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    Summary
    EudraCT Number:2022-000686-40
    Sponsor's Protocol Code Number:pulsar
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2023-08-21
    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 ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2022-000686-40
    A.3Full title of the trial
    Prospective, monocentric, exploratory phase II study for the evaluation of the diagnostic use of the tracer PET (18F) -Flutemetamol (Vizamyl®) in patients with cardiac amyloidosis
    Studio prospettico, monocentrico, esplorativo di fase II per la valutazione dell'impiego diagnostico del tracciante PET (18F)-FlUtemetamolo (Vizamyl®) in pazienti con amiLoidoSi cARdiaca
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Study for the evaluation of the diagnostic use of the tracer PET (18F) -Flutemetamol in patients with cardiac amyloidosis
    Studio per la valutazione dell'impiego diagnostico del tracciante PET (18F)-FlUtemetamolo in pazienti con amiLoidoSi cARdiaca
    A.3.2Name or abbreviated title of the trial where available
    pulsar
    pulsar
    A.4.1Sponsor's protocol code numberpulsar
    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 SponsorFONDAZIONE TOSCANA GABRIELE MONASTERIO
    B.1.3.4CountryItaly
    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 supportGE HEALTHCARE LIMITED
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationFondazione Toscana 'Gabriele Monasterio'
    B.5.2Functional name of contact pointUOC Farmacia Ospedaliera
    B.5.3 Address:
    B.5.3.1Street Addressvia aurelia sud
    B.5.3.2Town/ cityMassa
    B.5.3.3Post code54100
    B.5.3.4CountryItaly
    B.5.4Telephone number0585493507
    B.5.5Fax number0585493508
    B.5.6E-mailfarmicisti@ftgm.it
    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 Yes
    D.2.1.1.1Trade name VIZAMYL - 400 MBQ/ML - SOLUZIONE INIETTABILE - USO ENDOVENOSO - FLACONCINO (VETRO) - 1-15 ML - 1 FLACONCINO
    D.2.1.1.2Name of the Marketing Authorisation holderGE HEALTHCARE LIMITED
    D.2.1.2Country which granted the Marketing AuthorisationItaly
    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 nameVizamyl 400MBQ/ML - Soluzione iniettabile
    D.3.2Product code [Vizamyl 400MBQ/ML]
    D.3.4Pharmaceutical form Solution for injection
    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.3.9.2Current sponsor code18F-flutemetamolo
    D.3.10 Strength
    D.3.10.1Concentration unit MBq/ml megabecquerel(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number400
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product Yes
    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 No
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    cardiac amyloidosis
    Amiloidosi cardiaca
    E.1.1.1Medical condition in easily understood language
    cardiac amyloidosis
    Amiloidosi cardiaca
    E.1.1.2Therapeutic area Diseases [C] - Cardiovascular Diseases [C14]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10007509
    E.1.2Term Cardiac amyloidosis
    E.1.2System Organ Class 10007541 - Cardiac disorders
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Establish the affinity of the tracer [18F] -Flutemetamol for cardiac amyloid deposits in patients with cardiac amyloidosis ATTRwt, ATTRv and AL.
    Stabilire l’affinità del tracciante [18F]-Flutemetamolo per i depositi di amiloide cardiaca in pazienti con diagnosi di amiloidosi cardiaca ATTRwt, ATTRv e AL.
    E.2.2Secondary objectives of the trial
    1. Compare the kinetics and the extent of radiopharmaceutical cardiac uptake among patients diagnosed with ATTR and AL and control subjects with non-infiltrative left ventricular hypertrophy;
    2. Check for any correlation between the radiopharmaceutical uptake entity and the type of TTR mutation;
    3. Evaluate the diagnostic performance of the radiopharmaceutical in the subgroup of patients with reduced or absent cardiac uptake of the osteophilic radiopharmaceutical assessed by scintigraphy (Perugini score: 0 - 1);
    4. Evaluate the potential use of the tracer [18F] -Flutemetamol for the detection of extra cerebral and extra cardiac amyloid deposits.
    1. Confrontare la cinetica e l’entità di captazione del radiofarmaco a livello miocardico fra pazienti con diagnosi di ATTR e AL e soggetti di controllo con ipertrofia ventricolare sinistra di natura non infiltrativa;
    2. Verificare l’eventuale correlazione esistente fra entità di captazione del radiofarmaco e tipo di mutazione di TTR;
    3. Valutare la performance diagnostica del radiofarmaco nel sottogruppo di pazienti con una ridotta o assente captazione del radiofarmaco osteofilo allo studio scintigrafico (Perugini score: 0 – 1);
    4. Valutare il potenziale utilizzo del tracciante [18F]-Flutemetamolo nella valutazione di depositi extra cerebrali ed extra cardiaci di amiloide.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Patients with cardiac amyloidosis:
    male and female, age greater or equal 18 years diagnosed with cardiac amyloidosis. In accordance with the recommendations of the European Society of Cardiology, all of the following conditions must be present:
    - clinical suspicion of disease based on one or more of the following exams: cardiac examination, biomarker assay (NT-proBNP, HS-TnT, plasma protein electrophoresis, serum and urinary immunofixation, free light chains), baseline EKG, baseline echocardiography, cardiac magnetic resonance;
    - clearly positive osteophilic radiopharmaceutical scintigraphy (Perugini 2-3) in the absence of serum and/or urinary monoclonal component OR abdominal fat biopsy and/or endomyocardial biopsy showing ATTR or AL amyloidosis;
    - genetic characterization to identify patients with ATTRv;
    - ability to provide consent to the study.

    Control subjects:
    male and female, age greater or equal 18 years diagnosed with not-infiltrative left ventricular hypertrophy;
    ability to consent to the study.
    Gruppi di pazienti con ATTR (sia ATTRwt che ATTRv) e AL:
    maschi o femmine, età maggiore o uguale 18 anni con diagnosi di amiloidosi cardiaca.
    In accordo alle raccomandazioni della Società Europea di Cardiologia, tutte le seguenti condizioni devono essere presenti:
    - sospetto clinico di malattia basato su uno o più dei seguenti esami: Visita cardiologica; Dosaggio biomarcatori (NT-proBNP, HS-TnT, elettroforesi delle proteine plasmatiche, immunofissazione serica e urinaria, catene leggere libere); ECG basale; ecocardiografia basale; risonanza magnetica cardiaca;
    - scintigrafia con radiofarmaco osteofilo positiva in assenza di componente monoclonale sierica e/o urinaria OPPURE biopsia del grasso addominale e/o biopsia endomiocardica con dimostrazione di amiloidosi ATTR o AL;
    - caratterizzazione genetica per identificare i pazienti con ATTRv;
    - capacità di fornire il consenso allo studio.

    Soggetti di controllo:
    - maschi o femmine, età maggiore o uguale 18 anni con ipertrofia ventricolare sinistra di natura non infiltrativa;
    - capacità di fornire il consenso allo studio.
    E.4Principal exclusion criteria
    pregnancy confirmed by plasma beta-HCG on women with childbearing potential and sexually active not employing highly effective contraceptive methods with a low dependency on the user (from the screening to the end of visit 1), which include: i. abstinence, ii. sexual intercourse only with same-sex partners, iii. monogamous relationship with a partner with prior vasectomy, iv. intrauterine device, v. combined hormonal contraception including estrogens and progesteron-like hormones plus the inhibition of ovulation (oral, intravaginal or transdermal), vi. hormonal contraception
    based on progesterone-like compounds plus the inhibition of ovulation (oral, injectable, implantable), viii. intrauterine device with hormone release. The highly effective contraceptive measures above are not required for women made sterile by surgical means (for example through tube ligation, hysterectomy, bilateral salpingectomy, bilateral ovariectomy) or after the menopause, defined as 12 months of spontaneous amenorrhea without another clinical cause and with elevated FSH levels in agreement with the expected values for the menopause. For patients with true abstinence or with just same-sex partners, contraception is not required, as far as this is in line with their preferred and habitual lifestyle. Periodical abstinence (for example, estimate of the timing of ovulation or assessment of body temperature) and coitus interruptus are not acceptable contraceptive methods. If a patient stops to be abstinent, she must use the highly effective contraceptive methods above. The pregnancy status in women potentially fertile will be checked at baseline through the measurement of beta human gonadotropin on the serum;
    breastfeeding;
    known ischemic heart disease;
    hypersensitivity to the active substance or to any of the excipients listed in the chapter 6.1 of the simplified IMPD;
    severe hepatic insufficiency [alteration in the presence of known chronic liver disease of AST (male normal range> 34 IU / L; female <30 IU / L), ALT (male normal range 10-40 IU / L; female 7-35 IU / L), gamma-GT (normal range 7-64 IU / L), albumin (normal range 3.5-5 g / dl), prothrombin activity (normal range PT 70-120%) and bilirubin (normal range> 1,2 mg/dl)];
    severe renal insufficiency [GFR estimated from creatinine and BUN <30 mL/ min/1.73 m2];
    PET/CT or scintigraphic examination 24 hours prior to enrolment;
    participation in a clinical study with an investigational drug administered within 30 days before the screening or 5 half-lives of the study drug, whichever the longest.
    Gravidanza confermata da dosaggio di beta-HCG plasmatica su donne fertili sessualmente attive in assenza di metodi contraccettivi altamente efficaci, con bassa dipendenza dall’utilizzatore, che comprendono: i. Astinenza; ii. Rapporti sessuali solo con persone dello stesso sesso; iii. Relazione monogama con partner vasectomizzato; iv. Dispositivo intrauterino; v. Contraccezione ormonale combinata contenente estrogeni e progestinici associata all’inibizione dell’ovulazione (orale, intravaginale, transdermica); vi. Contraccezione ormonale a base di soli progestinici associata all’inibizione dell’ovulazione (orale, iniettabile, impiantabile); vii. Sistema intrauterino a rilascio di ormoni. Le misure contraccettive altamente efficaci indicate in precedenza non sono previste per le pazienti chirurgicamente sterili (per es. occlusione delle tube, isterectomia, salpingectomia bilaterale, ovariectomia bilaterale) o in post-menopausa definita come 12 mesi di amenorrea spontanea senza una diversa causa clinica e livelli elevati di FSH in accordo all'intervallo previsto per la post-menopausa. Per i pazienti che praticano una vera astinenza o che hanno esclusivamente partner dello stesso sesso non è necessario l’uso della contraccezione, a condizione che ciò sia in linea con il loro stile di vita preferito e abituale. L’astinenza periodica (ad es. metodo del calendario, dell’ovulazione, sintotermico o post-ovulazione) e il coito interrotto non sono metodi di contraccezione accettabili. Lo stato di gravidanza in donne potenzialmente fertili sarà verificato mediante dosaggio ematico della gonadotropina corionica umana al momento dello screening;
    allattamento al seno;
    cardiopatia ischemica nota;
    ipersensibilità al principio attivo o ad uno qualsiasi degli eccipienti elencati nel l’IMPD semplificato del radiofarmaco come indicato al pgf 6.1;
    insufficienza epatica severa [alterazione in presenza di epatopatia cronica nota di AST (range normalità maschi >34 UI/L; femmine <30 UI/L), ALT (range normalità maschi 10-40 UI/L; femmine 7- 35 UI/L), gamma-GT (range normalità 7-64 UI/L), albuminemia (range normalità 3,5-5 g/dl), attività protrombinica (range normalità PT 70-120%) e bilirubinemia (range normalità >1,2 mg/dl)];
    Insufficienza renale severa [GFR stimato dai valori di creatininemia ed azotemia < 30 mL/min/1.73 m2];
    PET/TC o esame scintigrafico 24 ore prima dell'arruolamento;
    partecipazione ad uno studio in cui sia stato somministrato un farmaco sperimentale entro 30 giorni dallo screening o 5 emivite del farmaco in studio a seconda di quale fra i due periodi sia il più lungo.
    E.5 End points
    E.5.1Primary end point(s)
    Quantification by PET parameters of myocardial uptake of the tracer in patients with cardiac amyloidosis ATTRwt, ATTRv and AL.
    Quantificazione mediante parametri PET dell’uptake miocardico del tracciante in pazienti con diagnosi di amiloidosi cardiaca ATTRwt, ATTRv e AL.
    E.5.1.1Timepoint(s) of evaluation of this end point
    at visit 1 (the endpoint evaluation is concomitant with the PET examination)
    Alla visita 1 (la rilevazione dell'endpoint è contestuale all'esame PET)
    E.5.2Secondary end point(s)
    Quantification of myocardial uptake of the tracer in patients with ATTRv, in patients with ATTRwt, in patients with AL and in control subjects;; Quantification of myocardial uptake of the tracer in patients with ATTRv, in patients with ATTRwt, in patients with AL and in control subjects;; Quantitative differentiation of myocardial tracer uptake in patients with different ATTRv genotypes;; Quantification of myocardial uptake of the tracer in patients with ATTR and weakly positive or negative scintigraphy (Perugini 0–1);; Identification and quantification of any areas of systemic uptake of the radiopharmaceutical referred to the presence of amyloid deposits (systemic amyloidosis)
    Quantificazione dell’uptake miocardico del tracciante nei pazienti con ATTRv, nei pazienti con ATTRwt, nei pazienti con AL e nei soggetti di controllo;; Quantificazione dell’uptake miocardico del tracciante nei pazienti con ATTRv, nei pazienti con ATTRwt, nei pazienti con AL e nei soggetti di controllo;; Differenziazione quantitativa dell’uptake miocardico del tracciante nei pazienti con diversi genotipi ATTRv;; Quantificazione dell’uptake miocardico del tracciante nei pazienti con ATTR e scintigrafia debolmente positiva o negativa (Perugini 0 – 1);; Individuazione e quantificazione di eventuali aree di iperaccumulo del radiofarmaco a livello sistemico compatibili con la presenza di depositi tissutali di amiloide (amiloidosi sistemica)
    E.5.2.1Timepoint(s) of evaluation of this end point
    at visit 1 (the endpoint evaluation is concomitant with the PET examination);; at visit 1 (the endpoint evaluation is concomitant with the PET examination);; at visit 1 (the endpoint evaluation is concomitant with the PET examination);; at visit 1 (the endpoint evaluation is concomitant with the PET examination);; at visit 1 (the endpoint evaluation is concomitant with the PET examination)
    Alla visita 1 (la rilevazione dell'endpoint è contestuale all'esame PET);; Alla visita 1 (la rilevazione dell'endpoint è contestuale all'esame PET);; Alla visita 1 (la rilevazione dell'endpoint è contestuale all'esame PET);; Alla visita 1 (la rilevazione dell'endpoint è contestuale all'esame PET);; Alla visita 1 (la rilevazione dell'endpoint è contestuale all'esame PET)
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis Yes
    E.6.2Prophylaxis No
    E.6.3Therapy No
    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) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    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 No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial1
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.4.1Number of sites anticipated in Member State concerned1
    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 Information not present in EudraCT
    E.8.7Trial has a data monitoring committee No
    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
    LVLS
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months6
    E.8.9.2In all countries concerned by the trial days0
    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: 30
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 15
    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 No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    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 state45
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 45
    F.4.2.2In the whole clinical trial 45
    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)
    not applicable
    non applicabile
    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 Decision2023-05-04
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2023-01-19
    P. End of Trial
    P.End of Trial StatusOngoing
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