Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43839   clinical trials with a EudraCT protocol, of which   7280   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2012-003056-36
    Sponsor's Protocol Code Number:CBAF312A2304
    National Competent Authority:Czechia - SUKL
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2012-09-12
    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 ConcernedCzechia - SUKL
    A.2EudraCT number2012-003056-36
    A.3Full title of the trial
    A multicenter, randomized, double-blind, parallel-group, placebo-controlled variable treatment duration study evaluating the efficacy and safety of Siponimod (BAF312) in patients with secondary progressive multiple sclerosis followed by extended treatment with open-label BAF312
    Multicentrické, randomizované, dvojitě zaslepené, v paralelních skupinách uspořádané, placebem kontrolované klinické hodnocení sledující účinnost a bezpečnost siponimodu (BAF312) s variabilní dobou léčby u pacientů se sekundárně progresivní roztroušenou sklerózou následované rozšířenou částí s otevřenou léčbou BAF312.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Study of efficacy, safety and tolerability data for BAF312 compared to placebo in patients with secondary progressive multiple sclerosis followed by extended treatment with BAF312
    Studie sledující účinnost, bezpečnost a snášenlivost přípravku BAF312 v porovnání s placebem u pacientů se sekundárně progresivní roztroušenou sklerózou následované rozšířenou částí s léčbou BAF312.
    A.3.2Name or abbreviated title of the trial where available
    EXPAND
    EXPAND
    A.4.1Sponsor's protocol code numberCBAF312A2304
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT01665144
    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 s.r.o.
    B.5.2Functional name of contact pointInformační služba - klin. hodnocení
    B.5.3 Address:
    B.5.3.1Street AddressNa Pankráci 1724/129
    B.5.3.2Town/ cityPraha 4
    B.5.3.3Post code140 00
    B.5.3.4CountryCzechia
    B.5.4Telephone number+420225 775 207
    B.5.5Fax number+420225 775 205
    B.5.6E-maildotazy.klinickehodnoceni@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.3.1Product nameSiponimod 2 mg tablet
    D.3.2Product code BAF312A
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNSiponimod
    D.3.9.1CAS number 1234627-85-0
    D.3.9.2Current sponsor codeBAF312
    D.3.9.3Other descriptive nameBAF312 hemifumarate
    D.3.9.4EV Substance CodeSUB31412
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    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.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.3.1Product nameSiponimod 1 mg tablet
    D.3.2Product code BAF312A
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNSiponimod
    D.3.9.1CAS number 1234627-85-0
    D.3.9.2Current sponsor codeBAF312
    D.3.9.3Other descriptive nameBAF312 hemifumarate
    D.3.9.4EV Substance CodeSUB31412
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1
    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: 3
    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 nameSiponimod 0.5 mg tablet
    D.3.2Product code BAF312A
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNSiponimod
    D.3.9.1CAS number 1234627-85-0
    D.3.9.2Current sponsor codeBAF312
    D.3.9.3Other descriptive nameBAF312 hemifumarate
    D.3.9.4EV Substance CodeSUB31412
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number0.5
    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: 4
    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 nameSiponimod 0.25 mg tablet
    D.3.2Product code BAF312A
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNSiponimod
    D.3.9.1CAS number 1234627-85-0
    D.3.9.2Current sponsor codeBAF312
    D.3.9.3Other descriptive nameBAF312 hemifumarate
    D.3.9.4EV Substance CodeSUB31412
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number0.25
    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 placeboFilm-coated tablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Secondary progressive multiple sclerosis
    Sekundárně progresivní roztroušená skleróza
    E.1.1.1Medical condition in easily understood language
    Secondary progressive multiple sclerosis
    Sekundárně progresivní roztroušená skleróza
    E.1.1.2Therapeutic area Diseases [C] - Nervous System Diseases [C10]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10063400
    E.1.2Term Secondary progressive multiple sclerosis
    E.1.2System Organ Class 10029205 - Nervous system disorders
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Primary objective: To demonstrate the efficacy of Siponimod (BAF312) relative to placebo in delaying the time to 3-month confirmed disability progression in patients with secondary progressive multiple sclerosis (SPMS) as measured by expanded disability status scale (EDSS)

    E.2.2Secondary objectives of the trial
    First key secondary objective: To demonstrate the efficacy of Siponimod relative to placebo in delaying the time to 3-month confirmed worsening of at least 20% from Baseline in the timed 25-foot walk test (T25W)
    Second key secondary objective: To demonstrate the efficacy of Siponimod relative to placebo in reducing the increase in T2 lesion volume from Baseline

    For further secondary objectives please see protocol

    Extension part: To evaluate the long-term safety, tolerability and efficacy of BAF312


    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    1. Exploratory blood and CSF biomarker sub-study
    (2012-7-12, Version 00)
    - Characterization of changes in biomarker levels in the CSF and peripheral blood during study course
    2. Exploratory optical coherence tomography (OCT) sub-study
    (2012-7-12, Version 00)
    -Exploration of the utility of retinal layer thickness as a marker of axonal degeneration and disability progression in SPMS
    3. Magnetic resonance imaging (MRI) sub-study
    (2012-07-12, Version 00)
    -Exploration of the use of MRI techniques that may provide additional information about the extent and nature of structural damage due to demyelination or axonal loss, in patients with SPMS treated with Siponimod and placebo, respectively
    -In addition to the conventional MRI, MTR (magnetization transfer ratio) and high resolution structural imaging will be implemented at centers meeting pre-specified technical requirements to evaluate structural integrity of the brain lesions visible on conventional MRI and in the normal appearing brain tissue as well as the grey matter volume of the patients participating in the CBAF312A2304 study
    4. Exploratory fluorescence-activated cell sorting (FACS) sub-study
    (2012-07-12, Version 00)
    -Investigation of the influence of pre-treatment peripheral lymphocyte composition on the on-treatment absolute lymphocyte count (ALC)
    -Increase understanding of the effect of Siponimod on different lymphocyte subpopulations, follow their longitudinal changes on treatment and relate these changes to the clinical and MR outcomes
    E.3Principal inclusion criteria
    Prior history of relapsing remitting MS

    Secondary progressive multiple sclerosis (SPMS) defined as progressive increase of disability in at least 6 months

    EDSS score of 3.0 to 6.5

    No relapse or corticosteroid treatment within 3 months

    Other protocol-defined inclusion criteria may apply
    E.4Principal exclusion criteria
    Women of child bearing potential must use reliable forms of contraception.

    Diagnosis of Macular edema during screening period

    Any medically unstable condition determined by investigator

    Unable to undergo MRI scans

    Hypersensitivity to any study drugs or drugs of similar class

    Other protocol-defined exclusion criteria may apply
    E.5 End points
    E.5.1Primary end point(s)
    The delay in time to 3-month confirmed disability progression by Siponimod (BAF312) relative to placebo as measured by expanded disability status scale (EDSS)

    Confirmed disability is defined as an increase of score of 1 point in patients with baseline score of 3.0-5.0 and 0.5 point increase with baseline score of 5.5 to 6.5.
    E.5.1.1Timepoint(s) of evaluation of this end point
    baseline, every three months
    E.5.2Secondary end point(s)
    The first key secondary endpoint is the delay in time to 3-month confirmed worsening of at least 20% from Baseline in the timed 25-foot walk test (T25W) by Siponimod (BAF312) compared to placebo.

    The second key secondary endpoint is the efficacy of Siponimod (BAF312) relative to placebo in reducing the increase in T2 lesion volume from Baseline

    For further secondary endpoints please see protocol.
    E.5.2.1Timepoint(s) of evaluation of this end point
    1.) baseline, every three months, up to the maximum of 3 years
    2.) baseline, every year, up to the maximum of 3 years
    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 Yes
    E.6.11Pharmacogenomic Yes
    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 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 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 EEA173
    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
    Argentina
    Australia
    Canada
    China
    Israel
    Japan
    United States
    Austria
    Estonia
    France
    Latvia
    Lithuania
    Poland
    Sweden
    Bulgaria
    Netherlands
    Romania
    Spain
    Switzerland
    Czechia
    Germany
    Greece
    Italy
    Belgium
    Hungary
    Ireland
    Portugal
    Russian Federation
    Slovakia
    Turkey
    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
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years10
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years10
    E.8.9.2In all countries concerned by the trial months0
    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 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: 1530
    F.1.3Elderly (>=65 years) No
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception 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 1031
    F.4.2.2In the whole clinical trial 1530
    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)
    The investigator must provide follow-up medical care for patients prematurely withdrawing from, or completing, the trial, or must refer them for appropriate ongoing care. This care may include initiating another treatment as deemed appropriate by the investigator or referring the patient to enter another open-label BAF312 study if the patient is eligible and such a trial is offered.
    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 Decision2012-11-08
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2012-09-20
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2023-03-31
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Tue Apr 16 07:45:34 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA