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    Summary
    EudraCT Number:2014-000650-11
    Sponsor's Protocol Code Number:HEP002
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2014-10-20
    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 ConcernedSpain - AEMPS
    A.2EudraCT number2014-000650-11
    A.3Full title of the trial
    A prospective, open label, multi-country, multicenter, efficacy and safety study of several infusions of Promethera HepaStem in Urea Cycle Disorders pediatric patients
    HEP002: Estudio prospectivo, abierto, multi-país, multicéntrico, de eficacia y seguridad de varias infusiones de Promethera HepaStem en pacientes pediátricos con Trastornos del Ciclo de la Urea.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    HEP002 is a clinical study designed for paediatric patients with urea cycle disorders (UCD). UCD patients will receive several infusions of HepaStem. The efficacy as well as the safety of the medicinal product will be assessed during the year following infusions.
    HEP002 es un estudio clínico diseñado para los pacientes pediátricos con trastornos del ciclo de la urea (UCD). Pacientes con UCD Recibirán varias infusiones de HepaStem. La eficacia y la seguridad del medicamento será evaluado durante el año siguiente infusiones.
    A.4.1Sponsor's protocol code numberHEP002
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation PlanP/313/2013
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorPromethera Biosciences
    B.1.3.4CountryBelgium
    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 supportPromethera Biosciences
    B.4.2CountryBelgium
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationPromethera Biosciences
    B.5.2Functional name of contact pointVinciane Wouters
    B.5.3 Address:
    B.5.3.1Street AddressRue Granbonpré, 11
    B.5.3.2Town/ cityMont-Saint-Guibert
    B.5.3.3Post code1435
    B.5.3.4CountryBelgium
    B.5.4Telephone number3210394311
    B.5.5Fax number3210394301
    B.5.6E-mailvinciane.wouters@promethera.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/3/13/1161-1167
    D.3 Description of the IMP
    D.3.1Product nameHepaStem
    D.3.4Pharmaceutical form Suspension for injection
    D.3.4.1Specific paediatric formulation Yes
    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 INNCelulas hepatocitos troncales adultas alogenicas de higado expandidas
    D.3.9.2Current sponsor codeHHALPC
    D.3.10 Strength
    D.3.10.1Concentration unit million organisms/ml million organisms/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    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 Yes
    D.3.11.3.5.1CAT classification and reference numberSomatic Cell Therapy Product ref nr: EMA/CAT/243155/2011
    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
    The urea cycle disorders are inborn errors of metabolism that affect the transfer of nitrogen into urea. There are eight disorders: N-Acetylglutamate synthase deficiency, Carbamoyl phosphate synthetase I deficiency, Ornithine transcarbamylase deficiency, citrullinemia type I, argininosuccinic aciduria, argininemia, HHH syndrme and citrullinemia type II.
    Mutations in each of the enzymes have been identified, resulting in failed production of urea, the end product of the urea cycle.
    Los trastornos del ciclo de la urea son errores congénitos del metabolismo que afecta a la transferencia de nitrógeno en la urea. Hay 8 trastornos: deficiencia de N-acetil glutamato sintetasa, deficiencia de carbamoil-fosfato sintasa I, deficiencia de ornitina transcarbamilasa, citrulinemia tipo I, aciduria arginosuccínica, argininemia, síndrome HHH y citrulinemia tipo II. Las mutaciones en cada una de las enzimas han sido identificadas, resultando en la producción fallida de urea.
    E.1.1.1Medical condition in easily understood language
    Metabolic disease of the urea cycle in the liver that result in failed detoxification of ammonia.
    Trastorno metabolico del ciclo de la urea en el higado que resulta en la ausencia parcial o completa de la desintoxicación de amoníaco.
    E.1.1.2Therapeutic area Diseases [C] - Nutritional and Metabolic Diseases [C18]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.0
    E.1.2Level LLT
    E.1.2Classification code 10013373
    E.1.2Term Disorders of urea cycle metabolism
    E.1.2System Organ Class 100000004861
    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 efficacy of HepaStem during the year following HepaStem infusions (biochemical parameter NH3 (ammonia).
    Evaluar la eficacia de HepaStem al año siguiente de varias infusiones de HepaStem con parámetros bioquímicos NH3 (amoníaco).
    E.2.2Secondary objectives of the trial
    1. To evaluate the efficacy of HepaStem infusions in terms of functional,
    clinical, and biochemical parameters
    2. To evaluate the safety during the year following HepaStem infusions.
    1. Evaluar la eficacia de infusiones de HepaStem (en materia de parámetros funcionales, clínicos y bioquímicos).
    2. Evaluar la seguridad durante el año siguiente a varias infusiones de HepaStem.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    A patient who meets all of the following inclusion criteria will be eligible
    for participation in the study:
    1. The patient is a pediatric patient <12 years prior to infusion.
    2. The patient presents with one of the following UCDs
    (carbamoylphosphate synthetase I [CPS I] deficiency [CPS ID],
    ornithine transcarbamylase [OTC] deficiency [OTCD], argininosuccinic
    acid synthetase [ASS] deficiency [ASSD], argininosuccinic acid lyase
    [ASL] deficiency [ASLD], arginase [ARG] deficiency [ARGD],
    Nacetylglutamate
    synthase [NAGS] deficiency [NAGSD]) and citrine
    deficiency
    - of such severity that treatment alternatives are warranted despite full
    conservative therapy, and/or
    -experiences serious impairment in quality of life (QoL) despite full
    conservative therapy.
    3. The patient shows patency of the portal vein and its branches
    including mesenteric veins, with normal flow velocity as confirmed by
    Doppler US and accessibility of the portal vein and /or affluants.
    4. The patient (if capable of signing) and parents or legal representative
    have signed a written informed assent/consent form.
    Serán elegibles para su participación en el estudio los pacientes que cumplan todos los siguientes criterios de inclusión:
    1. El paciente es un paciente pediátrico menor de <12 años de edad antes de la infusión.
    2. Pacientes que presentan alguno de los siguientes TCU: (déficit de carbamoifosfato sintetasa I [CPS I], déficit de ornitina transcarbamilasa [OTC], déficit de ácido argininosuccínico sintetasa [ASS], déficit de ácido argininosuccínico liasa [ASL] [ASLD], déficit de arginasa [ARG], déficit de N-acetilglutamato sintetasa [NAGS]) y déficit de citrina
    - de tal gravedad que se garanticen un alternativas de tratamiento a pesar de un tratamiento conservador pleno, y/o
    - presentan una alteración grave en su calidad de vida (QoL) a pesar de tratamiento conservador pleno.
    3. El paciente presenta permeabilidad de la vena porta y sus ramas, incluyendo las venas mesentéricas, con velocidad de flujo normal confirmadas mediante ecoDoppler, y accesibilidad a la vena porta y/o sus afluentes.
    4. El paciente (si puede firmar) y los padres o el representante legal han firmado un documento de consentimiento/asentimiento informado.
    E.4Principal exclusion criteria
    A patient who meets any of the following exclusion criteria will not be enrolled in the study:
    1. The patient has mild disease severity, easily controlled under standard of care therapy, with no recurrent metabolic crises.
    2. The patient is registered on a liver transplant waiting list or is scheduled for living donor liver transplantation before the end of the study.
    3. The patient presents acute liver failure.
    4. The patient presents clinical or radiological evidence of liver cirrhosis.
    5. The patient presents or has a history of hepatic or extrahepatic malignancy.
    6. The patient has a known clinically significant cardiac malformation.
    7. The patient has a personal history of venous thrombosis, or has a clinically significant abnormal value for protein S, protein C, antithrombin III, and /or activated Protein C Resistance (aPCR) at screening. In case of known family history, a complete coagulation work-up should be performed. In all above described cases, results need to be discussed with PB before enrolling the patient in the study.
    8. The patient participates currently in another clinical trial – except disease registry and observational HepaStem study.
    9. The patient underwent previous mature liver cell or stem cell transplantation or received an organ liver transplant or received HepaStem infusion.
    10. The patient has a contraindication to methylprednisolone, tacrolimus.
    11. The patient has a known hypersensitivity or allergy to bivalirudin.
    12. The patient has a known hypersensitivity or allergy to the antibiotics
    preventing post-operative infections that are prescribed according to institutional guidelines, and no alternative prophylaxis can be found.
    13. The patient had or has a renal insufficiency treated by dialysis.
    14. The patient requires valproate therapy.
    15. The patient has a known hypersensitivity or allergy to contrast
    agents (if applicable) that cannot be treated adequately.
    16. The patient has a thrombosis of the portal vein or persisting impairment of anterograde portal blood flow.
    17. The patient has a porto systemic shunt or fistula assessed by Doppler US.
    18. The site where the catheter is intended to be placed has previously suffered from venous thrombosis or vascular surgical procedures.
    19. The patient has an ongoing infection or suffered from an infection in the last 2 weeks (including active EBV infection at screening). The patient may be enrolled after resolution of the infection.
    20. There is any significant condition or disability that, in the Investigator's opinion, may interfere with the patient's optimal participation in the study.
    No se incluirán en el estudio los pacientes que cumplan alguno de los siguientes criterios de exclusión:
    1. Pacientes con enfermedad de gravedad leve, con fácil control con el tratamiento estándar, sin crisis metabólicas recurrentes.
    2. Pacientes incluidos en lista de espera para trasplante hepático programados para un trasplante de hígado de donante vivo antes del fin del estudio.
    3. Pacientes con fallo hepático agudo.
    4. Pacientes con evidencia clínica o radiológica de cirrosis hepática.
    5. Pacientes que presentan o con antecedentes de neoplasias hepáticas o extrahepáticas.
    6. Pacientes con malformaciones cardíacas clínicamente importantes
    conocidas.
    7. Pacientes con antecedentes personales de trombosis venosa o tiene un valor anormal, clínicamente significativo, de la proteína S, proteína C, antitrombina III, y / o resistencia a proteína C activada (aPCR) durante la selección. En caso de historia familiar conocida, se deberá realizar un estudio completo de coagulación. En todos los casos descritos anteriormente, los resultados se deberán comentar con PB antes de la inclusión de dicho paciente en el estudio.
    8. Pacientes que participan actualmente en otro ensayo clínico – con la excepción de registros de enfermedades y el estudio HepaStem observacional.
    9. Pacientes que han recibido previamente un trasplante de células hepáticas maduras o células madre hepáticas, o han recibido un trasplante hepático o una infusión de HepaStem.
    10. Pacientes con contraindicaciones a metilprednisolona o tacrolimus.
    11. Pacientes con alergia o hipersensibilidad conocidas a la bivalirudina.
    12. Pacientes con hipersensibilidad o alergia conocidas a los antibióticos para prevención de infecciones postoperatorias que se prescriben de acuerdo con las directrices de la institución, y en las que no se pueden encontrar una profilaxis alternativa.
    13. Pacientes en insuficiencia renal o con antecedentes de insuficiencia renal, ambas tratadas mediante diálisis.
    14. Pacientes que precisa tratamiento con valproato.
    15. Pacientes con hipersensibilidad o alergia conocidas a los agentes de contraste (en caso preciso) que no se puede tratar de forma apropiada.
    16. Pacientes con trombosis de la vena porta o alteración persistente del flujo sanguíneo portal anterógrado.
    17. Pacientes con una derivación o una fistula portosistémica, evaluada mediante eco-Doppler.
    18. La localización prevista de ubicación del catéter ha sufrido previamente trombosis venosa o ha sido sometida a procedimientos quirúrgicos vasculares.
    19. Pacientes con infecciones activas o que han presentado una infección en las últimas 2 semanas (incluyendo infección con el virus Epstein-Barr (EBV) durante la selección). Se podrá reclutar al paciente después de haber combatido la infección.
    20. Existe alguna patología importante o incapacidad que, en la opinión del investigador, puede interferir con la participación óptima del paciente en el estudio quirúrgicos vasculares.
    E.5 End points
    E.5.1Primary end point(s)
    Efficacy up to 12 months post-first infusion day for each individual
    patient and for all patients as compared to his/her prior medical
    condition* based on change of ammonia (fasting condition postinfusion)
    as measured at 3m, at 4,5m, at 6m, at 7,5m, at 9m, at 10,5m
    and at 12m follow-up visits .
    *The "prior medical condition" related to NH3 of each patient is
    constituted of all NH3 values collected during the retrospective period
    (max of 3 yrs) as well as the values collected at the baseline (BL) visits.
    The prior medical condition value of ammonia will be calculated as the
    median of the individual records collected during this retrospective
    period and at BL visits.
    Eficacia hasta 12 meses después del primer día de infusión para cada paciente individualmente o para todos los pacientes en comparación a su condición médica previa* en base al cambio de amoníaco (en situación de ayuno después de la infusión), medida en las visitas de seguimiento a los 3 meses, 4,5 meses, 6 meses, 7,5 meses, 9 meses, 10,5 meses y a los 12 meses.
    * La "condición médica previa" relacionada con el NH3 de cada paciente estará constituida por todos los valores de NH3 recogidos durante el período retrospectivo (máximo de 3 años), así como los valores recogidos en las visitas basales (BL). El valor de la condición médica previa del amoníaco se calculará como el promedio de los registros individuales recogidos durante este periodo retrospectivo y en las visitas basales (BL).
    E.5.1.1Timepoint(s) of evaluation of this end point
    Change of ammonia (fasting condition post-infusion) measured at 3m, at 4,5m, at 6m, at 7,5m, at 9m, at 10,5m and at 12m follow-up visits .
    Cambio de amoníaco (en situación de ayuno después de la infusión), medida en las visitas de seguimiento a los 3 meses, 4,5 meses, 6 meses, 7,5 meses, 9 meses, 10,5 meses y a los 12 meses.
    E.5.2Secondary end point(s)
    1. Efficacy up to 12 months post-first infusion day for each individual
    patient and for all patients as compared to his/her prior medical
    condition* based on:
    - de novo ureagenesis (C13 Tracer method): absolute 13C blood urea
    AUC-120 as measured at BL**, at 3m, at 6m, at 9m, and at 12m followup
    visits.
    - Ammonia (considering all collected values during prior medical
    condition*, during active treatment period, during each quarter of
    follow-up period (from 3-12 months) and over the entire 12 months
    study period.
    - Amino acids (AAs) in plasma (fasting) as measured at 3m, at 4,5m, at
    6m, at 7,5m, at 9m, at 10,5m and at 12m follow-up visits.
    - Amino acids in plasma (considering all collected values during prior
    medical condition*, during active treatment period, during each quarter
    of follow-up period (from 3-12 months) and over the entire 12 months
    study period.
    - Evaluation of UCD condition (report of metabolic decompensations,
    report on actual supportive treatment and adjustment of protein
    restriction [low protein diet], amino acids supplements, report on
    behavior, cognitive skills and health-related QoL indicators) at BL (can
    be data collected at either baseline visit or during retrospective period
    (prior medial condition), at 3m, at 4,5m, at 6m, at 7,5m, at 9m, at 10,5m
    and at 12m follow-up visits.
    *The "prior medical condition" related to NH3 of each patient is
    constituted of all NH3 values collected during the retrospective period
    (max of 3 yrs) as well as the values collected at the baseline (BL) visits.
    The prior medical condition value of ammonia will be calculated as the
    median of the individual records collected during this retrospective
    period and at BL visits.
    **C13 Tracer method: Baseline value of absolute 13C blood urea AUC-
    120 is defined as the mean of 2 measurements before infusion: one test
    at Baseline Part 2 and one test before the first infusion day.
    2. Safety during the year following HepaStem infusions in terms of:
    - Clinical status (physical examination and vital signs)
    - Portal-vein hemodynamics
    - Morphology of the liver, bile ducts, and portal system
    - Laboratory tests
    - De novo detection of donor-specific circulating anti-human leukocyte
    antigen (HLA) antibodies, and/or other immune-related markers
    - Serious Adverse Events (SAEs) and clinically significant Adverse Events
    (AEs) related to HepaStem (infusion and follow-up), technical intervention, and concomitant treatments.
    1. Eficacia hasta los 12 meses posteriores al primer día de infusión para cada paciente individual, en comparación con su situación médica* basal antes del inicio del tratamiento, en base a:
    - Nueva ureagenésis (método con indicador C13): pleno 13 C en urea en la sangre AUC-120 medidos en visitas base** de seguimiento a los 3 meses, 6 meses, 9 meses y 12 meses.
    - Amoníaco teniendo en cuenta todos los valores recogidos durante el período antes de la condición médica*, durante el período de tratamiento activo, durante cada cuartal del período de seguimiento (de 3 a 12 meses) y durante el período total de 12 meses del estudio.
    - Aminoacidograma (AAs) en plasma (situación de ayuno, medido en las visitas de seguimiento a los 3 meses, 4,5 meses,
    6 meses, 7,5 meses, 9 meses, 10,5 meses y a los 12 meses.
    - Aminoacidograma en plasma (teniendo en cuenta todos los valores recogidos durante el período antes de la condición médica*, durante el período de tratamiento activo, durante cada cuartal del período de seguimiento (de 3 a 12 meses) y durante el período total de 12 meses del estudio.
    - Evaluación de la situación del TCU (informes de descompensaciones metabólicas, informes sobre el tratamiento de mantenimiento actual y ajuste de la restricción proteica [dieta baja en proteínas], suplementos de aminoácidos, informes conductuales, habilidades cognitivas e indicadores relacionados con la calidad de vida [QoL]) durante las visitas basales (BL) (pueden ser datos recogidos durante la visita basal o durante el período retrospectivo (condición médica previa) en las visitas de seguimiento a los 3 meses, 4,5 meses, 6 meses, 7,5 meses, 9 meses, 10,5 meses y a los 12 meses.
    * La "condición médica previa" relacionada con el NH3 de cada paciente estará constituida por todos los valores de NH3 recogidos durante el período retrospectivo (máximo de 3 años), así como los valores recogidos en las visitas basales (BL). El valor de la condición médica previa del amoníaco se calculará como el promedio de los registros individuales recogidos durante este periodo retrospectivo y en las visitas basales (BL).
    **Método con indicador C13: valor basal o pleno 13C en urea en la sangre AUC-120 definido como el promedio de 2 medidas antes
    de la infusión: una prueba en visita basal, parte 2 y una prueba antes del primer día de infusión.
    2. Seguridad durante el año siguiente a varias infusiones en términos de:
    - Situación clínica (exploración física y constantes vitales)
    - Hemodinámica de la vena porta
    - Morfología del hígado, vías biliares y sistema portal
    - Pruebas analíticas
    - Detección de novo de anticuerpos anti antígeno leucocito humano
    (HLA) circulantes y/o otros marcadores relacionados con la inmunidad
    - Acontecimientos adversos graves (AAG) y Acontecimientos adversos (AA) clínicamente significativos relacionados con HepaStem (infusión y seguimiento), intervención técnica y tratamientos concomitantes.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Efficacy periods:
    - Active Treatment
    - Follow-up.
    The safety parameters will be assessed for 5 time windows:
    1) Screening Period
    - Time window 1 = first visit - end of Screening Period.
    2) Active Treatment Period
    - Time window 2 (inpatient period) = D0 - Ddischarge.
    - Time window 3 = Ddischarge - next infusion day or end of Active
    Treatment Period.
    3) Follow-up Period
    - Time window 4 (outpatient period) = Visit (V)3 months post-first
    infusion day - V12 months post-first infusion day.
    - Time window 5 = screening - V12 months post-first infusion day.
    Periodos de eficacia:
    - Período de tratamiento activo
    - Período de seguimiento

    Estos parámetros de seguridad se evaluaran en 5 ventanas de tiempo:
    1) Periodo de selección
    Ventana de tiempo 1 = primera Visita – final del Periodo de selección.
    2) Periodo de tratamiento activo
    - Ventana de tiempo 2 (periodo de ingreso hospitalario*) = D0 - D de alta hospitalaria (primer día de infusión).
    - Ventana de tiempo 3 = D de alta hospitalaria – próximo día de infusión o fin de Periodo de tratamiento activo.
    3) Periodo de seguimiento
    Ventana de tiempo 4 (periodo ambulatorio) = Visita (V) de los 3 meses tras el primer día de infusión – V 12 meses tras el primer día de infusión.
    Ventana de tiempo 5 = Selección - V12 meses tras el primer día de infusión.
    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 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) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) 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 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 No
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned5
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA11
    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 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
    Last patient, last visit
    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 months32
    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 months32
    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: 20
    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: 2
    F.1.1.4Infants and toddlers (28 days-23 months) Yes
    F.1.1.4.1Number of subjects for this age range: 6
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 12
    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 Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Paediatric patients
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state5
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 20
    F.4.2.2In the whole clinical trial 20
    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)
    A long term safety surveillance of the patients following infusion with HepaStem is planned. The surveillance will mimic as much as possible the standard follow-up of the respective diseases (standard of care).
    The surveillance in the remit of this trial, will end when the patient is undergoing an organ transplant or takes part in another research study.
    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 Decision2015-04-13
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-03-06
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2017-09-28
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