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    Summary
    EudraCT Number:2019-000667-24
    Sponsor's Protocol Code Number:ST-920-201
    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:2021-09-23
    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 number2019-000667-24
    A.3Full title of the trial
    A Phase I/II, Multicenter, Open-Label, SingleDose, Dose-Ranging Study to Assess the Safety and Tolerability of ST-920, an AAV2/6 Human Alpha Galactosidase A Gene Therapy in Subjects with Fabry Disease
    Studio dose-ranging di fase I/II, multicentrico, in aperto, a dose singola per valutare la sicurezza e la tollerabilità di ST-920, una terapia genica con alfa-galattosidasi A umana AAV2/6 in soggetti affetti da malattia di Fabry
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Phase I/II Study to Assess the Safety and Tolerability of ST-920, an AAV2/6 Human Alpha Galactosidase A Gene Therapy, in Subjects with Fabry Disease
    Studio di fase I/II, per valutare la sicurezza e la tollerabilità di ST-920, una terapia genica con alfa-galattosidasi A umana AAV2/6 in soggetti affetti da malattia di Fabry
    A.3.2Name or abbreviated title of the trial where available
    STAAR
    STAAR
    A.4.1Sponsor's protocol code numberST-920-201
    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 SponsorSangamo 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 supportSangamo Therapeutics, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationSangamo Therapeutics, Inc.
    B.5.2Functional name of contact pointST-920-201 Information Desk
    B.5.3 Address:
    B.5.3.1Street Address7000 Marina Blvd.
    B.5.3.2Town/ cityBrisbane, CA
    B.5.3.3Post code94005
    B.5.3.4CountryUnited States
    B.5.4Telephone number+16282527495
    B.5.5Fax number+15103238182
    B.5.6E-mailclinicaltrials@sangamo.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 numberEU/3/19/2241
    D.3 Description of the IMP
    D.3.1Product nameRecombinant Adeno-associated virus 2/6 vector encoding the cDNA for human alpha galactosidase A
    D.3.2Product code [ST-920]
    D.3.4Pharmaceutical form Solution for injection/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 codeST-920
    D.3.9.3Other descriptive nameAdeno-associated virus serotype 2/6 encoding human alpha-galactosidase A cDNA
    D.3.10 Strength
    D.3.10.1Concentration unit Other
    D.3.10.2Concentration typeup to
    D.3.10.3Concentration number1
    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.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 Yes
    D.2.1.1.1Trade name PARACETAMOLO DOC GENERICI - 1000 MG COMPRESSA 16 COMPRESSE
    D.2.1.1.2Name of the Marketing Authorisation holderDOC GENERICI SRL
    D.2.1.2Country which granted the Marketing AuthorisationItaly
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameParacetamolo
    D.3.2Product code [Paracetamolo]
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    Oral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPARACETAMOLO
    D.3.9.2Current sponsor code-
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number650
    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 Yes
    D.2.1.1.1Trade name ALISERIN - 25 MG GRANULATO EFFERVESCENTE 20 BUSTINE
    D.2.1.1.2Name of the Marketing Authorisation holderFARMAKOPEA S.P.A.
    D.2.1.2Country which granted the Marketing AuthorisationItaly
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product namedifenidramina cloridrato
    D.3.2Product code [difenidramina cloridrato]
    D.3.4Pharmaceutical form Effervescent granules
    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 INNDIFENIDRAMINA CLORIDRATO
    D.3.9.2Current sponsor code-
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number25 to 50
    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: 4
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name PREDNISONE DOC GENERICI - "5 MG COMPRESSE" 10 COMPRESSE IN BLISTER PVC-PVDC/ALU
    D.2.1.1.2Name of the Marketing Authorisation holderDOC GENERICI SRL
    D.2.1.2Country which granted the Marketing AuthorisationItaly
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product namePrednisone
    D.3.2Product code [Prednisone]
    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 INNPREDNISONE
    D.3.9.2Current sponsor code-
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeup to
    D.3.10.3Concentration number60
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Fabry Disease (X-linked lysosomal storage disease)
    Malattia di Fabry (malattia da accumulo lisosomiale legata al cromosoma X)
    E.1.1.1Medical condition in easily understood language
    Fabry Disease
    Malattia di Fabry
    E.1.1.2Therapeutic area Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10016016
    E.1.2Term Fabry's disease
    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
    To assess the safety and tolerability of ST-920
    Valutare la sicurezza e la tollerabilità di ST-920
    E.2.2Secondary objectives of the trial
    •To assess a-Gal A activity and the presence of its substrates in plasma over time
    •To assess impact of ST-920 on ERT administration required for subjects on ERT
    •To assess the impact of ST-920 on renal function
    •To assess the impact of ST-920 on cardiac function and left ventricular hypertrophy
    •To evaluate ST-920 vector DNA shedding over time
    Exploratory Objectives:
    • To assess clinical impact of ST-920 on Fabry disease
    • To assess the a-Gal activity overtime in skin and leukocytes
    • To assess the presence of Gb3 inclusion levels substrates in skin in ERT-naïve and ERT-pseudo-naïve subjects (defined as not having received ERT treatment during the 6 months prior to consent)
    • To assess the presence of a-Gal A substrates in urine for all subjects over time
    • To assess immune response to AAV2/6
    • To assess immune response to a-Gal A
    • To assess the impact of ST-920 on substrate deposition in the kidney (via renal biopsy)in ERT-naïve and ERT pseudo-naïve subjects
    Valutare l’attività di a-Gal A e la presenza dei suoi substrati nel plasma nel tempo
    Valutare l’impatto di ST-920 sulla somministrazione dell’ERT richiesta per i soggetti sottoposti a ERT
    Valutare l’impatto di ST-920 sulla funzionalità renale
    Valutare l’impatto di ST-920 sulla funzionalità cardiaca e sull’ipertrofia ventricolare sinistra
    Valutare la diffusione del DNA vettoriale di ST-920 nel tempo
    Obiettivi esplorativi:
    Valutare l’impatto clinico di ST-920 sulla malattia di Fabry
    Valutare l’attività di a-Gal A nel tempo nella cute e nei leucociti
    Valutare la presenza di livelli di inclusione di Gb3 nella cute in soggetti naïve all’ERT e pseudo-naïve all’ERT
    Valutare la presenza di substrati di a-Gal A nelle urine per tutti i soggetti nel tempo
    Valutare la risposta immunitaria ad AAV2/6
    Valutare la risposta immunitaria ad a-Gal A
    Valutare l’impatto di ST-920 sulla deposizione di substrato nel rene (mediante biopsia renale) in soggetti naïve all’ERT e pseudo-naïve all’ERT
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Subjects must meet all of the following criteria to be included in the study:
    1. >=18 years of age
    2. Signed, written informed consent
    3. Diagnosis of Fabry disease
    4. One or more of the following symptoms: i) cornea verticillata, ii) acroparesthesia, iii) anhidrosis, iv) angiokeratoma
    5. Subjects who are on ERT or are ERT-naïve or are ERT-pseudo-naïve (defined as not having received ERT treatment in the 6 months prior to consent). For subjects receiving ERT, ERT must have been administered at a stable dose for at least 6 months (defined as not having missed more than 3 doses of ERT during the 6 months prior to consent) and regimen (14 days ± 3 days for at least 3 months prior to screening); except for Cohort 3d (see inclusion criterion 8),who must have been on ERT for at least the past year prior to screening.
    6. Male subjects must agree to use an effective form of contraception (e.g., sexual abstinence, documented vasectomy, condom) and refrain from sperm donation from the time of ST-920 administration until a minimum of 3 consecutive semen samples are negative for AAV2/6 after administration of ST-920 and a minimum of 90 days after ST-920 administration.
    7. Female subjects from menarche until becoming post-menopausal or permanently sterile must have a negative serum pregnancy test at screening and must agree to use a highly effective contraception method from screening through the end of the study. Highly effective contraception in females includes:
    • combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal or transdermal)
    • progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable or implantable)
    • intrauterine device (IUD)
    • intrauterine hormone-releasing system (IUS)
    • bilateral tubal occlusion or vasectomized partner
    • sexual abstinence

    AND
    FOR OTHERS INCLUSION CRITERIA PLEASE REFERS TO STUDY PROTOCOL
    I soggetti che incontrano tutti i seguenti criteri di inclusione sarannò inclusi nello studio:
    1. Età>=18 anni
    2. Consenso informato scritto firmato
    3. Diagnosi della malattia di Fabry
    4. Uno o più dei seguenti sintomi: i) cornea verticillata, ii) acroparestesia, iii) anidrosi, iv) angiocheratoma
    5. Soggetti in terapia con ERT o naïve all’ERT o pseudo-naïve all’ERT (definiti come soggetti che non hanno ricevuto il trattamento con ERT nei 6 mesi precedenti il consenso). Per i soggetti che ricevono ERT, la ERT deve essere stata somministrata a una dose stabile per almeno 6 mesi (definita come non aver saltato più di 3 dosi di ERT durante i 6 mesi precedenti il consenso) e regime stabile (14 giorni ±3 giorni per almeno 3 mesi prima dello screening), fatta eccezione per la Coorte 3d (vedere il criterio di inclusione 8), i cui soggetti devono essere stati sottoposti a ERT almeno nell’ultimo anno che precede lo screening.
    6. I soggetti di sesso maschile devono accettare di utilizzare un metodo contraccettivo efficace (ad es. astinenza sessuale, vasectomia documentata, preservativo) ed astenersi dalla donazione di sperma dal momento della somministrazione di ST-920 fino a quando un minimo di 3 campioni consecutivi di liquido seminale non risultino negativi per AAV2/6 dopo la somministrazione di ST-920 e un minimo di 90 giorni dopo la somministrazione di ST-920.
    7. I soggetti di sesso femminile dal menarca fino all’ingresso nella fase post-menopausa o fino a quando diventano permanentemente sterili devono risultare negativi a un test di gravidanza sul siero allo screening e devono accettare di utilizzare un metodo contraccettivo altamente efficace dallo screening fino alla fine dello studio. I metodi contraccettivi altamente efficaci comprendono:
    • contraccettivi ormonali (orali, intravaginali o transdermici) combinati (contenenti estrogeni e progestinici);
    • contraccettivo ormonale contenente solo progestinici (orale, iniettabile, impiantabile) associato a inibizione dell’ovulazione;
    • dispositivo intrauterino (IUD);
    • dispositivo intrauterino a rilascio di ormoni (IUS);
    • occlusione tubarica bilaterale o partner vasectomizzato;
    • astinenza sessuale.

    PER GLI ALTRI CRITERI DI INCLUSIONE FARE RIFERIMENTO AL PROTOCOLLO DI STUDIO
    E.4Principal exclusion criteria
    Subjects who meet any of the following criteria will be excluded from participating in the study:

    1. Known to be unresponsive to ERT in the opinion of the Site Investigator and Medical Monitor (e.g., no documented substrate level decrease on ERT)
    2. Current treatment with migalastat (Galafold™) or prior treatment within 3 months of informed consent
    3. Positive neutralizing antibodies to AAV6
    4. Intercurrent illness expected to impair evaluation of safety or efficacy during the observation period of the study in the opinion of the Site Investigator or Medical Monitor
    5. eGFR <= 40 ml/min/1.73m2
    6. Active infection with hepatitis A virus (HAV RNA positive), active or occult hepatitis B virus infection (positive HBV-DNA or anti-HBc positive), active infection with hepatitis C virus (HCV RNA positive), infection with the human immunodeficiency virus (HIV) as measured by quantitative polymerase chain reaction (qPCR) or active or latent infection with tuberculosis (TB) measured by quantiferon test
    7. Breastfeeding at screening or planning to become pregnant (self or partner) or breastfeed during required period of contraception.
    8. History of liver disease such as clinically significant steatosis, fibrosis, non-alcoholic steatohepatitis (NASH) and cirrhosis, biliary disease within
    6 months of informed consent; except for Gilbert's syndrome
    9. Elevated circulating serum AFP
    10. For subjects receiving ERT, recent or recurrent hypersensitivity reaction manifested by significant infusion reaction to ERT treatment within 6 months prior to consent, in the opinion of the Site Investigator and Medical Monitor

    FOR OTHERS EXCLUSION CRITERIA PLEASE REFERS TO STUDY PROTOCOL
    I soggetti che incontrano uno dei seguenti criteri di esclusione saranno esclusi dallo studio:

    1.Non responsività nota all’ERT secondo il parere dello sperimentatore del centro e del responsabile del monitoraggio medico (ad es. nessuna diminuzione documentata del livello di substrato durante l’ERT)
    2.Trattamento attuale con migalastat (Galafold™) o precedente trattamento entro 3 mesi dal consenso informato
    3.Positività agli anticorpi neutralizzanti per AAV6
    4.Malattia intercorrente che ci si aspetta possa compromettere la valutazione della sicurezza o dell’efficacia durante il periodo di osservazione dello studio a giudizio dello sperimentatore del centro o del responsabile del monitoraggio medico
    5.eGFR <=40 ml/min/1,73 m2
    6.Infezione attiva da virus dell’epatite A (positività per l’RNA di HAV), infezione attiva od occulta da virus dell’epatite B (positività per HBV-DNA o positività per gli anticorpi anti-HBc), infezione attiva da virus dell’epatite C (positività per l’RNA di HCV), infezione da virus dell’immunodeficienza umana (HIV) misurata mediante reazione a catena della polimerasi quantitativa (qPCR) o infezione attiva o latente con tubercolosi (TB) misurata mediante test quantiferon
    7.Allattamento al seno allo screening o intenzione di iniziare una gravidanza (da parte del soggetto stesso o della sua partner) o allattamento al seno durante il periodo di contraccezione richiesto
    8.Anamnesi di malattia epatica come steatosi clinicamente significativa, fibrosi, steatoepatite non alcolica (NASH), cirrosi e malattia biliare entro 6 mesi dal consenso informato, fatta eccezione per la sindrome di Gilbert
    9.Livelli elevati di AFP sierica circolante
    10.Per i soggetti che ricevono ERT, reazione di ipersensibilità recente o ricorrente manifestata da una significativa reazione da infusione al trattamento con ERT nei 6 mesi precedenti il consenso, a giudizio dello sperimentatore del centro e del responsabile del monitoraggio medico.

    PER GLI ALTRI CRITERI DI ESCLUSIONE FARE RIFERIMENTO AL PROTOCOLLO DI STUDIO
    E.5 End points
    E.5.1Primary end point(s)
    • Incidence of treatment-emergent adverse events (TEAEs)

    Additional safety evaluations will include:

    o Routine hematology, chemistry, and liver tests, vital signs, ECG and ECHO
    o Serial alpha fetoprotein (AFP) testing and MRI of liver (or equivalent imaging modality) to monitor for any liver mass
    • Incidenza di eventi avversi emergenti dal trattamento (TEAE)

    Ulteriori valutazioni di sicurezza includeranno:

    o Esami ematologici, chimici ed epatici di routine, segni vitali, elettrocardiogramma (ECG) ed ecocardiogramma (ECO)
    o Test seriali dell’alfa fetoproteina (AFP) e risonanza magnetica per immagini (RMI) del fegato (o modalità di diagnostica per immagini equivalente) per monitorare la massa epatica
    E.5.1.1Timepoint(s) of evaluation of this end point
    -AE Assessment: Screening, Baseline(BL), Day 1, 2, 8 , Weeks (Wks) 2, 4, 6, 8, 12, 16, 20, 24, 28, 32,36, 40, 44, 48, 52 (EOS) & Early Termination Visit (ETV)
    -Clinical laboratory tests: Screening, BL, Day 1, 2, Weeks 2, 4, 6, 8, 12, 16, 20, 24, 36, 52 & ETV
    -Liver Panel: Screening, BL, twice weekly during the first 20 weeks after ST-920 infusion while the subject is on prednisone or other equipotent steroid, Weekly for 4 Wks (Wks 21, 22, 23, 24 [±2 days]) following discontinuation of immunosuppression & then monthly thereafter
    -Vital Signs: Screening, BL, Day 1, 2, 8, Wks 2, 4, 6, 8, 12, 16, 20, 24, 36, 52 & ETV
    -ECG: Screening,BL, Day 8, Weeks 24, 52 & ETV
    -ECHO: Screening, EOS & ETV
    -AFP testing: Screening, Wks 4, 8, 12, 24, 52 & ETV
    -MRI of liver: Screening, Wks 24, 52 & ETV
    - EA:Screening, Baseline, Giorni 1,2,8, Settimane 2, 4, 6, 8, 12, 16, 20, 24, 28, 32,36, 40, 44, 48, 52 (EOS) e ETV
    - Esami clinici di laboratorio: Screening, , Baseline, Giorni 1, 2, Settimane 2, 4, 6, 8, 12, 16, 20, 24, 36, 52 e ETV
    - Esami epatici: Screening, BL, due volte a settimana per le prime 20 settimane post infusione di ST-920 (durante trattamento del paziente con steroidi), settimanalmente per 4 Settimane (21, 22, 23, 24 [±2 giorni]) dopo interruzione immunosoppressione e poi mensilmente;
    - Segni vitali:Screening, BL, Giorni 1, 2, 8, Settimane 2, 4, 6, 8, 12, 16, 20, 24, 36, 52 e ETV
    - ECG:Screening,BL, Giorni 8, Settimane 24, 52 e ETV
    - ECO: Screening, EOS e ETV
    - AFP: Screening, Settimane 4, 8, 12, 24, 52 e ETV
    - RMI del fegato: Screening, Settimane 24, 52 e ETV
    E.5.2Secondary end point(s)
    • Change from baseline at specific time points over the 1-year study period in:
    o a-Gal A activity in plasma
    o Gb3 and/or lyso-Gb3 levels in plasma

    • Change from baseline at specific time points over the 1-year study period in:
    o Frequency of ERT infusion
    o Estimated glomerular filtration rate (eGFR) using the CKD-EPI formula
    o Ejection fraction, global longitudinal strain, l Left ventricular mass index (LVMI), left ventricular systolic function measured by cardiac magnetic resonance imaging (CMR)
    • ST-920 vector clearance measured by level of vector genome in blood (plasma), saliva, urine, stool, and semen

    Exploratory Endpoints:
    • Change from baseline at specific time points over the 1-year study period in:
    o Late gadolinium enhancement (LGE), native myocardial T1 values and T2 mapping measured by cardiac MRI
    o Functional capacity evaluated by maximum oxygen consumption (VO2 max) during cardiopulmonary testing
    o High sensitivity Troponin T, N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) and microRNA assay
    o Minnesota Living With Heart Failure Questionnaire (MLHF-Q) summary score
    o Urine protein to creatinine ratio (UPCR) and urine albumin to creatinine ratio (UACR)
    o Biomarkers of renal function in urine
    o Neuropathic pain measured by the Brief Pain Inventory (BPI)
    o Frequency of pain medication use
    o Gastrointestinal (GI) symptoms measured by the GI symptoms rating scale
    o Mainz Severity Score Index (MSSI)
    o Quality of life (QOL) patient-reported outcome measured by the SF 36 questionnaire
    o a-Gal A activity measured in skin and leukocytes
    o Gb3 inclusion levels measured in skin in ERT-naïve and ERT-pseudonaïve subjects
    o Gb3 and/or lyso-Gb3 levels in urine for all subjects over time
    • Measurement of antibodies to AAV2/6
    • Assessment of cell mediated immune response to AAV2/6
    • Measurement of antibodies to a-Gal A
    • Substrate deposition in the kidney (assessed by renal biopsy) in ERT naïve and ERT-pseudo-naïve subjects
    •Variazione rispetto al valore basale in punti temporali specifici durante il periodo di studio di 1 anno in termini di:
    oAttività di a-Gal A nel plasma
    oLivelli di Gb3 e/o lyso-Gb3 nel plasma
    •Variazione rispetto al valore basale in punti temporali specifici durante il periodo di studio di 1 anno in termini di:
    oFrequenza dell’infusione di ERTVariazione rispetto al valore basale in punti temporali specifici durante il periodo di studio di 1 anno in termini di:
    oVelocità di filtrazione glomerulare stimata (eGFR) utilizzando la formula di Collaborazione epidemiologica per la malattia renale cronica (CKD-EPI)

    Endpoint esplorativi:
    • Variazione rispetto al valore basale in punti temporali specifici durante il periodo di studio di 1 anno in termini di:
    o Acquisizione tardiva di gadolinio (LGE), valori T1 nativi del tessuto miocardico e mappatura T2 misurati mediante RMI cardiaca
    o Capacità funzionale valutata in base al consumo massimo di ossigeno (VO2 max) durante il test cardiopolmonare
    o Troponina T ad alta sensibilità, frammento N-terminale del pro-peptide natriuretico di tipo B (NT-proBNP) e test del microRNA
    o Punteggio riepilogativo del Questionario Minnesota sulla vita con insufficienza cardiaca (MLHF-Q)
    o Rapporto proteine/creatinina nelle urine (UPCR) e rapporto albumina/creatinina nelle urine (UACR)
    o Biomarcatori della funzione renale nelle urine
    o Dolore neuropatico misurato mediante il questionario breve sul dolore (BPI)
    o Frequenza di utilizzo di antidolorifici
    o Sintomi gastrointestinali (GI) misurati mediante la scala di valutazione dei sintomi GI
    o Indice del punteggio di gravità di Mainz (MSSI)
    o Esito riferito dal paziente sulla qualità della vita (QOL) misurato mediante il questionario con Modulo breve a 36 voci (SF-36)
    o Attività di a-Gal A misurata nella cute e nei leucociti
    o Livelli di inclusione di Gb3 misurati nella cute in soggetti naïve all’ERT e pseudo-naïve all’ERT
    o Livelli di Gb3 e/o lyso-Gb3 nelle urine per tutti i soggetti nel tempo
    o Misurazione degli anticorpi anti AAV2/6
    o Valutazione della risposta immunitaria cellulo-mediata ad AAV2/6
    o Misurazione degli anticorpi anti-a-Gal A
    o Deposito di substrato nel rene (valutato mediante biopsia renale) in soggetti naïve all’ERT e pseudo-naïve all’ERT
    E.5.2.1Timepoint(s) of evaluation of this end point
    -a-Gal A, Gb3 &/or Lyso-Gb3 levels: Twice weekly during the first 20 wks after ST-920 infusion, then week 24, 28, 32, 36,40, 44, 48, 52 & ETV
    -ERT administration log: Before & after ST-920 infusion (All timepoints except day 2)
    -eGFR: Screening, BL, Day 8, Wk 4, 8,12,16,20,24,28,32,36,40,44,48,52 & ETV
    -AAV2/6 clearance: BL, Day 8,Wk 2,4,8,12,16,20,24,36,52
    Exploratory:
    Cardiac MRI, GI Symptoms rating scale, MSSI, QOL: BL,Wk 24,52 &ETV
    Protein & albumin to creatinine ratio in urine, Neuropathic pain: BL,Wk 12,24,36,52 &ETV
    Frequency of pain medication use: All intervals except Day 1,2& 8 AAV Immunogenicity: BL,Wk 4,12,24,36,52(Additional samples when liver toxicity is suspected)
    Immune response to a-Gal A: Screening,BL,Wk 4,8,12,16,24,36,52&ETV Renal Biopsy:BL &Wk
    -Livelli di a-Gal A, Gb3 &/or Lyso-Gb3 : Due volte alla settimana per le prime 20 settimane dopo infusione di ST-920, poi Settimane 24, 28, 32, 36,40, 44, 48, 52 e ETV
    -Log sulla somministrazione dell' ERT: Prima e dopo infusione di ST-920 (sempre eccetto giorno 2)
    -eGFR: Screening, BL, Giorno 8, Settimane 4, 8,12,16,20,24,28,32,36,40,44,48,52 e ETV
    -clearance di AAV2/6 : BL, Giorno 8,Settimane 2,4,8,12,16,20,24,36,52

    Per i tempi di rilevazione degli endpoints esplorativi, fare riferimento alla sezione in inglese.
    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 Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    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 Yes
    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 No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    NA: studio non controllato
    NA: not controlled study
    E.8.2.4Number of treatment arms in the trial1
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.4.1Number of sites anticipated in Member State concerned1
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA4
    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
    Australia
    Canada
    Taiwan
    United States
    Germany
    Italy
    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 (last visit las subject)
    LVLS (Ultima visita dell'ultimo soggetto)
    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: 48
    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 state4
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 10
    F.4.2.2In the whole clinical trial 48
    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)
    Upon completion of this study, subjects will be encouraged to participate in a separate long-term follow-up study for at least 5 years from infusion to monitor the long term safety of the study treatment.
    Al termine di questo studio, i soggetti saranno incoraggiati a partecipare a uno studio di follow-up a lungo termine separato per almeno 5 anni dall'infusione per monitorare la sicurezza a lungo termine del trattamento in studio.
    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 Decision2022-03-28
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2022-03-01
    P. End of Trial
    P.End of Trial StatusOngoing
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