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    Summary
    EudraCT Number:2019-002076-13
    Sponsor's Protocol Code Number:NS-065/NCNP-01-301
    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:2021-01-05
    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 number2019-002076-13
    A.3Full title of the trial
    A Phase 3 Randomized, Double-blind, Placebo-controlled, Multi-center Study to Assess the Efficacy and Safety of Viltolarsen in Ambulant Boys with Duchenne Muscular Dystrophy (DMD)
    Studio multicentrico di fase 3 randomizzato, in doppio cieco, controllato con placebo per valutare l’efficacia e la sicurezza di viltolarsen in ragazzi deambulanti con distrofia muscolare di Duchenne (DMD)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    This is a randomized, double-blind, Placebo-controlled sudy to evaluate the Efficacy and Safety of Viltolarsen in Ambulant Boys with Duchenne Muscular Dystrophy (DMD)
    Questo è uno studio randomizzato, in doppio cieco, controllato con placebo, per valutare l'efficacia e la sicurezza di Viltolarsen in ragazzi deambulanti con distrofia muscolare di Duchenne (DMD)
    A.3.2Name or abbreviated title of the trial where available
    RACER-53
    RACER-53
    A.4.1Sponsor's protocol code numberNS-065/NCNP-01-301
    A.5.4Other Identifiers
    Name:US INDNumber:127474
    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 SponsorNS Pharma, Inc
    B.1.3.4CountryUnited States
    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 supportNS Pharma, Inc.
    B.4.2CountryUnited States
    B.4.1Name of organisation providing supportNippon Shinyaku Co., Ltd
    B.4.2CountryJapan
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMedpace
    B.5.2Functional name of contact pointWendy Van den Branden
    B.5.3 Address:
    B.5.3.1Street AddressTechnologielaan 11
    B.5.3.2Town/ cityLeuven
    B.5.3.3Post codeB-3001
    B.5.3.4CountryBelgium
    B.5.4Telephone number0032163918702703
    B.5.5Fax number003278480351
    B.5.6E-mailregsubmissions@medpace.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 No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameViltolarsen
    D.3.2Product code [NS-065/NCNP-01]
    D.3.4Pharmaceutical form Solution for infusion
    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 INNVILTOLARSEN
    D.3.9.1CAS number 2055732-84-6
    D.3.9.2Current sponsor codeNS-065/NCNP-01
    D.3.9.4EV Substance CodeSUB195543
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/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 Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for infusion
    D.8.4Route of administration of the placeboIntravenous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Duchenne Muscular Dystrophy (DMD)
    Distrofia Muscolare di Duchenne
    E.1.1.1Medical condition in easily understood language
    Muscular Dystrophy
    Distrofia Muscolare
    E.1.1.2Therapeutic area Diseases [C] - Musculoskeletal Diseases [C05]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10013801
    E.1.2Term Duchenne muscular dystrophy
    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 compare the efficacy of viltolarsen administered intravenously at weekly doses of 80 mg/kg over a 48-week treatment period vs. placebo controls in ambulant boys ages 4 to <8 years with DMD using Time to Stand Test (TTSTAND) as a measure of strength and function.
    Confrontare l’efficacia di viltolarsen somministrato per via endovenosa in dosi settimanali da 80 mg/kg nell’arco di un periodo di trattamento di 48 settimane rispetto a controlli con placebo in ragazzi deambulanti di età compresa tra 4 e <8 anni affetti da DMD mediante test del tempo impiegato per alzarsi in piedi (Time to Stand Test, TTSTAND) come misura di forza e funzionalità.
    E.2.2Secondary objectives of the trial
    -To compare the efficacy of viltolarsen administered intravenously at weekly doses of 80 mg/kg in ambulant boys ages 4 to <8 years with DMD over a 48-week treatment period vs. placebo controls using hierarchical strength and endurance outcomes
    -To evaluate the safety and tolerability of viltolarsen administered intravenously at weekly doses of 80 mg/kg in ambulant boys ages 4 to <8 years with DMD
    -Confrontare l’efficacia di viltolarsen somministrato per via endovenosa in dosi settimanali da 80 mg/kg in ragazzi deambulanti di età compresa tra 4 e <8 anni affetti da DMD nell’arco di un periodo di trattamento di 48 settimane rispetto a controlli con placebo usando esiti gerarchici di forza e resistenza
    -Valutare la sicurezza e la tollerabilità di viltolarsen somministrato per via endovenosa in dosi settimanali da 80 mg/kg in ragazzi deambulanti di età compresa tra 4 e < 8 anni affetti da DMD;
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1-Participant’s parent(s) or legal guardian(s) has (have) provided written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization, where applicable, prior to any study-related procedures; participants will be asked to give written or verbal assent according to local requirements;
    2. Participant has a confirmed diagnosis of DMD defined as:
    a. Participant is male with clinical signs compatible with DMD; and
    b. Participant has a confirmed DMD mutation(s) in the dystrophin gene that is amenable to skipping of exon 53 to restore the dystrophin mRNA reading frame including determination of unambiguously defined exon boundaries (using techniques such as multiplex ligation-dependent probe amplification [MLPA], comparative genomic hybridization [CGH] array or other techniques with similar capability);
    3. Participant is = 4 years and <8 years of age at time of first infusion in the study;
    4. Participant is able to walk independently without assistive devices;
    5. Participant is able to complete the TTSTAND without assistance in <10 seconds, as assessed at the Screening Visit;
    6. Participant and parent(s)/guardian(s) are willing and able to comply with scheduled visits, study drug administration plan, and study procedures;
    7. Participant must be on a stable dose of glucocorticoid (GC) for at least 3 months prior to first dose of study drug and is expected to remain on stable
    1. I genitori o tutori legali del partecipante hanno fornito il consenso informato scritto e l’autorizzazione della Legge sulla portabilità e responsabilità delle polizze di assicurazione sanitaria (Health Insurance Portability and Accountability Act, HIPAA), ove applicabile, prima di iniziare qualsiasi procedura correlata allo studio; ai partecipanti sarà chiesto di dare il proprio assenso scritto o verbale secondo i requisiti locali;
    2. Il partecipante presenta una diagnosi confermata di DMD definita come:
    a. Il partecipante è di sesso maschile con segni clinici compatibili con la DMD; e
    b. Il partecipante presenta una o più mutazioni della DMD confermate a livello del gene della distrofina, trattabili con skipping dell’esone 53 volto a ripristinare il frame di lettura dell’RNA messaggero (messenger RNA, mRNA) della distrofina, inclusa la determinazione dei confini dell’esone definiti in modo univoco (usando tecniche quali amplificazione legatura-dipendente multipla della sonda (multiplex ligation-dependent probe amplification, MLPA), matrice di ibridazione genomica comparativa (comparative genomic hybridization, CGH) o altre tecniche con capacità simile);
    3. Il partecipante ha un’età compresa tra =4 e <8 anni al momento della prima infusione nello studio;
    4. Il partecipante è in grado di camminare da solo senza dispositivi di assistenza;
    5. Il partecipante è in grado di completare il TTSTAND senza assistenza in <10 secondi, secondo la valutazione della visita di screening;
    6. Il partecipante e i genitori o tutori legali sono disposti a, e in grado di, attenersi alle visite programmate, al piano di somministrazione del farmaco dello studio e alle procedure dello studio;
    7. Il partecipante deve assumere una dose stabile di glucocorticoide (GC) per almeno i 3 mesi precedenti alla prima dose del farmaco in studio e deve continuare a farlo per tutta la durata dello studio.
    E.4Principal exclusion criteria
    1. Participant has current or history of chronic systemic fungal or viral infections;
    2. Participant has had an acute illness within 4 weeks prior to the first dose of study drug based on the Principal Investigator's judgment/discretion;
    3. Participant has evidence of symptomatic cardiomyopathy (Note: Asymptomatic cardiac abnormality on investigation would not be exclusionary);
    4. Participant has an allergy or hypersensitivity to the study drug or to any of its constituents;
    5. Participant has severe behavioral or cognitive problems that preclude participation in the study, in the opinion of the investigator;
    6. Participant has previous or ongoing medical condition, medical history, physical findings or laboratory abnormalities that could affect safety, make it unlikely that treatment and follow-up will be correctly completed or impair the assessment of study results, in the opinion of the investigator;
    7. Participant has had surgery within the 3 months prior to the first anticipated administration of study drug or surgery is planned for anytime during the duration of the study;
    8. Participant has positive test results for hepatitis B antigen, hepatitis C antibody or human immunodeficiency virus (HIV) antibody at screening;
    9. Participant is currently taking any other investigational drug or has taken any other investigational drug within 3 months prior to the first dose of study drug or within 5 times the halflife of a medication, whichever is longer;
    10. Participant was previously enrolled in an interventional study of viltolarsen.
    11. Participant is currently taking any other exon skipping agent or has taken any other exon skipping agent within 3 months prior to the first dose of study drug.
    12. Participant has taken any gene therapy.
    13.Participant has inadequate renal function, as defined by serum Cystatin C greater than 1.5 × upper limit of normal (ULN) at the Screening Visit. If the value is greater than 1.5 × ULN, the serum Cystatin C will be repeated once; if the repeated test result is still greater than 1.5 × ULN, the participant should be excluded
    1. Il partecipante presenta attualmente, o in anamnesi, infezioni micotiche o virali sistemiche croniche;
    2. Il partecipante ha avuto una malattia acuta nelle 4 settimane precedenti la prima dose di farmaco dello studio, in base al giudizio/a discrezione dello Sperimentatore principale;
    3. Il partecipante presenta evidenza di cardiomiopatia sintomatica (NB: un’anomalia cardiaca asintomatica in fase di analisi non comporterebbe l’esclusione);
    4. Il partecipante presenta allergia o ipersensibilità al farmaco dello studio o a qualsiasi suo componente;
    5. Il partecipante presenta problemi comportamentali o cognitivi seri che, a parere dello sperimentatore, precludono la partecipazione allo studio;
    6. Il partecipante presenta una condizione medica precedente o attuale, un’anamnesi medica, risultati fisici o anomalie di laboratorio che potrebbero compromettere la sicurezza, rendere improbabile che il trattamento e il follow-up siano completati correttamente o compromettere la valutazione dei risultati dello studio, a parere dello sperimentatore;
    7. Il partecipante ha subito un’intervento chirurgico nei 3 mesi precedenti la prima somministrazione prevista del farmaco dello studio oppure si pianifica un intervento chirurgico in qualsiasi momento nel corso dello studio;
    8. Il partecipante presenta risultati positivi al test per gli antigeni dell’epatite B, degli anticorpi dell’epatite C o del virus dell’immunodeficienza umana (human immunodeficiency virus, HIV) allo screening;
    9. Il partecipante sta attualmente assumendo un altro farmaco sperimentale o ne ha assunto uno nei 3 mesi precedenti la prima dose di farmaco dello studio o in 5 volte il tempo di emivita di un farmaco, a seconda di quale sia il periodo più lungo;
    10. Il partecipante è stato precedentemente arruolato in uno studio interventistico di viltolarsen;
    11. Il partecipante sta attualmente assumendo un altro agente per lo skipping dell’esone o ne ha assunto uno nei 3 mesi precedenti la prima dose di farmaco dello studio;
    12. Il partecipante ha assunto una terapia genica.
    13.Il partecipante ha una funzione renale inadeguata, come definita dai livelli di cistatina C sierica 1,5 volte maggiori rispetto al limite superiore della normalità (Upper Limit of Normal, ULN) alla Visita di screening. Se il valore è 1,5 volte maggiore rispetto all’ULN, il test della cistatina C sierica sarà ripetuto una volta; se il risultato del test ripetuto è ancora 1,5 volte maggiore rispetto all’ULN, il partecipante deve essere escluso
    E.5 End points
    E.5.1Primary end point(s)
    TTSTAND
    TTSTAND
    E.5.1.1Timepoint(s) of evaluation of this end point
    At 48 weeks treatment
    A 48 settimane di trattamento
    E.5.2Secondary end point(s)
    - Hierarchical analyses of the following strength and endurance measures:
    - Time to Run/Walk 10 Meters Test (TTRW)
    - Six-minute Walk Test (6MWT)
    - North Star Ambulatory Assessment (NSAA)
    - Time to Climb 4 Steps Test (TTCLIMB)
    - Hand-held dynamometer (elbow extension, elbow flexion, knee extension and knee flexion on the dominant side only)
    - Analisi gerarchica a 48 settimane di trattamento delle seguenti misure di forza e resistenza:
    - Time to Run/Walk 10 Meters Test (TTRW)
    - Six-minute Walk Test (6MWT)
    - North Star Ambulatory Assessment (NSAA)
    - Time to Climb 4 Steps Test (TTCLIMB)
    - Forza muscolare quantitativa misurata mediante dinamometro palmare (estensione e flessione del gomito, estensione e flessione del ginocchio solo sul lato dominante)
    E.5.2.1Timepoint(s) of evaluation of this end point
    At 48 weeks treatment (first 5 bullets)
    At each study visit (last 10 bullets)
    A 48 settimane di trattamento (primi 5 punti)
    Ad ogni visita di studio (ultimi 10 punti)
    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 Yes
    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) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    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 No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    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 Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    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 Yes
    E.8.5.1Number of sites anticipated in the EEA13
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Australia
    Brazil
    Canada
    Chile
    Japan
    Korea, Republic of
    Russian Federation
    Taiwan
    Turkey
    United States
    Belgium
    France
    Italy
    Netherlands
    Poland
    Spain
    United Kingdom
    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
    The end of study date is defined as the date when the last participant at the site is assessed or receives an intervention for evaluation in the study (i.e., last participant last visit).
    La data di fine studio è definita come la data in cui l'ultimo partecipante al centro viene valutato o riceve un intervento per la valutazione nello studio (ovvero ultima visita dell'ultimo partecipante).
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months9
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months6
    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) No
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 74
    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 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 Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Assent only to be provided, where appropriate, due to patient age
    A causa dell'età del paziente sarà richiesto il solo assenso
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state2
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 28
    F.4.2.2In the whole clinical trial 74
    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 completion of the study, an open-label extension study may be available to patients (who successfully complete the double-blind study) in countries where Viltolarsen is not commercially available.
    Al completamento dello studio, potrebbe essere disponibile uno studio di estensione in aperto per i pazienti (che completano con successo lo studio in doppio cieco) in paesi in cui Viltolarsen non è disponibile in commercio.
    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 Decision2020-01-27
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-10-10
    P. End of Trial
    P.End of Trial StatusOngoing
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