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    Summary
    EudraCT Number:2021-005733-16
    Sponsor's Protocol Code Number:DNLI-H-0001
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Temporarily Halted
    Date on which this record was first entered in the EudraCT database:2022-05-12
    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 ConcernedSpain - AEMPS
    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
    Estudio de fase I/II, multicéntrico, aleatorizado, controlado con placebo, doble ciego, de dosis única y dosis múltiples para evaluar la seguridad, la
    tolerabilidad, la farmacocinética y la farmacodinámica de DNL593 en participantes sanos y participantes con demencia, seguido de una extensión sin enmascaramiento.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A 3 Part first-in-human study of DNL593 in healthy volunteers and patients with frontotemporal dementia (FTD)
    Estudio de 3 partes de primera administración en humanos de DNL593 en voluntarios sanos y en pacientes con demencia frontotemporal (DFT).
    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 estudio 1ª administraciónn en humanos de DNL593 en voluntarios sanos y pacientes DFT
    A.4.1Sponsor's protocol code numberDNLI-H-0001
    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 Blvd.
    B.5.3.2Town/ citySouth San Francisco
    B.5.3.3Post codeCA 94080
    B.5.3.4CountryUnited States
    B.5.4Telephone number+34900834223
    B.5.6E-mailRegistroEspanolDeEstudiosClinicos@druginfo.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
    Subcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNN/A
    D.3.9.1CAS number N/A
    D.3.9.2Current sponsor codeDNL593
    D.3.9.3Other descriptive nameDNL593
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number37.00 to 43.00
    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 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)
    Demencia Frontotemporal (DFT)
    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
    DFT - condición del cerebro asociada a la pérdida de células cerebrales, afectando al comportamiento, al proceso de juicio, lenguaje, memoria y
    habilidades motoras.
    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
    - Se evaluarán la seguridad y la tolerabilidad de dosis múltiples de DNL593 en participantes con demencia frontotemporal causada por mutaciones en el gen de granulina (DFT-GRN).
    Parte C
    - Se evaluarán la seguridad y la tolerabilidad de dosis múltiples de DNL593 en participantes con DFT-GRN hasta 18 meses.
    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
    - Determinar la FC sérica de DNL593 después de administrar dosis múltiples de DNL593 en participantes con DFT-GRN.
    - Determinar la concentración de DNL593 en el LCR después de administrar dosis múltiples en participantes con DFT-GRN.
    Parte C
    - Determinar la FC sérica de DNL593 después de administrar dosis múltiples de DNL593 en participantes con DFT-GRN.
    - Determinar la concentración de DNL593 en el LCR después de administrar dosis múltiples de DNL593 en participantes con DFT-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 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. Edad de ≥ 18 a ≤ 80 años
    2. IMC ≥ 18 y ≤ 32 kg/m2
    3. Disposición y capacidad para otorgar el consentimiento informado para participar en el estudio o presencia de un cuidador o representante
    legal dispuestos y capaces de otorgar su consentimiento.
    4. Acompañante en el estudio capaz de cumplimentar de forma fiable la escala CDR más FTLD del NACC (escala de valoración de la demencia
    clínica más dominios de degeneración lobular frontotemporal del NACC) con el participante, y que le acompañe a las visitas del estudio o esté
    disponible para los contactos telefónicos en los momentos designados. El acompañante en el estudio deberá tener contacto frecuente con el
    participante (más de 10 horas por semana) y ser capaz de participar razonablemente en todas las evaluaciones de la CDR más FTLD del NACC
    durante el período del estudio.
    Nota: puede haber un segundo acompañante en el estudio como reserva, pero es preferible que sea uno el responsable principal de las evaluaciones de la CDR más FTLD del NACC.
    5. Capacidad de comunicarse con el investigador y el personal de forma independiente o a través de un cuidador.
    6. Disposición y capacidad para cumplir los requisitos del estudio, incluidas las visitas programadas, las restricciones del estudio, las pruebas analíticas y todos los demás procedimientos del estudio. En opinión del investigador, tanto el participante como el cuidador son capaces de realizar todos los procedimientos y visitas del estudio obligatorios durante el período de 24 semanas de la parte B.
    7. Mujeres sin capacidad de quedar embarazadas, es decir, deben haber sido esterilizadas quirúrgicamente (histerectomía, ovariectomía/salpingectomía bilateral o ligadura de trompas bilateral; se requiere documentación adecuada) más de 3 meses antes del
    tratamiento (no se acepta la colocación del espiral Essure en las trompas de Falopio como esterilización quirúrgica debido a su elevado índice de
    fallos) o ser posmenopáusicas (amenorrea durante más de 12 meses consecutivos antes del tratamiento, con una concentración de FSH >40
    UI/l en la selección).
    Se permitirá la participación de mujeres con posibilidad de quedar embarazadas que utilicen métodos anticonceptivos muy eficaces y poco
    dependientes de la usuaria.
    8. Varones: Cuando mantengan relaciones sexuales con una mujer con posibilidad de quedar embarazada, tanto el varón participante como su
    pareja deberán utilizar anticoncepción muy eficaz consistente en dos métodos anticonceptivos, uno de los cuales deberá ser un método de barrera masculino (como un preservativo de látex o poliuretano), desde el inicio de la administración, durante todo el período del estudio y durante 90 días después de la última administración de la intervención del estudio.
    9. Varones: El participante no debe donar semen en ningún momento desde el inicio del tratamiento, durante todo el período del estudio ni durante 90 días después de la última administración de la intervención del estudio.
    10. Diagnóstico de demencia frontotemporal (DFT), incluido el diagnóstico probable de DFTvc (variable conductual de la DFT) o afasia progresiva primaria (APP). Se permiten otros diagnósticos relacionados con el síndrome de DFT, entre otros, síndrome corticobasal (SCB) o síndrome de parálisis supranuclear progresiva (PSP), a la espera del acuerdo del promotor y del investigador.
    11. Puntuación global en la escala CDR más FTLD del NACC ≥ 0,5.
    12. Mutación de GRN confirmada mediante análisis genéticos o registros históricos disponibles para su revisión por el investigador.
    13. Las dosis de otros medicamentos con receta de uso crónico que puedan afectar a la función cognitiva o a la conducta en la determinación
    del investigador deberán haberse mantenido estables durante ≥ 1 mes antes de la selección; se espera que el participante permanezca con una
    pauta estable durante todo el estudio. Los participantes que hayan empezado un medicamento o modificado la dosis (descrito anteriormente) en el mes previo a la selección podrán volver a pasar por el proceso de selección tras la estabilización de la dosis.
    Parte C
    - Los participantes de la parte B que completen el período de doble enmascaramiento hasta la visita de seguimiento de la seguridad podrán incorporarse al período de 18 meses.
    - Parte C, extensión sin enmascaramiento, a criterio del investigador y el promotor. Cada participante volverá a otorgar su consentimiento para la
    extensión sin enmascaramiento.
    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.
    Parte B
    1. Antecedentes de enfermedades psiquiátricas, endocrinas, pulmonares, cardiovasculares, digestivas, hepáticas, pancreáticas, renales, metabólicas, hematológicas, inmunitarias o alérgicas inestables o mal controladas, u otros trastornos importantes. Se permite la presencia de enfermedades bien controladas si el investigador y el promotor están de acuerdo.
    2. Antecedentes de neoplasia maligna en los 5 años previos a la selección, excepto carcinoma basocelular totalmente resecado u otras neoplasias malignas (como el cáncer de próstata) con un riesgo bajo de recidiva, en función de la conformidad del investigador y el monitor médico.
    3. Antecedentes de trastornos neurológicos clínicamente importantes distintos de la demencia frontotemporal (DFT) (solo en la parte B), como
    ictus, deterioro cognitivo por causas distintas de la DFT o crisis epilépticas en los 5 años previos a la selección, o traumatismo craneoencefálico con pérdida del conocimiento en los 2 años previos a la selección.
    Nota: la incidencia aislada de crisis provocadas con una causa clara puede ser aceptable con la aprobación del investigador y el promotor.
    4. Presencia de cualquier contraindicación para la RM cerebral.
    5. Trastorno psiquiátrico importante en la actualidad, ideas suicidas en los 6 meses previos, evaluadas mediante la versión basal/de selección de la escala C-SSRS (solo en la parte B).
    6. Signos de insuficiencia hepática, como ALT o AST >2 veces el LSN o bilirrubina >1,5 veces el LSN en la visita de selección o el momento basal.
    7. Antecedentes de insuficiencia renal clínicamente significativa o FGe<45 ml/min/1,73 m2 en la visita de selección.
    8. Antecedentes o presencia de una anomalía clínicamente significativa en el ECG.
    9. Donación o pérdida de más de 500 ml de sangre completa en los 30 días previos a la incorporación al período de tratamiento.
    10. Vacunación (incluso segundas dosis o cualquier vacuna de refuerzo) contra el SARS-CoV-2 en las 4 semanas previas al comienzo del tratamiento.
    11. Cualquier otro problema que, en opinión del investigador, impida que el participante sea incluido en el estudio.
    Para conocer todos los criterios de exclusión de la parte B, véase la sección 5.1.2.2 del protocolo.
    Parte C
    Todos los participantes que completen la parte B de este ensayo podrán incorporarse a una extensión sin enmascaramiento de 18 meses si son
    capaces de acudir a las visitas del estudio y no presentan AAST clínicamente significativos no resueltos que puedan representar un riesgo para la seguridad de los participantes si continúan con el tratamiento. Cada participante volverá a otorgar su consentimiento para la extensión sin enmascaramiento.
    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
    - Incidencia, intensidad y gravedad de los AAST durante el período con doble enmascaramiento de 24 semanas.
    - Variación con respecto al momento basal de los valores analíticos de la seguridad, las constantes vitales, los resultados del ECG, la puntuación
    en la escala para evaluar el riesgo de suicidio de la Universidad de Columbia (C-SSRS) y los datos obtenidos en la exploración física y neurológica durante el período con doble enmascaramiento de 24 semanas.
    Parte C
    - Incidencia, intensidad y gravedad de los AAST durante el período de ESE.
    - Variación con respecto al momento basal de los valores analíticos de la seguridad, las constantes vitales, los resultados del ECG, la puntuación
    en la escala C-SSRS y los datos obtenidos en la exploración física y neurológica durante el período de ESE.
    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.
    AA
    - Parte A, B y C - Los AA se recogerán desde la firma del consentimiento informado hasta la visita de seguimiento post-estudio en cada parte.
    Los criterios primarios de valoración restantes serán evaluados, en cada parte, en los siguientes períodos:
    Parte B - Desde la selección a la semana 29
    Parte C - Desde la semana 29 a la semana 109
    Para conocer el esquema completo y los detalles de las evaluaciones del estudio en los distintos momentos temporales, refiéranse al protocolo.
    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 (AUCτ)
    - 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
    - AUCτ
    - t1/2
    - Accumulation ratio
    DNL593 concentration 24 hours post dose at multiple time points
    - DNL593 CSF:serum concentration ratio at multiple time points
    Los criterios de valoración secundarios de este estudio son los parámetros farmacocinéticos séricos de DNL593 y la concentración de DNL593 en el líquido cefalorraquídeo (LCR):
    Parte B
    Parámetros FC séricos de DNL593 (cuando sea posible):
    - Cmáx
    - tmáx
    - Concentración mínima (Cmín)
    - AUCúlt
    - AUC desde el momento 0 hasta el final del intervalo de administración
    (AUCτ)
    - t1/2
    - Cociente de acumulación
    Concentraciones de DNL593 en el LCR 24 horas después de la administración en la semana 25.
    Cociente de la concentración de DNL593 en LCR: suero en la semana 25.
    Parte C
    Parámetros FC séricos de DNL593 (cuando sea posible):
    - Cmáx
    - tmáx
    - Cmín
    - AUCúlt
    - AUCτ
    - t1/2
    - Cociente de acumulación
    Concentración de DNL593 24 horas después de la administración en varios puntos temporales.
    Cociente de la concentración de DNL593 en LCR/suero en varios puntos temporales.
    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
    FC séricos:
    Parte B - 41 muestras desde el día 1 pre-dosis a la semana 29
    Parte C - 51 muestras desde la semana 29 pre-dosis a la semana 109
    LCR:
    Parte B - El día -1, la semana 13 y la semana 25
    Parte C - Selección (12 semanas antes de la semana 29), la semana 41 y la semana 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 concerned4
    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 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
    Argentina
    Brazil
    Colombia
    United States
    France
    Sweden
    Netherlands
    Spain
    Czechia
    Italy
    Belgium
    Portugal
    Serbia
    Turkey
    United Kingdom
    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 months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years3
    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 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 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
    Pacientes con DFT con acompañante en el estudio como representante legal dispuesto a otorgar su consentimiento
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state15
    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.
    No aplica, ya que, es una terapia experimental - después de la finalización de la visita de seguimiento post-estudio, todos los participantes se retirarán del estudio siempre que el investigador lo
    considere oportuno.
    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 Decision2022-07-19
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2022-06-27
    P. End of Trial
    P.End of Trial StatusTemporarily Halted
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