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    The EU Clinical Trials Register currently displays   41232   clinical trials with a EudraCT protocol, of which   6757   are clinical trials conducted with subjects less than 18 years old.
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    Clinical Trial Results:
    A Randomised, Double-blind, Parallel Group, Multicentre Clinical Study to Evaluate the Efficacy, Safety, Tolerability, Pharmacokinetics and Immunogenicity of SB5 Compared to Humira® in Subjects with Moderate to Severe Rheumatoid Arthritis despite Methotrexate Therapy

    Summary
    EudraCT number
    2013-005013-13
    Trial protocol
    CZ   LT   PL   BG  
    Global end of trial date
    19 Oct 2015

    Results information
    Results version number
    v1(current)
    This version publication date
    02 Nov 2016
    First version publication date
    02 Nov 2016
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    SB5-G31-RA
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    -
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Samsung Bioepis Co., Ltd.
    Sponsor organisation address
    107, Cheomdan-daero, Yeonsu-gu, Incheon, Korea, Republic of, 21987
    Public contact
    Information Desk, Samsung Bioepis Co., Ltd. , +82 324553114, bioepisinfo@samsung.com
    Scientific contact
    Information Desk, Samsung Bioepis Co., Ltd. , +82 324553114, bioepisinfo@samsung.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    19 Oct 2015
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    19 Oct 2015
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The primary objective of this study is to demonstrate the equivalence of SB5 to Humira® atWeek 24, in terms of American College of Rheumatology 20% response criteria (ACR20) response rate in subjects with moderate to severe rheumatoid arthritis (RA) despite methotrexate (MTX) therapy.
    Protection of trial subjects
    The study and clinical study protocols were reviewed and approved by Independent Ethics Committee (IEC) or Institutional Review Board (IRB). This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki (2008) and that are consistent with International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) guidelines (ICH E6) and applicable local regulatory requirements and laws. The nature and purpose of the study was fully explained to each subject and written informed consent was obtained at Screening from each subject before any study related procedures were performed. The consent documents for the study was reviewed and approved by the appropriate IEC or IRB prior to use.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    12 May 2014
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    Safety
    Long term follow-up duration
    2 Months
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Poland: 216
    Country: Number of subjects enrolled
    Bulgaria: 51
    Country: Number of subjects enrolled
    Czech Republic: 90
    Country: Number of subjects enrolled
    Lithuania: 35
    Country: Number of subjects enrolled
    Bosnia and Herzegovina: 65
    Country: Number of subjects enrolled
    Korea, Republic of: 87
    Worldwide total number of subjects
    544
    EEA total number of subjects
    392
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    475
    From 65 to 84 years
    69
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    -

    Pre-assignment period milestones
    Number of subjects started
    747 [1]
    Number of subjects completed
    544

    Pre-assignment subject non-completion reasons
    Reason: Number of subjects
    subject lost to follow up: 3
    Reason: Number of subjects
    Consent withdrawn by subject: 33
    Reason: Number of subjects
    Adverse event, non-fatal: 1
    Reason: Number of subjects
    Other: 6
    Reason: Number of subjects
    does not meet Inclusion/Exclusion Criteria: 160
    Notes
    [1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: the Sponsor used data from 'Randomised Set', not 'Enrolled Set' to fill in 'Population of trial subjects' section, thus the total worldwide subject number is same with the overall number of baseline participants. Screened(Pre-assignment) subjects: 747, Randomised subjects: 544.
    Period 1
    Period 1 title
    Randomised, Double-blind
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Carer, Assessor, Subject, Investigator, Monitor, Data analyst

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    SB5 (Proposed Biosimilar to Adalimumab)
    Arm description
    SB5 40 mg every other week via subcutaneous injection SB5 (proposed biosimilar to adalimumab)
    Arm type
    Experimental

    Investigational medicinal product name
    SB5 (proposed adalimumab biosimilar)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects self-administered 40 mg of either SB5 or EU-sourced Humira® every other week, via subcutaneous injection, up to Week 50 (a total of 26 administrations of IP) unless they withdrew early from the study.

    Arm title
    Humira (Adalimumab)
    Arm description
    Humira 40 mg every other week via subcutaneous injection to Week 24, then randomised again in a 1:1 ratio to either continue on Humira® 40 mg (Humira®/Humira®) or be transitioned to SB5 40 mg (Humira®/SB5) every other week up to Week 50.
    Arm type
    Active comparator

    Investigational medicinal product name
    Humira®
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects self-administered 40 mg of either SB5 or EU-sourced Humira® every other week, via subcutaneous injection, up to Week 50 (a total of 26 administrations of IP) unless they withdrew early from the study.

    Number of subjects in period 1
    SB5 (Proposed Biosimilar to Adalimumab) Humira (Adalimumab)
    Started
    271
    273
    Completed
    254
    254
    Not completed
    17
    19
         Other
    3
    -
         Lack of efficacy
    1
    2
         Adverse event, non-fatal
    2
    9
         Consent withdrawn by subject
    11
    8
    Period 2
    Period 2 title
    Transition-extension
    Is this the baseline period?
    No
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Carer, Assessor, Subject, Investigator, Monitor, Data analyst

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    SB5 (Proposed Biosimilar to Adalimumab)
    Arm description
    SB5 40 mg every other week via subcutaneous injection SB5 (proposed biosimilar to adalimumab)
    Arm type
    Experimental

    Investigational medicinal product name
    SB5 (proposed adalimumab biosimilar)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects self-administered 40 mg of either SB5 or EU-sourced Humira® every other week, via subcutaneous injection, up to Week 50 (a total of 26 administrations of IP) unless they withdrew early from the study.

    Arm title
    Humira (Adalimumab), Switch to SB5
    Arm description
    From Week 24, SB5 40 mg (Humira®/SB5) every other week up to Week 50.
    Arm type
    Experimental

    Investigational medicinal product name
    SB5 (proposed adalimumab biosimilar)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects self-administered 40 mg of either SB5 or EU-sourced Humira® every other week, via subcutaneous injection, up to Week 50 (a total of 26 administrations of IP) unless they withdrew early from the study.

    Arm title
    Humira (Adalimumab), Continue as Humira
    Arm description
    From Week 24, Humira® 40 mg (Humira®/Humira®) every other week up to Week 50.
    Arm type
    Active comparator

    Investigational medicinal product name
    Humira®
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects self-administered 40 mg of either SB5 or EU-sourced Humira® every other week, via ubcutaneous injection, up to Week 50 (a total of 26 administrations of IP) unless they withdrew early from the study.

    Number of subjects in period 2
    SB5 (Proposed Biosimilar to Adalimumab) Humira (Adalimumab), Switch to SB5 Humira (Adalimumab), Continue as Humira
    Started
    254
    125
    129
    Completed
    248
    117
    124
    Not completed
    6
    8
    5
         Other
    1
    1
    -
         Lack of efficacy
    -
    1
    1
         Adverse event, non-fatal
    2
    2
    3
         Consent withdrawn by subject
    2
    4
    1
         Lost to follow-up
    1
    -
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    SB5 (Proposed Biosimilar to Adalimumab)
    Reporting group description
    SB5 40 mg every other week via subcutaneous injection SB5 (proposed biosimilar to adalimumab)

    Reporting group title
    Humira (Adalimumab)
    Reporting group description
    Humira 40 mg every other week via subcutaneous injection to Week 24, then randomised again in a 1:1 ratio to either continue on Humira® 40 mg (Humira®/Humira®) or be transitioned to SB5 40 mg (Humira®/SB5) every other week up to Week 50.

    Reporting group values
    SB5 (Proposed Biosimilar to Adalimumab) Humira (Adalimumab) Total
    Number of subjects
    271 273 544
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    242 233 475
        From 65-84 years
    29 40 69
    Age continuous
    Units: years
        median (standard deviation)
    51 ± 12.67 55 ± 11.91 -
    Gender categorical
    Units: Subjects
        Female
    217 224 441
        Male
    54 49 103

    End points

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    End points reporting groups
    Reporting group title
    SB5 (Proposed Biosimilar to Adalimumab)
    Reporting group description
    SB5 40 mg every other week via subcutaneous injection SB5 (proposed biosimilar to adalimumab)

    Reporting group title
    Humira (Adalimumab)
    Reporting group description
    Humira 40 mg every other week via subcutaneous injection to Week 24, then randomised again in a 1:1 ratio to either continue on Humira® 40 mg (Humira®/Humira®) or be transitioned to SB5 40 mg (Humira®/SB5) every other week up to Week 50.
    Reporting group title
    SB5 (Proposed Biosimilar to Adalimumab)
    Reporting group description
    SB5 40 mg every other week via subcutaneous injection SB5 (proposed biosimilar to adalimumab)

    Reporting group title
    Humira (Adalimumab), Switch to SB5
    Reporting group description
    From Week 24, SB5 40 mg (Humira®/SB5) every other week up to Week 50.

    Reporting group title
    Humira (Adalimumab), Continue as Humira
    Reporting group description
    From Week 24, Humira® 40 mg (Humira®/Humira®) every other week up to Week 50.

    Primary: American College of Rheumatology 20% Response Criteria (ACR20) response rate in subjects

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    End point title
    American College of Rheumatology 20% Response Criteria (ACR20) response rate in subjects
    End point description
    End point type
    Primary
    End point timeframe
    at Week 24
    End point values
    SB5 (Proposed Biosimilar to Adalimumab) Humira (Adalimumab)
    Number of subjects analysed
    239
    237
    Units: number
    173
    171
    Statistical analysis title
    Equivalence test
    Comparison groups
    Humira (Adalimumab) v SB5 (Proposed Biosimilar to Adalimumab)
    Number of subjects included in analysis
    476
    Analysis specification
    Pre-specified
    Analysis type
    equivalence
    Method
    Parameter type
    Risk difference (RD)
    Point estimate
    0
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.15
         upper limit
    0.15
    Variability estimate
    Standard error of the mean

    Secondary: American College of Rheumatology 20% Response Criteria (ACR20) response rate in subjects

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    End point title
    American College of Rheumatology 20% Response Criteria (ACR20) response rate in subjects
    End point description
    End point type
    Secondary
    End point timeframe
    at Week 52
    End point values
    SB5 (Proposed Biosimilar to Adalimumab) Humira (Adalimumab), Switch to SB5 Humira (Adalimumab), Continue as Humira
    Number of subjects analysed
    212
    106
    111
    Units: number
    163
    86
    79
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    at Week 24
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    17.0
    Reporting groups
    Reporting group title
    SB5 (Proposed Biosimilar to Adalimumab)
    Reporting group description
    SB5 40 mg every other week via subcutaneous injection SB5 (proposed biosimilar to adalimumab)

    Reporting group title
    Humira (Adalimumab)
    Reporting group description
    Humira 40 mg every other week via subcutaneous injection to Week 24, then randomised again in a 1:1 ratio to either continue on Humira® 40 mg (Humira®/Humira®) or be transitioned to SB5 40 mg (Humira®/SB5) every other week up to Week 50.

    Serious adverse events
    SB5 (Proposed Biosimilar to Adalimumab) Humira (Adalimumab)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    9 / 268 (3.36%)
    16 / 273 (5.86%)
         number of deaths (all causes)
    0
    2
         number of deaths resulting from adverse events
    0
    0
    Injury, poisoning and procedural complications
    Craniocerebral injury
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 273 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ulna fracture
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 273 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular pseudoaneurysm
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 273 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Small cell lung cancer
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 273 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Glioblastoma multiforme
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 273 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphoma
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 273 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to spine
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 273 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Papillary thyroid cancer
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 273 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seminoma
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 273 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 273 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 273 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 273 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nasal inflammation
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 273 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 273 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Blood and lymphatic system disorders
    Eosinophilia
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 273 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Lumber radiculopathy
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 273 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multiple sclerosis
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 273 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Retinal oedema
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 273 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Femoral hernia, obstructive
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 273 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Rheumatoid arthritis
         subjects affected / exposed
    1 / 268 (0.37%)
    1 / 273 (0.37%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Escherichia urinary tract infection
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 273 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 273 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 273 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchopneumonia
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 273 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 268 (0.00%)
    2 / 273 (0.73%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Staphylococcal sepsis
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 273 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 273 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    SB5 (Proposed Biosimilar to Adalimumab) Humira (Adalimumab)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    35 / 268 (13.06%)
    44 / 273 (16.12%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    11 / 268 (4.10%)
    14 / 273 (5.13%)
         occurrences all number
    13
    15
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    24 / 268 (8.96%)
    30 / 273 (10.99%)
         occurrences all number
    27
    34

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? No

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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