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    Summary
    EudraCT Number:2009-017346-32
    Sponsor's Protocol Code Number:201228
    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:2010-04-26
    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 number2009-017346-32
    A.3Full title of the trial
    A PHASE I/II CLINICAL TRIAL OF HAEMATOPOIETIC STEM CELL GENE THERAPY FOR THE WISKOTT-ALDRICH SYNDROME
    Studio clinico di fase I/II: terapia genica con cellule staminali ematopoietiche per il trattamento della Sindrome di Wiskott-Aldrich (WAS).
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    HAEMATOPOIETIC STEM CELL GENE THERAPY
    Terapia genica con cellule staminali ematopoietiche
    A.3.2Name or abbreviated title of the trial where available
    TIGET-WAS
    TIGET-WAS
    A.4.1Sponsor's protocol code number201228
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation PlanP/083/2016
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorOrchard Therapeutics (Europe) Ltd
    B.1.3.4CountryUnited Kingdom
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportOrchard Therapeutics (Europe) Limited
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationOrchard Therapeutics (Europe) Limited
    B.5.2Functional name of contact pointClinical
    B.5.3 Address:
    B.5.3.1Street Address108 Cannon Street
    B.5.3.2Town/ cityLondon
    B.5.3.3Post codeEC4N 6EU
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number004402033846700
    B.5.5Fax number004402037270797
    B.5.6E-mailclinical@orchard-tx.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 Yes
    D.2.1.1.1Trade name FLUDARABINA TEVA - 25 MG/ML CONCENTRATO PER SOLUZIONE INIETTABILE O PER INFUSIONE 1 FLACONCINO DI VETRO DA 2 ML
    D.2.1.1.2Name of the Marketing Authorisation holderTEVA ITALIA S.R.L.
    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 namena
    D.3.2Product code [na]
    D.3.4Pharmaceutical form Solution for 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.3.8INN - Proposed INNFLUDARABINA
    D.3.9.1CAS number 75607-67-9
    D.3.9.2Current sponsor codena
    D.3.9.3Other descriptive nameFLUDARABINA
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    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 Yes
    D.3.11.13.1Other medicinal product typechemioterapico
    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 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 Yes
    D.2.5.1Orphan drug designation numberEU/3/11/931
    D.3 Description of the IMP
    D.3.1Product namePLERIXAFOR
    D.3.2Product code [na]
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPLERIXAFOR
    D.3.9.1CAS number 0110078-46-1
    D.3.9.2Current sponsor codena
    D.3.9.3Other descriptive namePlerixafor
    D.3.9.4EV Substance CodeSUB28849
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    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 Yes
    D.3.11.13.1Other medicinal product typeImmunostimolanti
    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 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.3.1Product namena
    D.3.2Product code [na]
    D.3.4Pharmaceutical form Powder and solvent for solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNLENOGRASTIM
    D.3.9.1CAS number 135968-09-1
    D.3.9.2Current sponsor codena
    D.3.9.4EV Substance CodeSUB02888MIG
    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 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 Yes
    D.3.11.13.1Other medicinal product typecitochine
    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.3.1Product nameRITUXIMAB
    D.3.2Product code [na]
    D.3.4Pharmaceutical form Solution for 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.3.8INN - Proposed INNRITUXIMAB
    D.3.9.1CAS number 174722-31-7
    D.3.9.2Current sponsor codena
    D.3.9.3Other descriptive nameRITUXIMAB
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    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 Yes
    D.3.11.13.1Other medicinal product typeimmunologico
    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 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.3.1Product namena
    D.3.2Product code [na]
    D.3.4Pharmaceutical form Solution for 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.3.8INN - Proposed INNBUSULFANO
    D.3.9.1CAS number 55-98-1
    D.3.9.2Current sponsor codena
    D.3.9.3Other descriptive nameBUSULFAN
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    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 Yes
    D.3.11.13.1Other medicinal product typechemioterapico
    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 THYMOGLOBULINE - 5 MG/ML POLVERE PER CONCENTRATO PER SOLUZIONE PER INFUSIONE 1 FIALA DA 10 ML
    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.3.1Product namena
    D.3.2Product code [na]
    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 IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNIMMUNOGLOBULINA DI CONIGLIO ANTITIMOCITI UMANI
    D.3.9.2Current sponsor codena
    D.3.10 Strength
    D.3.10.1Concentration unit mg/kg milligram(s)/kilogram
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1
    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 Yes
    D.3.11.13.1Other medicinal product typeimmunoglobulina
    D.IMP: 7
    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/3/12/998
    D.3 Description of the IMP
    D.3.1Product nameautologous CD34+ cells transduced with a lentiviral vector encoding the WASP cDNA
    D.3.2Product code [NA]
    D.3.4Pharmaceutical form Suspension for injection
    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.3.8INN - Proposed INNOther hematological Agents
    D.3.9.2Current sponsor codeNA
    D.3.9.3Other descriptive nameautologous CD34+ cells transduced with a lentiviral vector encoding the WASP cDNA
    D.3.10 Strength
    D.3.10.1Concentration unit % percent
    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 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
    Wiskott-Aldrich Syndrom
    Sindrome di Wiskott-Aldrich
    E.1.1.1Medical condition in easily understood language
    rare genetic disease characterized by immune deficiency
    rara malattia genetica caratterizzata da deficit immunitario
    E.1.1.2Therapeutic area Diseases [C] - Immune System Diseases [C20]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10061598
    E.1.2Term Immunodeficiency
    E.1.2System Organ Class 10021428 - Immune system disorders
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Primary objectives: 1) To evaluate the safety of the administration of autologous CD34+ cells transduced with a lentiviral vector containing the WASP gene in patients with WAS, after a reduced intensity conditioning regimen. 2) To evaluate the long-term engraftment of WASP-expressing transduced cells. 3) To evaluate the efficacy of gene therapy assessed as: 3.1 Improvement of the patient s immune function (specially T cell function and antigen-specific responses to vaccinations). 3.2 Improvement of thrombocytopenia.
    Gli obiettivi principali dello studio sono: 1) La valutazione della sicurezza della somministrazione delle cellule CD34+ trasdotte con un vettore lentivirale contenente il gene WASP in pazienti affetti da WAS, dopo condizionamento ad intensità ridotta.
    2) La valutazione dell attecchimento a lungo termine delle cellule trasdotte esprimenti WASP.
    3) La valutazione dell efficacia della terapia genica misurata come:
    3.1) Il miglioramento delle funzioni immuni del paziente (specialmente della funzionalita' linfocitaria T e risposta antigene specifica alla vaccinazione)
    3.2) Il miglioramento della trombocitopenia.
    E.2.2Secondary objectives of the trial
    To evaluate the efficacy of gene therapy in improving the patients s clinical condition, assessed by a reduction in frequency of severe infections, and bleeding episodes and reduction of auto-immunity phenomena and eczema.
    Valutazione dell’efficacia della terapia genica nel migliorare le condizioni cliniche del paziente, misurata come riduzione della frequenza delle infezioni severe, episodi di ecchimosi e sanguinamento e riduzione dei fenomeni autoimmuni e dell’eczema
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1) Diagnosis of WAS defined by genetic mutation and at least one of the following criteria: -severe WAS mutation -absent WASP expression -severe clinical score (Zhu clinical score >= 3); 2) No HLA-identical sibling donor; and 3.1) Negative search for a matched unrelated donor (10/10) or an adequate unrelated cord blood donor (5-6/6) within 4-6 months; or 3.2) Patients of > 5 years of age who are not candidate to unrelated allogeneic transplant based on clinical conditions and 4) Parental/guardian/patient signed informed consent
    1) Diagnosi di WAS definita da mutazione genetica e almeno uno dei seguenti criteri: - una mutazione grave WAS - espressione di WASP assente - grave punteggio clinico (punteggio clinico Zhu >= 3) 2) Nessun parente HLA-identico; e 3.1) Ricerca negativa per un donatore compatibile non correlato (10/10) o un adeguata unità di sangue cordonale (5-6/6) entro 4-5 mesi; o 3.2) Pazienti con più di 5 anni di età che non siano candidabili a trapianto allogenico da donatore non correlato in base alle condizioni cliniche e 4) Consenso informato firmato da genitore/tutore/paziente.
    E.4Principal exclusion criteria
    Patients who meet any of the following criteria will be excluded from study admission: 1) Patients positive for HIV-infection 2) Patients affected by neoplasia 3) Patients with cytogenetic alterations typical of MDS/AML 4) Patients with end-organ functions or any other severe disease which, in the judgement of the investigator, would make the patient inappropriate for entry into this study 5) Patients who underwent an allogeneic haematopoietic stem cell transplantation in the previous 6 months 6) Patients who underwent an allogeneic haematopoietic stem cell transplantation with evidence of residual cells of donor origin
    1) Pazienti positivi per infezione da HIV 2) Pazienti affetti da neoplasia 3) Pazienti con alterazioni citogenetiche caratteristiche per AML/MDS 4) Pazienti con gravi disfunzioni organiche o altre patologie debilitanti che, a parere del medico, potrebbero rendere il paziente non eleggibile allo studio 5) Pazienti sottoposti a trapianto allogenico nei precedenti 6 mesi 6) Pazienti sottoposti a trapianto allogenico con evidenza di presenza di cellule di origine del donatore
    E.5 End points
    E.5.1Primary end point(s)
    Primary safety endpoints 1) Conditioning regimen-related safety, consisting in the absence of prolonged aplasia and surveillance of non haematological regimen related toxicity (for clinical features NCI >2, for metabolic/laboratory NCI >3) 2) Safety of lentivirus gene transfer into HSC -short-term safety and tolerability of lentiviral-transduced cell infusion -long-term safety of lentiviral-transduced cell infusion (absence of Replication competent lentivirus (RCL) and abnormal clonal proliferation). Primary efficacy endpoints 1) overall survival 2) Sustained engraftment of genetically corrected haematopoietic stem cells in peripheral blood and/or in bone marrow 3) Expression of vector-derived WASP 4) Improved T-cell functions 5) Antigen-specific responses to vaccination 6) Improved platelet count
    Sicurezza
    1) Sicurezza del regime di condizionamento, che consiste nell assenza di aplasia prolungata e di tossicità non ematologica >=3 per le analisi di laboratorio/metaboliche secondo i criteri NCI, e >=2 per i paramentri clinici, valutati nel follow up a breve e lungo termine dei pazienti.
    2) Sicurezza relativa all infusione delle cellule staminali ematopoietiche trasdotte con il vettore lentivirale:
    -sicurezza e tollerabilità a breve termine dell’infusione delle cellule trasdotte;
    -sicurezza a lungo termine dell’infusione delle cellule che sarà valutata come assenza di virus competente per la replicazione (RCL) e di proliferazioni clonali anomale.
    Efficacia
    1) Sopravvivenza globale
    2) Attecchimento persistente delle cellule ematopoietiche trasdotte nel sangue periferico e/o nel midollo osseo
    3) Espressione di WASP derivato dal vettore
    4) Miglioramento delle funzioni immunitarie T
    5) Risposta antigene-specifica alle vaccinazioni
    6) Miglioramento delle conte piastriniche e normalizzazione volume piastrinico medio
    E.5.1.1Timepoint(s) of evaluation of this end point
    -Ematologic recovery: + 60 days-Safety to quickly treated cell infusion: absence of adverse reactions within 48 hours-long term Safety of infusion treated cells: RCL at baseline, after 1, 3, 6, 12 months and 24 months.
    -Ricostituzione ematologica: + 60 giorni -Safety a tempi brevi dell`infusione delle cellule trasdotte: assenza di reazioni avverse entro 48 ore -Safety a lungo termine dell`infusion delle cellule trasdotte: RCL al baseline, dopo 1,3,6,12 mesi e 24 mesi.
    E.5.2Secondary end point(s)
    Efficacy and safety-multilineage engraftment of cells genetically corrected – reduced frequency of serious infections reduced episodes of bruising and bleeding-reduction of Autoimmunity and eczema-improving the quality of life
    Efficacia e sicurezza -attecchimento multilineare di cellule geneticamente corrette –frequenza ridotta di infezioni gravi a ridotti episodi di ecchimosi e sanguinamento -riduzione dei fenomeni di autoimmunità ed eczema -miglioramento della qualità della vita
    E.5.2.1Timepoint(s) of evaluation of this end point
    -lack of immune response to transgene measured using WASP antibodies (immunoblot analysis): na presence of cells and expression of the gene proper WASp: screening, baseline, + 30 days, 60 days, 90 days, 180 days, 1 year, 2 years +1.5 years, +2.5 years, 3 years
    -mancanza di risposta immunitaria al transgene misurata mediante anticorpi WASP (analisi immunoblot): nd presenza di cellule e di espressione del gene corretto WASp: al basale, a + 180 giorni, 1 anno, 2 anni, 3 anni
    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) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open No
    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 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.8.6 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 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
    the end of the study is the year 8° of Follow Up of the last patient
    la fine dello studio coincide con l'8° anno di F. Up dell'ultimo paziente
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years10
    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 years10
    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 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) Yes
    F.1.1.4.1Number of subjects for this age range: 1
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 5
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 1
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 1
    F.1.3Elderly (>=65 years) No
    F.2 Gender
    F.2.1Female No
    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 No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others Yes
    F.3.3.7.1Details of other specific vulnerable populations
    minors
    minori
    F.4 Planned number of subjects to be included
    F.4.1In the member state8
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 8
    F.4.2.2In the whole clinical trial 8
    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)
    At the end of the study the clinical and laboratory evaluation will continue at each patient house with periodic telephone contact (once a year) for an extended period of time following the end of the study.
    Alla conclusione dello studio la valutazione clinica e di laboratorio proseguirà presso la residenza di ciascun paziente con contatti telefonici periodici (una volta all’anno) per un periodo esteso di tempo.
    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 Decision2010-03-15
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2009-12-03
    P. End of Trial
    P.End of Trial StatusOngoing
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