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    Summary
    EudraCT Number:2011-000917-38
    Sponsor's Protocol Code Number:CBPR277X2101
    National Competent Authority:Germany - BfArM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2011-07-18
    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 ConcernedGermany - BfArM
    A.2EudraCT number2011-000917-38
    A.3Full title of the trial
    A first–in-human study to evaluate safety and tolerability of repeated topical administrations of BPR277 ointment in healthy volunteers, and safety, tolerability, and preliminary efficacy of multiple topical administrations of BPR277 in patients with atopic dermatitis and Netherton syndrome
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    CBPR277X2101
    A.4.1Sponsor's protocol code numberCBPR277X2101
    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 SponsorNovartis Pharma Services AG
    B.1.3.4CountrySwitzerland
    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 supportNovartis Pharma Services AG
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationNovartis Pharma GmbH
    B.5.2Functional name of contact pointMedizinischer Infoservice
    B.5.3 Address:
    B.5.3.1Street AddressRoonstr. 25
    B.5.3.2Town/ cityNürnberg
    B.5.3.3Post code90429
    B.5.3.4CountryGermany
    B.5.4Telephone number+491802232300
    B.5.5Fax number+4991127312160
    B.5.6E-mailinfoservice.novartis@novartis.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.3.2Product code BPR277
    D.3.4Pharmaceutical form Ointment
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPTopical use (Noncurrent)
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNnot available
    D.3.9.2Current sponsor codeBPR277
    D.3.9.3Other descriptive nameBPR277
    D.3.10 Strength
    D.3.10.1Concentration unit mg/g milligram(s)/gram
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product 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 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.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation 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.3.2Product code BPR277
    D.3.4Pharmaceutical form Ointment
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPTopical use (Noncurrent)
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNnot available
    D.3.9.2Current sponsor codeBPR277
    D.3.9.3Other descriptive nameBPR277
    D.3.10 Strength
    D.3.10.1Concentration unit mg/g milligram(s)/gram
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2
    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 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 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 placeboOintment
    D.8.4Route of administration of the placeboTopical use (Noncurrent)
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Part 2: Atopic Dermatitis (AD)
    Part 3: Netherton Syndrome (NS)
    E.1.1.1Medical condition in easily understood language
    AD:Skin disease with severe itching, redness, scaling & sometimes oozing and crusting. NS:Hereditary condition with hair shaft abnormality, scaling skin disorder & signs of hypersensitivity syndrome.
    E.1.1.2Therapeutic area Diseases [C] - Skin and Connective Tissue Diseases [C17]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.1
    E.1.2Level LLT
    E.1.2Classification code 10003639
    E.1.2Term Atopic dermatitis
    E.1.2System Organ Class 100000004858
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.1
    E.1.2Level PT
    E.1.2Classification code 10062909
    E.1.2Term Netherton's syndrome
    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
    •Demonstrate tolerability (systemic and local) of repeated twice daily topical applications of BPR277 ointment in adult subjects, and in patients with AD and NS (all parts)
    •In Part 2, evaluate whether BPR277 1% ointment maintains a treatment effect, induced by topical corticosteroids, by assessing that TLSS increase is at most half of that of its vehicle in AD patients.
    •In Part 3A, assess the potential of BPR277 1% ointment b.i.d. to improve clinically severity of lesional skin (TLSS-NS) in the majority of NS patients at end of treatment versus baseline of ≥ 2 points.
    •In Part 3 (cohorts A, AA & AB), assess dose regimen relationship on clinical severity of lesional skin (TLSS-NS) in NS patients after treatment with two regimens of BPR277 (1% ointment, applied either b.i.d. or q.d.)
    E.2.2Secondary objectives of the trial
    •Evaluate systemic steady state pharmacokinetics in human after topical administration of BPR277 ointment.
    •Determine BPR277 concentrations in the skin and the urinary excretion of BPR277 after repeated topical administration of BPR277 ointment in adult HV subjects and patients with AD and NS (for NS only in Part 3A).
    •Assess the ability of repeated topical applications of BPR277 to restore the skin barrier function in AD and NS patients as demonstrated by the change in Transepidermal Water Loss (TEWL) and skin capacitance (Part 2/3A)
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Subjects eligible for inclusion in this study have to fulfill all of the following criteria. Other protocol-defined inclusion criteria apply in addition to those listed hereafter:

    Part 1:
    1.Written informed consent must be obtained before any assessment is performed.
    2.Healthy male and female subjects of non childbearing potential, 18 to 65 years of age inclusive and in good health
    3.Subjects must weigh at least 50kg to participate in the study, and must have a body mass index (BMI) within the range of 18-35kg/m2.
    4.Study subjects must be able to communicate well with the investigator, to understand and comply with the requirements of the study.

    Part 2:
    1.Written informed consent must be obtained before any assessment is performed.
    2.Male and female subjects, 18 to 65 years of age inclusive and having passed screening examinations
    3.Presence of atopic dermatitis confirmed by Itchy skin condition in the past 12 months (must have)
    Plus three or more of the following:
    •History of involvement of the skin creases
    •Personal history of asthma or hay fever
    •History of generally dry skin in the past year
    •Onset before age of 2 years
    •Visible flexural dermatitis
    4.Diagnosis of at least moderate atopic dermatitis by the IGA of the to-be-treated area at screening; and a 250 cm2 to-be-treated area of skin containing at least ~50% AD affected skin. The 250 cm2 treatment area is to be ideally situated on the forearm including the antecubital fossa with a total lesional sign score (TLSS) of at least 10 at screening. Alternative locations for the treatment area are detailed in the protocol. Areas that
    must not be chosen are: hands and feet, head and neck, back, armpits and the groin.
    5.A total lesional sign score (TLSS) at baseline of 2-4 within the study treatment area.
    6.Subjects must weigh at least 50 kg to participate in the study, and must have a body mass index (BMI) within the range of 18-42 kg/m2.
    7.Study subjects must be able to communicate well with the investigator, to understand and comply with the requirements of the study

    Part 3 Cohort A, AA and AB (patients with Netherton Syndrome):
    • Patients with Netherton syndrome, male and female subjects, 18 to 65 years of age inclusive and having passed screening examinations
    • Confirmed diagnosis of Netherton syndrome (SPINK5 mutation or LEKTI deficiency in the skin).
    • Minimum total lesional sign score NS (TLSS-NS) of 5-9 for two selected target areas at baseline. The TLSS-NS values need to be similar between the two areas at baseline.

    Other protocol-defined inclusion/exclusion criteria may apply. Refer to protocol for details.
    E.4Principal exclusion criteria
    Subjects fulfilling any of the following criteria are not eligible for inclusion in this study. Other protocol-defined exclusion criteria apply in addition to those listed hereafter:

    Part 1:
    1.Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer.
    2.History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes or history of serious allergic reaction.
    3.A history of clinically significant ECG abnormalities, or ECG abnormalities at Screening or Baseline.
    4.History of malignancy of any organ system, treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
    5.Use of any prescription drugs, herbal supplements, within four (4) weeks prior to initial dosing, and/or over-the-counter (OTC) medication, dietary supplements (vitamins included) within two (2) weeks prior to initial dosing.
    6.Total WBC count which falls outside the range of 4500–11,000/µl, or platelets <100,000/µl, or hemoglobin levels below 12.0 g/dl at screening.
    7.Donation or loss of 400 ml or more of blood within eight (8) weeks prior to initial dosing, or longer if required by local regulation.
    8.Recent and/or recurrent history of autonomic dysfunction
    9.Liver disease or liver injury as indicated by abnormal liver function tests
    10.History or presence of impaired renal function
    11.Evidence of urinary obstruction or difficulty in voiding at screening.
    12.History of hypertrophic scarring.
    13.History of immunodeficiency diseases.

    Part 2:
    1.Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer.
    2.History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes or history of serious allergic reaction.
    3.History of abnormal skin reactivity to UV light. Unusual exposure to UV light in the previous 3 weeks to study start (screening), including tanning and sun beds.
    4.Pregnant or nursing (lactating) women.
    5.Women of child-bearing potential must use highly effective contraception (as further defined in study protocol) during the study and the duration of the study.
    6.Use of topical prescription treatment for eczema (topical corticosteroids, calcineurin inhibitors, antibiotics, etc...) on the selected study treatment area within 1 week prior to initial dosing of topical corticosteroids (TCS).
    7.Recent previous treatment with phototherapy, biological therapy, immunosuppressive agents such as cyclosporine, mycophenolate, pimecrolimus or tacrolimus. A washout period will be required for such patients to be eligible to participate in the trial.
    8.Donation or loss of 400 ml or more of blood within eight (8) weeks prior to initial dosing, or longer if required by local regulation.
    9.History of malignancy of any organ system, treated or untreated, within the past 5 years.
    10.History of clinically significant ECG abnormalities or Screening/Baseline ECG abnormalities
    11.Inability or unwillingness to undergo multiple venipunctures
    12.History of hypertrophic scarring.

    Part 3 Cohorts A, AA & AB (patients with Netherton Syndrome):
    • History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes or history of serious allergic reaction.
    • History of abnormal skin reactivity to UV light. Unusual exposure to UV light in the previous 3 weeks to study start (screening), including tanning and sun beds.
    • Pregnant or nursing (lactating) women.
    • Women of child-bearing potential must use highly effective contraception (as further defined in study protocol)
    • Use of topical prescription treatment within 2 week prior to initial dosing of study drug.
    • Recent previous treatment with systemic treatment. A washout period will be required for such patients to be eligible to participate in the trial.

    Other protocol-defined inclusion/exclusion criteria may apply. Refer to protocol for details.
    E.5 End points
    E.5.1Primary end point(s)
    Maximum skin tolerability score
    Part 2, Total Lesional Signs Score
    Part 3, Clinical response using NS (TLSS-NS) score
    Part 3 Cohort AA & AB, assess the potential of BPR277 (1% ointment, applied either b.i.d. or q.d.) to improve the clinical severity of lesional skin (TLSS-NS) in NS patients.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Maximum skin tolerability score:
    Part 1: Day(D)1, D2-D14, and D22
    Part 2: D-7, D-4, D-2, D1, D8, D15, D22, D29 & D43
    Part 3: D-7, D1, D8, D15, D22, D29 & D43

    Part 2, Total Lesional Signs Score: D-7, D-4, D-2, D1, D8, D15, D22, D29 and D43
    Part 3, Clinical response using NS (TLSS-NS) score:
    Part 3 Chohort A, D-7, D1, D8, D15, D22, D29 and D43
    Part 3 Cohort AA & AB, D-7, D1, D8, D15, D29, D43
    E.5.2Secondary end point(s)
    Efficacy/Pharmacodynamics:
    Part 2
    Scores for each of the six clinical signs comprising the total lesional sign score; Lesional itch VAS; Investigator Global Assessment and Patient’s Global Severity Assessment

    Part 3
    Total lesional sign score for NS; Scores for each of the four clinical signs comprising the total lesional sign score for NS; Lesional itch VAS; Investigator Global Assessment and Patient’s Global Severity Assessment

    Safety (All parts):
    Vital signs, AEs, concomitant medications/significant non-drug therapies; ECG evaluations and standard clinical laboratory evaluations
    E.5.2.1Timepoint(s) of evaluation of this end point
    Efficacy/Pharmacodynamics:
    Part 2-completed
    Part 3 Cohort A-completed

    Part 3 Cohort AA & AB
    Total Lesional Sign Score for NS; D-7, D1, D8, D15, D29, D43.
    Lesional itch VAS & Investigator Global Assessment; D-7, D1, D8, D15, D29, D43.
    Patient’s global severity assessment: D-7, D1, D8, D15, D29, D43.
    Vital signs (VS); D-7, D1, D15, D29, D43.
    AEs, Concomitant medications/ significant non-drug therapies; D-7 [except concomitant medications], D1, D8, D15, D29, D43.
    ECGs; D-7, D1, D29, D43.
    Standard laboratory evaluations: D-7, D1, D15, D29, D43.
    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 Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Quality of life
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Yes
    E.7.1.1First administration to humans Yes
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled 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 Yes
    E.8.1.6Cross over No
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    Part 1 and Part 3 is intra-individual and Part 2 is parallel group comparison.
    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 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 concerned3
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA5
    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 No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    France
    Germany
    Netherlands
    United States
    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
    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 months6
    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 months5
    E.8.9.2In all countries concerned by the trial days15
    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: 85
    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 Yes
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations No
    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 No
    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 state20
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 30
    F.4.2.2In the whole clinical trial 85
    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)
    Standard of care
    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 Decision2011-09-14
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2011-09-01
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2014-02-13
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