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    The EU Clinical Trials Register currently displays   41448   clinical trials with a EudraCT protocol, of which   6807   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2012-002120-33
    Sponsor's Protocol Code Number:HLSCS01-11
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2013-06-12
    Trial results View 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 number2012-002120-33
    A.3Full title of the trial
    Human Liver Stem Cells (HLSCs) in patients suffering from liver-based inborn metabolic diseases causing life-threatening neonatal onset of hyperammonemic encephalopathy
    Utilizzazione delle Cellule staminali del fegato (HLSCs) in neonati con iperammoniemia ed encefalopatia dovute a malattie metaboliche genetiche
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Human Liver Stem Cells (HLSCs) in liver metabolic diseases
    Utilizzazione delle Cellule staminali del fegato (HLSCs) nelle malattie metaboliche del fegato
    A.3.2Name or abbreviated title of the trial where available
    HLSCs in liver-based inborn metabolic diseases
    HLSCs nelle malattie metaboliche del fegato
    A.4.1Sponsor's protocol code numberHLSCS01-11
    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 SponsorAZIENDA SANITARIA OSPEDALIERA O.I.R.M. - S. ANNA
    B.1.3.4CountryItaly
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportEUDAX srl
    B.4.2CountryItaly
    B.4.1Name of organisation providing supportAreta International srl
    B.4.2CountryItaly
    B.4.1Name of organisation providing supportFresenius Medical Care
    B.4.2CountryGermany
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationCentro Malattie Metaboliche/ Presidio Ospedaliero Regina Margherita
    B.5.2Functional name of contact pointDr. Marco Spada
    B.5.3 Address:
    B.5.3.1Street AddressPiazza Polonia 94
    B.5.3.2Town/ cityTorino
    B.5.3.3Post code10126
    B.5.3.4CountryItaly
    B.5.4Telephone number390113135857
    B.5.5Fax number390113134631
    B.5.6E-mailmarco.spada@unito.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 Yes
    D.2.5.1Orphan drug designation numberEU/11/904
    D.3 Description of the IMP
    D.3.1Product nameHuman Liver Stem Cells (HLSCs)
    D.3.4Pharmaceutical form Suspension for injection
    D.3.4.1Specific paediatric formulation Yes
    D.3.7Routes of administration for this IMPNot mentioned (Noncurrent)
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNNA
    D.3.9.3Other descriptive nameHeterologous human adult liver-derived stem cells
    D.3.10 Strength
    D.3.10.1Concentration unit Other
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number22000000 to 44000000
    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 Yes
    D.3.11.3.2Gene therapy medical product No
    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
    neonatal hyperammonemic encephalopathy associated with inborn liver metabolic diseases
    iperammoniemia e encefalopatia in neonati con malattie metaboliche congenite del fegato
    E.1.1.1Medical condition in easily understood language
    inborn metabolic hepatic diseases
    malattie metaboliche congenite del fegato
    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 14.1
    E.1.2Level PT
    E.1.2Classification code 10059521
    E.1.2Term Methylmalonic aciduria
    E.1.2System Organ Class 10010331 - Congenital, familial and genetic disorders
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.1
    E.1.2Level PT
    E.1.2Classification code 10058299
    E.1.2Term Argininosuccinate lyase deficiency
    E.1.2System Organ Class 10010331 - Congenital, familial and genetic disorders
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.1
    E.1.2Level PT
    E.1.2Classification code 10052450
    E.1.2Term Ornithine transcarbamoylase deficiency
    E.1.2System Organ Class 10010331 - Congenital, familial and genetic disorders
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.1
    E.1.2Level PT
    E.1.2Classification code 10058297
    E.1.2Term Carbamoyl phosphate synthetase deficiency
    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 hepatic and extra-hepatic complications after liver intraparenchymal HLSC injection in neonates suffering from inborn liver metabolic diseases causing life-threatening neonatal-onset of hyperammonemic encephalopathy
    valutare le complicanze epatiche ed extra-epatiche a seguito della somministrazione intraparenchimale delle HLSCs in neonati con iperammonemia e encefalopatia dovute a malattie metaboliche genetiche
    E.2.2Secondary objectives of the trial
    To evaluate plasma ammonia levels (< 100 µmol/l) following the treatment; To evaluate the daily protein intake maintaining plasma ammonia levels < 100 µmol/l (measure: quantification of daily protein tolerance increase (g/kg/day) following the treatment); To reduce clinically significant hyperammonemic episodes (measure: number of hyperammonemic episodes following the treatment); To defer the time of liver transplantation from the scheduled time (measure: difference in months between the age at liver transplantation following the treatment and the age previously scheduled)
    Valutare i livelli di ammonemia (< 100 µmol/l) dopo il trattamento; Valutare l’assunzione giornaliera di proteine mantenendo livelli di ammoniemia < 100 µmol/l (misurare: quantificare la toleranza giornaliera di proteine (g/kg/giorno) dopo il trattamento); Ridurre gli episodi clinicamente rilevanti di iperammoniemia (misurare: il numero di episodi di iperammoniemia dopo il trattamento); Valutare la possibilità di posticipare il trapianto di fegato (misurare: la differenza in mesi tra l’età del neonato al momento del trapianto dopo trattamento e quella al trapianto determinato precedentemente)
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    neonatal-onset hyperammonemic encephalopathy; formal biochemical diagnosis of one of the five inborn metabolic diseases, as listed in the Table 1; formal evaluation for early liver transplantation; being referred to the Presidio Ospedaliero Infantile Regina Margherita, Centro delle Malattie Metaboliche, Torino, Italy;
    encefalopatia iperammoniemica neonatale; diagnosi con una conferma biochimica di uno dei 5 deficit elencati in Tabella 1; valutazione formale di idoneità al trapianto di fegato; essere ricoverati presso il Presidio Ospedaliero Infantile Regina Margherita, Centro delle Malattie Metaboliche, Torino, Italia
    E.4Principal exclusion criteria
    Refusal of signing the specific informed consent for entering the study; Evidence of uncontrolled coagulopathy;
    rifiuto dei genitori/tutori di firmare il modulo per il consenso informato; evidenza di coagulopatia incontrollabile
    E.5 End points
    E.5.1Primary end point(s)
    Safety endpoints:
    Hepatic complications: portal vein thrombosis, intrahepatic hematoma, injury of the hepatic artery, arterio-portal, portal-biliary and arterio-biliary fistula, acute hepatic cytolysis > 20 times normal, clinical and biochemical signs of liver failure (ascites, development of jaundice with conjugated bilirubin above 3 mg/dL, alterations in INR > 2.5), appearance of cancer-like liver nodular lesions.
    Extra-hepatic complications: pulmonary embolism, significant extra-hepatic (abdominal and/or chest) haemorrhage (requiring blood transfusion and / or specific treatment), documented sepsis with bacteremia, adverse reactions to sedative drugs administered for interventional radiological procedure.
    Endpoints di sicurezza:
    Complicanze epatiche: trombosi della vena portale, ematoma intraepatico, lesione dell'arteria epatica, fistola arterio-portale, porta-biliare o arero-biliare, citolisi acuta epatica, evidenze cliniche e di laboratorio di insufficienza epatica (ascite, sviluppo di itterizia in associazione a bilirubina superiore a 3 mg/dL, alterazioni dell’INR > 2.5), comparsa di lesioni nodulari epatiche, simil-tumorali.
    Complicanze extra-epatiche: embolia polmonare, emorragia extra-epatica toracica e/o addominale di entità significativa (con necessità di trasfusione e/o trattamento specifico), sepsi accompagnata da batteriemia, reazioni avverse a sedativi somministrati nel corso della procedura di radiologia interventistica
    E.5.1.1Timepoint(s) of evaluation of this end point
    The primary endpoint will be evaluated daily by monitoring adverse events, in the 15 days following the treatment. Other safety parameters will be evaluated weekly. A Safety Follow-up visit is planned, 4 weeks after last dose administration.
    l'endpoint primario sarà valutato giornalmente mediante accertamento degli eventi avversi, nei 15 giorni successivi al trattamento. Altri parametri di sicurezza saranno valutati settimanalmente. E' prevista una visita di Safety Follow-up 4 settimane dopo la somministrazione dell'ultima dose.
    E.5.2Secondary end point(s)
    to evaluate plasma ammonia levels (< 100 µmol/l following the treatment); to evaluate the daily protein intake, maintaining plasma ammonia levels < 100 µmol/l (measure: quantification of daily protein tolerance increase (g/kg/day) following the treatment); to reduce clinically significant hyperammonemic episodes (measure: number of hyperammonemic episodes following the treatment); to defer the time of liver transplantation from the scheduled time (measure: difference in months between the age at liver transplantation following the treatment and the age previously scheduled)
    Valutare i livelli di ammonio nel plama (< 100 µmol/l) dopo il trattamento; Valutare l’assunzione giornaliera di proteine, mantenendo livelli di ammonio nel plama inferiori a 100 µmol/l (quantificare l’aumento di tolleranza giornaliera di proteine (g/kg/giorno) dopo il trattamento); Ridurre in maniera significativa gli episodi clinicamente rilevanti di iperammoniemia (misurare: il numero di episodi di iperammoniemia dopo il trattamento); Valutare la possibilità di posticipare il trapianto di fegato (misurare: la differenza in mesi tra l’età del neonato al momento del trapianto dopo trattamento e quella al trapianto determinato precedentemente)
    E.5.2.1Timepoint(s) of evaluation of this end point
    Secondary endpoints will be evaluated weekly and at the Safety Follow-up visit, 4 weeks after administration of last dose
    gli endpoints secondari saranno valutati settimanalmente e nella visita di Safety Follow-up prevista 4 settimane dopo la somministrazione dell'ultima dose
    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 No
    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 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.8.5The 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 No
    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
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months8
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months8
    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: 3
    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) Yes
    F.1.1.3.1Number of subjects for this age range: 3
    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) 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 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
    neonates suffering from inborn liver metabolic diseases causing hyperammonemic encephalopathy
    neonati con iperammonemia ed encefalopatia dovute a malattie metaboliche genetiche
    F.4 Planned number of subjects to be included
    F.4.1In the member state3
    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)
    Children enrolled in the study will also be evaluated by Liver Transplantation Centre team. The eligibility for OLT in conjunction with the timing for inclusion in the transplantation waiting list should be declared at the beginning of the study for each patient. Inactivation from the waiting list may be decided on the basis of signs of metabolic stability, such as to indicate that the transplant can be delayed or even avoided
    E' previsto che i pazienti siano sottoposti a Trapianto Ortotopico di fegato, dopo aver completato la partecipazione allo studio. I neonati arruolati nello studio saranno valutati anche dal Centro Nazionale Trapianti. La sospensione dalla lista d'attesa potrebbe essere decisa in base a segni di stabilità metabolica, indicanti che il trapianto può essere ritardato o evitato.
    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 Decision2013-06-21
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2013-12-06
    P. End of Trial
    P.End of Trial StatusCompleted
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