Egeszsegugyi Kozpont; Fázis I-es Klinikai Farmakológiai Vizsgálóhely
Budapest, H-1077
Vasutegeszsegugyi Nonprofit KiemeltenKozhasznu Kft
Debrecen, 4025
Markhot Ferenc Oktato Korhaz es Rendelointezet
Eger, 3300
Petz Aladar Megyei Oktato Korhaz
Győr, 9024
Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktato Korhaz; II. Belgyogyaszat
Miskolc, 3526
Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont
Szeged, 6720
Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz
Székesfehérvár, 8000
Czechia8 sites
Vojenska nemocnice Brno
Brno, 636 00
Fakultni nemocnice Hradec Kralove
Hradec Králové, 500 05
Oblastni nemocnice Kladno, a.s., nemocnice Stredoces. kraje; Endoskopicke centrum
Kladno, 272 59
Mestska Nemocnice Ostrava
Ostrava, 728 80
Pardubicka krajska nemocnice, a.s.
Pardubice, 532 03
ISCARE a.s.
Prague, 170 04
Krajska zdravotni, a.s. - Masarykova nemocnice v Usti nad Labem, o.z., Ocni oddeleni
Ústí nad Labem, 401 13
Krajska nemocnice T. Bati, a.s.
Zlín, 76001
France8 sites
CHU de Caen - Hopital Cote de Nacre
Caen, 14033
CHU Tours - Hôpital Trousseau
Chambray-lès-Tours, 37170
CHU Clermont Ferrand - Hôtel Dieu
Clermont-Ferrand, 63000
Hôpital Beaujon
Clichy, 92110
CHU Hopital Saint Eloi
Montpellier, 34295
CHU Nice - Hopital de l'Archet 2
Nice, 06202
Centre Hospitalier Lyon Sud; Service de Gastro-Enterologie
Pierre-Bénite, 69495
Hôpital de Brabois Adultes
Vandœuvre-lès-Nancy, 54511
Belgium7 sites
GZA Ziekenhuizen - Campus Sint-Vincentius
Antwerp, 2018
Imeldaziekenhuis
Bonheiden, 2820
CHU St Pierre (St Pierre)
Brussels, 1000
Universitair Ziekenhuis Brussel; Neurology
Brussels, 1090
Cliniques Universitaires Saint-Luc; Pharmacy
Brussels, 1200
UZ Gent
Ghent, 9000
AZ Sint Elisabeth Herentals
Herentals, 2200
Germany7 sites
Charite Universitaetsmedizin Berlin - Campus Benjamin Franklin
Berlin, 12200
DRK Kliniken Berlin Westend
Berlin, 14050
Krankenhaus Waldfriede e. V.
Berlin, 14163
Universitätsklinikum Koeln
Cologne, 50937
Universitätsklinikum Freiburg; Innere Medizin I; Hämatologie, Onkologie und Stammzelltransplantation
Freiburg im Breisgau, 79106
Gastroenterologie Eppendorfer Baum
Hamburg, 20249
Universitaetsklinikum Schleswig-Holstein, Campus Kiel
Kiel, 24116
Spain7 sites
Fundacion Hospital de Alcorcon; Servicio de Digestivo
Alcorcón, Madrid, 28922
Centro Médico Teknon
Barcelona
Complejo Hospitalario Universitario de Ferrol
Ferrol, LA Coruña, 15405
Hospital Universitario de la Princesa
Madrid, 28006
Hospital Universitario La Paz
Madrid, 280146
Corporacio Sanitaria Parc Tauli
Sabadell, Barcelona, 08208
Hospital Universitari i Politecnic La Fe
Valencia, 46026
Canada6 sites
University of Calgary; Heritage Medical Research Clinic
Calgary, Alberta, T2N 4Z6
Zeidler Ledcor Centre - University of Alberta; Division of Gasroenterology
Edmonton, Alberta, T6G 2X8
Centre de santé et de services sociaux Champlain-Charles-Le Moyne
Greenfield Park, Quebec, J4V 2H1
Guelph GI & Surgery Clinic
Guelph, Ontario, N1H 3R3
Hôpital Maisonneuve - Rosemont
Montreal, Quebec, H1T 2M4
Royal University Hospital
Saskatoon, Saskatchewan, S7N 0W8
Romania6 sites
S.C MedLife S.A
Bucharest, 010719
Institutul Clinic Fundeni Bucuresti
Bucharest, 022328
Centrul Medical Unirea SRL
Bucharest, 040055
Spitalul Clinic Colentina
Bucharest, 772202
Spitalul Clinic Judetean Mures
Târgu Mureş, 540103
Centrul de Gastroenterologie Dr. Goldis
Timișoara, 300002
Netherlands4 sites
Amsterdam UMC Location VUMC
Amsterdam, 1081 HV
Amsterdam UMC Location AMC
Amsterdam, 1105 AZ
Maastricht University Medical Center
Maastricht, 6229 HX
Radboudumc
NL -nijmegen, 6525 GA
South Africa3 sites
Netcare Universitas Private Hospital
Bloemfontein, 9301
Dr MJ Prins Practice
Cape Town, 7500
Dr Corne Kruger Inc.
Cape Town, 7550
Israel2 sites
Rabin Medical Center-Beilinson Campus
Petah Tikva, 4941492
Chaim Sheba Medical Center; Pediatrics B North and Pediatric Endocrinology Unit
Tel HaShomer, 52621
Portugal2 sites
Hospital de Braga
Braga, 4710-243
Hospital da Senhora da Oliveira Guimarães
Guimarães, 4835-044
Switzerland2 sites
Inselspital-Universitaetsspital Bern
Bern, 3010
Universitätsspital Zürich
Zurich, 8091
About this study
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
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.
- Conditions
- Ulcerative Colitis
- Being tested
- Etrolizumab, Infliximab, Placebo (IV), Placebo (Injection)
- Medical subject headings
- Colitis, Ulcerative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EtrolizumabDrug
Also called PRO145223, RO5490261, RG7413
105 mg administered by subcutaneous (SC) injection once every 4 weeks (Q4W) until Week 52.
InfliximabDrug
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 (IV)Other
Administered by (IV) infusion at Weeks 0, 2, and 6 and then every 8 weeks until Week 46.
Placebo (Injection)Other
Administered by SC injection Q4W until Week 52
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Etrolizumab; Other: 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. Receives: Drug: Infliximab; Other: Placebo (Injection) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Week 10, Week 54
Secondary outcomes (21)
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.
Measured: Week 10
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.
Measured: Week 54
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.
Measured: 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
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.
Measured: Week 10 and Week 54
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.
Measured: Baseline to Week 10
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.
Measured: Baseline to Week 54
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.
Measured: Baseline to Week 10, Week 54
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.
Measured: Week 54
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.
Measured: Week 10
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.
Measured: Week 10, Week 54
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.
Measured: Week 54
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.
Measured: Baseline until the end of study (up to 66 weeks)
Number of Participants With Adverse Events Leading to Study Drug Discontinuation
Measured: Baseline until the end of study (up to 66 weeks)
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.
Measured: Baseline until the end of study (up to 66 weeks)
Number of Participants With Serious Infection-Related Adverse Events
Measured: Baseline until the end of study (up to 66 weeks)
Number of Participants With Malignancies
Measured: Baseline until the end of study (up to 66 weeks)
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.
Measured: Baseline until the end of study (up to 66 weeks)
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.
Measured: Baseline until the end of study (up to 66 weeks)
Pharmacokinetics: Etrolizumab Serum Concentration
Measured: Weeks 2, 10, 12, 30, and 54
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.
Measured: Weeks 10, 30, and 54
Number of Participants With Anti-Therapeutic Antibodies (ATAs) to Etrolizumab
Measured: Weeks 0, 4, 10, 12, 30, and 54
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2014 (estimated)
- Study start24 Dec 2014
- Primary completion23 Jun 2020
- Study completion23 Jun 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Ulcerative ColitisStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 397 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02136069
- Sponsor's protocol ID
- GA29103
- Other IDs
- 2013-004282-14
- Acronym
- GARDENIA
- Status last verified
- Dec 2021
- First submitted
- 15 Apr 2014
- Last updated
- 3 Dec 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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).
Publications
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.
PubMed 34798038Sandborn 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.
PubMed 32445184
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02136069
- Acronym / sponsor ID
- GARDENIA / GA29103
- Conditions
- Ulcerative Colitis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 397 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 24 Dec 2014 (actual)
- Primary completion
- 23 Jun 2020 (actual)
- Study completion
- 23 Jun 2020 (actual)
- First posted
- 12 May 2014 (estimated)
- Results
- Posted 13 Aug 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Etrolizumab + Placebo (IV) | Experimental | Drug: Etrolizumab, Other: Placebo (IV)Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46. |
| Infliximab + Placebo (Injection) | Active comparator | Drug: Infliximab, Other: 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EtrolizumabAlso: PRO145223, RO5490261, RG7413105 mg administered by subcutaneous (SC) injection once every 4 weeks (Q4W) until Week 52. | Drug | Etrolizumab + Placebo (IV) |
| Infliximab5 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. | Drug | Infliximab + Placebo (Injection) |
| Placebo (IV)Administered by (IV) infusion at Weeks 0, 2, and 6 and then every 8 weeks until Week 46. | Other | Etrolizumab + Placebo (IV) |
| Placebo (Injection)Administered by SC injection Q4W until Week 52 | Other | Infliximab + Placebo (Injection) |
Primary outcome
Percentage of Participants With Both Clinical Response at Week 10 and Clinical Remission at Week 54, as Determined by the Mayo Clinic Score (MCS)
Time frame: Week 10, Week 54
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.
21 secondary outcomes
Percentage of Participants Achieving Clinical Remission at Week 10, Defined as MCS ≤2 With Individual Subscores ≤1
Time frame: Week 10
Percentage of Participants Achieving Clinical Remission at Week 54, as Determined by the MCS
Time frame: Week 54
Percentage of Participants Achieving Clinical Remission at Both Week 10 and Week 54, as Determined by the MCS
Time frame: 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
Time frame: Week 10 and Week 54
Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Week 10, Determined by the MCS
Time frame: Baseline to Week 10
Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Week 54, as Determined by the MCS
Time frame: Baseline to Week 54
Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Both Week 10 and Week 54, as Determined by the MCS
Time frame: Baseline to Week 10, Week 54
Percentage of Participants With Endoscopic Remission at Week 54, as Determined by the MCS
Time frame: Week 54
Percentage of Participants Achieving Clinical Response at Week 10, as Determined by the MCS
Time frame: Week 10
Percentage of Participants Achieving Clinical Response at Both Weeks 10 and 54, as Determined by the MCS
Time frame: Week 10, Week 54
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
Time frame: Week 54
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)
Time frame: Baseline until the end of study (up to 66 weeks)
Number of Participants With Adverse Events Leading to Study Drug Discontinuation
Time frame: Baseline until the end of study (up to 66 weeks)
Number of Participants With Infection-Related Adverse Events, Severity Determined According to the NCI CTCAE v4.0
Time frame: Baseline until the end of study (up to 66 weeks)
Number of Participants With Serious Infection-Related Adverse Events
Time frame: Baseline until the end of study (up to 66 weeks)
Number of Participants With Malignancies
Time frame: Baseline until the end of study (up to 66 weeks)
Number of Participants With Injection-Site Reactions, Severity Determined According to the NCI CTCAE v4.0
Time frame: Baseline until the end of study (up to 66 weeks)
Number of Participants With Hypersensitivity Reaction Events, Severity Determined According to the NCI CTCAE v4.0
Time frame: Baseline until the end of study (up to 66 weeks)
Pharmacokinetics: Etrolizumab Serum Concentration
Time frame: Weeks 2, 10, 12, 30, and 54
Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Overall Score at Weeks 10, 30, and 54
Time frame: Weeks 10, 30, and 54
Number of Participants With Anti-Therapeutic Antibodies (ATAs) to Etrolizumab
Time frame: Weeks 0, 4, 10, 12, 30, and 54
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Dec 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34798038Danese 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.
- Derived from this study: PubMed 32445184Sandborn 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.
- Individual participant dataSharing planned: Yes. 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).
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
119 sites in 20 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Etrolizumab and Infliximab in people with Ulcerative Colitis, run by Hoffmann-La Roche at 119 sites in 20 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 119 sites in South Korea, Italy, United Kingdom, Hungary, Czechia and 15 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Aug 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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) (time frame: Week 10, Week 54). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02136069, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Dec 2021.