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    Summary
    EudraCT Number:2019-002375-34
    Sponsor's Protocol Code Number:EFC15299
    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:2021-06-17
    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 number2019-002375-34
    A.3Full title of the trial
    A multicenter, multinational, randomized, double-blind, placebo-controlled study to assess the efficacy, pharmacodynamics, pharmacokinetics, safety, and tolerability of venglustat in late-onset GM2 gangliosidosis (Tay-Sachs disease and Sandhoff disease) together with a separate basket for juvenile/adolescent late-onset GM2 gangliosidosis and ultra-rare diseases within the same and similar glucosylceramide-based sphingolipid pathway
    Studio multicentrico, internazionale, randomizzato, in doppio cieco, controllato con placebo volto a valutare l’efficacia, la farmacodinamica, la farmacocinetica, la sicurezza e la tollerabilità di venglustat nella gangliosidosi GM2 a esordio tardivo (malattia di Tay-Sachs e malattia di Sandhoff), insieme ad una coorte separata per la gangliosidosi GM2 giovanile/adolescenziale a esordio tardivo e per malattie ultra rare riconducibili ad alterazioni della stessa via metabolica, o similari, degli sfingolipidi a base di glucosilceramide
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A multinational, randomized, double-blind, placebo-controlled study to assess the efficacy, pharmacodynamics, pharmacokinetics, and safety of
    venglustat in late-onset GM2
    Studio internazionale, randomizzato, in doppio cieco, controllato con placebo per valutare l’efficacia, la farmacodinamica, la farmacocinetica e la sicurezza di venglustat nella GM2 a esordio tardivo
    A.3.2Name or abbreviated title of the trial where available
    AMETHIST
    AMETHIST
    A.4.1Sponsor's protocol code numberEFC15299
    A.5.3WHO Universal Trial Reference Number (UTRN)U1111-1197-7905
    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 SponsorGENZYME CORPORATION
    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 supportGENZYME CORPORATION
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationSANOFI S.p.A.
    B.5.2Functional name of contact pointCONTACT POINT
    B.5.3 Address:
    B.5.3.1Street AddressVIALE BODIO 37/B
    B.5.3.2Town/ cityMILANO
    B.5.3.3Post code20158
    B.5.3.4CountryItaly
    B.5.4Telephone number800226343
    B.5.5Fax number0239394168
    B.5.6E-mailinformazioni.medicoscientifiche@sanofi.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 nameVenglustat
    D.3.2Product code [GZ402671]
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNVenglustat
    D.3.9.1CAS number 1401090-53-6
    D.3.9.2Current sponsor codeGZ402671
    D.3.9.3Other descriptive nameGenz-682452-AU
    D.3.9.4EV Substance CodeSUB166602
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number15
    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 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.IMP: 2
    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 nameVenglustat
    D.3.2Product code [GZ402671]
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation Yes
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNvenglustat
    D.3.9.1CAS number 1401090-53-6
    D.3.9.2Current sponsor codeGZ402671
    D.3.9.3Other descriptive nameGenz-682452-AU
    D.3.9.4EV Substance CodeSUB166602
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number6
    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 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.IMP: 3
    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 nameVenglustat
    D.3.2Product code [GZ402671]
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation Yes
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNVenglustat
    D.3.9.1CAS number 1401090-53-6
    D.3.9.2Current sponsor codeGZ402671
    D.3.9.3Other descriptive nameGenz-682452-AU
    D.3.9.4EV Substance CodeSUB166602
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number4
    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 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 placeboTablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Tay-Sachs disease
    Sandhoff disease
    malattia di Tay-Sachs
    malattia di Sandhoff (codice MedDRA PT 10081314, versione 21.1 non trovato a sistema: è stato quindi inserito il termine SOC 10010331, di cui il PT 10081314 fa parte)
    E.1.1.1Medical condition in easily understood language
    Tay-Sachs disease
    Sandhoff disease
    malattia di Tay-Sachs
    malattia di Sandhoff
    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 23.0
    E.1.2Level LLT
    E.1.2Classification code 10043147
    E.1.2Term Tay-Sachs disease
    E.1.2System Organ Class 10010331 - Congenital, familial and genetic disorders
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level SOC
    E.1.2Classification code 10010331
    E.1.2Term Congenital, familial and genetic disorders
    E.1.2System Organ Class 10010331 - Congenital, familial and genetic disorders
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    - Primary population: To assess the efficacy and pharmacodynamics (PD) of daily oral dosing of venglustat when administered over a 104-week period.
    - Secondary population: To assess PD response (plasma and CSF GL-1 biomarker and disease specific biomarkers) of venglustat when administered once daily over a 104-week period
    - Popolazione primaria:
    Valutare l’efficacia e la farmacodinamica (PD) del dosaggio orale giornaliero di venglustat somministrato in un periodo di 104 settimane
    Popolazione secondaria:
    • Valutare la risposta PD (biomarcatore GL-1 del plasma e del CSF e biomarcatori specifici della malattia) di venglustat somministrato una volta al giorno in un periodo di 104 settimane.
    E.2.2Secondary objectives of the trial
    Primary population (adult participants with late-onset GM2 gangliosidosis):
    - To assess the effect of venglustat on selected performance test and scale over a 104-week period
    - To determine the safety and tolerability of venglustat when administered orally once daily over a 104-week period
    - To assess the pharmacokinetics (PK) of venglustat in plasma and cerebrospinal fluid (CSF)

    Secondary population (participants with juvenile/adolescent late-onset GM2 gangliosidosis, GM1 gangliosidosis, saposin C deficiency, sialidosis type 1 or juvenile/adult galactosidosis):
    - To assess the effect of venglustat on selected performance tests and scale over a 104-week period
    - To determine the safety and tolerability of venglustat when administered once daily over a 104-week period
    - To assess the PK of venglustat in plasma and CSF.
    Popolazione primaria (partecipanti adulti con gangliosidosi GM2 a esordio tardivo):
    -Valutare l’effetto di venglustat sulla base dei test e delle scale delle prestazioni selezionati in un periodo di 104 settimane.
    -valutare la sicurezza e la tollerabilità di venglustat quando somministrato per via orale una volta al giorno in un periodo di 104 settimane.
    - valutare la farmacocinetica (PK) di Venglustat nel plasma e nel liquido cerebrospinale (CSF).
    Popolazione secondaria (partecipanti con gangliosidosi GM2giovanile/adolescenziale a insorgenza tardiva, gangliosidosi GM1, deficit di saposina C, sialidosi di tipo 1 o galattosialidosi giovanile/adulta)
    - Valutare l’effetto di venglustat sulla base dei test e delle scale delle prestazioni selezionati in un periodo di 104 settimane.
    - valutare la sicurezza e la tollerabilità di venglustat quando somministrato per via orale una volta al giorno in un periodo di 104 settimane.
    - la PK di Venglustat nel plasma e nel liquido cerebrospinale (CSF)
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    - Primary population and adult secondary population: age >/= 18 years
    - Juvenile/adolescent secondary population: 2 >/= age < 18 years with weight >/= 10 kg
    - Participants with a diagnosis of late onset GM2 gangliosidosis (Tay-Sachs disease and Sandhoff disease) caused by genetic ß-hexosaminidase deficiency resulting from mutations in the HEXA or HEXB genes (primary population only); a secondary population will enroll patients with diagnosis of juvenile/adolescent GM2 gangliosidosis, GM1 gangliosidosis, saposin C deficiency, sialidosis type 1 or juvenile adult galactosialidosis
    - For primary population, the participant has the ability to perform the 9- HPT at the screening visit in </= 240 seconds for the 2 consecutive trials of the dominant hand and the 2 consecutive trials of the nondominant hand.
    - Participants with a history of seizures well controlled by medication other than strong or moderate inducer or inhibitor of CYP3A4
    - Participant is cooperative, able to ingest or chew and swallow oral medication, willing to travel to a study site (if applicable), and able to comply with all aspects of the study, including all assessments, according to the Investigator's judgement
    - Signed written informed assent/consent
    - Contraception for sexually active male participants or female patient; not pregnant or breastfeeding.
    -Popolazione primaria e popolazione secondaria adulta: età >/= 18 anni
    -Bambini/adolescenti appartenenti alla popolazione secondaria: età compresa tra >/= 2 e < 18 anni con un peso >/= 10 kg
    -Partecipanti con una diagnosi clinica di gangliosidosi GM2 a insorgenza tardiva (malattia di Tay-Sachs e malattia di Sandhoff) causata dal deficit di ß-esosaminidasi derivante da mutazioni nei geni HEXA o HEXB
    (solo popolazione primaria); nella popolazione secondaria possono essere arruolati pazienti con diagnosi clinica di gangliosidosi GM2 giovanile/adolescenziale a insorgenza tardiva, gangliosidosi GM1, deficit di saposina C, sialidosi di tipo 1 o galattosialidosi giovanile/adulta.
    Per la popolazione primaria, il partecipante ha la capacità di eseguire il test 9-HPT alla visita di screening in </= 240 secondi valutato in 2 tentativi consecutivi eseguiti con la mano dominante e in 2 tentativi consecutivi con la mano non dominante.
    -Partecipante con un’anamnesi di crisi convulsive ben controllate con il farmaco appropriato, non classificato come induttore o inibitore forte o moderato dell’enzima CYP3A4
    -Il partecipante è collaborativo, in grado di ingerire o masticare e deglutire farmaci orali, disposto a recarsi in un centro dello studio (se applicabile) e in grado di rispettare tutti gli impegni dello studio, comprese tutte le valutazioni, secondo il giudizio dello sperimentatore.
    -Firma del consenso informato/assenso
    -Contraccezione per partecipanti di sesso maschile o femminile sessualmente attivi; non incinta o in allattamento
    E.4Principal exclusion criteria
    - Participant has clinical features of Tay-Sachs or Sandhoff disease, not caused by ß-hexosaminidase deficiency resulting from mutations in the HEXA or HEXB genes and/or is without clinical features
    -For primary population and participants with juvenile/adolescent late onset GM2 gangliosidosis and GM1 gangliosidosis, the participant cannot understand and perform all age-appropriate study assessments with the exception of 25FWT.
    - Relevant medical disorders that would compromise his/her safety
    - Documented diagnosis of hepatitis B, C, human immunodeficiency virus 1 or 2
    - World Health Organization (WHO) grade > 2 cortical cataract or a grade > 2 posterior subcapsular cataract; patients with nuclear cataracts will be accepted
    - Participant who requires invasive ventilatory support
    - Current treatment by anticoagulants, cataractogenic medications or any medications that may worsen the vision of patient with cataract
    - Previous treatment with substrate reduction therapy (SRT) within 3 months prior to study enrollment, strong or moderate inducers or inhibitors of CYP3A4 within 14 days or 5 half-lives prior to enrollment
    - Current participation in another study
    - Use of investigational medicinal product (IMP) within 3 months or 5 half-lives prior to enrollment, whichever is longer, before study enrollment (for N-acetyl-leucine, within 5 half-lives before study enrollment).
    - Liver enzymes (alanine aminotransferase [ALT]/aspartate aminotransferase [AST]) or total bilirubin > 2 x the upper limite of normal (ULN) at the time of screening unless the participant has the diagnosis of Gilbert syndrome and maintains a level of bilirubin < 5 mg/dl and direct bilirubin < 20% (1 mg/dl) of total bilirubin level
    - Renal insufficiency is defined by estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m2 at the screening visit
    -Il partecipante presenta caratteristiche cliniche della malattia di Tay-Sachs o di Sandhoff, non dovuto a deficit di ß-esosaminidasi causato da mutazioni nei geni HEXA o HEXB e/o non presenta caratteristiche cliniche
    Per la popolazione primaria e i partecipanti con gangliosidosi GM2 a insorgenza in età giovanile/adolescenziale e gangliosidosi GM1, il partecipante non è in grado di comprendere ed eseguire tutte le valutazioni dello studio appropriate all’età, ad eccezione del 25FWT.
    -Disturbi medici clinicamente rilevanti che potrebbero compromettere la sua sicurezza.
    -Diagnosi documentata di epatite B, epatite C, virus dell’immunodeficienza umana 1 o 2
    -Secondo la classificazione dell’Organizzazione mondiale della sanità (OMS) il partecipante presenta una cataratta corticale > Grado 2 o una cataratta sottocapsulare posteriore > Grado 2. I partecipanti con cataratta nucleare non saranno esclusi.
    -Il partecipante richiede l’uso di un supporto ventilatorio invasivo
    -Il partecipante è sottoposto a trattamento in corso con anticoagulanti, farmaci catarattogenici o altri farmaci che potrebbero peggiorare la visione del paziente con cataratta.
    -Precedenti trattamento con terapie di riduzione del substrato (SRT) nei 3 mesi precedenti l’arruolamento nello studio, induttori o inibitori, forti o moderati, dell’enzima CYP3A4 nei 14 giorni o nelle 5 emivite precedenti l’arruolamento nello studio.
    -Attuale partecipazione a un altro studio interventistico sperimentale.
    -Uso dell’IMP, nei 3 mesi o nelle 5 emivite prima dell'arruolamento nello studio, a seconda del periodo più lungo, (per N-acetil-leucina, entro 5 emivite prima dell'arruolamento nello studio
    -Enzimi epatici (alanina aminotransferasi [ALT]/aspartato aminotransferasi [AST]) o bilirubina totale >2 volte il limite superiore della norma (ULN) al momento dello screening, a meno che il partecipante non presenti una diagnosi di sindrome di Gilbert e mantenga un livello di bilirubina totale <5 mg/dl e bilirubina diretta <1 mg/dl (20%) del livello di bilirubina totale.
    Insufficienza renale definita dalla velocità di filtrazione glomerulare stimata < 30 ml/min/1,73 m2 alla visita di screening.
    E.5 End points
    E.5.1Primary end point(s)
    1 - Change in cerebrospinal fluid (CSF) GM2 biomarker ; Percent change in CSF GM2 biomarker from baseline to Week 104 in primary population
    2 - Change in the 9-hole pegboard test (9-HPT) ; Annualized rate of change in the 9-HPT from baseline to Week 104 in primary population
    3 - Assessment of pharmacodynamic (PD) response in plasma and CSF:
    - GL-1, GM1 biomarkers ; Concentration of GL-1 biomarker with pathway specific biomarker GM1 for GM1 gangliosidosis in secondary population
    - GL-1, GM2 biomarkers ; Concentration of GL-1 with GM2 for GM2 gangliosidosis in secondary population
    - GL-1, GM2, GM3 biomarkers ; Concentration of GL-1 with GM2, GM3 for sialidosis in secondary population
    - GL-1, GM1, GM3 biomarkers ; Concentration of GL-1 with GM1, GM3 for galactosialidosis in secondary population
    - GL-1 biomarker ; Concentration of GL-1 for saposin C deficiency in secondary population.
    1-Variazione del biomarcatore GM2 nel fluido cerebrospinale (CSF); variazione percentuale del biomarcatore GM2 nel liquido cerebrospinale (CSF) dal basale alla Settimana 104 nella popolazione primaria.
    2-Variazione nel test dei 9 pioli (9-HPT): tasso annualizzato di variazione nel test dei 9 pioli (9-HPT) dal basale alla Settimana 104 nella popolazione primaria.
    3-Valutazione della risposta farmacodinamica (PD) nel plasma e nel CSF:
    - biomarcatori GL-1, GM1; Concentrazione del biomarcatore GL-1 con il biomarcatore GM1 specifico per il pathway per la gangliosidosi GM1 nella popolazione secondaria
    - biomarcatori GL-1, GM2; Concentrazione di GL-1 con GM2 per la gangliosidosi GM2 nella popolazione secondaria
    - biomarcatori GL-1, GM2, GM3; Concentrazione di GL-1 con GM2, GM3 per la sialidosi nella popolazione secondaria
    - biomarcatori GL-1, GM1, GM3; Concentrazione di GL-1 con GM1, GM3 per la galactosialidosi nella popolazione secondaria
    - biomarcatore GL-1; Concentrazione di GL-1 per il deficit di saposina C nella popolazione secondaria
    E.5.1.1Timepoint(s) of evaluation of this end point
    1, 2, 3 : From baseline to Week 104.
    1,2,3,: da basale alla settimana 104.
    E.5.2Secondary end point(s)
    1 - Safety/tolerability: Adverse events ; Number of patients with adverse events
    2 - Assessment of pharmacokinetic (PK) parameters in plasma: Cmax ; Maximum venglustat concentration (Cmax)
    Assessment of PK parameters in plasma: tmax ; Time to maximum venglustat concentration (tmax)
    Assessment of PK parameters in plasma: AUC0-24h ; Concentration versus time curve calculated using the trapezoidal method from time 0 to 24 hours (AUC0-24h)
    3 - Assessment of PK parameters in CSF: Cmax ; Maximum venglustat concentration (Cmax)
    Assessment of PK parameters in CSF: tmax ; Time to maximum venglustat concentration (tmax)
    Assessment of PK parameters in CSF: AUC0-24h ; Concentration versus time curve calculated using the trapezoidal method from time 0 to 24 hours (AUC0-24h)
    4 - Change in 25-foot walk test (FWT) ; Change in timed 25-FWT from baseline to Week 104 (in patients able to walk at baseline)
    5 - Change in Friedreich's Ataxia Rating Scale (FARS) ; Change in FARS score from baseline to Week 104
    6 - Change in 9-hole peg test (9-HPT) ; Annualized rate of change in the 9-HPT from baseline to Week 104 in secondary population.
    1. Sicurezza /tollerabilità: eventi avversi; Numero di pazienti con eventi avversi
    2. Valutazione dei parametri di farmacocinetica (PK) nel plasma: Cmax; Concentrazione massima di venglustat (Cmax)
    Valutazione dei parametri PK nel plasma: tmax; tempo alla concentrazione massima di venglustat (tmax)
    Valutazione dei parametri PK nel plasma: AUC 0-24h; area sotto la concentrazione rispetto alla curva del tempo usando il metodo trapezoidale dal tempo 0 alle 24 ore (AUC 0-24h)
    3. Valutazione dei parametri di farmacocinetica (PK) nel CSF: Cmax; Concentrazione massima di venglustat (Cmax)
    Valutazione dei parametri PK nel CSF: tmax; tempo alla concentrazione massima di venglustat (tmax)
    Valutazione dei parametri PK nel CSF: AUC 0-24h; area sotto la concentrazione rispetto alla curva del tempo usando il metodo trapezoidale dal tempo 0 alle 24 ore (AUC 0-24h)
    4. Variazione nel 25FWT: Variazione nel 25FWT dal basale alla Settimana 104 (nei partecipanti in grado di camminare al basale)
    5. Variazione nell’esame neurologico della scala FARS ; Variazione nell’esame neurologico della scala FARS dal basale alla Settimana 104
    6. Variazione nel test 9-HPT; Tasso annualizzato di variazione nel test 9-HPT dal basale alla Settimana 104 nella popolazione secondaria
    E.5.2.1Timepoint(s) of evaluation of this end point
    1,2,3,4,5,6: from baseline to week 104.
    1,2,3,4,5,6: dal basale alla settimana 104.
    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 Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    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 No
    E.8.1.6Cross over No
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    per popolazione secondaria: trattamento in aperto con solo venglustat
    for secondary population: open label treatment with venglustat only
    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 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 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 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
    Austria
    Brazil
    Czechia
    France
    Germany
    Italy
    Japan
    Portugal
    Russian Federation
    Spain
    Turkey
    United Kingdom
    United States
    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
    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 months8
    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 months6
    E.8.9.2In all countries concerned by the trial days14
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    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) Yes
    F.1.1.5.1Number of subjects for this age range: 4
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 6
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 73
    F.1.3Elderly (>=65 years) No
    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 No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state1
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 40
    F.4.2.2In the whole clinical trial 83
    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 who complete the Week 110 assessments of the current study will be given the option to enroll in a long-term safety (LTS) follow-up study to assess safety and tolerability of venglustat.
    Ai Partecipanti che completano la valutazione della settimana 110 del presente studio verrà data la possibilità di partecipare ad unoc studio di follow-up di sicurezza a lungo termine (LTS) per valutare la sicurezza e la tollerabilità di venglustat.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2019-12-13
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-03-04
    P. End of Trial
    P.End of Trial StatusOngoing
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