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    Summary
    EudraCT Number:2008-002113-48
    Sponsor's Protocol Code Number:CRAD001M2302
    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:2010-06-22
    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 number2008-002113-48
    A.3Full title of the trial
    Estudio aleatorizado, doble ciego y controlado con placebo de RAD001 en el tratamiento del angiomiolipoma en pacientes con Complejo de Esclerosis Tuberosa (CET) o linfangioleiomiomatosis esporádica (LAM)
    A.4.1Sponsor's protocol code numberCRAD001M2302
    A.7Trial is part of a Paediatric Investigation Plan Information not present in EudraCT
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorNovartis Farmacéutica, S.A.
    B.1.3.4CountrySpain
    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 support
    B.4.2Country
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisation
    B.5.2Functional name of contact point
    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 nameRAD001
    D.3.2Product code RAD001
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    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 INNEVEROLIMUS
    D.3.9.1CAS number 159351696
    D.3.9.2Current sponsor codeRAD001
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    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) Information not present in EudraCT
    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 Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    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 Information not present in EudraCT
    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 placeboTablet
    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
    Angiomiolipoma en pacientes con Complejo de Esclerosis Tuberosa (CET) o linfangioleiomiomatosis esporádica (LAM)
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 9.1
    E.1.2Level LLT
    E.1.2Classification code 10051810
    E.1.2Term Angiomyolipoma
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Comparar la tasa de respuesta del angiomiolipoma al RAD001 frente al placebo en pacientes con angiomiolipomas asociados con el complejo de esclerosis tuberosa o linfangioleiomatosis esporádica.
    E.2.2Secondary objectives of the trial
    Comparar RAD001 con placebo en relación con:
    1. El tiempo transcurrido hasta la progresión del angiomiolipoma.
    2. La tasa de respuesta de las lesiones cutáneas.
    3. Los cambios con respecto a la situación basal en los niveles en plasma de moléculas angiogénicas, por ejemplo VEGF, FGF básico, PLGF, receptor soluble 1 del VEGF y receptor soluble 2 del VEGF.
    4. La función renal evaluada usando el aclaramiento de creatinina calculado
    5. La seguridad, evaluada mediante los criterios comunes de terminología para acontecimientos adversos (CTCAE), versión 3.0, del Instituto Nacional del Cáncer (NCI).
    En el grupo de tratamiento con RAD001:
    1. Caracterizar la farmacocinética del RAD001 en esta población de pacientes, específicamente en términos de exposición.
    2. Describir el tiempo transcurrido hasta la respuesta del angiomiolipoma, la duración de esta respuesta y la duración de la respuesta de lesión cutánea.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1.Varones o mujeres &#8805; 18 años de edad.
    2.Diagnóstico clínicamente definitivo de esclerosis tuberosa según los criterios modificados de Gomez (Roach y col., 1998; Hyman y Whittemore, 2000, Tabla 5-1Tabla 5-1) o LAM esporádica (confirmada mediante biopsia o TC torácica compatible). El diagnóstico clínicamente definitivo de esclerosis tuberosa según los criterios modificados de Gomez se define como cualquiera de los siguientes:
    •Dos características principales de la Tabla 5-1Tabla 5-1.
    •Una característica principal más dos características secundarias de la Tabla 5-1Tabla 5-1.
    3.Diagnóstico clínicamente definitivo de angiomiolipoma renal.
    4.Presencia de al menos un angiomiolipoma con su diámetro mayor &#8805; 3 cm observado en TC/RM.
    5.En caso de las mujeres en edad fértil, prueba de embarazo negativa documentada antes del reclutamiento. Las pacientes premenopáusicas y sexualmente activas (y las parejas femeninas de pacientes varones) deben utilizar medidas anticonceptivas adecuadas durante todo el estudio y hasta transcurridas 8 semanas desde la finalización del tratamiento.
    6.Consentimiento informado escrito de acuerdo con las normas locales.
    E.4Principal exclusion criteria
    1.Pacientes con angiomiolipomas que, en opinión del investigador, requieran cirugía en el momento de la aleatorización.
    2.Hemorragia o embolización relacionada con angiomiolipoma durante los 6 meses anteriores a la aleatorización.
    3.Antecedentes de infarto de miocardio, angina o ictus relacionados con aterosclerosis.
    4.Deterioro de la función pulmonar definido como:
    Para pacientes sin linfangioleiomiomatosis (LAM)
    Deterioro conocido de la función pulmonar (p.ej. FEV1 o DLco &#8804; 70% del previsto)
    Nota: la prueba de la función pulmonar basal no es necesaria para pacientes sin LAM
    Para pacientes con LAM
    •DLco &#8804; 35%, o
    •Saturaciones de O2 inferiores a lo normal en reposo, o
    •Saturación de O2 &#8804; 88% en la prueba de caminar durante 6 minutos con hasta 6 litros de O2/minuto de oxígeno nasal
    5.Ascitis quilosa suficiente para afectar a la función del diafragma o a las pruebas de función pulmonar.
    6.Anomalía hematológica o hepática significativa (es decir, niveles de transaminasa > 2,5 veces el límite superior de la normalidad (LSN), bilirrubina sérica > 1,5 × LSN, hemoglobina < 9g/dl, plaquetas < 80.000/mm3 o recuento absoluto de neutrófilos (ANC) < 1.000/mm3).
    7.Embarazo o lactancia.
    8.Infección intercurrente en la fecha de aleatorización.
    9.Antecedentes de trasplante de órganos.
    10.Cirugía reciente (que implique la entrada en una cavidad corporal o requiera suturas) en los 2 meses anteriores a la aleatorización.
    11.Tratamiento previo con inhibidores de mTOR (por ejemplo, sirolimus, temsirolimus, everolimus).
    12.Uso de un fármaco en fase de investigación en los 30 días previos a la aleatorización.
    13.Hiperlipidemia no controlada: Niveles séricos de colesterol en ayunas > 300 mg/dl (o > 7,75 mmol/l) Y niveles de triglicéridos en ayunas > 2,5 × LSN.
    14.Diabetes mellitus no controlada definida por una glucemia en ayunas >1,5 x LSN.
    15.Pacientes con diátesis hemorrágica o en tratamiento oral con anti-vitamina K (a excepción de dosis bajas de warfarina).
    16.Pacientes con antecedentes conocidos de seropositividad al VIH.
    17.Incapacidad para acudir a las visitas clínicas programadas.
    18.Para las evaluaciones por RM:
    •Implantes metálicos ferromagnéticos cuyo uso no esté aprobado en RM (p. ej., pulseras, algunos tipos de pinzas de aneurismas, metralla)
    •Pacientes que sufren claustrofobia no controlable o que no caben físicamente en la máquina (p. ej., por obesidad, etc.).
    Nota: se permite la realización de TC del angiomiolipoma en pacientes con estimulantes del nervio vago, a menos que no lo permitan las legislaciones locales o nacionales.
    19.Creatinina sérica > 1,5 x LSN.
    20.Antecedentes de neoplasia maligna en los últimos dos años, aparte de cáncer de piel de células escamosas o de células basales.
    21.Cualquier afección médica grave y/o no controlada que pueda producir riesgos de seguridad inaceptables o comprometer el cumplimiento del protocolo
    E.5 End points
    E.5.1Primary end point(s)
    La respuesta de los angiomiolipomas se definirá de la forma siguiente:
    •una reducción en volumen de los angiomiolipomas de al menos 50% con respecto al inicial, donde el volumen de los angiomiolipomas es la suma de los volúmenes de todos angiomiolipomas diana identificados en la visita inicial, y confirmados con un segundo escáner realizado aproximadamente 12 semanas después (y no antes de 8 semanas después).
    Además, la respuesta de los angiomiolipomas requiere satisfacer todos los criterios siguientes:
    •que no se identifiquen angiomiolipomas nuevos &#8805; 1,0 cm de diámetro más largo
    •ninguno de los dos riñones aumente de volumen en más del 20% desde el punto más bajo (donde el punto más bajo es el menor volumen renal obtenido por el paciente, por separado para cada riñón, previamente durante el ensayo incluido el volumen inicial)
    •el paciente no presenta hemorragia relacionada con los angiomiolipomas de grado &#8805;2 (tal y como se define en los CTCAE del NCI, versión 3.0).
    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 Information not present in EudraCT
    E.7.1.2Bioequivalence study Information not present in EudraCT
    E.7.1.3Other Information not present in EudraCT
    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.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA11
    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 Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    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
    LPLV
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years6
    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 years6
    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 Information not present in EudraCT
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) Information not present in EudraCT
    F.1.1.3Newborns (0-27 days) Information not present in EudraCT
    F.1.1.4Infants and toddlers (28 days-23 months) Information not present in EudraCT
    F.1.1.5Children (2-11years) Information not present in EudraCT
    F.1.1.6Adolescents (12-17 years) Information not present in EudraCT
    F.1.2Adults (18-64 years) Yes
    F.1.3Elderly (>=65 years) Yes
    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 Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Parents or legal guardians must sign the informed consent for patients with developmental delays.
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state5
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 58
    F.4.2.2In the whole clinical trial 99
    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 Decision2010-09-16
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2010-08-06
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2015-11-06
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    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
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