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    Summary
    EudraCT Number:2011-005724-17
    Sponsor's Protocol Code Number:AFLIBC06097
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2012-07-09
    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 number2011-005724-17
    A.3Full title of the trial
    A Multicenter, Single arm, Open Label Clinical Trial to Evaluate the Safety and Health-Related Quality of Life of Aflibercept in Patients with Metastatic Colorectal Cancer (mCRC) Previously Treated with an Oxaliplatin-Containing Regimen
    Ensayo clínico abierto, multicéntrico, de un único brazo, para evaluar la seguridad y calidad de vida relacionada con la salud de aflibercept en pacientes con cáncer colorrectal metastásico (CCRm) previamente tratados con un régimen conteniendo oxaliplatino
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Safety and Quality of Life study of Aflibercept in patients with metastatic Colorectal
    Cancer previously treated with an oxaliplatin-based regimen
    Seguridad y calidad de vida relacionada con aflibercept en pacientes con cáncer colorrectal metastásico previamente tratados con un régimen conteniendo oxaliplatino
    A.4.1Sponsor's protocol code numberAFLIBC06097
    A.5.3WHO Universal Trial Reference Number (UTRN)U1111-1125-8949
    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 SponsorSanofi aventis Groupe
    B.1.3.4CountryFrance
    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 supportSanofi aventis Groupe
    B.4.2CountryFrance
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationsanofi-aventis, s.a.
    B.5.2Functional name of contact pointCSU Director
    B.5.3 Address:
    B.5.3.1Street Addressc/ Josep Pla nº2, 5ª planta
    B.5.3.2Town/ cityBarcelona
    B.5.3.3Post code08019
    B.5.3.4CountrySpain
    B.5.4Telephone number+34934859466
    B.5.5Fax number+34934895466
    B.5.6E-mailbibiana.figueres@sanofi.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 nameAflibercept
    D.3.2Product code AVE0005
    D.3.4Pharmaceutical form Concentrate for 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 INNAFLIBERCEPT
    D.3.9.1CAS number 862111-32-8
    D.3.9.2Current sponsor codeAVE0005
    D.3.9.3Other descriptive nameVEGF TRAP
    D.3.9.4EV Substance CodeSUB26987
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    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 typeRecombinant protein VEGF receptor extracellular domain fused to Fc portion of human IgG
    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
    Colorectal Neoplasms
    Neoplasias Colorrectales
    E.1.1.1Medical condition in easily understood language
    Colorectal Neoplasms
    Neoplasias Colorrectales
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.1
    E.1.2Level PT
    E.1.2Classification code 10052358
    E.1.2Term Colorectal cancer metastatic
    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 provide mCRC patients (similar to the patients evaluated in the VELOUR phase III trial) and Investigators with access to aflibercept, prior to its marketing authorisation and/or commercial availability and to document the aflibercept overall safety in this patient population.
    Proporcionar acceso a aflibercept a pacientes con CCRm (similares a los pacientes evaluados en el ensayo de fase III VELOUR) e Investigadores, antes de su autorización de comercialización y/o disponibilidad comercial y documentar la seguridad global de aflibercept en esta población de pacientes.
    E.2.2Secondary objectives of the trial
    To document the Health-Related Quality of Life (HRQL) of aflibercept in this patient population.
    Documentar la Calidad de Vida Relacionada con la Salud (HRQL) de aflibercept en esta población de pacientes.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Histologically or cytologically proven adenocarcinoma of the colon or rectum
    Metastatic disease
    Eastern Cooperative Oncology Group performance status 0-1
    One and only one prior chemotherapeutic regimen for metastatic disease. This
    prior chemotherapy must be an oxaliplatin containing regimen. Patients must
    have progressed during or after the oxaliplatin based chemotherapy. Patients
    relapsed within 6 months of completion of oxaliplatin adjuvant chemotherapy are
    eligible.
    - Adenocarcinoma de colon o recto demostrado histológicamente o citológicamente.
    - Enfermedad metastásica.
    - ECOG PS 0-1.
    Uno y solo un régimen de quimioterapia previo para enfermedad metastásica. Esta quimioterapia previa debe ser un régimen que contenga oxaliplatino. Los pacientes deben haber progresado durante o después de la última administración de quimioterapia con oxaliplatino. Los pacientes que recaigan en un plazo de 6 meses desde que finalizaron la quimioterapia adyuvante de oxaliplatino también son elegibles.
    E.4Principal exclusion criteria
    Prior therapy with irinotecan
    Inadequate bone marrow, liver and renal function: neutrophils < 1.5x109/L,
    platelets < 100x109/L, hemoglobin < 9.0 g/dL, total bilirubin >1.5 x upper normal
    limit (ULN), transaminases >3 x ULN (unless liver metastasis are present),
    alkaline phosphatase >3 x ULN (unless liver metastasis are present), serum
    creatinine > 1.5 x ULN.
    Less than 4 weeks from prior radiotherapy, prior chemotherapy, prior major
    surgery (or until the surgical wound is fully healed).
    Treatment with any investigational drug within the prior 30 days.
    Treatment with concomitant anticonvulsivant agents that are CYP3A4 inducers
    (phenytoin, phenobarbital, carbamazepine), unless discontinued >7 days.
    History of brain metastases, uncontrolled spinal cord compression, or
    carcinomatous meningitis or new evidence of brain or leptomeningeal disease.
    Prior malignancy (other than colorectal) including prior malignancy from which the
    patient has been disease free for < 5 years (except adequately treated basal or
    squamous cell skin cancer or carcinoma in situ of the cervix).
    Any of the following within 6 months prior to study inclusion: myocardial infarction,
    severe/unstable angina pectoris, coronary/peripheral artery bypass graft, severe
    congestive heart failure, stroke or transient ischemic attack.
    Any of the following within 3 months prior study inclusion: severe gastrointestinal
    bleeding/hemorrhage, treatment resistant peptic ulcer disease, erosive
    oesophagitis or gastritis, infectious or inflammatory bowel disease, diverticulitis,
    pulmonary embolism or other uncontrolled thromboembolic event.
    Occurrence of deep vein thrombosis within 4 weeks, prior to study inclusion.
    Known dihydropyrimidine dehydrogenase deficiency.
    Predisposing colonic or small bowel disorders in which the symptoms were
    uncontrolled.
    Prior history of chronic enteropathy, inflammatory enteropathy, chronic diarrhea,
    unresolved bowel obstruction/sub-obstruction, more than hemicolectomy,
    extensive small intestine resection with chronic diarrhea.
    Known Gilbert?s syndrome.
    Unresolved or unstable toxicity from any prior anti cancer therapy at the time of
    inclusion.
    History of anaphylaxis or known intolerance to atropine sulphate or loperamide or
    appropriate antiemetics to be administered in conjunction with FOLFIRI
    (irinotecan, 5-Fluorouracil, leucovorin).
    Severe acute or chronic medical condition, which could impair the ability of the
    patient to participate to the study.
    Urine protein-creatinine ratio (UPCR) >1 on morning spot urinalysis or proteinuria
    > 500 mg/24-h.
    Uncontrolled hypertension within 3 months prior to study inclusion.
    Patients on anticoagulant therapy with unstable dose of warfarin and/or having an
    out-of-therapeutic range INR within the 4 weeks prior to study inclusion.
    Evidence of clinically significant bleeding predisposition or underlying
    coagulopathy, non-healing wound.
    Pregnant or breast-feeding women.
    Patients with reproductive potential who do not agree to use an accepted
    effective method of contraception.
    - Terapia previa con irinotecan.
    - Función inadecuada de la médula ósea:
    Neutrófilos inferior a 1,5 x 109/L
    Recuento de plaquetas inferior a 100 x 109/L
    ? Hemoglobina inferior a 9,0 g/dL
    - Pruebas de función hepática inadecuada:
    ? Bilirrubina total superior a 1,5 x LSN
    ? Transaminasas superior a 3 x LSN (a menos que haya presencia de metástasis hepáticas, 5 x LSN en dicho caso)
    ? Fosfatasa alcalina superior a 3 x LSN (a menos que haya presencia de metástasis hepáticas, 5 x LSN en dicho caso)
    - Que hayan pasado menos de 4 semanas desde la radioterapia previa o quimioterapia previa hasta el momento de la inclusión. Menos de 4 semanas después de cirugía mayor hasta el momento de la inclusión o hasta que la herida quirúrgica esté totalmente curada, lo que suceda más tarde (48 horas en caso de procedimiento quirúrgico menor o hasta que se observe curación total de la herida).
    - Tratamiento con algún fármaco en investigación durante los 30 días previos a la inclusión.
    - Acontecimientos adversos (a excepción de alopecia, neuropatía sensorial periférica y los listados en criterios de exclusión específicos) de alguna terapia anticancerosa previa de grado superior a 1 (Criterios Comunes del Instituto Nacional del Cáncer [NCI CTCAE] v.4.0) en el momento de la inclusión.
    - Antecedentes de metástasis cerebral, compresión de médula espinal no controlada, o meningitis carcinomatosa o nueva evidencia de enfermedad del cerebro o leptomeníngea.
    - Otro tumor previo. Se permite cáncer de piel de células basales o células escamosas, carcinoma in situ de cervix / cuello de utero o cualquier otro cáncer tratado adecuadamente, del cual el paciente ha estado libre durante superior a 5 años.
    - Cualquiera de los siguientes en los 6 meses previos a la inclusión: infarto de miocardio, angina pectoris grave / inestable, injerto de puentes coronarios / periféricos arteriales, insuficiencia cardiaca congestiva de clase III o IV de la NYHA, ictus o ataque isquémico transitorio.
    - Alguno de los siguientes en los 3 meses previos a la inclusión: sangrado/hemorragia gastrointestinal de grado 3-4, enfermedad de úlcera péptica resistente al tratamiento, esofagitis o gastritis erosiva, enfermedad intestinal infecciosa o inflamatoria, diverticulitis, embolismo pulmonar u otro acontecimiento tromboembólico no controlado.
    - Episodio de trombosis venosa profunda en las 4 semanas previas a la inclusión.
    - Síndrome de inmunodeficiencia adquirida (enfermedades relacionadas con el SIDA) conocido o enfermedad VIH conocida que precisa tratamiento antirretroviral.
    - Cualquier condición médica grave aguda o crónica, que pueda alterar la capacidad del paciente para participar en el estudio o que interfiera con la interpretación de los resultados del estudio.
    - Deficiencia de dihidropirimidina deshidrogenasa conocida.
    - Predisposición a alteraciones de colon o intestino delgado en que los síntomas no estaban controlados como indicaba una basal de superior a 3 heces blandas diarias.
    - Antecedentes previos de enteropatía crónica, enteropatía inflamatoria, diarrea crónica, obstrucción/sub-obstrucción intestinal no resuelta, más que hemicolectomía, resección extensa de intestino delgado con diarrea crónica.
    - Antecedentes de anafilaxis o intolerancia conocida a sulfato de atropina o loperamida o antieméticos adecuados a ser administrados conjuntamente con FOLFIRI.
    - Tratamiento con agentes anticonvulsivantes concomitantes que son inductores del CYP3A4 (fenitoína, fenobarbital, carbamazepina), a menos que se haya interrumpido superior a 7 días.
    - Pacientes con síndrome de Gilbert conocido.
    - Mujer embarazada o en periodo de lactancia. Prueba de embarazo positiva (?-HCG en suero u orina) para mujeres en edad fértil
    - Pacientes en edad fértil (mujer y hombre) que no acepte utilizar un método anticonceptivo efectivo aceptado durante el periodo de tratamiento del estudio y durante al menos los 6 meses siguientes a la finalización del tratamiento del estudio. La definición de método efectivo se dejará a criterio del investigador.
    - Para pacientes mujeres incluidas en el Reino Unido, los siguientes métodos anticonceptivos son aceptables: anticonceptivos orales acompañados por el uso de un segundo método anticonceptivo, puesto que se desconoce cómo interaccionan los anticonceptivos orales con las medicaciones del estudio o el Dispositivo IntraUterino (DIU) o mujeres que hayan sido esterilizadas quirúrgicamente, o mujeres que sean post-menopáusicas u otras razones que no tengan posibilidad de quedarse embarazadas.
    E.5 End points
    E.5.1Primary end point(s)
    - Number of participants reporting adverse events
    - Number of participants reporting laboratory
    abnormalities
    - Número de pacientes que manifiesten acontecimientos adversos
    - Número de pacientes que tengan Anomalías de laboratorio
    E.5.1.1Timepoint(s) of evaluation of this end point
    Up to 30 days after the end of
    treatment
    Hasta 30 días después de la finalización del tratamiento
    E.5.2Secondary end point(s)
    Health-Related Quality of Life (HRQL) assessed by
    using changes from baseline in scores derived from
    the 3 HRQL questionnaires
    Calidad de Vida Relacionada con la Salud (HRQL) evaluada a partir de los cambios desde la basal en las puntuaciones obtenidas de los siguientes cuestionarios:
    - EORTC QLQ-C30 (versión 3);
    - EQ-5DTM (versión 4)
    E.5.2.1Timepoint(s) of evaluation of this end point
    Every 4 weeks
    Cada 4 semanas
    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 No
    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 Yes
    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 No
    E.8.1.1Randomised Information not present in EudraCT
    E.8.1.2Open Information not present in EudraCT
    E.8.1.3Single blind Information not present in EudraCT
    E.8.1.4Double blind Information not present in EudraCT
    E.8.1.5Parallel group Information not present in EudraCT
    E.8.1.6Cross over Information not present in EudraCT
    E.8.1.7Other Information not present in EudraCT
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Information not present in EudraCT
    E.8.2.2Placebo Information not present in EudraCT
    E.8.2.3Other Information not present in EudraCT
    E.8.2.4Number of treatment arms in the trial1
    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 concerned7
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA82
    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
    Belgium
    Canada
    Chile
    Colombia
    Denmark
    Finland
    Germany
    India
    Israel
    Italy
    Netherlands
    Norway
    Spain
    Sweden
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    In each country, patient recruitment will end when
    aflibercept becomes commercially available (i.e. accessible to the patient as per each country
    regulation). Patients already included will continue to be treated until disease progression,
    death, unacceptable toxicity, Investigator?s decision or patient?s refusal of further treatment.
    En cada país, el reclutamiento de pacientes acabará cuando
    aflibercept esté disponible comercialmente (es decir, accesible para el paciente en cada país de acuerdo a su regulación). Los pacientes ya incluidos continuarán siendo tratados hasta la progresión de la enfermedad,
    la muerte, toxicidad inaceptable, la decisión del investigador o la negativa del paciente de un tratamiento adicional.
    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 months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial 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: 300
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 600
    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 state70
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 600
    F.4.2.2In the whole clinical trial 900
    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)
    Not applicable
    No aplica
    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 Decision2012-09-07
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2012-08-10
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2017-01-31
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