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    Summary
    EudraCT Number:2011-000914-21
    Sponsor's Protocol Code Number:161003
    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:2011-12-21
    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 number2011-000914-21
    A.3Full title of the trial
    A PHASE 3 RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF THE SAFETY AND EFFECTIVENESS OF IMMUNE GLOBULIN INTRAVENOUS (HUMAN), 10% SOLUTION (IGIV, 10%) FOR THE TREATMENT OF MILD TO MODERATE ALZHEIMER?S DISEASE (AD)
    Estudio de Fase 3, aleatorizado, en doble ciego y controlado con placebo, de la
    seguridad y la eficacia de una inmunoglobulina intravenosa (humana) en
    solución al 10% (IGIV, 10%) en el tratamiento de la enfermedad de Alzheimer
    (EA) de grado leve a moderado
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    CLINICAL TRIAL OF THE SAFETY AND EFFECTIVENESS OF IMMUNE GLOBULIN INTRAVENOUS (HUMAN), 10% SOLUTION (IGIV, 10%) FOR THE TREATMENT OF MILD TO MODERATE ALZHEIMER?S DISEASE (AD)
    Ensayo clínico de seguridad y eficacia de una solución al 10% de inmunoglobulina intravenosa (humana) para el tratamiento de la enfermedad de Alzheimer (EA) de grado leve a moderado.
    A.3.2Name or abbreviated title of the trial where available
    Phase 3 IGIV, 10% in AD
    Fase 3 IgIV 10% en EA
    A.4.1Sponsor's protocol code number161003
    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 SponsorBaxter Innovations GmbH
    B.1.3.4CountryAustria
    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 supportBaxter Innovations GmbH
    B.4.2CountryAustria
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationBaxter Innovations GmbH
    B.5.2Functional name of contact pointGuido Wuerth, MD
    B.5.3 Address:
    B.5.3.1Street AddressWagramer Strasse 17-19
    B.5.3.2Town/ cityVienna
    B.5.3.3Post codeA-1221
    B.5.3.4CountryAustria
    B.5.4Telephone number+43(01)201003489
    B.5.5Fax number+43(01)20100717
    B.5.6E-mailguido_wuerth@baxter.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 Yes
    D.2.1.1.1Trade name KIOVIG 100 mg/ml solution for infusion
    D.2.1.1.2Name of the Marketing Authorisation holderBaxter AG
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNHuman normal immunoglobulin
    D.3.9.3Other descriptive nameHUMAN NORMAL IMMUNOGLOBULIN (IV)
    D.3.9.4EV Substance CodeSUB12041MIG
    D.3.10 Strength
    D.3.10.1Concentration unit % percent
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    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 Yes
    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
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for infusion
    D.8.4Route of administration of the placeboIntravenous use
    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 (AD)
    Enfermedad de Alzheimer (EA) de grado leve a moderado
    E.1.1.1Medical condition in easily understood language
    Mild to moderate Alzheimer?s disease (AD)
    Enfermedad de Alzheimer (EA) de grado leve a moderado
    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 HLT
    E.1.2Classification code 10001897
    E.1.2Term Alzheimer's disease (incl subtypes)
    E.1.2System Organ Class 10029205 - Nervous system disorders
    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 the efficacy of IGIV, 10% treatment on change in cognitive performance and functional activities in subjects with mild to moderate AD, as compared to placebo.
    Evaluar la eficacia del tratamiento con IGIV al 10% sobre el cambio en la capacidad cognitiva y las
    actividades funcionales en sujetos con enfermedad de Alzheimer de grado leve a moderado, en
    comparación con placebo.
    E.2.2Secondary objectives of the trial
    1. To evaluate the effects of IGIV, 10% treatment on additional outcomes, including global clinical status, neuropsychiatric behaviors, and changes in volumetric magnetic resonance imaging (MRI) parameters.
    2. To examine the effects of IGIV, 10% treatment on quality of life of subjects with mild to moderate AD and of their caregivers.
    3. To assess the safety of IGIV, 10% treatment in subjects with mild to moderate AD.
    1. Evaluar los efectos del tratamiento con IGIV al 10% sobre ciertos criterios de valoración adicionales, como el estado clínico general, las conductas neuropsiquiátricas y los cambios en los
    parámetros de la resonancia magnética (MRI) volumétrica.
    2. Examinar los efectos del tratamiento con IGIV al 10% sobre la calidad de vida de sujetos con enfermedad de Alzheimer de grado leve a moderado y de sus cuidadores.
    3. Evaluar la seguridad del tratamiento con IGIV al 10% en sujetos con enfermedad de Alzheimer de grado leve a moderado.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1.Males or females of age 50 to 89 years inclusive at the time of screening.
    2.Written informed consent obtained from either the subject or the subject?s legally acceptable representative prior to any study-related procedures.
    3.Written informed consent obtained from an able and competent caregiver who is willing to comply with the requirements of the protocol pertaining to him/her, including facilitating the subject?s participation in the study.
    4.Diagnosis of Probable AD according to National Institute of Neurological and Communicative Disorders and Stroke - Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) 1984 criteria.
    5.Dementia of mild to moderate severity (MMSE 16-26 inclusive at the time of screening).
    6.Neuroimaging (computed tomography [CT] or MRI) performed after symptom onset consistent with AD diagnosis.
    7.Willingness to comply with the requirements of the protocol and ability to comply with testing and infusion regimen, including adequate corrected visual acuity and hearing ability.
    8.For at least 12 weeks prior to screening, on stable doses of AD medication(s) approved by local regulatory authorities.
    9.Venous access for repeated infusion and phlebotomy.
    10.If receiving psychoactive medications (e.g., antidepressants other than monoamine oxidase inhibitors [MAOIs] and most tricyclics, antipsychotics, anxiolytics, anticonvulsants, mood stabilizers, etc.), must be on stable doses for at least 6 weeks prior to screening.
    11.For women of childbearing potential, the subject must have a negative pregnancy test at screening and must agree to employ adequate contraceptive measures (e.g. birth control pills/patches, intrauterine device, or diaphragm or condom [for male partner] with spermicidal jelly or foam) throughout the course of the study.
    Para ser elegibles para el estudio, los sujetos deberán cumplir TODOS los criterios siguientes:
    1. Hombres o mujeres de 50 a 89 años, ambos extremos incluidos, en el momento de la selección.
    2. Obtención del consentimiento informado por escrito del sujeto o de su representante legal antes de cualquier procedimiento del estudio.
    3. Obtención del consentimiento informado por escrito de un cuidador capaz y competente que esté de acuerdo en observar los requisitos del protocolo que le afecten, lo que incluye la
    facilitación de la participación del sujeto en el estudio.
    4. Diagnóstico de enfermedad de Alzheimer probable de acuerdo a los criterios del National Institute of Neurological and Communicative Disorders and Stroke - Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) de 1984.
    5. Demencia de severidad leve a moderada (MMSE, puntuación 16-26, ambas incluidas, en el momento de la selección).
    6. Estudio de neurodiagnóstico por imagen (tomografía computerizada [CT] o resonancia magnética [MRI]), practicado después del comienzo de los síntomas, compatible con el diagnóstico de enfermedad de Alzheimer.
    7. Deseo de observar los requisitos del protocolo y capacidad de cumplir con el régimen de estudios y de infusiones, lo que incluye una agudeza visual con corrección y una capacidad auditiva adecuadas.
    8. Durante como mínimo las 12 semanas anteriores a la selección, con dosis estables de medicación o medicaciones para la enfermedad de Alzheimer aprobadas por las autoridades reguladoras locales
    9. Acceso venoso para infusiones y flebotomías repetidas
    10. Si el sujeto está recibiendo psicofármacos (por ejemplo, antidepresivos distintos de los
    inhibidores de la monoamino oxidasa y la mayoría de tricíclicos, antipsicóticos, ansiolíticos, anticonvulsivos, estabilizantes del estado de ánimo, etc.), deberá haberlos mantenido a dosis estables durante como mínimo las 6 semanas previas a la selección.
    11. En el caso de las mujeres potencialmente fértiles, deberán tener una prueba de embarazo negativa en la selección y estar de acuerdo en utilizar medidas anticonceptivas adecuadas (por
    ejemplo, píldoras/parches anticonceptivos orales/en parches, dispositivo intrauterino, o diafragma o preservativo [para la pareja masculina] con gel o espuma espermicida) a lo largo del estudio.
    E.4Principal exclusion criteria
    1.Possible AD by NINCDS-ADRDA criteria or non-Alzheimer dementia (e.g. vascular dementia, dementia with Lewy bodies, frontotemporal dementia, or dementia arising from other diseases or conditions such as Parkinson?s disease, vitamin B12 deficiency, thyroid abnormalities).
    2.Current residence in a skilled nursing facility.
    3.Contraindication to undergoing MRI (e.g. pacemaker, severe claustrophobia, ferromagnetic implants such as a metal plate).
    4.Clinically significant congestive heart failure (e.g. New York Heart Association [NYHA] Class III/IV symptoms or untreated Class II).
    5.History of unstable angina or myocardial infarction within the 12 months prior to screening.
    6.Uncontrolled hypertension defined as systolic blood pressure > 160 mm Hg and/or diastolic > 100 mm Hg confirmed upon repeated measures.
    7.History of thrombosis and/or thromboembolic disease (central or peripheral) within the 12 months prior to screening.
    8.Known history of procoagulant abnormalities (e.g. factor V Leiden, antiphospholipid syndrome, protein S/protein C deficiency, AT III deficiency).
    9.History of intracerebral hemorrhage within the 5 years prior to screening.
    10.Evidence of greater than 4 microhemorrhages (regardless of their anatomical location or diagnostic characterization as ?possible? or ?definite?), a single area of superficial siderosis, a macrohemorrhage, major stroke, or multiple lacunae by a recent (within 3 months prior to screening) and/or the baseline MRI, as confirmed by an independent qualified central reviewer.
    11.Head trauma with loss of consciousness, contusion, or open head injury within the 12 months prior to screening.
    12.Uncontrolled seizure disorder as defined by two or more breakthrough seizures per year despite adequate antiepileptic drug (AED) treatment.
    13.Modified Hachinski score > 4 at time of screening.
    14.Subjects with active malignancy or history of malignancy within 5 years prior to screening with the exception of the following: adequately treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, and stable prostate cancer not requiring treatment.
    15.Active autoimmune or neuro-immunologic disorder.
    16.Untreated major depression, psychosis, or other major psychiatric disorder(s).

    17.Poorly controlled diabetes, defined as glycosylated (or glycated) hemoglobin (HbA1c) ? 6.5% for subjects with abnormal fasting glucose at screening.
    18.Creatinine clearance < 50% of normal adjusted for age and gender, as calculated according to the Cockcroft-Gault formula, at the time of screening.
    19. Known history of untreated vitamin B12 deficiency within 6 months prior to screening, or clinically significant abnormally low vitamin B12 at the time of screening
    20.Abnormal clinical chemistry panel or hematology panel meeting any one of the following criteria:
    a.Serum alanine aminotransferase (ALT) > 2.5 x upper limit of normal (ULN)
    b.Clinically significant anemia that precludes repeated blood sampling or hemoglobin (Hgb) < 10.0 g/dL
    c.Absolute neutrophil count (ANC) < 1000 cells/µL
    d.Known coagulopathy or platelet counts < 100,000 cells/µL
    e.Total serum protein > 9 g/dL
    21.Known history of or positive serology at screening for one or more of the following: hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) type 1/2 antibody.
    22.Immunoglobulin A (IgA) deficiency (< 7 mg/dL).
    23.Known history of hypersensitivity following infusions of human blood or blood components (e.g. human immunoglobulins or human albumin).
    24.Currently receiving or received any immunomodulatory monoclonal antibody therapies within 12 weeks prior to screening.
    25.Currently receiving or has received IGIV treatment within the 2 years prior to screening.
    26.Currently receiving or has received any investigational biologic(s) (e.g. active immunization or passive immunotherapies with monoclonal or polyclonal antibodies) for AD at any time.
    27.Subject has participated in another clinical study involving an IP or investigational device within 12 weeks prior to screening or is scheduled to participate in another clinical study involving an IP or investigational device during the course of this study.
    28.The subject is nursing or intends to begin nursing during the course of the study.
    29. Any disorder or disease, or clinically significant abnormality on laboratory or other clinical test(s) (e.g. blood tests, urine tests, electrocardiogram, chest x-ray), that in medical judgment may impede the subject?s participation in the study, pose increased risk to the subject, or confound the results of the study.
    NO serán elegibles para el estudio los sujetos que cumplan CUALQUIERA de los siguientes criterios:1.EA posible según los criterios NINCDS-ADRDA o demencia distinta del Alzheimer(p.e.,demencia vascular, demencia con cuerpos de Lewy, demencia frontotemporal o demencia consecuencia de otras enf.o procesos, como enf. de Parkinson, def. de vit B12, tras.tiroideos).2.Residencia actual en un centro de enfermería especializado.3. Contraindicación para la RM(p.e., marcapasos,claustrofobia severa, implantes ferromagnéticos,como una placa metálica).4.Insf. cardiaca congestiva clínicamente impte (p.e.síntomas de Clase III/IV de la New York Heart Association [NYHA] o Clase II no atada).5.Antecedentes de angina inestable o de IM en los 12 meses previos a la selección. 6.Hipertensión no controlada, definida como presión arterial sistólica >160 mmHg y/o diastólica >100 mmHg confirmada mediante repetición. 7. Antecedentes de trombosis y/o enf. tromboembólica (central o periférica) en el plazo de los 12 meses previos a la selección.8.Antecedentes de anomalías procoagulantes (p.e.factor V de Leiden, sínd.antifosfolipídico, def. de prot S/prot C, deficiencia de AT III). 9. Antecedentes de hemorragia cerebral en el plazo de los 5 años previos a la elección.10.Evidencia de másde4microhemorragias (independientemente de su localización anatómica o caracterización diagnóstica como "posible" o "clara"),una sola área de siderosis superficial,una macrohemorragia, ictus mayor o lagunas múltiples en una RM reciente (en el plazo de los 3 meses previos a la selección) y/o en la basal, en su confirmación por un revisor central cualificado independiente.11.Traumatismo craneal con pérdida del conocimiento, contusión o herida craneal abierta en el plazo de los 12 meses anteriores a la selección.12.Tras. epiléptico no controlado, definido como 2 o más convulsiones intercurrentes al año a pesar del trat. antiepiléptico adecuado. 13. Puntuación de Hachinski modificada>4 en la selección.14.Sujetos con neoplasia maligna activa o antecedentes de neoplasia maligna en los 5 años previos a la selección, con excepción de: carcinoma cutáneo de cél. basales o escamosas o carcinoma in situ de cuello uterino tratadosadecuadamente, y cáncer de próstata estable que no precisa trat. 15. Tras. autoinmunitario o neuroinmunológico activo. 16.Depresión mayor,psicosis u otro trastornopsiquiátrico mayor no tratados. 17.Diabetes mal controlada,definida como unahemoglobina glucosilada (o glicada) (HbA1c)?6,5% en un sujeto con glucosa en ayunas anormal en la selección. 18. Aclaramiento de creatinina <50% del normal ajustado por edad y sexo, calculado con la fórmula de Cockcroft-Gault,ii en la selección.1 19. Ante.de defic. de vit B12 no tratada en el plazo de los 6 meses previos a la selección,o valores de vit B12 anormalmente bajos de forma clínica importante en la selección. 20. Valores de bioquímica o hematología que cumplan uno cualquiera de los siguientes criterios:iii a. Alanina aminotransferasa (ALT) sérica>2,5xlímite superior de la normalidad b.Anemia clínicamente impte. que impide la obtención repetida de muestras de sangre o hemoglobina (Hb)<10,0g/dL c.Recuento absoluto de neutrófilos(RAN)<1.000/?L d. Coagulop. conocida o recuento de plaquetas <100.000/?L e. Proteínas séricas totales >9 g/dL 21. Anteced. o presencia de serología positiva en la selección para uno o más de los siguientes: antígeno de superf de la HB (HBsAg), antic frente al HCV o antic frente al HIV de tipo 1/2. 22. Def.de IgA(<7 g/dL).23. Antecedentes de hipersensibilidad tras infusiones de sangre o de hemoderivados humanos (p.e.Igs humanas o albúmina humana).24. Recepción de cualquier trat. con antic monoclonales inmunomoduladores en el momento actual o en el plazo de las 12 semanas anteriores a la selección.25. Recepción de trat con IGIV en el momento actual o en el plazo de los 2 años anteriores a la selección.26.Recepción de cualquier agente(s)biológico en fase de investigación (p.e.inmunización activa o inmunoterapia pasiva con antic monoclonales o policlonales) para la EA en el momento actual o en cualquier otro momento.27.Sujeto que ha participado en otro est.clí. con un mdto o prod sanitario en investigación en el plazo de las 12 semanas anteriores a la selección o que se encuentra programado para participar en otro est clí con un medto o prod sanitario en investigación durante el curso de este estudio.28 Familiar o empleado del investigador.29.Sujeto que está amamantando o va a a amamantar durante el curso del estudio.30.Todo trastorno o enf, o anomalía clíni impte de laboratorio o de otros exámenes clínicos (p.e.analítica sanguínea, análisis de orina, electrocardiograma,radiografía de tórax), que,a criterio médico, podría impedir la participación del sujeto en el estudio, suponerle un mayor riesgo o confundir los resultados del estudio.
    E.5 End points
    E.5.1Primary end point(s)
    1. The cognitive subscale of the Alzheimer?s Disease Assessment Scale (ADAS-Cog)
    2. Alzheimer?s Disease Cooperative Study (ADCS)-Activities of Daily Living (ADL) inventory
    1. La subescala cognitiva de la Alzheimer?s Disease Assessment Scale (ADAS-Cog) a los 18 meses
    2. El Alzheimer?s Disease Cooperative Study (ADCS)-Activities of Daily Living (ADL) inventory a los 18 meses
    E.5.1.1Timepoint(s) of evaluation of this end point
    1. ADAS-Cog: Baseline, 3 months, 6 months, 9 months, 12 months, 15 months and 18 months (as well as at the early termination visit if applicable)
    2. ADCS-ADL: Baseline, 3 months, 6 months, 9 months, 12 months, 15 months and 18 months (as well as at the early termination visit if applicable)
    1. ADAS-Cog:inicio, 3 meses, 6 meses, 9 meses, 12 meses, 15 meses y 18 meses (así como en una visita temprana de terminación, si es aplicable).
    2. ADCS-ADL:inicio, 3 meses, 6 meses, 9 meses, 12 meses, 15 meses y 18 meses (así como en una visita temprana de terminación, si es aplicable).
    E.5.2Secondary end point(s)
    Efficacy
    1.ADCS-Clinical Global Impression of Change (CGIC)
    2.Neuropsychiatric Inventory (NPI)
    3.Logsdon Quality of Life in Alzheimer?s Disease (QOL-AD)
    4.Impact of Alzheimer?s Disease on Caregiver Questionnaire (IADCQ)
    5.Rate of whole brain atrophy and ventricular enlargement using volumetric MRI
    Safety
    1.Number (percentage) of subjects experiencing related adverse events (AEs) and/or serious adverse events (SAEs)
    2.Number (percentage) of subjects experiencing any AEs and/or SAEs
    3.Number (percentage) of infusions temporally associated (defined as during or within 72 hours of completion of an infusion) with AEs and/or SAEs
    4.Number (percentage) of infusions associated with AEs and/or SAEs occurring during or within 7 days of completion of an infusion
    5.Number (percentage) of infusions causally associated with AEs and/or SAEs
    6.Number and proportion of infusions discontinued, slowed, or interrupted due to an AE
    Eficacia
    1. ADCS-Clinical Global Impression of Change (CGIC) a los 18 meses
    2. Neuropsychiatric Inventory (NPI) a los 18 meses
    3. Logsdon Quality of Life in Alzheimer?s Disease (QOL-AD)
    4. Impact of Alzheimer?s Disease on Caregiver Questionnaire (IADCQ)
    5. Ritmo de atrofia cerebral global y de dilatación ventricular, mediante resonancia magnética volumétrica, a los 18 meses
    Seguridad
    1. Número (porcentaje) de sujetos que presenten acontecimientos adversos y/o acontecimientos adversos graves relacionados con el tratamiento
    2. Número (porcentaje) de sujetos que presenten cualquier tipo de acontecimientos adversos y/o
    acontecimientos adversos graves
    3. Número (porcentaje) de infusiones asociadas en el tiempo (lo que se define como durante o en el plazo de las 72 horas siguientes a la finalización de una infusión) a acontecimientos adversos y/o
    acontecimientos adversos graves
    4. Número (porcentaje) de infusiones asociadas a acontecimientos adversos y/o acontecimientos adversos graves producidos durante o en el plazo de los 7 días siguientes a la finalización de una
    infusión
    5. Número (porcentaje) de infusiones asociadas causalmente a acontecimientos adversos y/o acontecimientos adversos graves
    6. Número y porcentaje de infusiones suspendidas, enlentecidas o interrumpidas por un acontecimiento adverso
    E.5.2.1Timepoint(s) of evaluation of this end point
    1. ADCS-CGIC: Baseline, 3 months, 6 months, 9 months, 12 months, 15 months and 18 months (as well as at the early termination visit if applicable)
    2. NPI: Baseline, 3 months, 6 months, 9 months, 12 months, 15 months and 18 months (as well as at the early termination visit if applicable)
    3. QOL-AD: Baseline, 6 months, 9 months, 12 months and 18 months
    4. IADCQ: Baseline, 6 months, 9 months, 12 months and 18 months
    5. Rate of whole brain atrophy and ventricular enlargement: Baseline, 9 months and 18 months
    1. ADCS-CGIC:inicio, 3 meses, 6 meses, 9 meses, 12 meses, 15 meses y 18 meses (así como en una visita temprana de terminación, si es aplicable).
    2. NPI:inicio, 3 meses, 6 meses, 9 meses, 12 meses, 15 meses y 18 meses (así como en una visita temprana de terminación, si es aplicable).
    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 No
    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) 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.8.2.4Number of treatment arms in the trial3
    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 EEA21
    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
    Australia
    Belgium
    Canada
    Germany
    Israel
    Poland
    Spain
    United Kingdom
    United States
    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
    LVLS
    Última visita y último sitio
    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 months11
    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 months11
    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: 100
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 302
    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 state35
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 115
    F.4.2.2In the whole clinical trial 402
    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)
    There are no plans for treatment with the investigational product after the subject has ended participation in the trial (whether they completed the trial or discontinued early). All subjects in the trial are already receiving standard of care because they are required to be on AD medication(s) approved by local regultory authorities for at least 12 weeks prior to screening and throughout the course of their participation.
    No hay planes para el tratamiento con el producto en investigación después de que el sujeto haya finalizado su participación en el estudio (tanto si han completado el estudio como si lo han discontinuado de manera temprana). Todos los sujetos del estudio ya se encuentran recibiendo cuidados estándar ya que se requiere que se encuentren en tratamiento durante al menos 12 semanas antes de la selección y durante su participacióncon un medicamento autorizado para la enfermedad de Alzheimer.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2012-02-27
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2012-02-14
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
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