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    Summary
    EudraCT Number:2021-005733-16
    Sponsor's Protocol Code Number:DNLI-H-0001
    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:2022-09-14
    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 number2021-005733-16
    A.3Full title of the trial
    A Phase 1/2, Multicenter, Randomized, Placebo-Controlled, Double-Blind
    Single Dose and Multiple Dose Study to Evaluate the Safety, Tolerability,
    Pharmacokinetics, and Pharmacodynamics of DNL593 in Healthy
    Participants and Participants With Frontotemporal Dementia Followed by
    an Open-Label Extension
    Studio di fase 1/2, multicentrico, randomizzato, controllato con placebo, a dose singola e multidose in doppio cieco, per valutare la sicurezza, la tollerabilità, la farmacocinetica e la farmacodinamica di DNL593 in partecipanti sani e partecipanti affetti da demenza frontotemporale, seguito da un’estensione in aperto
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Part first-in-human study of DNL593 in healthy volunteers and patients
    with frontotemporal dementia (FTD)
    Parte dello studio first-in-human di DNL593 in volontari e pazienti sani con demenza frontotemporale (FTD)
    A.3.2Name or abbreviated title of the trial where available
    Part B, C of first in human study of DNL593 in healthy volunteers & FTD patients
    Parte B, C del primo studio sull'uomo di DNL593 in volontari sani e pazienti FTD
    A.4.1Sponsor's protocol code numberDNLI-H-0001
    A.5.1ISRCTN (International Standard Randomised Controlled Trial) NumberISRCTN00000000
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT12345678
    A.5.3WHO Universal Trial Reference Number (UTRN)U1234-1234-1234
    A.5.4Other Identifiers
    Name:NANumber:NA
    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 SponsorDenali Therapeutics Inc.
    B.1.3.4CountryUnited States
    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 supportDenali Therapeutics Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationDenali Therapeutics Inc.
    B.5.2Functional name of contact pointRegulatory Affairs
    B.5.3 Address:
    B.5.3.1Street Address161 Oyster Point Boulevard, South San Francisco
    B.5.3.2Town/ citySouth San Francisco
    B.5.3.3Post codeCA 94080
    B.5.3.4CountryUnited States
    B.5.4Telephone number0016502384979
    B.5.5Fax number0016502384979
    B.5.6E-mailkratz@denali.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 nameDNL593 Sterile Lyophilisate
    D.3.2Product code [DNL593]
    D.3.4Pharmaceutical form Lyophilisate 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.3.9.2Current sponsor codeDNL593
    D.3.9.3Other descriptive nameDNL593
    D.3.10 Strength
    D.3.10.1Concentration unit % (W/V) percent weight/volume
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number37 to 43
    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 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 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 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
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboLyophilisate for solution 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
    Frontotemporal Dementia (FTD)
    Demenza Fronto-temporale
    E.1.1.1Medical condition in easily understood language
    FTD - condition of the brain associated with loss of brain cells, affecting behaviour, judgement, language, memory and motor skills
    Demenza frontotemporale - condizione del cervello associata a perdita di cellule cerebrali, che influisce su comportamento, giudizio, linguaggio, memoria e capacità motorie
    E.1.1.2Therapeutic area Diseases [C] - Nervous System Diseases [C10]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10068968
    E.1.2Term Frontotemporal dementia
    E.1.2System Organ Class 10029205 - Nervous system disorders
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Part B
    - To investigate the safety and tolerability of multiple doses of DNL593 in
    participants with FTD-GRN.
    Part C
    - To investigate the safety and tolerability of multiple doses of DNL593 in
    participants with FTD-GRN up to 18 months.
    Parte B
    - Studiare la sicurezza e la tollerabilità di dosi multiple di DNL593 in partecipanti con FTD-GRN.
    Parte C
    - Studiare la sicurezza e la tollerabilità di dosi multiple di DNL593 in partecipanti con FTD-GRN fino a 18 mesi.
    E.2.2Secondary objectives of the trial
    Part B
    - To characterize the serum PK of DNL593 following multiple doses of
    DNL593 in participants with FTD-GRN.
    - To characterize the concentration of DNL593 in CSF following multiple
    doses in participants with FTD-GRN.
    Part C
    - To characterize the serum PK of DNL593 following multiple doses of
    DNL593 in participants with FTD-GRN.
    - To characterize the concentration of DNL593 in CSF following multiple
    doses of DNL593 in participants with FTDGRN.
    Parte B
    - Caratterizzare la PK sierica di DNL593 dopo dosi multiple di DNL593 in partecipanti con FTD-GRN.
    - Caratterizzare la concentrazione di DNL593 nel liquido cerebrospinale (LCS) dopo dosi multiple in partecipanti con FTD-GRN.
    Parte C
    - Caratterizzare la PK sierica di DNL593 dopo dosi multiple di DNL593 in partecipanti con FTD-GRN.
    - Caratterizzare la concentrazione di DNL593 nell’LCS dopo dosi multiple
    di DNL593 in partecipanti con FTD-GRN.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Part B
    1.Aged = 18 to = 80 years
    2.Have a BMI of = 18 to = 32 kg/m2
    3.Are willing and able to give informed consent for study participation or
    have a care partner or LAR who is willing and
    able to provide consent
    4.Have a study partner who is able to reliably complete the CDR plus
    NACC FTLD with participant and will accompany
    the participant to study visits or be available by telephone at designated
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    times. Study partner must have frequent
    contact with participant (> 10 hours per week) and be able to
    reasonably participate in all CDR plus NACC FTLD
    assessments in the study period.
    Note: A second study partner may serve as backup, but it is preferred
    that one study partner be primarily responsible
    for the CDR plus NACC FTLD assessments.
    5.Are able to communicate with the investigator and staff either
    independently or through a caregiver
    6.Are willing and able to comply with the requirements of the study,
    including scheduled visits, study restrictions,
    laboratory tests, and all other study procedures. In the investigator's
    opinion, both participant and caregiver are able to
    complete all required study procedures and visits during the Part B
    period of 24 weeks.
    7.Women of non-childbearing potential, defined as must have been
    surgically sterilized (hysterectomy, bilateral
    oophorectomy/salpingectomy, or bilateral tubal ligation; proper
    documentation required) > 3 months prior to dosing
    (Essure fallopian tube coil placement is not accepted as surgical
    sterilization because of the high failure rate), or be
    postmenopausal (amenorrheic for > 12 consecutive months before
    dosing, with a FSH level of > 40 IU/L at screening).
    Women who are of childbearing potential but on highly effective, low
    user dependent contraceptive methods will be
    allowed.
    8.For men: When engaging in sex with a WOCBP, both the male
    participant and his female partner must use highly
    effective contraception consisting of two forms of birth control, one of
    which must be a male barrier method (such as a
    latex or polyurethane condom), from the start of dosing, throughout the
    study period, and for 90 days after the final
    administration of study intervention.
    9.For men: The participant must not donate sperm at any time from the
    start of dosing, throughout the study period,
    and for 90 days after the final administration of study intervention.
    10.Have a diagnosis of FTD, including the probable bvFTD or PPA. Other
    diagnosis related to FTD syndrome,
    including, but not limited to, CBS or progressive supranuclear palsy
    (PSP) syndrome, are allowed pending Sponsor
    and investigator agreement.
    11.Have a CDR plus NACC FTLD global score = 0.5
    12.Have confirmed GRN mutation via genetic testing or historical records
    available for review by investigator
    13.Doses of other chronic prescription medications that may affect
    cognition or behaviour at the determination of the
    investigator must be stable for = 1 month prior to screening; participant
    is expected to stay on a stable regimen
    throughout the study. Participants who initiated or changed medication
    (described above) doses within 1 month prior
    to screening may be rescreened after dose stabilization.
    Part C
    Participants from Part B who complete the double-blind period through
    the SFU visit are eligible to enter the 18-month
    Part C OLE, at the discretion of the investigator and Sponsor. Each
    participant will be reconsented for the OLE.
    Parte B 1. Età compresa tra =18 e =80 anni 2. Presentare un IMC da =18 a =32 kg/m2 3. Disponibilità e capacità di fornire il consenso informato per la partecipazione allo studio o presenza di un partner per assistenza o rappresentante legalmente autorizzato che sia disposto e in grado di fornire il consenso 4. Avere un partner per lo studio in grado di compilare in modo affidabile la scala di valutazione di demenza clinica associata alla valutazione della Degenerazione lobare frontotemporale secondo il Centro Coordinatore Nazionale sull’Alzheimer (National Alzheimer’s Coordinating Center, [NACC] frontotemporal lobar degeneration, con il partecipante e che accompagnerà il partecipante alle visite dello studio o sarà disponibile per telefono agli orari designati. Il partner per lo studio deve avere frequenti contatti con il partecipante ed essere in grado di partecipare adeguatamente a tutte le valutazioni CDR più NACC FTLD nel periodo dello studio. 5. Capacità di comunicare con lo sperimentatore e il personale in modo indipendente o tramite un caregiver 6. Disponibilità e capacità di attenersi ai requisiti dello studio, comprese le visite programmate, le restrizioni dello studio, gli esami di laboratorio e tutte le altre procedure dello studio. A giudizio dello sperimentatore, sia il partecipante sia il caregiver sono in grado di completare tutte le procedure e le visite dello studio richieste durante il periodo della Parte B di 24 settimane. 7. Donne non in età fertile, definite come donne che devono essere state sottoposte a sterilizzazione chirurgica (isterectomia, ovariectomia/salpingectomia bilaterale o legatura delle tube bilaterale; è richiesta una documentazione adeguata) >3 mesi prima della somministrazione o essere in post-menopausa.È consentita la partecipazione di donne in età fertile ma che utilizzano metodi contraccettivi altamente efficaci e a bassa dipendenza dall’utente.8. Per gli uomini: nel caso di rapporti sessuali con una donna in età fertile sia il partecipante sia la sua partner devono utilizzare metodi contraccettivi altamente efficaci costituiti da due forme di contraccezione, una delle quali deve essere un metodo barriera maschile (come un preservativo in lattice o poliuretano), dall’inizio della somministrazione, per tutto il periodo dello studio e per 90 giorni dopo la somministrazione finale del trattamento dello studio.9. Per gli uomini: il partecipante non deve donare sperma in alcun momento dall’inizio della somministrazione, per tutto il periodo dello studio e per 90 giorni dopo la somministrazione finale del trattamento dello studio.10. Diagnosi di FTD, compresa la probabile variante comportamentale (behavioral variant, o di afasia progressiva primaria. Sono consentite altre diagnosi correlate alla sindrome da FTD, tra cui, a titolo esemplificativo ma non esaustivo, la sindrome corticobasaleo la sindrome da paralisi sopranucleare progressiva se lo sponsor e lo sperimentatore concordano.11. Punteggio globale CDR più NACC FTLD =0,512. Presenza di una mutazione GRN confermata tramite test genetici o documentazione anamnestica disponibile per la revisione da parte dello sperimentatore13. Le dosi di altri farmaci con prescrizione cronica che possono influenzare la capacità cognitiva o il comportamento secondo quanto determinato dallo sperimentatore devono essere stabili per =1 mese prima dello screening; il paziente dovrà continuare a seguire un regime stabile per tutta la durata dello studio. I partecipanti che hanno iniziato o modificato le dosi del farmaco (descritte sopra) entro 1 mese prima dello screening possono essere sottoposti a nuovo screening dopo la stabilizzazione della dose.Parte - I pazienti della Part B che completano il periodo in doppio cieco fino alla visita di FU di sicurezza sono idonei a partecipare al periodo di 18 mesi della Parte C di estensione in aperto a discrezione dello sperimentatore e dello sponsor.
    E.4Principal exclusion criteria
    Part B
    1.Have any history of unstable or poorly controlled psychiatric,
    endocrine, pulmonary, cardiovascular, gastrointestinal,
    hepatic, pancreatic, renal, metabolic, hematologic, immunologic, or
    allergic disease, or other major disorders. Well
    controlled conditions are permitted if investigator and Sponsor agree.
    2.Have a history of malignancy within 5 years before screening, except
    fully resected basal cell carcinoma or other
    malignancies (such as prostate cancer) at low risk of recurrence,
    depending on investigator and medical monitor
    agreement
    3.Have a history of clinically significant neurologic disorders other than
    FTD (for Part B only), including stroke, cognitive
    impairment due to causes other than FTD, or seizure within 5 years of
    screening, or head trauma with loss of
    consciousness within 2 years of screening. Note: Single incidence of
    provoked seizure with a clear cause may be
    acceptable with Investigator and Sponsor approval.
    4.Have the presence of any contraindication to MRI of the brain
    5.Have a current significant psychiatric disorder, suicidal ideation in the
    previous 6 months as assessed by the
    Baseline/Screening version of the C-SSRS (for Part B only)
    6.Have evidence of hepatic impairment, including ALT or AST > 2 × ULN
    or bilirubin> 1.5 × ULN at screening or
    baseline.
    7.Have a history of clinically significant renal impairment or an eGFR <
    45 mL/min/1.73 m2 at screening
    8.Have a history or presence of a clinically significant ECG abnormality
    9.Have donated or lost > 500 mL whole blood within 30 days before
    entry in the treatment period
    10.Received vaccination (including second dose or any booster shots)
    against SARS-CoV-2 within 4 weeks of the start
    of dosing.
    11.Have any other issue that, in the opinion of the investigator, would
    make the participant ineligible for study
    participation
    For full exclusion criterion for Part B, please refer to Section 5.1.2.2 of
    the protocol.6.10.
    1.Anamnesi di malattia psichiatrica, endocrina, polmonare, cardiovascolare, gastrointestinale,
    epatica, pancreatica, renale, metabolica, ematologica, immunologica o allergica instabile o scarsamente controllata o altri disturbi maggiori. Condizioni adeguatamente controllate sono consentite se lo sperimentatore e lo sponsor concordano.
    2.Anamnesi di tumore maligno nei 5 anni precedenti lo screening, ad eccezione del carcinoma basocellulare completamente resecato o di altre neoplasie maligne (come il carcinoma prostatico) a basso rischio di recidiva, in base a quanto concordato dallo sperimentatore e dal medical monitor
    3. Anamnesi di disturbi neurologici clinicamente significativi diversi dalla FTD (solo per la Parte B), compresi ictus, compromissione cognitiva dovuta a cause diverse dalla FTD o crisi convulsive entro 5 anni dallo screening, oppure trauma cranico con perdita di coscienza entro 2 anni dallo screening. Nota: una singola incidenza di crisi convulsiva provocata con una chiara causa può essere accettabile con l’approvazione dello sperimentatore e dello sponsor.
    4. Presenza di qualsiasi controindicazione alla risonanza magnetica (RM) cerebrale.
    5. Presenza di un attuale disturbo psichiatrico significativo, ideazione suicidaria nei 6 mesi precedenti, valutata mediante la versione basale/screening della Scala della Columbia University per la valutazione della gravità del rischio di suicidio (Columbia-Suicide Severity Rating Scale [C-SSRS]) (solo per la Parte B)Avere evidenza di compromissione epatica, inclusi ALT o AST > 2 × ULN
    o bilirubina> 1,5 × ULN allo screening o
    riferimento.
    7.Avere una storia di compromissione renale clinicamente significativa o un eGFR < 45 ml/min/1,73 m2 allo screening 8.Avere una storia o la presenza di un'anomalia ECG clinicamente significativa 9.Aver donato o perso > 500 ml di sangue intero entro 30 giorni prima
    ingresso nel periodo di trattamento 10. Vaccinazione ricevuta (inclusa la seconda dose o eventuali colpi di richiamo)
    contro SARS-CoV-2 entro 4 settimane dall'inizio
    di dosaggio.
    11.Avere qualsiasi altro problema che, a giudizio dell'investigatore, sarebbe
    rendere il partecipante non idoneo allo studio
    partecipazione
    Per il criterio di esclusione completa per la parte B, fare riferimento alla sezione 5.1.2.2 di
    il protocollo.
    E.5 End points
    E.5.1Primary end point(s)
    Part B
    - Incidence, severity, and seriousness of TEAEs during the 24-week
    double-blind period
    - Change from baseline in safety laboratory values, vital sign
    measurements, ECG results, Columbia-Suicide Severity
    Rating Scale (C-SSRS), and physical and neurological examination
    findings during the 24-week double-blind period
    Part C
    - Incidence, severity, and seriousness of TEAEs during the OLE period
    - Change from baseline in safety laboratory values, vital sign
    measurements, ECG results, C-SSRS, and
    physical/neurological examination findings during the OLE period
    Parte B
    - Incidenza, severità e gravità degli eventi avversi emergenti dal trattamento (Treatment emergent Adverse Events, [TEAE]) durante il periodo in doppio cieco di 24 settimane
    - Variazione rispetto al basale nei valori di laboratorio di sicurezza, nelle misurazioni dei parametri vitali, nei risultati dell’ECG, nella gravità del rischio di suicidio secondo la scala di valutazione della Columbia University (C-SSRS) ed esiti dell’esame obiettivo e neurologico durante il periodo in doppio cieco di 24 settimane
    Parte C
    - Incidenza, severità e gravità dei TEAE durante il periodo OLE
    - Variazione rispetto al basale nei valori di laboratorio di sicurezza, nelle misurazioni dei parametri vitali, nei risultati dell’ECG, negli esiti della valutazione secondo la C-SSRS e nei risultati dell’esame obiettivo/neurologico durante il periodo OLE
    E.5.1.1Timepoint(s) of evaluation of this end point
    AE
    Part A, B & C - AEs will be recorded from the point of informed consent
    up to final post-study follow up visit in each
    part.
    The remaining primary endpoints will be evaluated at set timepoints in
    each study part within the following periods:
    Part B - Set timepoints from screening to Week 29
    Part C - Set timepoints from Week 29 to Week 109
    Please see full schedule of assessments within the study protocol for full
    details of timepoints for evaluation.
    EA
    - Parte A, B e C - Gli EA saranno registrati dal momento del consenso informato fino alla visita finale di follow-up post-studio in ciascuna parte.
    I restanti endpoint primari saranno valutati in base a timepoint prestabiliti in
    ogni parte di studio entro i seguenti periodi:
    Parte B - Impostare i timepoint dallo screening alla Settimana 29
    Parte C - Impostare i tempi dalla settimana 29 alla settimana 109
    Si prega di consultare il programma completo delle valutazioni all'interno del protocollo di studio per il pieno
    dettagli dei punti temporali per la valutazione.
    E.5.2Secondary end point(s)
    The secondary outcome measures for this study are pharmacokinetic
    parameters for the analysis of serum
    concentrations of DNL593 and cerebrospinal fluid (CSF) concentrations
    of DNL593.
    Endpoints are defined as follows:
    Part B
    DNL593 serum PK parameters (when feasible):
    - Cmax
    - tmax
    - Trough concentration (Ctrough)
    - AUClast
    - AUC from time 0 to the end of the dosing interval (AUCt)
    - t1/2
    - Accumulation ratio
    DNL593 CSF concentrations 24 hours post dose at Week 25
    - DNL593 CSF:serum concentration ratio at Week 25
    Part C
    DNL593 serum PK parameters (when feasible):
    - Cmax
    - tmax
    - Ctrough
    - AUClast
    - AUCt
    - t1/2
    - Accumulation ratio
    DNL593 concentration 24 hours post dose at multiple time points
    - DNL593 CSF:serum concentration ratio at multiple time points
    Le misure di esito secondarie per questo studio sono parametri farmacocinetici per l’analisi delle concentrazioni nel siero di DNL593 e delle concentrazioni nel liquido cerebrospinale (LCS) di DNL593.
    Gli endpoint sono definiti come segue:
    Parte B
    Parametri della PK sierica di DNL593 (se possibile):
    - Cmax
    - Tmax
    - Concentrazione minima (Cmin)
    - AUClast
    - AUC dall’ora 0 alla fine dell’intervallo di somministrazione (AUCT)
    - t1/2
    - Rapporto di accumulo
    Concentrazioni di DNL593 nell’LCS 24 ore post-dose alla Settimana 25
    - DNL593 LCS: rapporto di concentrazione sierica alla Settimana 25
    Parte C
    Parametri della PK sierica di DNL593 (se possibile):
    - Cmax
    - Tmax
    - Cmin
    - AUClast
    - AUCt
    - t1/2
    - Rapporto di accumulo
    Concentrazione di DNL593 24 ore post-dose in diversi punti temporali
    - DNL593 LCS: rapporto di concentrazione sierica in diversi punti temporali
    E.5.2.1Timepoint(s) of evaluation of this end point
    Serum PK
    Part B - 41 samples from Day 1 pre-dose to Week 29
    Part C - 51 samples from Week 29 pre-dose to Week 109
    CSF
    Part B - Day -1, Week 13 & Week 25
    Part C - Screening (12 weeks before Week 29), Week 41 & Week 53
    PK sierica
    Part B - 41 campioni dal day 1 pre-dose alla week 29
    Part C - 51 campioni dalla Week 29 pre-dose alla Week 109
    CSF
    Part B - Day -1, week13 & Week 25
    Part C - Screening (12 sett prima della Week 29),settimana 41 & 53
    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 No
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    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) Yes
    E.7.1.1First administration to humans Yes
    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 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 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 concerned5
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA16
    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 Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Argentina
    Brazil
    Colombia
    United States
    France
    Sweden
    Netherlands
    Spain
    Czechia
    Italy
    Belgium
    Hungary
    Portugal
    Turkey
    United Kingdom
    Serbia
    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 years3
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months0
    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: 11
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 17
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers Yes
    F.3.2Patients No
    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 Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Patients with FTD with appointed study partner as an authorized
    representative to provide consent
    Pazienti con FTD con partner di studio designato come autorizzato
    rappresentante per fornire il consenso
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state12
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 28
    F.4.2.2In the whole clinical trial 40
    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 as this is an experimental therapy - following completion
    of the post-study follow up visit, all participants
    will be discharged from the study provided that the Investigator deems
    it appropriate to do so
    Non applicabile in quanto si tratta di una terapia sperimentale - dopo il completamento
    della visita di follow-up post-studio, tutti i partecipanti
    saranno dimessi dallo studio a condizione che lo sperimentatore ritenga
    è opportuno farlo
    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 Decision2023-02-14
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2022-07-12
    P. End of Trial
    P.End of Trial StatusOngoing
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