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    The EU Clinical Trials Register currently displays   43874   clinical trials with a EudraCT protocol, of which   7294   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:2022-002568-62
    Sponsor's Protocol Code Number:AVB-PGRN-001
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2023-01-16
    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 ConcernedSpain - AEMPS
    A.2EudraCT number2022-002568-62
    A.3Full title of the trial
    A Phase 1/2 Open-Label, Ascending Dose, Multicenter Study to Evaluate the Safety and Preliminary Efficacy of AVB-101 Administered by Bilateral Intrathalamic Infusion in Subjects With Frontotemporal Dementia With Progranulin Mutations (FTD-GRN)
    Estudio de fase 1/2, abierto, de dosis ascendentes y multicéntrico para evaluar la seguridad y la eficacia preliminar de AVB-101 administrado mediante infusión intratalámica bilateral en sujetos con demencia frontotemporal con mutaciones en el gen de la progranulina (DFT-GRN).
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study to test whether AVB-101 is both safe and efficacious in a sub-population of genetically defined FTD patients that currently have no other treatment options
    Un estudio para probar si AVB-101 es seguro y eficaz en una subpoblación de pacientes con DFT genéticamente definidos que actualmente no tienen otras opciones de tratamiento.
    A.3.2Name or abbreviated title of the trial where available
    Ph1/2 study of AVB-101 in Subjects with Frontotemporal Dementia with Progranulin Mutations (FTD-GRN)
    A.4.1Sponsor's protocol code numberAVB-PGRN-001
    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 SponsorAviadoBio Ltd
    B.1.3.4CountryUnited Kingdom
    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 supportAviadoBio Limited
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMedpace
    B.5.2Functional name of contact pointClinical Trial Management
    B.5.3 Address:
    B.5.3.1Street AddressVia Olona 2
    B.5.3.2Town/ cityMilan
    B.5.3.3Post code20123
    B.5.3.4CountryItaly
    B.5.4Telephone number390283413400
    B.5.6E-mailS.Zambruno@Medpace.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 Yes
    D.2.5.1Orphan drug designation numberEMA/OD/0000068610
    D.3 Description of the IMP
    D.3.1Product nameRecombinant AAV-9 vector expressing the human progranulin protein
    D.3.2Product code AVB-101
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntracerebral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNAVB-101
    D.3.9.2Current sponsor codeAVB-101
    D.3.9.4EV Substance CodeSUB216576
    D.3.10 Strength
    D.3.10.1Concentration unit vector genomes (vg)/mL
    D.3.10.2Concentration typenot less then
    D.3.10.3Concentration number800000000000
    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) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) Yes
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product Yes
    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 No
    D.3.11.10Medicinal product containing genetically modified organisms Yes
    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
    Frontotemporal Dementia With Progranulin Mutations (FTD-GRN)
    Demencia Frontotemporal con mutaciones en el gen de la progranulina (DFT-GRN)
    E.1.1.1Medical condition in easily understood language
    Dementia
    Demencia
    E.1.1.2Therapeutic area Diseases [C] - Nervous System Diseases [C10]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the safety and tolerability of a one-time, bilateral, intrathalamic administration of AVB-101 in subjects with FTD-GRN.
    Evaluar la seguridad y la tolerabilidad de una administración intratalámica única de AVB-101 en sujetos con DFT-GRN.
    E.2.2Secondary objectives of the trial
    To evaluate the preliminary clinical and biomarker measures of efficacy of a one-time, bilateral, intrathalamic administration of AVB-101 in subjects with FTD-GRN.
    Evaluar las variables clínicas y de biomarcadores preliminares de la eficacia de una administración intratalámica bilateral única de AVB-101 en sujetos con DFT-GRN.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Male or female, 30 to 75 years of age, inclusive, at Screening;
    2. Carriers of a pathogenic granulin (GRN) mutation as confirmed by a sponsor approved genetic test;
    3. EITHER symptomatic frontotemporal dementia (FTD) OR pre-symptomatic carrier of a pathogenic GRN mutation at risk of conversion based on plasma neurofilament light chain >20 pg/mL;
    4. If symptomatic, presence of 1 or more of the criteria for diagnosis of possible behavioral variant FTD or Primary Progressive Aphasia;
    5. Identified, informed study partner able to support the subject for the duration of the study
    6. The subject and/or legally authorized representative is able and willing to give written informed consent prior to study participation. If a subject lacks capacity to consent in the investigator’s opinion, the subject’s assent should be obtained, if required in accordance with local laws, regulations and customs, plus the written informed consent of a legal representative should be obtained. In countries where local laws, regulations, and customs do not permit subjects who lack capacity to consent to participate in this study, they will not be enrolled.
    1. Ser varón o mujer de entre 30 y 75 años, ambos inclusive, en el momento de selección.
    2. Ser portador de una mutación patógena en el gen de la granulina (GRN) confirmada mediante un análisis genético aprobado por el promotor.
    3. Tener demencia frontotemporal (DFT) sintomática O ser portador presintomático de una mutación patógena en el gen GRN con riesgo de conversión según una concentración plasmática de cadenas ligeras de los neurofilamentos (NfL) >20 pg/ml.
    4. En caso de encontrarse sintomático, presencia de uno o más de los criterios diagnósticos de una posible variante conductual de DFT o de afasia progresiva primaria.
    5. Contar con un acompañante para el estudio identificado e informado que pueda ayudar al sujeto durante todo el estudio.
    6. Las mujeres en edad fértil deberán tener una prueba de embarazo en suero negativa en la fase de selección, así como una prueba en orina con tira reactiva negativa y no estar amamantando en las dos semanas previas al tratamiento.
    7. Los sujetos sexualmente activos deberán comprometerse a utilizar un método anticonceptivo de barrera muy eficaz hasta que se obtengan al menos tres muestras negativas consecutivas de diseminación del vector en sangre (o en semen en los varones, si es posible) con una semana de diferencia como mínimo.
    8. Capacidad y disposición para cumplir todos los procedimientos y el calendario de visitas del estudio descritos en el protocolo.
    9. El sujeto o su representante legal pueden y están dispuestos a otorgar su consentimiento informado por escrito antes de participar en el estudio. Si, en opinión del investigador, un sujeto no es capaz de otorgar su consentimiento, deberá obtenerse su asentimiento, si así lo exigen las leyes, normativas y costumbres locales, además del consentimiento informado por escrito de un representante legal. En los países en que las leyes, normativas y costumbres locales no permitan la participación de sujetos que carezcan de la capacidad para otorgar su consentimiento para participar en este estudio, no se incluirá a este tipo de sujetos.
    E.4Principal exclusion criteria
    1. Classification of the mutation in the GRN gene as “not pathogenic,” “likely benign variant,” or “benign variant” in the Alzheimer’s Disease and Frontotemporal Dementia Mutation Database;
    2. Severe dementia that precludes ability to comply with study procedures and/or poses unacceptable safety risk to the subject (i.e. CDR+ NACC FTLD score of 3.0);
    3. Concurrent disease that may cause cognitive impairment unrelated to mutations in the GRN gene, such as other causes of dementia, neurosyphilis,
    hydrocephalus, stroke, small vessel ischemic disease, uncontrolled hypothyroidism, or vitamin B12 deficiency;
    4. Clinically significant abnormality on magnetic resonance imaging (MRI) at Screening considered to be a contraindication to intrathalamic infusion;
    5. Surgically significant pattern of brain atrophy on MRI at Screening that interferes with planned surgical trajectory;
    6. Previous treatment with any gene or cell therapy;
    7. Previous treatment with any investigational medicinal product within 60 days or 5 half-lives (whichever is longer) prior to study drug dosing;
    8. Concomitant disease or treatment which, in the opinion of the Investigator, may pose an unacceptable safety risk to the participant or interfere with study conduct or the subject's ability to comply with study procedures;
    9. Contraindications to MRI as per local guidelines;
    10. Contraindications to gadolinium-based contrast agents per local guidelines;
    11. Contraindications to general anesthesia for a period of up to 10 hours and/or cardiopulmonary disorders that would result in a higher ASA risk classification;
    12. Contraindications to lumbar puncture as per local guidelines;
    1. Tener una mutación en el gen GRN clasificada como “no patógena”, “variante probablemente benigna” o “variante benigna” en la Alzheimer’s Disease and Frontotemporal Dementia Mutation Database.
    2. Presentar demencia grave, definida como una puntuación global de 3,0 en la escala CDR+NACC FTLD (Escala de valoración clínica de la demencia + degeneración del lóbulo frontotemporal del National Alzheimer’s Coordinating Center), que impida el cumplimiento de los procedimientos del estudio o suponga un riesgo inaceptable para la seguridad del sujeto.
    3. Presentar cualquier enfermedad concomitante que pueda causar deterioro cognitivo no relacionado con mutaciones en el gen GRN, como otras causas de demencia, neurosífilis, hidrocefalia, ictus, enfermedad isquémica de pequeños vasos, hipotiroidismo no controlado o carencia de vitamina B12.
    4. Tener una anomalía clínicamente significativa en la resonancia magnética (RM) de selección que se considere una contraindicación de la infusión intratalámica.
    5. Patrón quirúrgicamente significativo de atrofia cerebral en la RM de selección que interfiera en la trayectoria neuroquirúrgica prevista.
    6. Tratamiento previo con terapia génica o celular.
    7. Tratamiento previo con cualquier medicamento en investigación en los 60 días o el equivalente a 5 semividas (lo que suponga más tiempo) previos al tratamiento con el fármaco del estudio.
    8. Haber tenido una enfermedad, cualquier anomalía analítica clínicamente significativa o tratamiento concomitante que, en opinión del investigador, pueda suponer un riesgo inaceptable para la seguridad del sujeto o interferir en la realización del estudio o en su capacidad para cumplir los procedimientos del estudio.
    9. Neoplasia maligna en los 5 años previos a la selección, excepto carcinoma basocelular o espinocelular de piel o carcinoma in situ de cuello uterino tratado con éxito.
    10. Tener contraindicaciones de la RM según las directrices locales.
    11. Tener contraindicaciones del uso de medios de contraste con gadolinio según las directrices locales.
    12. Tener contraindicaciones de la anestesia general durante un período de hasta 10 horas o trastornos cardiopulmonares que supondrían un mayor riesgo según la clasificación de la American Society of Anesthesiology.
    13. ener contraindicaciones de la punción lumbar según las directrices locales.
    14. Hospitalización por cualquier procedimiento médico o quirúrgico importante con anestesia general en las 12 semanas previas a la selección o procedimiento previsto durante el estudio.
    15. Uso activo de anticoagulantes en la fase de selección o necesidad prevista de los mismos durante el período de tratamiento. Los antiagregantes plaquetarios se consideran medicamentos concomitantes aceptables siempre que puedan suspenderse al menos 48 horas antes del tratamiento.
    16. Antecedentes de enfermedad por coronavirus de 2019 (COVID-19) grave o reciente, definida como 1) antecedentes de hospitalización por enfermedad grave en cualquier momento, 2) antecedentes de síntomas respiratorios importantes en cualquier momento o 3) positividad para COVID-19 presintomática o levemente sintomática en las 12 semanas previas al tratamiento previsto.
    17. Análisis toxicológico positivo para drogas.
    18. Antecedentes de trastorno por abuso de sustancias.
    19. Tener un dispositivo implantado de estimulación cerebral profunda, una derivación ventriculoperitoneal u otra derivación del líquido cefalorraquídeo u otro dispositivo implantado.
    20. Tener indicios de riesgo de suicidio, evaluado mediante la Escala de valoración del riesgo de suicidio de Columbia y definido como un intento de suicidio en los 6 meses previos a la selección o tener un riesgo importante de suicidio según el criterio del investigador.
    21. Intolerancia o hipersensibilidad conocida o sospechada al fármaco del estudio o a cualquiera de sus componentes indicados.
    E.5 End points
    E.5.1Primary end point(s)
    Over a 26-week initial and 5year total follow up period:
    • Number and incidence of AEs, SAEs, and clinically meaningful laboratory test abnormalities;
    • Change from baseline in vital signs, ECG parameters, and physical and neurological examinations, and MMSE
    • Change from baseline in mini-mental state examination (MMSE);
    • Change from baseline in biochemistry and hematology safety laboratory tests;
    • Time to achieve clearance of vector genomes in plasma and semen (male only)
    • Incidence of treatment emergent suicidal ideation or behavior as measured using the C-SSRS.
    • Change from baseline in MRI including oedema, inflammation, pre-symptomatic/symptomatic hemorrhage and other structural changes
    Durante un período inicial de 26 semanas y un período total de seguimiento de 5 años:
    • Número e incidencia de AA, AAG y anomalías analíticas clínicamente significativas.
    • Variación de las constantes vitales, los parámetros electrocardiográficos y las exploraciones físicas y neurológicas con respecto al momento basal.
    • Variación de la puntuación MEC con respecto al momento basal.
    • Variación de los análisis clínicos de bioquímica y hematología con respecto al momento basal.
    • Tiempo en lograr la eliminación de los genomas del vector en plasma y semen (únicamente en varones).
    • Incidencia de ideas o comportamientos suicidas surgidos durante el tratamiento, según lo determinado mediante la escala C-SSRS.
    • Variación de los resultados de la RM, como edema, inflamación, hemorragia presintomática/sintomática y otros cambios estructurales, con respecto al momento basal.
    E.5.1.1Timepoint(s) of evaluation of this end point
    26 weeks and 5 years
    26 semanas y 5 años
    E.5.2Secondary end point(s)
    Over a 26-week initial and 5-year total follow up period:
    • Change from baseline in PGRN protein levels in CSF and blood;
    Over a 52-week initial and 5-year total follow up period:
    • Change from baseline in NfL levels in CSF and blood
    Over a 5-year follow up period:
    • Change from baseline in CDR+NACC FTLD-SB score;
    • Change in CGI C, PGI-C, CaGI-C
    Durante un período inicial de 26 semanas y un período total de seguimiento de 5 años:
    • Variación de la concentración de proteína PGRN en LCR y sangre con respecto al momento basal.
    Durante un período inicial de 52 semanas y un período total de seguimiento de 5 años:
    • Variación de la concentración de NfL en LCR y sangre con respecto al momento basal.
    Durante un período de seguimiento de 5 años:
    • Variación de la puntuación CDR+NACC FTLD-SB con respecto al momento basal.
    • Variación de las puntuaciones CGI-C, PGI-C y CaGI-C
    E.5.2.1Timepoint(s) of evaluation of this end point
    26 weeks and 5 years
    26 semanas y 5 años
    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 Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    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 No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    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 Information not present in EudraCT
    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.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA12
    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
    United States
    United Kingdom
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    LPLV
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years6
    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 years6
    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: 8
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 7
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Participants will not be enrolled if they are unable to consent at initial screening/consent, but patients' disease may progress during the 5 year follow up period of the
    study, such that they will lack capacity to consent for themselves.
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state5
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 7
    F.4.2.2In the whole clinical trial 15
    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)
    Participants will receive their usual standard of care.
    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 Decision2023-05-18
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2023-02-03
    P. End of Trial
    P.End of Trial StatusOngoing
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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
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