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 are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   42556   clinical trials with a EudraCT protocol, of which   7007   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 in adults and that are not part of an agreed PIP are not public in the EU CTR (refer to European Guidance 2008/C 168/02   Art. 3 par. 2 and   Commission Guideline 2012/C 302/03,   Art. 5) .

    Clinical Trials marked as "Trial now transitioned" were transitioned to the Clinical Trial Regulation 536/2014 and can be further followed in the Clinical Trial Information System  
     
    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:2018-001521-97
    Sponsor's Protocol Code Number:M18ACX
    National Competent Authority:Netherlands - Competent Authority
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2018-07-12
    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 ConcernedNetherlands - Competent Authority
    A.2EudraCT number2018-001521-97
    A.3Full title of the trial
    Phase II single arm study of afatinib in combination with cetuximab in EGFR exon 20 insertion positive non-small-cell lung cancer
    Fase II één-armige studie met afatinib in combinatie met cetuximab bij EGFR exon 20 insertie positieve niet-kleincellig long kanker
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Afatinib in combination with cetuximab in EGFR exon 20 insertion positive non-small-cell lung cancer
    Afatinib in combinatie met cetuximab bij EGFR exon 20 insertie positieve niet-kleincellig long kanker
    A.4.1Sponsor's protocol code numberM18ACX
    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 SponsorStichting Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis
    B.1.3.4CountryNetherlands
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportStichting Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek
    B.4.2CountryNetherlands
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationStichting Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek
    B.5.2Functional name of contact pointDr. A.J. de Langen
    B.5.3 Address:
    B.5.3.1Street AddressPlesmanlaan 121
    B.5.3.2Town/ cityAmsterdam
    B.5.3.3Post code1066 CX
    B.5.3.4CountryNetherlands
    B.5.4Telephone number0031205129111
    B.5.5Fax number0031205122572
    B.5.6E-mailj.d.langen@nki.nl
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Giotrif
    D.2.1.1.2Name of the Marketing Authorisation holderBoehringer Ingelheim International GmbH
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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 nameAfatinib
    D.3.2Product code BIBW 2992
    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 INNAfatinib
    D.3.9.1CAS number 850140-72-6
    D.3.9.3Other descriptive nameAFATINIB
    D.3.9.4EV Substance CodeSUB32268
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    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 Yes
    D.2.1.1.1Trade name erbitux
    D.2.1.1.2Name of the Marketing Authorisation holderMerck KGaA
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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 namecetuximab
    D.3.2Product code L01XC06
    D.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNCetuximab
    D.3.9.1CAS number 205923-56-4
    D.3.9.3Other descriptive nameCETUXIMAB
    D.3.9.4EV Substance CodeSUB01178MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    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 No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    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 Yes
    D.3.11.13.1Other medicinal product typechimeric monoclonal IgGl antibody produced in a mammalian cell line (Sp2/0) by recombinant DNA technology
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    EGFR exon 20 insertion positive non-small cell lung cancer
    Positieve EGFR exon 20 insertie niet-kleincellig longkanker
    E.1.1.1Medical condition in easily understood language
    non-small cell lung cancer
    niet-kleincellig longkanker
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10029522
    E.1.2Term Non-small cell lung cancer stage IV
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To determine the disease control rate at 18 weeks of afatinib and cetuximab treatment in patients with NSCLC harboring an EGFR exon 20 insertion mutation.
    Bepalen van DCR (ziekte controle ratio) bij 18 weken behandeling met afatinib en cetuximab bij patiënten met NSCLC die een EGFR-exon 20-insertie mutatie bevatten.
    E.2.2Secondary objectives of the trial
    • To assess anti-tumor activity of afatinib and cetuximab in NSCLC patients harboring an EGFR exon 20 insertion.
    • To assess safety of afatinib and cetuximab combination treatment.
    • At baseline, during treatment and at progression, cfDNA will be collected to analyse possible resistance mechanisms.
    • Om de antitumoractiviteit van afatinib en cetuximab te bepalen bij NSCLC-patiënten die een EGFR-exon 20-insertie bevatten.
    • Om de veiligheid van combinatie van afatinib en cetuximab te beoordelen.
    • Bij baseline, tijdens de behandeling en bij progressie, zal cfDNA worden verzameld om mogelijke resistentie mechanismen te analyseren.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    • Pathologically or cytologically confirmed stage IV NSCLC, harboring an EGFR exon 20 insertion mutation.
    • 18 years or older at time of study entry.
    • Life expectancy of at least three months.
    • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (see Appendix 1).
    • Measurable disease, according to RECIST 1.1.
    • At baseline adequate fresh or archived tissue from a histological biopsy or a cellblock obtained by fine needle aspiration of a tumor lesion that is not radiated prior to biopsy, must be available. Baseline tissue samples must be obtained after the last line of systemic therapy prior to study entry.
    • Adequate normal organ and marrow function as defined below:
    • Absolute leukocyte count ≥ 3 x 109/L (> 3000 per mm3)
    • Platelet count ≥ 75 x 109/L (>75,000 per mm3)
    • Aspartate amino transferase (AST) or alanine amino transferase (ALT) ≤ 3 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤ 5x ULN.
    • Serum creatinine CL>30 mL/min by the Cockcroft-Gault formula or by 24-hour urine collection for determination of creatinine clearance.
    • Women of child-bearing potential: these subjects must have a negative serum pregnancy test within 7 days prior to the first dose of study treatment and agree to use highly effective contraception, as defined in section 5.2.2, from 7 days prior to enrollment, throughout the treatment period and for seven months after completion of the treatment with cetuximab.
    • Males must agree to take appropriate precautions to avoid fathering a child from the first dose of study treatment through 3 months after the final administration of investigational drugs.
    • Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
    • Ability to give written informed consent before patient registration.
    • Pathologisch of cytologisch bevestigd stadium IV NSCLC, met een EGFR-exon 20-insertie mutatie.
    • 18 jaar of ouder op het moment van deelname aan de studie.
    • Levensverwachting van minimaal drie maanden.
    • Eastern Cooperative Oncology Group (ECOG) performance status van 0-2 (zie Appendix 1).
    • Meetbare ziekte, volgens RECIST 1.1.
    • Bij baseline moet er adequaat vers of gearchiveerd weefsel van een histologisch biopt of een celblok dat verkregen wordt door fijne naald aspiratie van een tumor laesie die niet bestraald is voorafgaand aan het biopt beschikbaar zijn. Baseline weefselmonsters moeten verkregen zijn na de laatste lijn van systemische therapie voorafgaand aan deelname aan het onderzoek.
    • Adequate normale orgaan- en beenmergfunctie zoals hieronder gedefinieerd:
    • Absoluut aantal leukocyten ≥ 3 x 109 / L (> 3000 per mm3)
    • Aantal bloedplaatjes ≥ 75 x 109 / L (> 75.000 per mm3)
    • Aspartaat-aminotransferase (AST) of alanine-aminotransferase (ALT) ≤ 3 x de institutionele bovenlimiet van normaal tenzij levermetastasen aanwezig zijn, in welk geval het ≤ 5x ULN moet zijn.
    • Serum creatinine CL> 30 ml / min volgens de Cockcroft-Gault-formule of door 24-uurs urineverzameling voor de bepaling van de creatinine klaring.
    • Vrouwen in de vruchtbare leeftijd: deze proefpersonen moeten een negatieve serum zwangerschapstest ondergaan binnen de 7 dagen voorafgaand aan de eerste dosis van de onderzoeksbehandeling en ermee instemmen om zeer effectieve anticonceptie te gebruiken, zoals gedefinieerd in sectie 5.2.2, vanaf 7 dagen voor inschrijving, gedurende de behandelingsperiode en gedurende zeven maanden na voltooiing van de behandeling met cetuximab.
    • Mannen moeten ermee instemmen passende voorzorgsmaatregelen te nemen om te voorkomen dat een kind wordt verwekt vanaf de eerste dosis van de onderzoeksbehandeling tot drie maanden na de laatste toediening van geneesmiddelen voor
    • De proefpersoon is bereid en in staat om te voldoen aan het protocol gedurende de duur van het onderzoek, inclusief het ondergaan van de behandeling en de geplande bezoeken en onderzoeken inclusief follow-up.
    • Mogelijkheid om schriftelijke geïnformeerde toestemming te geven vóór de registratie van de patient.
    E.4Principal exclusion criteria
    • Participation in another clinical study with an investigational product during the last 2 weeks.
    • Prior treatment with EGFR targeting antibodies (prior treatment with EGFR TKI’s is allowed).
    • Other active malignancy.
    • History of hypersensitivity to afatinib or cetuximab.
    • Major surgery (excluding diagnostic procedures e.g. mediastinoscopy or VATS biopsy) within 28 days of the start of study treatment.
    • Radiotherapy less than two weeks prior to the start of study treatment.
    • Symptomatic brain metastases.
    • Breast feeding
    • Uncontrolled intercurrent illness including ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, myocardial infarction within 12 months prior to the study entry, or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent.
    • Any other concomitant serious illness or organ system dysfunction which in the opinion of the investigator would either compromise patient safety or interfere with the evaluation of the safety and anti-tumor activity of the test drugs.
    • Deelname aan een ander klinisch onderzoek met een onderzoeksmiddel gedurende de laatste 2 weken.
    • Voorafgaande behandeling met EGFR-gerichte antilichamen (voorafgaande behandeling met EGFR-TKI's is toegestaan).
    • Andere actieve maligniteit.
    • Voorgeschiedenis van overgevoeligheid voor afatinib of cetuximab.
    • Grote operatie (exclusief diagnostische procedures zoals bijvoorbeeld mediastinoscopie of VATS-biopt) binnen 28 dagen na aanvang van de onderzoeksbehandeling.
    • Radiotherapie minder dan twee weken voorafgaand aan de start van de onderzoeksbehandeling.
    • Symptomatische hersenmetastasen.
    • Borstvoeding
    • Ongecontroleerde bijkomende ziekte waaronder doorlopende of actieve infectie, symptomatisch congestief hartfalen, ongecontroleerde hypertensie, onstabiele angina pectoris, hartritmestoornissen, actieve maagzweer aandoening of gastritis, hartinfarct binnen 12 maanden voorafgaand aan de start van het onderzoek, of psychiatrische aandoeningen / sociale situaties die de naleving van de onderzoeksvereisten zou beperken of het vermogen van het individu om schriftelijke geïnformeerde toestemming te geven in gevaar zou brengen.
    • Elke andere gelijktijdige ernstige ziekte of disfunctie van het orgaansysteem die naar de mening van de onderzoeker de veiligheid van de patiënt in gevaar zou brengen of de evaluatie van de veiligheids- en antitumoractiviteit van de testgeneesmiddelen zou verstoren.
    E.5 End points
    E.5.1Primary end point(s)
    • Disease control rate after three cycles of a 6-week treatment course (i.e. 18 weeks)
    • Ziekte controle na 3 kuren van een 6-wekelijkse behandelingskuur (d.w.z. bij 18 weken).
    E.5.1.1Timepoint(s) of evaluation of this end point
    At 18 weeks
    Bij 18 weken
    E.5.2Secondary end point(s)
    • Objective tumor response (CR and PR), determined by RECIST v1.1.
    • Duration of response, determined by RECIST v1.1.
    • Progression-free survival (PFS), defined as the interval between initiation of study treatment and the date of radiological progression, determined by RECIST v1.1 or death.
    • Overall survival (OS), defined as the interval between initiation of study treatment and the date of death.
    • Safety as indicated by intensity and incidence of adverse events, graded according to NCI CTCAE Version 4.03.
    • Objectieve tumorrespons (CR en PR), vastgesteld door RECIST v1.1.
    • Duur van de respons, vastgesteld door RECIST v1.1.
    • Progressie vrije overleving, gedefinieerd als het interval tussen de start van de onderzoeksbehandeling en de datum van radiologische progressie, vastgesteld door RECIST v1.1 of overlijden.
    • Totale overleving, gedefinieerd als het interval tussen de start van de onderzoeksbehandeling en de datum van overlijden.
    • Veiligheid aangegeven dmv intensiteit en incidentie van bijwerkingen, beoordeeld volgens NCI CTCAE Versie 4.03.
    E.5.2.1Timepoint(s) of evaluation of this end point
    PFS, Objective tumor response and OS: 6 weekly until progression or death
    Safety: 2 weekly during treatment, thereafter every 6 weeks
    Progressie vrije overleving, objectieve tumorrespons en totale overleving: elke 6 weken tot progressie of overlijden
    Veiligheid: elke 2 weken tijdens de behandeling, daarna elke 6 weken
    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 No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    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) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    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 No
    E.8.2.3Other No
    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 concerned5
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    Laatste visite van de laatste patient
    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 months6
    E.8.9.1In the Member State concerned 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: 20
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 17
    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 state37
    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)
    none
    geen
    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 Decision2018-07-11
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-11-20
    P. End of Trial
    P.End of Trial StatusOngoing
    For support, visit the EMA Service Desk , log in using your EMA account and open a ticket specifying "EU CTR" in your request.
    If you do not have an account, please visit the EMA Account management page page click on "Create an EMA account" and follow the instructions.
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2022 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA