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    The EU Clinical Trials Register currently displays   44339   clinical trials with a EudraCT protocol, of which   7369   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).

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    Summary
    EudraCT Number:2014-001287-35
    Sponsor's Protocol Code Number:SHH-CM
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2014-11-13
    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 ConcernedSpain - AEMPS
    A.2EudraCT number2014-001287-35
    A.3Full title of the trial
    A randomized phase II pilot study to evaluate safety and efficacy of the addition of vismodegib to standard neoadjuvant chemotherapy in triple negative breast cancer patients.
    Estudio piloto aleatorizado fase II para evaluar la seguridad y eficacia de la adición de vismodegib a la quimoterapia convencional en el tratamiento neoadyuvante del cáncer de mama triple negativo
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A randomized phase II pilot study to evaluate safety and efficacy of the addition of vismodegib to standard neoadjuvant chemotherapy in triple negative breast cancer patients.
    Estudio piloto aleatorizado fase II para evaluar la seguridad y eficacia de la adición de vismodegib a la quimoterapia convencional en el tratamiento neoadyuvante del cáncer de mama triple negativo
    A.4.1Sponsor's protocol code numberSHH-CM
    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 SponsorClínica Universidad de Navarra/Universidad de Navarra
    B.1.3.4CountrySpain
    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 supportRoche
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationClinica Universidad de Navarra
    B.5.2Functional name of contact pointUCICEC
    B.5.3 Address:
    B.5.3.1Street AddressAvda. Pío XII, 36
    B.5.3.2Town/ cityPamplona
    B.5.3.3Post code31008
    B.5.3.4CountrySpain
    B.5.4Telephone number34948255 4001144
    B.5.5Fax number34948296 667
    B.5.6E-mailucicec@unav.es
    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 ERIVEDGE
    D.2.1.1.2Name of the Marketing Authorisation holderEU/1/13/848/001
    D.2.1.2Country which granted the Marketing AuthorisationSpain
    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 nameErivedge
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Breast cancer
    Cáncer de mama
    E.1.1.1Medical condition in easily understood language
    Breast cancer
    Cáncer de mama
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 17.1
    E.1.2Level PT
    E.1.2Classification code 10057654
    E.1.2Term Breast cancer female
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 17.1
    E.1.2Level PT
    E.1.2Classification code 10006200
    E.1.2Term Breast cancer stage II
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 17.1
    E.1.2Level PT
    E.1.2Classification code 10006202
    E.1.2Term Breast cancer stage IV
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 17.1
    E.1.2Level PT
    E.1.2Classification code 10006201
    E.1.2Term Breast cancer stage III
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 17.1
    E.1.2Level PT
    E.1.2Classification code 10006187
    E.1.2Term Breast cancer
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 17.1
    E.1.2Level PT
    E.1.2Classification code 10006199
    E.1.2Term Breast cancer stage I
    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 evaluate safety and efficacy of vismodegib with standard neoadjuvant chemotherapy in breast cancer patients based on the CTCAE v4 2010 scale.
    Evaluar la seguridad y tolerabilidad de vismodegib en combinación con el esquema de quimioterapia neoadyuvante en pacientes con cáncer de mama basada en la escala CTCAE v4 2010.
    E.2.2Secondary objectives of the trial
    1- To study changes in biomarkers involved in the HH pathway in the first biopsy as compared to the later one
    2- To detect predictive factors among patients who reached pathological complete response (pCR) as compared to those with no pCR
    3- To evaluate the role of the addition of vismodegib in the pCR rate
    4- To evaluate clinical responses by breast MRI and rates of breast conservative surgery after neoadjuvant chemotherapy
    5- To evaluate QOL with EORTC QLQ-C30 scale
    1- Estudiar las modificaciones en los biomarcadores descritos en el plan de estudio y procedimientos relacionados con la vía de señalización HH comparando las muestras al diagnóstico y tras el primer ciclo de tratamiento (a las 3 semanas).
    2- Detectar factores predictivos de respuesta en los pacientes que han alcanzado pCR comparado con las pacientes que no la han alcanzado.
    3- Valorar el efecto del vismodegib en la tasa de respuestas patológicas completas (pCR).
    4- Valorar la respuesta clínica por RNM mamaria y cuantificar las pacientes que se han podido beneficiar de cirugía conservadora tras el tratamiento neoadyuvante.
    5- Evaluar la calidad de vida según la escala de la EORTC QLQ-C30 (versión 3)
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Female sex
    2. Ability to give informed agreement and to carry out the whole study protocol during the study period
    3. The patient (sólo ella, no él, cámbialo en español también) should be able to carry out the needs of the clinical trial and have measurable disease
    4. The patient should be 18-75 year-old
    5. Triple negative breast cancer (ER<1%, PR<1%, non-overexpressing HER2). 1. Patients with oligometastatic disease (1-2 resectable metastases) could be included
    6. No previous systhemic therapies
    7. Patients who are going to benefit from neoadjuvant chemotherapy
    8. ECOG<2 or Karnofsky?70%
    9. Blood tests and biochemistry suitable: (absolut neutrophil count> 1500/uL; haemoglobin>9 gr/dL; platelets>100000/uL; total bilirrubin?1.5 the upper normal limit; GOT and GPT?twice the upper normal limit; fasting glucose?150 gr/dL; HbA1c?8%, serum creatinine?2 mg/dL.
    1. Sexo femenino
    2. Capacidad para otorgar consentimiento informado y expresar su deseo de cumplir todos los requisitos del protocolo durante el periodo de estudio
    3. El/la paciente debe, en opinión del investigador, ser capaz de cumplir con todos los requerimientos del ensayo clínico y tener enfermedad medible.
    4. La paciente deberá tener entre 18 y 75 años de edad.
    5. Cáncer de mama (estadios I-III) con subtipo triple negativo (RE<1%, RP<1%, HER2 no sobrexpresado). Extraordinariamente se pueden incluir pacientes con 1-2 metástasis (estadio IV oligometástatica) resecables.
    6. No haber recibido previamente quimioterapia ni terapia sistémica.
    7. Pacientes en las que esté indicado el tratamiento con la quimioterapia neoadyuvante establecida en el protocolo.
    8. ECOG<2 ó Karnofsky >70%
    9. Parámetros analíticos Adecuados (recuento absoluto de neutrófilos > 1500/uL; hemoglobina > 9 gr/dL; plaquetas >= 100.000/uL; bilirrubina total <= 1.5 veces el límite normal (LN); GOT y GPT <= 2 xLN; FA <= 2x LN; glucosa en ayunas <= 150 mg/dL y HbA1c <= 8%); creatinina sérica < 2 mg/dL.
    E.4Principal exclusion criteria
    1. Severe diseases or infectious diseases or liver, kidney or bone marrow failure that advise not to participate in the study according to investigator criteria
    2. Pregnancy or breast feeding period or fertility women who are not agree with contraception methods
    3. Other primary tumors except for breast CIS, CIN or localized skin tumors
    4. Inflammatory breast cancer or bilateral breast cancer
    5. Bone fractures, peptic ulcus or healing disorders
    6. Any local or systhemic therapy for breast cancer
    7. To be maintained on immunosuppressants (prednisone > 10 mgr daily or others), aspirine> 325 mgr per day or clopidrogel > 75 mgr daily
    8. Cardiomyopathy NYHA class II-IV; heart stroke in the previous 6 months; uncontrolled blood pressure (systolic > 150 mm Hg and /or dyastolic > 100 mm Hg), coagulopathy or hemorragic diseases
    9. Previous lung diseases
    10. Personal history of abdominal perforation, abdominal abscess, or abdominal fistula.
    11. Inability to swallow pills
    12. Intolerance to galactose, malabsorption to galactose or/and glucose, or primary hipolactase
    1. Infecciones o enfermedades graves o insuficiencia hepática, renal o medular que desaconsejen la participación del paciente en el estudio, según el criterio del investigador.
    2. Mujeres embarazadas o en período de lactancia o en edad fértil que no vayan a usar contracepción.
    3. Diagnóstico de otros tumores primarios a excepción de CIS de mama, tumores cutáneos localizados y CIN.
    4. Cáncer de mama inflamatorio ó cáncer de mama bilateral
    5. Problemas de cicatrización de heridas, ulcus péptico ó fracturas óseas
    6. Cualquier tratamiento previo (local ó sistémico) para cáncer de mama
    7. Necesidad de tratamiento más de 10 mg de prednisona al día de forma mantenida, otros inmunosupresores, aspirina > de 325 mg/día ó clopidogrel > 75 mg/día.
    8. Cardiopatía clase II, III ó IV de la NYHA; ó IAM en los 6 meses previos, HTA descontrolada (sistólica > 150 mm Hg y/ó diastólica > 100 mmHg), diátesis hemorrágica ó coagulopatías con riesgo de sangrado
    9. Enfermedad pulmonar preexistente
    10. Enfermedad actual o antecedentes de fístula abdominal, perforación gatrointestinal ó abscesos intraabdominales en los 6 meses previos
    11. Incapacidad para tragar las cápsulas.
    12. Intolerancia a galactosa, hipolactasia primaria, malabsorción de glucosa y/ó galactosa
    E.5 End points
    E.5.1Primary end point(s)
    Se recogerán datos de seguridad y tolerabilidad de vismodegib en combinación con el esquema de quimioterapia neoadyuvante en pacientes con cáncer de mama.
    Se recogerán datos tanto de las notificaciones espontáneas de los pacientes como de los derivados de las distintas pruebas realizadas.
    Se recogerán datos de seguridad y tolerabilidad de vismodegib en combinación con el esquema de quimioterapia neoadyuvante en pacientes con cáncer de mama.
    Se recogerán datos tanto de las notificaciones espontáneas de los pacientes como de los derivados de las distintas pruebas realizadas.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Markers of safety ans efficacy will be collected whith each systemic therapy. Toxicity will be evaluated based on CTCAE v4 2010 scale.
    Las variables de seguridad y eficacia se recogerán cuando la paciente acuda recibir a cada dosis de tratamiento sistémico. Para evaluar la seguridad (toxicidad) se empleará la escala de CTCAE v4.0 del año 2010 por aparatos y sistemas.
    E.5.2Secondary end point(s)
    1- Biomarkers related to HH pathway. A molecular study base don qPCR or NGS and IHC will be performed in the diagnostic biopsy and the later one, before 2nd cycle of paclitaxel (frozen and FFPE tissue)
    Statystical analysis will be stratified accoridng to pCR, TNM staging and molecular markers
    Other biomarkers that will be evaluates are: ki67, GLI1, SMO, Patch, Cyclin D1, Claudine 1, p16, Snail, E-cadherin, CD44, CD24, ALDH1, MMP, CD25 and Foxp3
    2- Based on Miller&Paine classification we will classified pathological CR in the breast, axilla and total (breast + axilla). pCR in the breast is defined as the abscensce of infiltrant carcinoma or residual CIS (in situ carcinoma)
    3- Clinical response
    4- Clinical response by breast MRI (breast and axilla) as well as perfussion imaging
    5- QOL based on EORTC QLQ-C30 (at diagnosis and by the end of systemic therapies)
    6- DFS and OS (out of the study we will perform a phone-based follow-up)
    1- Biomarcadores relacionados con la vía de señalización HH
    Se realizará el estudio molecular mediante qPCR o secuenciación masiva e IHC en la biopsia diagnóstica (tejido fresco congelado y parafinado) y la biopsia de la visita 2 (congelado y parafinado), tras el primer ciclo con paclitaxel.
    Se estratificará el análisis en función de las pacientes que han presentado o no pCR, expresión de marcadores biológicos y estadio inicial de enfermedad.
    Se evaluarán los biomarcadores Ki67, Gli1, Smo, Patch, Ciclina D1, claudina1, p16, Snail, E-cadherina, CD44, CD24, ALDH1, MMP, CD25 y Foxp3.
    2- Efecto del vismodegib en la tasa de respuestas patológicas completas (pCR) mediante la clasificación de Miller & Paine.
    Esta clasificación de Miller & Paine se utilizará para evaluar la respuesta tanto en la mama como a nivel regional (axila). La ausencia de carcinoma infiltrante y por tanto el CIS residual (Tis) se considera respuesta completa en la mama.
    3- Respuesta clínica.
    4- Respuesta clínica por RNM mamaria
    Se realizará la evaluación de la situación de T y N en cada caso, asi como la valoración de parámetros de perfusión.
    5- Calidad de vida según la escala de la EORTC QLQ-C30
    También se evaluará la calidad de vida al diagnóstico y al finalizar las terapias sistémicas mediante el test de la EORTC QLQ-C30 (versión 3).
    6- Supervivencia libre de eventos y supervivencia global
    Fuera del estudio se realizará un seguimiento para determinar SLE y SG en ambas cohortes, mediante seguimiento telefónico.
    E.5.2.1Timepoint(s) of evaluation of this end point
    1- Biomarker analysis will be performed centralized at CIMA diagnostics by the completion of the pilot study when every sample of every patient is available
    2- pCR will be measured after the surgery in the pathological sample by the Miller&Paine classification
    3- To evaluate clinical response we will employ physical exploration, and imaging by the diagnosis and by the end of neoadjuvant therapy prior to surgery
    4- Clinical response by breast ultrasound/MRI presurgery will be also stratified by therapy ( taxanes ± vismodegib)
    5- QOL by the start and by the end of chemotherapy
    6- DFS and OS will be studied out of this pilot study
    1- El análisis de biomarcadores se realizará cuando se hayan obtenido todas las muestras, una vez completado el estudio, y se centralizará en CIMA diagnostics.
    2- La respuesta patológica en las muestras de tumor se evaluará tras la intervención quirúrgica (clasificación de Miller & Paine).
    3- Para evaluar la respuesta clínica a las terapias, se utilizarán los datos de la exploración física de la paciente con cada ciclo y del seguimiento por imagen al menos al diagnóstico y antes de la cirugía.
    4- La respuesta a la ecografía y/ó RNM precirugía se comparará con la RNM mamaria tras el tratamiento con taxano +- vismodegib y al diagnóstico.
    5- Calidad de vida: Al diagnóstico y al finalizar las terapias sistémicas
    6- Supervivencia libre de eventos y supervivencia global: Fuera del estudio
    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 No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) 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 Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    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 No
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    Standard Group
    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 concerned4
    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
    UVUS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years
    E.8.9.1In the Member State concerned months23
    E.8.9.1In the Member State concerned days
    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: 35
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 5
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male No
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    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 No
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state40
    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)
    Se continuará con el tratamiento habitual para la patología.
    Se continuará con el tratamiento habitual para la patología.
    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 Decision2015-03-12
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-02-13
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2019-01-02
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