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    Summary
    EudraCT Number:2012-003242-33
    Sponsor's Protocol Code Number:GN28525
    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:2012-11-29
    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 number2012-003242-33
    A.3Full title of the trial
    A MULTICENTER, OPEN-LABEL, LONG-TERM SAFETY EXTENSION OF PHASE II STUDIES ABE4869g AND ABE4955g IN PATIENTS WITH MILD TO MODERATE ALZHEIMER?S DISEASE
    ESTUDIO MULTICÉNTRICO, ABIERTO, DE EXTENSIÓN A LARGO PLAZO SOBRE SEGURIDAD DE LOS ESTUDIOS EN FASE II ABE4869g Y ABE4955g EN PACIENTES CON ENFERMEDAD DE ALZHEIMER ENTRE LEVE Y MODERADA
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A MULTICENTER, OPEN-LABEL, LONG-TERM SAFETY EXTENSION OF PHASE II STUDIES ABE4869g AND ABE4955g IN PATIENTS WITH MILD TO MODERATE ALZHEIMER?S DISEASE
    ESTUDIO MULTICÉNTRICO, ABIERTO, DE EXTENSIÓN A LARGO PLAZO SOBRE SEGURIDAD DE LOS ESTUDIOS EN FASE II ABE4869g Y ABE4955g EN PACIENTES CON ENFERMEDAD DE ALZHEIMER ENTRE LEVE Y MODERADA
    A.4.1Sponsor's protocol code numberGN28525
    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 SponsorGenentech, Inc.
    B.1.3.4CountryUnited States
    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 supportGenentech, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationGenentech Inc., c/o F. Hoffmann-La Roche Ltd.
    B.5.2Functional name of contact pointTrial Information Support Line, TIS
    B.5.3 Address:
    B.5.3.1Street AddressGrenzacherstrasse 124
    B.5.3.2Town/ cityBasel
    B.5.3.3Post code4070
    B.5.3.4CountrySwitzerland
    B.5.4Telephone number8886626728
    B.5.5Fax number+34918066456
    B.5.6E-mailglobal.rochegenentechtrials@roche.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 nameCrenezumab
    D.3.2Product code MABT5102A
    D.3.4Pharmaceutical form Concentrate for solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    Subcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNCrenezumab
    D.3.9.1CAS number 1095207-05-8
    D.3.9.2Current sponsor codeMABT5102A
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number150
    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 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 nameCrenezumab
    D.3.2Product code MABT5102A
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    Subcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNCrenezumab
    D.3.9.1CAS number 1095207-05-8
    D.3.9.2Current sponsor codeMABT5102A
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number150
    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 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
    Mild to moderate Alzheimer?s disease
    Enfermedad de Alzheirmer de leve a moderada
    E.1.1.1Medical condition in easily understood language
    Mild to moderate Alzheimer?s disease
    Enfermedad de Alzheirmer de leve a moderada
    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 14.1
    E.1.2Level LLT
    E.1.2Classification code 10001896
    E.1.2Term Alzheimer's disease
    E.1.2System Organ Class 100000004852
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To assess the long-term safety and tolerability of crenezumab administered subcutaneously (SC) every 2 weeks (q2w) or intravenously (IV) every 4 weeks (q4w), in eligible patients with Alzheimer?s disease who participated in Study ABE4869g or ABE4955g and completed the Week 73 study visit, including brain MRI.
    Para evaluar la seguridad a largo plazo y la tolerabilidad de crenezumab administrado por vía subcutánea (SC) cada 2 semanas (C2S) o intravenosa (IV) cada 4 semanas (q4w), en pacientes elegibles con enfermedad de Alzheimer que participaron en el Estudio ABE4869g o ABE4955g y completaron la semana 73 visitas de estudio, incluida la resonancia magnética del cerebro.
    E.2.2Secondary objectives of the trial
    To evaluate the long term effect of crenezumab on disease progression and evaluation of:
    ? the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of crenezumab
    ? the PK/PD relationship of crenezumab using exploratory PD biomarkers
    ? changes in MRI biomarkers, such as global and regional brain volumes and functional connectivity
    Evaluar el efecto a largo plazo de crenezumab en progresión de la enfermedad y la evaluación de:
    ? La farmacocinética (PK) y farmacodinámica (PD) características de crenezumab
    ? la relación PK / PD de crenezumab utilizando biomarcadores exploratorios PD
    ? cambios en los biomarcadores de resonancia magnética, como los volúmenes cerebrales globales y regionales y la conectividad funcional
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    ? Ability to provide written informed consent by the patient or the patient?s authorized representative under applicable local law
    ? Ability and willingness of the patient to comply with the protocol?s requirements
    ? Previous participation in Study ABE4869g or ABE4955g and completion of the Week 73 visit
    ? Patients who discontinued from study treatment or from the study prior to completion of the Week 73 visit are not eligible.
    ? Adequate visual and auditory acuity, in the investigator's judgment, to allow for neuropsychological testing
    ? Availability of a person ("caregiver") who can provide information on activities of daily living and behavior in order to complete the study-specific assessments
    ? This caregiver must have sufficient cognitive capacity, in the judgment of the investigator, to accurately report upon the patient's function and behavior. In addition, the caregiver must spend sufficient time with the patient to be familiar with the overall function and behavior of the patient. As guidance, a caregiver would ordinarily need to spend an average of at least 8 hours per week with the patient in order for the caregiver to meet the requirements for this study.
    ? Diagnosis of probable Alzheimer?s disease according to the National Institute on Neurological and Communication Disease and Stroke/Alzheimer?s Disease and Related Disorders Association (NINCDS-ADRDA) criteria (McKhann et al. 1984)
    ? MMSE score of 12 or more at screening (Folstein et al. 1975)
    ? For male patients with partners with reproductive potential, agreement to use a reliable means of contraception (e.g., condoms) during the study
    ? For female patients, a negative serum ?-human chorionic gonadotropin (?-hCG) pregnancy test at screening
    • Capacidad del paciente o de su representante autorizado en virtud de la legislación local para proporcionar su consentimiento informado por escrito.
    • Capacidad y voluntad del paciente para cumplir con los requisitos del protocolo.
    • Participación previa en los estudios ABE4869g o ABE4955g y haber completado la visita de la semana 73.
    • Agudeza visual y auditiva adecuada, a criterio del investigador, para poder realizar las pruebas neuropsicológicas.
    • Disponibilidad de una persona («cuidador») que pueda proporcionar información sobre las actividades cotidianas y el comportamiento para realizar las evaluaciones
    específicas del estudio
    • Este cuidador debe tener una capacidad cognitiva suficiente, a juicio del investigador, para notificar de forma precisa los datos relativos a la función y el comportamiento del paciente.
    • Diagnóstico de enfermedad de Alzheimer probable según los criterios del Instituto Nacional de Trastornos Neurológicos y de la Comunicación y Asociación de la Enfermedad de Alzheimer/Ictus y Trastornos Relacionados
    • Puntuación de 12 o más en el MMSE de la selección (Folstein y cols. 1975)
    • En el caso de varones con pareja en edad fértil, aceptación del uso de métodos anticonceptivos fiables (p. ej., preservativos) durante el estudio.
    • En el caso de mujeres, prueba de embarazo negativa en la selección mediante el análisis de la gonadotropina coriónica humana b (b-hCG) en suero
    E.4Principal exclusion criteria
    ? Early treatment and/or study discontinuation prior to completion of the Week 73 visit of Genentech Study ABE4869g or ABE4955g
    ? Inability to tolerate MRI procedures or contraindication to MRI, including but not limited to pacemakers; implantable cardioverter defibrillators; cochlear implants; cerebral aneurysm clips; implanted infusion pumps; implanted nerve stimulators; metallic splinters in the eye; other magnetic, electronic, or mechanical implants; or any other clinical history or examination finding that, in the judgment of the investigator, would pose a potential hazard in combination with MRI
    ? Female patient with reproductive potential: Female patients must either have undergone documented surgical sterilization or have not experienced menstruation for at least 12 consecutive months.
    ? Severe or unstable medical condition that, in the opinion of the investigator or Sponsor, would interfere with the patient's ability to complete the study assessments or would require the equivalent of institutional or hospital care
    ? History or presence of clinically evident vascular disease potentially affecting the brain (e.g., stroke, clinically significant carotid or vertebral stenosis or plaque, aortic aneurysm, intracranial aneurysm, cerebral hemorrhage, arteriovenous malformation)
    ? History of severe, clinically significant (persistent neurologic deficit or structural brain damage) central nervous system trauma (e.g., cerebral contusion)
    ? History or presence of clinically relevant intracranial tumor (e.g., meningioma, glioma)
    ? Presence of infections that affect the brain function or history of infections that resulted in neurologic sequelae (e.g., syphilis, neuroborreliosis, viral or bacterial meningitis/encephalitis, HIV encephalopathy)
    ? History or presence of systemic autoimmune disorders potentially causing progressive neurologic disease (e.g., multiple sclerosis, lupus erythematosus, anti-phospholipid antibody syndrome, Behçet disease)
    ? History or presence of a neurologic disease other than Alzheimer?s disease that may affect cognition, including but not limited to Parkinson?s disease, corticobasal degeneration, dementia with Lewy bodies, Creutzfeldt?Jakob disease, progressive supranuclear palsy, frontotemporal degeneration, Huntington?s disease, normal pressure hydrocephalus, and hypoxia
    ? History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric, human, or humanized antibodies or fusion proteins
    ? Evidence of malignancies (except squamous cell cancer or basal cell cancer of the skin), acute infections, renal failure that requires dialysis, or other unstable medical disease not related to Alzheimer?s disease that, in the investigator?s opinion, would preclude patient participation
    ? Cancer that is not being actively treated with anti-cancer therapy or radiotherapy as well as cancers that are considered to have low probability of recurrence (with supporting documentation from the treating oncologist if possible) are allowed
    ? History or presence of atrial fibrillation that, in the investigator?s judgment, poses a risk for future stroke
    ? Chronic kidney disease of Stage ? 4, according to the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF KDOQI) guidelines for chronic kidney disease (CKD)
    ? Impaired hepatic function, as indicated by transaminases > 2 times the upper limit of normal (ULN) or abnormalities in synthetic function tests judged by the investigator to be clinically significant
    ? Impaired coagulation (aPTT > 1.2 × ULN)
    ? Platelet count < 100,000/?L
    ? Presence of superficial siderosis of central nervous system, more than eight cerebral microhemorrhages, or evidence of a prior cerebral macrohemorrhage as assessed by T2*-weighted gradient echo (GRE) MRI
    ? Presence of any other significant cerebral abnormalities, including ARIA-E, as assessed by MRI
    ? Treatment with anticoagulation medications (e.g., heparin, warfarin, thrombin inhibitors, Factor Xa inhibitors) within 75 weeks prior to enrollment
    ? Clopidogrel, dipyridamole, and aspirin are permitted.
    ? Treatment with anticholinergic antidepressants, typical antipsychotics, barbiturates, or narcotics within 5 half-lives or 3 months prior to screening, whichever is longer
    ? All other antidepressants and atypical antipsychotics are allowed. Chronic use of benzodiazepines is not allowed; however, the intermittent use of benzodiazepines is allowed, except within 2 days prior to any neurocognitive assessment.
    • Interrupción prematura del tratamiento y/o del estudio antes de completar la visita de la semana 73 de los estudios ABE4869g o ABE4955g de Genentech.
    • Incapacidad para tolerar los procedimientos de RM o contraindicación de la RM por presentar, entre otros, marcapasos, desfibriladores cardioversores implantables,
    implantes cocleares, pinzas para aneurisma cerebral, bombas de perfusión implantadas, neuroestimuladores implantados, esquirlas metálicas en el ojo, otros
    implantes magnéticos, electrónicos o mecánicos o cualquier antecedente clínico o signo en la exploración que, a criterio del investigador, supusiera un posible riesgo
    en combinación con la RM.
    • Mujeres en edad fértil: las mujeres deben haberse sometido a una esterilización quirúrgica documentada o no haber tenido la menstruación durante al menos 12 meses consecutivos.
    • Enfermedad grave o inestable que, a criterio del investigador o el promotor, pueda afectar a la capacidad del paciente para realizar las evaluaciones del estudio o
    requerir el equivalente a cuidados institucionales u hospitalarios.
    • Antecedentes o presencia de vasculopatía clínicamente manifiesta que pueda afectar al cerebro (p. ej., ictus, estenosis o placa carotídea o vertebral clínicamente
    significativa, aneurisma aórtico, aneurisma intracraneal, hemorragia cerebral o malformación arteriovenosa).
    • Antecedentes de traumatismo grave del sistema nervioso central clínicamente significativo (deficiencia neurológica persistente o daño cerebral estructural) (p. ej.,
    contusión cerebral).
    • Antecedentes o presencia de tumor intracraneal clínicamente significativo (p. ej., meningioma o glioma).
    • Presencia de infecciones que afecten a la función cerebral o antecedentes de infecciones que den lugar a secuelas neurológicas (p. ej., sífilis, neuroborreliosis, meningitis/encefalitis vírica o bacteriana o encefalopatía por VIH).
    • Antecedentes o presencia de trastornos autoinmunitarios sistémicos que puedan causar enfermedad neurológica progresiva (p. ej., esclerosis múltiple, lupus eritematoso, síndrome de anticuerpos antifosfolípidos o enfermedad de Behçet).
    • Antecedentes o presencia de enfermedad neurológica distinta de la enfermedad de Alzheimer que pueda afectar a la capacidad intelectual, como por ejemplo,
    enfermedad de Parkinson, degeneración corticobasal, demencia con cuerpos de Lewy, enfermedad de Creutzfeldt-Jakob, parálisis supranuclear progresiva,
    degeneración frontotemporal, enfermedad de Huntington, hidrocefalia de presión normal e hipoxia.
    • Antecedentes de alergia, reacciones anafilácticas u otras reacciones de hipersensibilidad intensas a anticuerpos quiméricos, humanos o humanizados o a proteínas de fusión.
    • Signos de neoplasia maligna (excepto carcinoma cutáneo de células escamosas o basocelular), infecciones agudas, insuficiencia renal que requiera diálisis u otra
    enfermedad inestable no relacionada con la enfermedad de Alzheimer que, en opinión del investigador, pudiera impedir la participación del paciente.
    • Se permiten los cánceres que no estén siendo tratados activamente con tratamiento antineoplásico o radioterapia y aquellos que se considere que tienen pocas probabilidades de recurrencia (con documentación de respaldo del oncólogo que lo trate, cuando sea posible).
    • Antecedentes o presencia de fibrilación auricular que, a juicio del investigador, supongan un riesgo de futuro ictus.
    • Enfermedad renal crónica en estadio ³ 4 según las directrices para la enfermedad renal crónica (ERC) de la Iniciativa para la calidad de los resultados de la
    insuficiencia renal de la Fundación Nacional del Riñón (National Kidney Foundation Kidney Disease Outcomes Quality Initiative, NKF KDOQI).
    • Insuficiencia hepática, indicada por niveles de transaminasas > 2 veces el límite superior normal (LSN) o anomalías en las pruebas de función sintética clínicamente
    significativas a criterio del investigador.
    • Trastornos de la coagulación (TTPa > 1,2 veces el LSN).
    • Recuento de plaquetas < 100.000/μl.
    • Presencia de siderosis superficial del sistema nervioso central, más de ocho microhemorragias cerebrales o signos de una macrohemorragia cerebral previa según la RM de eco de gradiente (GRE) ponderada en T2*.
    • Presencia de cualquier otra anomalía cerebral significativa, incluidas las ARIA-E, evaluada mediante RM.
    • Tratamiento con medicación anticoagulante (p. ej., heparina, warfarina, inhibidores de la trombina o inhibidores del factor Xa) durante las 75 semanas previas a la
    inclusión.
    • Tratamiento con antidepresivos anticolinérgicos, antipsicóticos típicos, barbitúricos u opiáceos durante 5 semividas o 3 meses antes de la selección, lo que suponga
    más tiempo.
    E.5 End points
    E.5.1Primary end point(s)
    Safety and tolerability will be assessed through regular neurologic and physical examinations
    and MRI assessments. In addition, the following information will be collected and analyzed:
    ? Frequency of adverse events during the treatment period
    ? Nature and severity of adverse events during the treatment period
    ? Changes in vital signs and physical and neurological findings
    ? Changes in clinical laboratory test results including routine hematology, chemistry, coagulation, and urinalysis
    ? Incidence of human anti-therapeutic antibody (ATA) formation
    ? Incidence of ARIA-E and amyloid-related imaging abnormalities-hemorrhage (ARIA-H)
    The end of this study is defined as the date when the last patient, last visit (LPLV) occurs or the
    date on which the last data point required for statistical analysis or safety follow-up is received
    from the last patient, whichever occurs later.
    La seguridad y la tolerabilidad se evaluarán mediante exploraciones físicas y neurológicas y RM periódicas. Además, se recopilará y analizará la siguiente información:
    • Frecuencia de los acontecimientos adversos surgidos durante el periodo de tratamiento.
    • Naturaleza e intensidad de los acontecimientos adversos surgidos durante el periodo de tratamiento.
    • Cambios en las constantes vitales y en los resultados de las exploraciones físicas y neurológicas.
    • Cambios en los resultados de las pruebas analíticas, incluido hematología, bioquímica, coagulación y análisis de orina de rutina.
    • Incidencia de la formación de anticuerpos antiterapéuticos (AAT) humanos.
    • Incidencia de las ARIA-E y de las anomalías de hemorragias en el estudio por imagen relacionadas con los amiloides (ARIA-H).
    E.5.1.1Timepoint(s) of evaluation of this end point
    105 weeks after the last patient is enrolled.
    105 semanas después del último patiente reclutado
    E.5.2Secondary end point(s)
    The exploratory outcome measures for this study are as follows:
    ? Change in ADAS-Cog (12-item) score from baseline to Week 97
    ? Change in CDR-SOB score from baseline to Week 97
    ? Change in ADCS-ADL score from baseline to Week 97
    ? Change in the following ENTP scores from baseline to Week 97:
    ? Free and Cued Selective Reminding Test (FCSRT)
    ? Trail-Making Test (TMT)
    ? Digit Span Test (DST)
    ? Digit Symbol Substitution Test (DSST)
    ? Letter Fluency Test (LFT)
    ? Category Fluency Test (CFT)
    ? Change in NPI score from baseline to Week 97
    ? Change in NPI Caregiver Distress Scale score from baseline to Week 97
    ? Change in Dependence Scale total score from baseline to Week 97
    ? Changes in MRI biomarkers, such as global and regional brain volumes, from baseline to Week 97
    ? Serum crenezumab concentration at protocol-specified time points; PK parameters including trough serum concentrations at steady state (Ctrough, ss) will be explored, as applicable
    ? Plasma Abeta1-40 and Abeta1-42 concentrations
    Los criterios de valoración exploratorios de este estudio son los siguientes:
    • Cambio en la puntuación ADAS-Cog (12 ítems) desde el inicio del estudio hasta la semana 97.
    • Cambio en la puntuación CDR-SOB desde el inicio del estudio hasta la semana 97.
    • Cambio en la puntuación ADCS-ADL desde el inicio del estudio hasta la semana 97.
    • Cambio en las siguientes puntuaciones ENTP desde el inicio del estudio hasta la semana 97:
    – Prueba de recuerdo selectivo libre y facilitado (FCSRT)
    – Prueba de trazado (TMT)
    – Prueba de amplitud de dígitos (DST)
    – Prueba de sustitución de dígitos-símbolos (DSST)
    – Prueba de fluidez fonética (LFT)
    – Prueba de fluidez semántica (CFT)
    • Cambio en la puntuación NPI desde el inicio del estudio hasta la semana 97.
    • Cambio en la puntuación de la escala de ansiedad del cuidador del NPI desde el inicio del estudio hasta la semana 97.
    • Cambio en la puntuación total de la escala de dependencia desde el inicio del estudio hasta la semana 97.
    • Cambios de los biomarcadores de la RM, como los volúmenes global y regional del cerebro, desde el inicio del estudio hasta la semana 97.
    • Concentración sérica de crenezumab en los puntos temporales especificados en el protocolo; cuando corresponda se estudiarán parámetros FC como las
    concentraciones séricas mínimas en equilibrio (Cmín., ee).
    • Concentraciones plasmáticas de Abeta1-40 y Abeta1-42.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Week 97 and week 105 (PK parameters)
    Semana 97 y semana 105 (parámetros PK)
    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 Yes
    E.6.7Pharmacodynamic Yes
    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 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 concerned6
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA32
    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
    Canada
    France
    Germany
    Spain
    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
    LVLS or the date on which the last data point required for statistical analysis or safety follow-up is received from the last patient, whichever occurs later.
    última visita del último paciente o la fecha en que se reciba el último punto de datos necesarios para el análisis estadístico o de seguimiento de la seguridad del último paciente, lo que ocurra más tarde.
    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 months1
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months1
    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: 70
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 280
    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
    Alzheimer's Patients
    Pacientes con Enfermedad de Alzheimer
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state24
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 50
    F.4.2.2In the whole clinical trial 350
    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
    Ninguno
    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 Decision2013-01-31
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2013-01-10
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2017-02-08
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