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    Summary
    EudraCT Number:2020-001953-36
    Sponsor's Protocol Code Number:GC2005
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2020-05-08
    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 ConcernedSpain - AEMPS
    A.2EudraCT number2020-001953-36
    A.3Full title of the trial
    A Multicenter, Randomized, Open-label, Parallel Group Pilot Study to Evaluate the Safety and Efficacy of Prolastin® plus Standard Medical Treatment (SMT) versus SMT alone in Hospitalized Subjects with COVID-19.
    Estudio piloto multicéntrico, aleatorizado, abierto y con grupos paralelos para evaluar la seguridad y eficacia de la alfa1-proteinasa (Prolastina®) junto con tratamiento médico estándar (TME) en comparación con el TME solo en sujetos hospitalizados con COVID-19.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Study to Evaluate the Safety and Efficacy of Prolastin in Hospitalized Patients with Coronavirus Disease (COVID-19)
    Estudio para evaluar la seguridad y eficacia de la Prolastina en pacientes hospitalizados con enfermedad por coronavirus (COVID-19).
    A.4.1Sponsor's protocol code numberGC2005
    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 SponsorInstituto Grifols, S.A
    B.1.3.4CountrySpain
    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 supportInstituto Grifols, S.A.
    B.4.2CountrySpain
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationInstituto Grifols, S.A.
    B.5.2Functional name of contact pointDepartment of Clinical Trials
    B.5.3 Address:
    B.5.3.1Street AddressAv. Generalitat 152
    B.5.3.2Town/ citySant Cugat del Vallès (Barcelona)
    B.5.3.3Post code08174
    B.5.3.4CountrySpain
    B.5.4Telephone number34935712000
    B.5.5Fax number34935712482
    B.5.6E-mailIGregulatory.affairs@grifols.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 Prolastina 1000 mg, polvo y disolvente para solución para perfusión
    D.2.1.1.2Name of the Marketing Authorisation holderGrifols Deutschland GmbH
    D.2.1.2Country which granted the Marketing AuthorisationSpain
    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 IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNAlpha1-Proteinase Inhibitor (Human)
    D.3.9.3Other descriptive nameHUMAN ALPHA1-PROTEINASE INHIBITOR
    D.3.9.4EV Substance CodeSUB130886
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1000
    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 No
    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 Yes
    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
    Patients with Coronavirus Disease (COVID-19)
    Pacientes con Enfermedad por Coronavirus (COVID-19)
    E.1.1.1Medical condition in easily understood language
    Therapy for subjects suffering Coronavirus Disease (COVID-19)
    Terapia para pacientes que padecen la enfermedad por Coronavirus
    (COVID-19)
    E.1.1.2Therapeutic area Diseases [C] - Virus Diseases [C02]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 23.0
    E.1.2Level PT
    E.1.2Classification code 10051905
    E.1.2Term Coronavirus infection
    E.1.2System Organ Class 10021881 - Infections and infestations
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 23.0
    E.1.2Level LLT
    E.1.2Classification code 10053983
    E.1.2Term Corona virus infection
    E.1.2System Organ Class 10021881 - Infections and infestations
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To determine if Prolastin plus SMT can reduce the proportion of subjects dying or requiring intensive care unit (ICU) admission on or before Day 15 or who are dependent on invasive mechanical ventilation on Day 15 versus SMT alone in hospitalized subjects with COVID-19.
    Determinar si la Prolastina junto con TME puede reducir la proporción de sujetos que mueren o requieren admisión en la unidad de cuidados intensivos (UCI) el día 15 o antes, o que dependen de ventilación mecánica invasiva en el día 15, en comparación con TME solo en sujetos hospitalizados con COVID-19
    E.2.2Secondary objectives of the trial
    To compare Prolastin plus SMT versus SMT alone with regard to clinical efficacy as assessed by clinical severity, duration of hospital stay, dependency on oxygen or new need for ventilatory support, or ICU admission, clinical response criteria including National Early Warning Score (NEWS), mortality and clinical status scale through Day 29 in hospitalized subjects with COVID-19.
    Comparar la Prolastina junto con TME versus TME solo en relación a la eficacia clínica evaluada a través de la severidad clínica, la duración de la estancia en el hospital, la dependencia de oxígeno o la nueva necesidad de asistencia respiratoria o admisión en UCI, los criterios de respuesta clínica incluyendo la puntuación de alerta temprana nacional (National Early Alert Score, NEWS), mortalidad y la escala de estado clínico hasta el día 29 en sujetos hospitalizados con COVID-19.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Hospitalized male or female patient ≥ 18 years of age at time of Screening who is being treated for COVID-19. Subjects must be screened within 48 hours (≤ 48 hours) of hospital admission.
    2. Has laboratory-confirmed novel coronavirus (SARS-CoV-2) infection as determined by qualitative PCR (reverse transcriptase [RT]-PCR), or other commercial or public health assay in any specimen < 72 hours prior to randomization.
    3. COVID-19 illness (symptoms) of any duration, including both of the following:
    a) Radiographic infiltrates by imaging (chest X-Ray, CT scan, etc.) and/or clinical assessment (evidence of rales/crackles on exam) with SpO2 <94% on room air
    b) Any One of the following related to COVID-19: i. Ferritin > 400ng/mL, ii. LDH > 300 U/L, iii. D-Dimers > reference range, or iv. C-reactive protein (CRP) > 40 mg/L
    4. Subject provides informed consent (ICF) prior to initiation of any study procedures.
    1.Hombre o mujer hospitalizado ≥ 18 años de edad en el momento de la selección que esté siendo tratado por COVID-19. Los sujetos deben ser seleccionados dentro de las 48 horas (≤ 48 horas) de su admisión en el hospital.
    2.Tener infección de novo por coronavirus (SARS-CoV-2) confirmada en laboratorio según la determinación por PCR cualitativa (transcriptasa reversa [RT]-PCR) u otra prueba comercial o de salud pública en cualquier espécimen < 72 horas previo a la aleatorización.
    3.Enfermedad por COVID-19 (síntomas) de cualquier duración incluyendo ambos criterios a continuación:
    a) infiltrados radiográficos por imagen (radiografía de pecho, tomografía computarizada, etc.) y/o evaluación clínica (evidencia de estertores/crepitantes) con SpO2 <94% en aire ambiental
    b) Cualquiera de los siguientes relacionados con COVID-19: i. Ferritina > 400ng/mL, ii. LDH > 300 U/L, iii. D-Dimeros > rango de referencia, o i.v Proteina C-reactiva iv. (PCR) > 40 mg/L
    4.El sujeto da su consentimiento informado (CI) antes de iniciar cualquier procedimiento del estudio.
    E.4Principal exclusion criteria
    1. Patients requiring invasive mechanical ventilation or ICU admission or with PaO2/FIO2 ≤ 150 mm Hg (ie, arterial oxygen in mm Hg divided by fraction inspired oxygen concentration [eg, 0.21 for room air]).
    2. Clinical evidence of any significant acute or chronic disease that, in the opinion of the investigator, may place the subject at undue medical risk.
    3. The subject has had a known serious anaphylactic reaction to blood, any blood-derived or plasma product, or known Selective IgA Deficiency with anti-IgA antibodies.
    4. A medical condition in which the infusion of additional fluid is contraindicated (e.g., decompensated congestive heart failure or renal failure with fluid overload).
    5. Shock that is unresponsive to fluid challenge and/or multiple vasopressors and accompanied by multiorgan failure considered not able to be reversed by the Principal Investigator.
    6. Known alpha-1 antitrypsin deficiency for which the patient is already receiving alpha1-proteinase inhibitor augmentation therapy.
    7. Women who are pregnant or breastfeeding. Female subjects of child-bearing potential must have a negative test for pregnancy blood or urine human chorionic gonadotropin (HCG)-based assay at Screening/Baseline Visit.
    8. Patients for whom there is limitation of therapeutic effort such as “Do not resuscitate” status Note: If the decision is made not to apply treatments or therapeutic procedures that will provide little benefit for the suffering or agony the patient is experiencing, such a patient would not be appropriate for participation in this study and should be excluded.
    9. Currently participating in another interventional clinical trial with investigational medical product or device
    10. Patients previously requiring long-term oxygen therapy (home oxygen therapy)
    1.Pacientes que requieran ventilación mecánica invasiva o admisión en la UCI o con PaO2/FIO2 ≤ 150 mm Hg (es decir la presión parcial de oxígeno arterial en mm Hg dividido por la fracción inspirada de oxígeno [por ejemplo, 0.21 en aire ambiental])
    2.Evidencia clínica de cualquier enfermedad aguda o crónica significativa que, en la opinión del investigador, pueda poner al sujeto bajo un riesgo médico indebido.
    3. Que el sujeto haya tenido una reacción anafiláctica grave conocida a la sangre, a cualquier producto derivado de la sangre o del plasma o una deficiencia conocida selectiva de IgA con anticuerpos anti-IgA.
    4. Una condición médica en la que la infusión adicional de fluidos esté contraindicada (por ejemplo, insuficiencia cardíaca congestiva descompensada o insuficiencia renal con sobrecarga de fluidos).
    5. Shock sin respuesta a la carga de volumen y/o vasopresores múltiples acompañado de fallo multiorgánico que el investigador principal considera que no puede ser revertido.
    6. Deficiencia conocida de alfa1-antitripsina para la cuál el paciente ya recibe un tratamiento de aumento con inhibidores de alfa1-proteinasa.
    7. Mujeres embarazadas o en periodo de lactancia. Mujeres en edad fértil deben dar negativo en la prueba de embarazo en sangre o en la prueba basada en gonadotropina coriónica humana (GCH) en orina en la visita de selección/inicio.
    8. Pacientes con limitación de esfuerzo terapéutico como por ejemplo estado de “no reanimación”.
    Nota: Si se toma la decisión de no aplicar tratamientos o procedimientos terapéuticos que proporcionen poco beneficio para el sufrimiento o la agonía que el paciente está experimentando, dicho paciente no sería apropiado para participar en este estudio y debería ser excluido
    9. Pacientes que están participando actualmente en otro ensayo clínico intervencionista con producto o dispositivo médico en investigación.
    10. Pacientes que hayan requerido previamente terapia de oxígeno a largo plazo (terapia de oxígeno domiciliaria).
    E.5 End points
    E.5.1Primary end point(s)
    The primary efficacy variable is the proportion of subjects dying or requiring ICU admission on or before Day 15 or who are dependent on invasive mechanical ventilation on Day 15.
    La variable principal de eficacia es la proporción de sujetos que mueren o requieren admisión en la UCI el día 15 o antes, o que dependen de ventilación mecánica invasiva el día 15.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Through Day 29
    Desde el inicio hasta el día 29
    E.5.2Secondary end point(s)
    •Assessment of Clinical Severity: Change in NEWS from baseline (Day 1 through Day 29)
    The NEWS has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness [Alert, Voice, Pain, Unresponsive]).
    •Time to clinical response: NEWS ≤ 2 maintained for 24 hours, Day 1 through Day 29
    •Time to hospital discharge: defined as duration of hospitalization from Day 1 of study
    •If admitted to ICU post randomization: Duration of ICU stay through Day 29
    •Duration of any oxygen use Day 1 through Day 29
    •If requiring mechanical ventilation post randomization: Duration mechanical ventilation through Day 29
    •Absolute value and mean change from baseline in the Ordinal scale Day 1 through Day 29
    The Ordinal scale is as follows:
    1) Death;
    2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO);
    3) Hospitalized, on non-invasive ventilation or high flow oxygen devices;
    4) Hospitalized, requiring supplemental oxygen;
    5) Hospitalized, not requiring supplemental oxygen;
    6) Not hospitalized, limitation on activities;
    7) Not hospitalized, no limitations on activities.
    •Proportion (percentage) of subjects in each severity category of the 7-point Ordinal scale at Day 15 and Day 29
    •Time to sustained normalization of temperature and proportion of patients with normalization of fever at all time points, defined as temperature < 36.6 °C armpit, < 37.2 °C oral, or < 37.8 °C rectal sustained for at least 24 hours
    •Number of subjects who develop Acute Respiratory Distress Syndrome (ARDS) through Day 29
    •Length of time to clinical progression through Day 29 (defined as the time to death, mechanical ventilation, or ICU admission)
    •Mortality through Day 29
    • Evaluación de la severidad clínica: cambios en NEWS desde el inicio (desde el día 1 hasta el día 29). La puntuación NEWS ha demostrado una habilidad para discriminar pacientes en riesgo de resultados deficientes. Esta puntuación está basada en 7 parámetros clínicos (frecuencia respiratoria, saturación de oxígeno, cualquier suplemento de oxígeno, temperatura, presión sanguínea sistólica, frecuencia cardíaca, nivel de conciencia [alerta, voz, dolor, inconsciencia]).
    • Tiempo hasta la respuesta clínica: NEWS ≤ 2 mantenido durante 24 horas, desde el día 1 hasta el día 29.
    • Tiempo hasta el alta hospitalaria: definido como la duración de la hospitalización desde el día 1.
    • Si es admitido en la UCI después de la aleatorización: duración de la estancia en la UCI hasta el día 29.
    • Duración de cualquier uso de oxígeno desde el día 1 al día 29.
    • Si requiere ventilación mecánica post aleatorización: duración de la ventilación mecánica hasta el día 29.
    • Valor absoluto y cambio medio desde el inicio del día 1 hasta el día 29 en la puntuación de la escala Ordinal:
    La puntuación de la escala Ordinal es según sigue:
    1) Muerte;
    2)Hospitalizado, en ventilación mecánica invasiva u oxigenación por membrana extracorpórea (OMEC);
    3) Hospitalizado, en ventilación no invasiva o dispositivos de oxígeno de alto flujo;
    4) Hospitalizado, con requerimiento de oxígeno suplementario;
    5) Hospitalizado, sin requerimiento de oxígeno suplementario;
    6) No hospitalizado, limitación en actividades;
    7) No hospitalizado, sin limitación en actividades.
    • Proporción (porcentaje) de sujetos en cada categoría de gravedad de la puntuación de la escala Ordinal de 7 puntos el día 15 y el día 29.
    • Tiempo hasta la normalización sostenida de la temperatura y la proporción de pacientes con normalización de la fiebre en todos los tiempos, definido como temperatura < 36.6 °C axilar, < 37.2 °C oral, o < 37.8 °C rectal sostenida durante al menos 24 horas.
    • Número de sujetos que desarrollan Síndrome de Distrés Respiratorio Agudo (SDRA) hasta el día 29.
    • Tiempo transcurrido hasta la progresión clínica hasta el día 29 (definido como tiempo hasta la muerte, ventilación mecánica o admisión en la UCI).
    • Mortalidad hasta el día 29.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Through Day 29
    Desde el día 1 hasta el día 29
    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) 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 Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    Tratamiento Médico Estándar
    Standartd Medical Treatment
    E.8.2.4Number of treatment arms in the trial2
    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 concerned4
    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 years0
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days30
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 50
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 50
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation Yes
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state100
    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)
    There will be a Final Phone Check at Day 60 for vital status (living or deceased), any hospital re-admissions or serious adverse events after the Day 29 Final Clinic Visit.
    En el día 60 se realizará un seguimiento final vía telefónica para conocer el estado del paciente (vivo o fallecido), cualquier reingreso hospitalario o acontecimientos adversos graves después de la visita clínica final el día 29.
    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 Decision2020-05-08
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-05-07
    P. End of Trial
    P.End of Trial StatusOngoing
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
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