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    The EU Clinical Trials Register currently displays   43857   clinical trials with a EudraCT protocol, of which   7284   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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    Summary
    EudraCT Number:2019-002578-29
    Sponsor's Protocol Code Number:2019-5787
    National Competent Authority:Netherlands - Competent Authority
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2019-10-16
    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 ConcernedNetherlands - Competent Authority
    A.2EudraCT number2019-002578-29
    A.3Full title of the trial
    Functional Improvement of non-infarcT relaTed coronary artery stenosis by Extensive LDL-C Reduction with a PCSK9 Antibody.
    Functionele verbetering van de niet-infarct gerelateerde coronairarterievernauwing door LDL Cholesterol reductie met behulp van een PCSK9 antilichaam.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Functional Improvement of coronary artery narrowing by cholesterol reduction with a PCSK9 Antibody
    A.3.2Name or abbreviated title of the trial where available
    FITTER
    A.4.1Sponsor's protocol code number2019-5787
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT04141579
    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 SponsorRadboudumc
    B.1.3.4CountryNetherlands
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportAmgen B.V.
    B.4.2CountryNetherlands
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationRadboudumc
    B.5.2Functional name of contact pointResearch Cardiology Department
    B.5.3 Address:
    B.5.3.1Street AddressGeert Grooteplein Zuid 10
    B.5.3.2Town/ cityNijmegen
    B.5.3.3Post code6525 AG
    B.5.3.4CountryNetherlands
    B.5.4Telephone number+31243092476
    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 nameEvolocumab or placebo
    D.3.2Product code AMG145
    D.3.4Pharmaceutical form Solution for injection in pre-filled pen
    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 INNEVOLOCUMAB
    D.3.9.3Other descriptive nameAMG145
    D.3.9.4EV Substance CodeSUB128552
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number140
    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 Yes
    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 No
    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 injector
    D.8.4Route of administration of the placeboSubcutaneous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Coronary artery disease (CAD)
    Optimal treatment approach for bystander lesions in non-infarct related arteries (non-IRA’s) has not been well established. Multiple RCT’s favor preventive PCI over medical treatment, however medical treatment wasn’t optimal in these studies.
    We want to investigate if optimizing LDL-lowering therapy after an ACS has an effect on functional impairment of a non-IRA lesion and could thus prevent mechanical intervention (PCI or CABG).
    Meervatslijden.
    Optimale behandeling van stenosen in de niet infarct gerelateerde coronairaterieën is nog controversieel. Uit de uitkomsten van meerdere RCT's zou preventieve PCI betere uitkomsten geven dan conservatieve medicamenteuze behandeling. In deze studies was medicamenteuze behandeling echter suboptimaal.
    Wij willen onderzoeken of het optimaliseren van LDL-C verlagende therapie na een ACS een effect heeft op de FFR over een stenose van de niet-infarct gerelateerde coronairarterie.
    E.1.1.1Medical condition in easily understood language
    Coronary artery disease.
    Sometimes there are multiple narrowings of the coronary arteries of the heart. We want to investigate if we can treat those narrowings with cholesterol lowering medication
    Meervatslijden (MVD)
    Soms zijn er meerdere vernauwingen in de slagaders van het hart. Wij willen onderzoeken of deze vernauwingen ook behandeld kunnen worden door cholesterolverlagende medicijnen.
    E.1.1.2Therapeutic area Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutic techniques [E02]
    MedDRA Classification
    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 effect of maximal LDL-C reduction by Evolocumab on top of optimal background lipid-lowering therapy (ESC guidelines) on FFR of non-IRA lesions, in patients presenting with MVD-ACS.
    Het evalueren van het effect van maximale LDL-C reductie met Evolocumab bovenop optimale behandeling met statines op FFR van stenoses van de niet infarct gerelateerde coronairarterie.
    E.2.2Secondary objectives of the trial
    Secondly to correlate baseline lipid core burden with changes in FFR and to investigate the relation between LDL reduction and change in pro-inflammatory monocyte phenotypes.
    Ten tweede, om de correlatie tussen baseline lipid core burden en reductie in FFR te onderzoeken.
    Ten derde, om de verandering van de therapie op het fenotype van monocyten te onderzoeken.
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Title: Effect of rapid lowering of LDL-C post-ACS on pro-inflammatory monocyte phenotype
    Date: 18-09-2019
    Version 1.0

    Study design: patients with ACS, with multivessel disease without intervention of bystander non-culprit lesions. Main aim is to evaluate the effect of maximal LDL reduction with PCSK9 inhibition, initiated immediately post invasive ACS treatment on functional impairment of bystander non-culprit coronary lesions in patients presenting with MVD-ACS.
    Immunological parameters: it is known that an ACS induces a rapid and transient systemic acceleration of atherosclerosis progression. This is mediated by activation of myelopoiesis and subsequent monocytosis and increased pro-inflammatory phenotype of circulating monocytes, which accelerate plaque progression. We recently showed that increased serum cholesterol by Western type diet also induced pro-inflammatory myeloid reprogramming. Therefore, we now hypothesize that rapid and profound cholesterol lowering can attenuate the pro-inflammatory myeloid cell reprogramming by the ACS.
    Population: N=40 patients, so 20 with PCSK9 and 20 with placebo.
    Main endpoint for immunological parameters is the comparison of monocyte phenotype between the groups at t=12 weeks post ACS.
    E.3Principal inclusion criteria
    - ACS with PCI of Infarct Related Artery (IRA)
    - Multi Vessel Disease (MVD)
    - FFR of non-IRA lesion 0.67 - 0.80
    Subjects must have an eligible LDL-C level via local lab assessment based on statin use at screening:
    - No statin use: ≥ 130 mg/dL (3.3 mmol/l)
    - Non-intensive statin use (see Table): ≥ 80 mg/dL (2.0 mmol/l)
    - Intensive statin use (see Table): ≥ 60 mg/dL (1.6 mmol/l)
    - Age ≥ 18 years at screening
    - ACS met PCI van de infarct gerelateerde coronairarterie
    - Meervatslijden
    - FFR van niet infarct gerelateerde stenose 0.67-0.80
    Proefpersonen moeten een geschikte hoeveelheid LDL-C in het bloed hebben, rekening houdend met statinegebruik:
    - Geen statinegebruik: ≥ 130 mg/dL (3.3 mmol/l)
    - Niet-intensief statinegebruik: ≥ 80 mg/dL (2.0 mmol/l)
    - Intensief statinegebruik≥ 60 mg/dL (1.6 mmol/l)
    - Leeftijd ≥ 18 jaar op moment van screening
    E.4Principal exclusion criteria
    - Refusal or inability to provide informed consent
    - Prior coronary artery bypass graft
    - Known left ventricular ejection fraction (LVEF) < 30%
    - Left main stem stenosis >50%
    - Contra-indication for dual antiplatelet therapy
    - Chronic total occlusion of a non-IRA
    - Non-IRA stenosis not amenable for PCI treatment (operator’s decision)
    - Complicated IRA treatment, with one or more of the following:
    - Extravasation
    - Permanent no re-flow after IRA treatment (TIMI flow 0-1)
    - Inability to implant a stent
    - Known severe cardiac valve dysfunction that will require surgery in the follow-up period.
    - Known severe kidney disease defined as an eGFR < 30 ml/min.
    - Severe liver disease defined as Child-Pugh score of 10-15.
    - Female subject is pregnant, breastfeeding or planning to become pregnant or planning to breastfeed during treatment and for an additional 15 weeks after the last dose of investigational product. Females of childbearing potential should only be included in the study after a confirmed menstrual period and a negative highly sensitive urine or serum pregnancy test.
    - Female subjects of childbearing potential unwilling to use 1 acceptable method of effective contraception during treatment and for an additional 15 weeks after the last dose of investigational product.
    - Female subject who has not used an acceptable method(s) of birth control for at least 1 month prior to screening, unless the female subject is sterilized or postmenopausal.
    - Informed consent niet gegeven of niet in staat om informed consent te geven
    - Eerdere bypassoperatie (CABG)
    - Bekende linkerventrikelfunctie <30%
    - Hoofdstamstenose >50% (LM)
    - Contra-indicatie voor duale plaatjes aggregatie remming (DAPT)
    - chronische totale occlusie van de niet-infarct gerelateerde coronairarterie
    - stenose van de niet-infarct gerelateerde coronairarterie komt niet in aanmerking voor PCI (beoordeeld door operateur)
    - Gecompliceerd verloop van PCI van infarct gerelateerde coronairarterie, met een of meer van de onderstaande zaken:
    - Extravasatie
    - Permanente no-reflow na behandeling van infarct gerelateerde coronairarterie
    (TIMI flow 0-1)
    - Niet mogelijk om een stent te plaatsen
    - Bekende ernstige hartklepvitia die operatief ingrijpen vereisen binnen de follow-up periode.
    - Ernstig nierfalen, gedefinieerd als een eGFR <30ml/min
    - Bekend ernstig leverfalen, gedefinieerd als een Child-Pugh score van 10-15.
    - Vrouwelijke deelnemer is zwanger, geeft borstvoeding of wil zwanger worden of borstvoeding geven gedurende de behandeling en tot 15 weken na de laatste dosis van het onderzoeksmedicijn. Vrouwen die mogelijk zwanger kunnen worden, worden alleen geïncludeerd na een bekende laatste menstruatie en nadien een negatieve hoog sensitieve urine of serum zwangerschapstest.
    - Vrouwelijke deelnemers die mogelijk zwanger kunnen worden die niet bereid zijn 1 acceptabele vorm van effectieve anticonceptie te gebruiken gedurende de behandeling en tot 15 weken na de laatste dosis van medicijn.
    - Vrouwelijke deelnemers die geen acceptabele vorm van anticonceptie hebben gebruikt voor ten minste 1 maand voor de screening, tenzij vrouwelijke deelnemer gesteriliseerd is of postmenopauzaal.
    E.5 End points
    E.5.1Primary end point(s)
    The primary study parameter is the change in FFR from baseline to follow-up in non-IRA lesions.
    De primaire uitkomstmaat is de verandering in FFR van de stenose van de niet-infarct gerelateerde coronairaterie van baseline tot follow up.
    E.5.1.1Timepoint(s) of evaluation of this end point
    At 14 weeks (12+2) participants will undergo FFR/NIRS for a second time, which whill produces the values needed for the primary endpoint.
    Na 14 weken (12+2) zullen deelnemers voor een tweede maal FFR/NIRS ondergaan, waardoor de data wordt verkregen voor ons primaire eindpunt.
    E.5.2Secondary end point(s)
    The secondary endpoint is the correlation between baseline Near-InfraRed Spectroscopy (NIRS) derived lipid core burden (MaxLCBI4mm) and change in FFR of the non-IRA.
    Het secundaire eindpunt is de correlatie tussen de baseline lipid core burden (MaxLCBI4mm) gemeten door Near-InfraRed Spectroscopy (NIRS) en de verandering in FFR van de niet-infarct gerelateerde coronairarterie.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Please see E.5.1.1
    Please see E.5.1.1
    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 Yes
    E.6.4Safety No
    E.6.5Efficacy No
    E.6.6Pharmacokinetic No
    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 No
    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) No
    E.7.4Therapeutic use (Phase IV) Yes
    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 No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    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 concerned6
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    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 study may be terminated if the study procedures are not being
    performed according to GCP and/or if patients are placed at undue risk
    because of clinically relevant findings.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years
    E.8.9.1In the Member State concerned months30
    E.8.9.1In the Member State concerned days
    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: 100
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 50
    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 Yes
    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 state150
    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)
    After a subject ends his/her participation in the trial, normal treatment
    post-ACS will be continued.
    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 Decision2019-10-17
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-01-21
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2024-03-21
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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