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    Summary
    EudraCT Number:2013-004282-14
    Sponsor's Protocol Code Number:GA29103
    National Competent Authority:Czech Republic - SUKL
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2014-07-18
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedCzech Republic - SUKL
    A.2EudraCT number2013-004282-14
    A.3Full title of the trial
    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
    Multicentrická, randomizovaná, dvojitě zaslepená studie fáze III hodnotící
    účinnost a bezpečnost Etrolizumabu v porovnání s Infliximabem u pacientů
    se střední až těžkou aktivní ulcerózní kolitidou bez předchozí léčby TNF
    inhibitory.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study to evaluate the effectiveness (efficacy) and safety of etrolizumab compared with infliximab in patients with moderate to severe ulcerative colitis who have not previously received TNF inhibitors
    Studie účinnosti a bezpečnosti etrolizumabu v porovnání s infliximabem u
    pacientů s aktivní ulcerózní kolitidou bez předchozí léčby TNF inhibitory.
    A.3.2Name or abbreviated title of the trial where available
    GARDENIA
    A.4.1Sponsor's protocol code numberGA29103
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT02136069
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorF. Hoffmann-La Roche Ltd
    B.1.3.4CountrySwitzerland
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportF. Hoffmann-La Roche Ltd
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationF. Hoffmann-La Roche Ltd
    B.5.2Functional name of contact pointTrial Information Support Line-TISL
    B.5.3 Address:
    B.5.3.1Street AddressGrenzacherstrasse 124
    B.5.3.2Town/ cityBasel
    B.5.3.3Post code4070
    B.5.3.4CountrySwitzerland
    B.5.6E-mailglobal.rochegenentechtrials@roche.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameEtrolizumab
    D.3.2Product code Ro 549-0261/F04
    D.3.4Pharmaceutical form Solution for injection in pre-filled syringe
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNEtrolizumab
    D.3.9.1CAS number 1044758-60-2
    D.3.9.2Current sponsor codeRO5490261
    D.3.9.3Other descriptive nameETROLIZUMAB
    D.3.9.4EV Substance CodeSUB75320
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number105
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product Yes
    D.3.11.13.1Other medicinal product typeHumanized monoclonal antibody
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Remicade
    D.2.1.1.2Name of the Marketing Authorisation holderJanssen Biologics B.V., The Netherlands
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Powder for concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNINFLIXIMAB
    D.3.9.1CAS number 170277-31-3
    D.3.9.2Current sponsor codeRO6897845
    D.3.9.4EV Substance CodeSUB02681MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product Yes
    D.3.11.13.1Other medicinal product typeMonoclonal antibody
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for injection in pre-filled syringe
    D.8.4Route of administration of the placeboSubcutaneous use
    D.8 Placebo: 2
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for infusion
    D.8.4Route of administration of the placeboIntravenous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Ulcerative Colitis
    E.1.1.1Medical condition in easily understood language
    A form of inflammatory bowel disease
    E.1.1.2Therapeutic area Diseases [C] - Digestive System Diseases [C06]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level LLT
    E.1.2Classification code 10045365
    E.1.2Term Ulcerative colitis
    E.1.2System Organ Class 100000004856
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the efficacy of etrolizumab compared with infliximab in achieving both clinical response at Week (W) 10, and clinical remission at W54 in patients with ulcerative colitis as determined by the Mayo Clinic Score (MCS)
    E.2.2Secondary objectives of the trial
    To evaluate:
    • Clinical remission at W10, W54
    • Clinical remission achieved at both W10 and W54
    • Clinical remission at W54 among patients with a clinical response at W10
    • Improvement in endoscopic appearance of the mucosa at W10, W54
    • Improvement in endoscopic appearance of the mucosa achieved at both W10 and W54
    • Endoscopic remission at W54
    • Clinical response at W10
    • Clinical response achieved at both W10 and W54
    • Corticosteroid-free clinical remission at W54 (off corticosteroids for at least 24 weeks prior to W54) in patients who were receiving corticosteroids at baseline
    • Change from baseline in patient-reported health-related QOL at W10, 30, and 54
    • The overall safety and tolerability of etrolizumab over a period of 54 weeks
    • Incidence and the clinical significance of anti-therapeutic antibodies to etrolizumab, or if necessary, infliximab
    • Etrolizumab serum concentration at the time of primary endpoint evaluation and at a predose timepoint W12
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    - 18-80 years of age, inclusive.
    - Diagnosis of UC established at least 3 months prior to Day 1 by clinical and endoscopic evidence
    - Moderately to severely active UC as determined by the Mayo Clinic Score assessment (MCS)
    - Evidence of UC extending a minimum of 20 cm from the anal verge as determined by baseline endoscopy
    - Naive to treatment with any anti-TNF inhibitor therapy
    - An inadequate response to, loss of response to, or intolerance to prior corticosteroid and/or immunosuppressant treatment
    - Background regimen for UC may include oral 5-aminosalicylic acid (5-ASA), oral corticosteroids, budenoside, probiotics, azathioprine (AZA), 6-mercaptopurine(6-MP), or methotrexate (MTX) if doses are stable, as defined by the protocol
    - Use of highly effective contraception as defined by the protocol
    - Received a colonoscopy within the past year or be willing to undergo a colonoscopy in lieu of a flexible sigmoidoscopy at screening
    E.4Principal exclusion criteria
    - Prior extensive colonic resection, subtotal or total colectomy, or planned surgery for UC
    - A history of or current conditions and diseases affecting the digestive tract, such as ileostomy or colostomy indeterminate colitis, suspicion of ischemic colitis, radiation colitis, or microscopic colitis, Crohn's disease, fistulas or abdominal abscesses, colonic mucosal dysplasia, intestinal obstruction, toxic megacolon, or unremoved adenomatous
    colonic polyps
    - Have received non-permitted inflammatory bowel disease (IBD) therapies (including etrolizumab or other anti-integrin agents such as natalizumab, vedolizumab, and efalizumab), as stated in the protocol
    - Any prior treatment with anti-adhesion molecules (e.g., anti-MAdCAM-1)
    - Any prior treatment with rituximab
    - Any treatment with tofacitinib during screening
    - History of moderate or severe allergic or anaphylactic/anaphylactoid reactions to chimeric, human, or humanized antibodies, fusion proteins, or murine proteins or hypersensitivity to etrolizumab or any of the excipients
    - Neurologic conditions or diseases that may interfere with monitoring for PML
    - History of demyelinating disease
    - Clinically significant abnormalities on screening neurologic examination (PML Objective/Subjective Checklists)
    - History of cancer, including hematologic malignancy, solid tumors, and carcinoma in situ, within 5 years before screening, as defined by the protocol
    - Congenital or acquired immune deficiency, chronic hepatitis B or C infection, HIV positive or history of tuberculosis (active or latent)
    - Evidence of or treatment for Clostridium difficile (as assessed by C. difficile toxin testing) within 60 days prior to Day 1 or other intestinal pathogens within 30 days prior to Day 1.
    - Evidence of or treatment for clinically significant cytomegalovirus (CMV) colitis within 60 days prior to Day 1.
    - History of recurrent opportunistic infections and/or history of severe disseminated viral infections, or organ transplant
    - Any serious opportunistic infection within the last 6 months
    - Any major episode of infection requiring treatment with IV antibiotics within 8 weeks prior to screening or oral antibiotics within 4 weeks prior to screening
    - Received a live attenuated vaccine within 4 weeks prior to Day 1
    E.5 End points
    E.5.1Primary end point(s)
    Both clinical response at W10 and clinical remission at W54 in patients with ulcerative colitis as determined by MCS
    E.5.1.1Timepoint(s) of evaluation of this end point
    W10 and 54
    E.5.2Secondary end point(s)
    1) Clinical remission at W10
    2) Clinical remission at W54
    3) Clinical remission achieved at both W10 and W54
    4) Clinical remission at W54 among patients with a clinical response at W10
    5) Improvement in endoscopic appearance of the mucosa at W10
    6) Improvement in endoscopic appearance of the mucosa at W54
    7) Improvement in endoscopic appearance of the mucosa achieved at both W10 and W54
    8) Endoscopic remission at W54
    9) Clinical response at W10
    10) Clinical response achieved at both W10 and W54
    11) Corticosteroid-free clinical remission at W54 in patients who were receiving corticosteroids at baseline
    12) Change from baseline in patient-reported health-related QOL at W10, 30, and 54, as assessed by the Inflammatory Bowel Disease Questionnaire
    13) Incidence and severity of adverse events
    14) Incidence of serious adverse events
    15) Incidence and severity of infection-related adverse events
    16) Incidence of serious infection-related adverse events
    17) Incidence and severity of injection-site reactions
    18) Incidence of adverse events leading to study drug discontinuation
    19) Incidence of laboratory abnormalities
    20) Incidence of malignancies
    21) Incidence of Anti-Therapeutic Antibodies (ATAs) to etrolizumab, or if necessary, infliximab
    22) Incidence and severity of hypersensitivity reaction events
    23) Serum concentration 2 weeks after the first dose and at steady state during the dosing period from W12 to W54
    24) Serum concentration at timepoints W10, 30, and 54
    E.5.2.1Timepoint(s) of evaluation of this end point
    1) W10
    2) W54
    3) W10, and 54
    4) W 54 among W10
    5) W10
    6) W54
    7) W10, and 54
    8) W54
    9) W10
    10) At W10, and 54
    11) Baseline and W54
    12) Baseline W10, 30, and 54
    13-16) Baseline up to end of study (up to W66)
    17, 18) W0 to W52
    19) Baseline up to W54
    20) Baseline up to end of study (up to W66)
    21) Baseline, W10 and W54
    22) Baseline up to end of study (up to W66)
    23) W2, W12 to W54
    24) W10, 30 and 54.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Tolerability, exploratory biomarkers
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    Double-dummy
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned10
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA130
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Austria
    Belgium
    Canada
    Czech Republic
    France
    Germany
    Hungary
    Israel
    Italy
    Korea, Republic of
    Netherlands
    Norway
    Portugal
    Romania
    Singapore
    South Africa
    Spain
    Sweden
    Switzerland
    United Kingdom
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The end of the study is defined as the last patient last safety follow-up visit in this protocol, or last patient in this protocol enrolled in to the OLE-SM study (GA28951), whichever is later.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years4
    E.8.9.1In the Member State concerned months4
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years4
    E.8.9.2In all countries concerned by the trial months4
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 370
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 20
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state24
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 312
    F.4.2.2In the whole clinical trial 390
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Patients with disease worsening, patients who receive defined rescue treatment, patients who complete 54 wks of the study, will transfer to the Open Label Extension (OLE, Part 1) of the OLE-Safety Monitoring (SM) study where, if eligible, they receive OL etrolizumab treatment.
    Patients not enrolling to Part 1 of OLE-SM study will enter a 12 wk safety FU phase after the last dose of study medication. They will then enroll into the SM (Part 2) of the OLE-SM for FU for PML for additional 92 wks.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2014-09-16
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2014-08-20
    P. End of Trial
    P.End of Trial StatusOngoing
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