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    Summary
    EudraCT Number:2017-002430-23
    Sponsor's Protocol Code Number:TigetT10_MPS1H
    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:2020-03-09
    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 number2017-002430-23
    A.3Full title of the trial
    A phase I/II study evaluating safety and efficacy of autologous hematopoietic stem and progenitor cells genetically modified with IDUA lentiviral vector encoding for the human α-L-iduronidase gene for the treatment of patients affected by Mucopolysaccharidosis Type I, Hurler variant
    Studio clinico di fase I/II per valutare la sicurezza ed efficacia del trapianto di cellule staminali ematopoietiche autologhe geneticamente modificate con un vettore lentivirale IDUA codificante per il gene della α-L-iduronidasi umana per il trattamento di pazienti affetti da Mucopolisaccaridosi di tipo I Hurler.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Gene therapy study with autologous hemapoietic stem cells for patients affected by MPSIH
    Studio di terapia genica con cellule staminali ematopoietiche autologhe per pazienti affetti da MPSIH
    A.3.2Name or abbreviated title of the trial where available
    TigetT10_MPS1H
    TigetT10_MPS1H
    A.4.1Sponsor's protocol code numberTigetT10_MPS1H
    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 SponsorOSPEDALE SAN RAFFAELE
    B.1.3.4CountryItaly
    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 supportFondazione Telethon
    B.4.2CountryItaly
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationOSPEDALE SAN RAFFAELE
    B.5.2Functional name of contact pointSR-TIGET Clinical Trial Office (TCT
    B.5.3 Address:
    B.5.3.1Street AddressVia Olgettina 60
    B.5.3.2Town/ cityMilano
    B.5.3.3Post code20132
    B.5.3.4CountryItaly
    B.5.4Telephone number0039 02 2643 6321
    B.5.5Fax number0039 02 2643 6545
    B.5.6E-mailtcto@hsr.postecert.it
    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.3.4Pharmaceutical form Suspension for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMP
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.2Current sponsor codeNA
    D.3.9.3Other descriptive nameCellule CD34+ autologhe trasdotte con IDUA LV codificante per il cDNA dell'alfa-L-iduronidasi
    D.3.10 Strength
    D.3.10.1Concentration unit Other
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    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 BUSILVEX - 6 MG/ML - CONCENTRATO PER SOLUZIONE PER INFUSIONE - USO ENDOVENOSO - FLACONCINO - 10 ML 8 FLACONCINI
    D.2.1.1.2Name of the Marketing Authorisation holderPIERRE FABRE MEDICAMENT
    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.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMP
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNBUSULFANO
    D.3.9.2Current sponsor codeNA
    D.3.9.3Other descriptive nameBUSULFANO
    D.3.10 Strength
    D.3.10.1Concentration unit mg/m2 milligram(s)/square meter
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number80
    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 FLUDARABINA ACCORD - "25 MG/ML CONCENTRATO PER SOLUZIONE INIETTABILE O PER INFUSIONE" 5 FLACONCINI IN VETRO DA 2 ML
    D.2.1.1.2Name of the Marketing Authorisation holderACCORD HEALTHCARE LIMITED
    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.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMP
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNFLUDARABINA FOSFATO
    D.3.9.2Current sponsor codeNA
    D.3.9.3Other descriptive nameFLUDARABINA FOSFATO
    D.3.10 Strength
    D.3.10.1Concentration unit mg/m2 milligram(s)/square meter
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number160
    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 MABTHERA - 2 FIALE 100 MG 10 ML
    D.2.1.1.2Name of the Marketing Authorisation holderROCHE REGISTRATION LIMITED
    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.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMP
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNRITUXIMAB
    D.3.9.2Current sponsor codeNA
    D.3.9.3Other descriptive nameRITUXIMAB
    D.3.10 Strength
    D.3.10.1Concentration unit mg/m2 milligram(s)/square meter
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number375
    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: 5
    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 MYELOSTIM - 34 1 FLACONCINO LIOFILIZZATO 33.6 MIU + SIRINGA PRERIEMPITA SOLVENTE 1 ML
    D.2.1.1.2Name of the Marketing Authorisation holderCHUGAI SANOFI AVENTIS
    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.3.4Pharmaceutical form Powder and solvent for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMP
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNLENOGRASTIM
    D.3.9.2Current sponsor codeNA
    D.3.9.3Other descriptive nameLENOGRASTIM
    D.3.10 Strength
    D.3.10.1Concentration unit IU/ml international unit(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number34
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 6
    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 MOZOBIL - 20 MG/ML - SOLUZIONE INIETTABILE - USO SOTTOCUTANEO - FLACONCINO (VETRO) - 24 MG/1.2 ML 1 FLACONCINO
    D.2.1.1.2Name of the Marketing Authorisation holderGENZYME EUROPE B.V.
    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.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMP
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPLERIXAFOR
    D.3.9.2Current sponsor codeNA
    D.3.9.3Other descriptive namePLERIXAFOR
    D.3.10 Strength
    D.3.10.1Concentration unit mg/kg milligram(s)/kilogram
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number0.24
    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
    Mucopolysaccharidosis type I Hurler
    Mucopolisaccaridosi di tipo I Hulrer
    E.1.1.1Medical condition in easily understood language
    Rare hereditary lysosomal storage disorder characterized by a lack/reduced activity of the IDUA, present in all tissues and particularly important in connective tissue, bone and in the nervous system
    Rara malattia genetica ereditaria caratterizzata da mancata/ridotta attività dell’IDUA, presente in tutti i tessuti e particolarmente importante nel tessuto connettivo e osseo e nel sistema nervoso
    E.1.1.2Therapeutic area Body processes [G] - Genetic Phenomena [G05]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level PT
    E.1.2Classification code 10056886
    E.1.2Term Mucopolysaccharidosis I
    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 evaluate the safety and tolerability of autologous CD34+ cell enriched fraction that contains HSC transduced with LV encoding the IDUA gene in pediatric patients with MPS IH following a myeloablative conditioning regimen
    Valutare la sicurezza e la tollerabilità dell’infusione di cellule staminali ematopoietiche (HSC) CD34+ autologhe trasdotte con un vettore lentivirale codificante il gene IDUA umano (LV-IDUA) in pazienti pediatrici affetti da MPS IH dopo terapia di condizionamento mieloablativa.
    E.2.2Secondary objectives of the trial
    To evaluate the efficacy of autologous CD34+ cell enriched fraction that contains HSC transduced with LV encoding the IDUA gene in pediatric patients with MPS IH following a myeloablative conditioning regimen
    Valutare l’efficacia dell’infusione di cellule staminali ematopoietiche (HSC) CD34+ autologhe trasdotte con un vettore lentivirale codificante il gene IDUA umano (LV-IDUA) in pazienti pediatrici affetti da MPS IH dopo terapia di condizionamento mieloablativa.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Written informed consent by parent/legal guardian
    2. Sex: Males or Females
    3. Age: ≥ 28 days and ≤ 11 years old
    4. Biochemically and molecularly proven MPS IH
    5. Lansky Index > 80 %
    6. Indication to HSCT
    7. Lack of a non-heterozygous (for mutated IDUA) HLA-matched sibling donor or a ≥7/8 (4 digits high-resolution typing) HLA-matched cord blood donor with a cellularity ≥5 x 107 Total Nucleated Cells (TNC)/Kg after 1-month search
    8. Adequate cardiac, renal, hepatic and pulmonary functions
    1. Consenso informato firmato dai genitori o tutori legali
    2. Sesso: maschi o femmine
    3. Età: ≥ 28 giorni e ≤ 11 anni
    4. Diagnosi biochimica e molecolare di MPS IH
    5. Indice di Lansky >80%
    6. Indicazione al trapianto di cellule staminali ematopoietiche
    7. Assenza di donatore non eterozigote (per IDUA) HLA-identico nel nucleo familiare o di donatore di sangue placentare matchato per il sistema HLA ≥ 7/8 (tipizzazione molecolare ad alta risoluzione a 4 cifre) con una cellularità ≥ 5 x107 cellule nucleate totali (TNC) /Kg, ad 1 mese dall’apertura della ricerca.
    8. Funzione cardiaca, renale, epatica e polmonare adeguate
    E.4Principal exclusion criteria
    1. Use of other investigational agents within 4 weeks prior to study enrolment (within 6 weeks if use of long-acting agents)
    2. Severe, active viral, bacterial, or fungal infection at eligibility evaluation
    3. Patients affected by malignant neoplasia or family history of familial cancer syndromes
    4. Cytogenetic alterations associated with high risk of developing hematological malignancies
    5. History of uncontrolled seizures
    6. Patients with end-organ damage or any other severe disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study
    7. Positivity for HIV (serology or RNA), and/or HbsAg and/or HBV DNA and/or HCV RNA and/or Treponema Pallidum or Mycoplasma active infection
    8. Patients with DQ/IQ <70
    9. Previous allogeneic HSCT or gene therapy with a different product
    10. Controindications to PeIMP (G-CSF, Plerixafor, Busulfan, Fludarabine, Rituximab)
    1. Utilizzo di un altro prodotto sperimentale nelle 4 settimane precedenti all’arruolamento nello studio (entro 6 settimane nel caso di prodotti a lunga durata d’azione)
    2. Gravi infezioni virali, batteriche o fungine attive al momento della valutazione dell’eleggibilità
    3. Pazienti affetti da neoplasie maligne o con storia familiare di sindromi neoplastiche
    4. Pazienti con alterazioni citogenetiche associate ad un alto rischio di sviluppare neoplasie ematologiche
    5. Storia di convulsioni non controllate
    6. Pazienti con insufficienza d’organo o qualsiasi altra malattia grave che, a giudizio dell’investigatore, potrebbe rendere il paziente non candidabile ad essere arruolato nello studio
    7. Positività a HIV (sierologia o RNA) e/o positività o infezione attiva da HbsAg e/o HBV e/o HCV e/o Treponema Pallidum e/o Mycoplasma.
    8. Pazienti con un DQ/IQ <70
    9. Precedente trapianto allogenico di cellule staminali ematopoietiche o terapia genica con un altro prodotto medicinale
    10. Controindicazioni ai PeIMP (G-CSF, Plerixafor, Busulfano, Fludarabina, Rituximab)
    E.5 End points
    E.5.1Primary end point(s)
    Safety
    1) Overall survival
    2) Achievement of hematological engraftment ≤ day +45 from Advanced Therapy Investigational Medicinal Product (ATIMP) injection. Hematologic engraftment is defined as the first of 3 consecutive days with neutrophil count > 500/mm3 and platelets > 20,000/mm3.
    3) Safety of the administration of autologous HSC transduced with LV-IDUA.
    4) Overall safety and tolerability measured by AE recording.

    Efficacy
    1) IDUA activity in blood (DBS) (up to supraphysiologic levels) at 1-year post-treatment
    Sicurezza
    1) Sopravvivenza globale
    2) Ottenimento dell’attecchimento ematologico entro il giorno +45 dall’infusione del prodotto medicinale di terapia avanzata (ATIMP). L’attecchimento ematologico viene definito come il primo di 3 giorni consecutivi con una conta di neutrofili > 500/mm3 e di piastrine > 20,000/mm3.
    3) Sicurezza della somministrazione delle HSC autologhe trasdotte con LV-IDUA.
    4) Sicurezza generale e tollerabilità; misurata tramite la registrazione degli eventi avversi (AE).

    Efficacia
    1) Attività IDUA nel sangue (su goccia di sangue essiccata su cartoncino, DBS) (fino a livelli sopra-fisiologici) a 1 anno dal trattamento.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Safety
    1) Overall survival
    2) Achievement of hematological engraftment ≤ day +45 from Advanced Therapy Investigational Medicinal Product (ATIMP) injection. Hematologic engraftment is defined as the first of 3 consecutive days with neutrophil count > 500/mm3 and platelets > 20,000/mm3.
    3) Safety of the administration of autologous HSC transduced with LV-IDUA.
    4) Overall safety and tolerability measured by AE recording.

    Efficacy
    1) IDUA activity in blood (DBS) (up to supraphysiologic levels) at 1-year post-treatment
    Sicurezza
    1) Sopravvivenza globale
    2) Ottenimento dell’attecchimento ematologico entro il giorno +45 dall’infusione del prodotto medicinale di terapia avanzata (ATIMP). L’attecchimento ematologico viene definito come il primo di 3 giorni consecutivi con una conta di neutrofili > 500/mm3 e di piastrine > 20,000/mm3.
    3) Sicurezza della somministrazione delle HSC autologhe trasdotte con LV-IDUA.
    4) Sicurezza generale e tollerabilità; misurata tramite la registrazione degli eventi avversi (AE).

    Efficacia
    1) Attività IDUA nel sangue (su goccia di sangue essiccata su cartoncino, DBS) (fino a livelli sopra-fisiologici) a 1 anno dal trattamento.
    E.5.2Secondary end point(s)
    Exploratory end-points of efficacy
    Polyclonal engraftment evaluated by integration analysis at 6 and 12 months post-treatment
    End-point esploratori di efficacia
    Attecchimento policlonale; valutato tramite analisi delle integrazioni lentivirali a 6 mesi e a 1 anno dal trattamento
    E.5.2.1Timepoint(s) of evaluation of this end point
    Exploratory end-points of efficacy
    Polyclonal engraftment evaluated by integration analysis at 6 and 12 months post-treatment
    End-point esploratori di efficacia
    Attecchimento policlonale; valutato tramite analisi delle integrazioni lentivirali a 6 mesi e a 1 anno dal trattamento
    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 No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Yes
    E.7.1.1First administration to humans Yes
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    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 Information not present in EudraCT
    E.8.1.6Cross over Information not present in EudraCT
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    Singolo braccio, in aperto
    Single arm, open label
    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.8.2.4Number 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 No
    E.8.5.1Number of sites anticipated in the EEA1
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA Information not present in EudraCT
    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
    Ultima visita dell'ultimo paziente
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years0
    E.8.9.1In the Member State concerned months30
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years0
    E.8.9.2In all countries concerned by the trial months30
    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 Yes
    F.1.1Number of subjects for this age range: 1
    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) Yes
    F.1.1.4.1Number of subjects for this age range: 4
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 2
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) No
    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 No
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation Yes
    F.3.3.6Subjects incapable of giving consent personally Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Minors
    Pazienti minori
    F.3.3.7Others Yes
    F.3.3.7.1Details of other specific vulnerable populations
    Patients with rare disease
    Pazienti affetti da una malattia rara
    F.4 Planned number of subjects to be included
    F.4.1In the member state6
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 6
    F.4.2.2In the whole clinical trial 6
    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)
    Due to the inherent nature of the gene therapy being a once-only treatment, there is no plan to offer further treatment/ doses of the ATIMP following the end of the study. After completion of 1 year follow-up, patients will be asked if they want to be enrolled in a long-term follow-up study and followed-up for at least 8 years after the gene therapy.
    Data la natura intrinseca della terapia genica che consiste in una monosomministrazione unica, non vi è alcun piano per offrire ulteriori trattamenti/dosi del ATIMP in studio a seguito della fine dello studio. Al termine dello studio (1 anno di follow-up dopo terapia genica) ai pazienti verrà proposto l'arruolamento in uno studio a lungo-termine per essere seguiti per almeno 8 anni dopo la terapia genica.
    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 Decision2018-03-14
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2017-10-12
    P. End of Trial
    P.End of Trial StatusOngoing
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