Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   43206   clinical trials with a EudraCT protocol, of which   7151   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).


    Phase 1 trials conducted solely in adults and that are not part of an agreed PIP are not public in the EU CTR (refer to European Guidance 2008/C 168/02   Art. 3 par. 2 and   Commission Guideline 2012/C 302/03,   Art. 5) .

    Clinical Trials marked as "Trial now transitioned" were transitioned to the Clinical Trial Regulation 536/2014 and can be further followed in the Clinical Trial Information System  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2021-001184-25
    Sponsor's Protocol Code Number:WN42444
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2021-12-07
    Trial 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 number2021-001184-25
    A.3Full title of the trial
    A PHASE III, MULTICENTER, RANDOMIZED, PARALLEL-GROUP, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY TO EVALUATE THE EFFICACY AND SAFETY OF GANTENERUMAB IN PARTICIPANTS AT RISK FOR OR AT THE EARLIEST STAGES OF ALZHEIMER’S DISEASE
    UN ESTUDIO DE FASE III, MULTICENTRO, ALEATORIZADO, GRUPO PARALELO, DOBLE CIEGO, CONTROLADO POR PLACEBO PARA EVALUAR LA EFICACIA Y SEGURIDAD DE GANTENERUMAB EN PARTICIPANTES EN RIESGO O EN LAS PRIMERAS ETAPAS DE LA ENFERMEDAD DE ALZHEIMER
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Study to Evaluate the Efficacy and Safety of Gantenerumab in Participants at Risk for or at the Earliest Stages of Alzheimer’s Disease
    Un estudio para evaluar la eficacia y seguridad de gantenerumab en participantes en riesgo de padecer la enfermedad de Alzheimer o en las primeras etapas
    A.4.1Sponsor's protocol code numberWN42444
    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 SponsorRoche Farma S. A. U. que realiza el ensayo en España y que actúa como representante F. Hoffmann-La Roche Ltd
    B.1.3.4CountrySwitzerland
    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 supportF.Hoffmann-La Roche Ltd.
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationF.Hoffmann-La Roche Ltd.
    B.5.2Functional name of contact pointTrial Information Support Line-TISL
    B.5.3 Address:
    B.5.3.1Street AddressGrenzacherstrasse 124
    B.5.3.2Town/ cityBasel
    B.5.3.3Post codeCH-4070
    B.5.3.4CountrySwitzerland
    B.5.6E-mailspain.start_up_unit@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 nameGantenerumab
    D.3.2Product code Ro 490-9832/F10-03
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNGANTENERUMAB
    D.3.9.2Current sponsor codeRo 490-9832/F10-03
    D.3.9.3Other descriptive nameGANTENERUMAB Ro 490-9832/F10-03
    D.3.9.4EV Substance CodeSUB190296
    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 nameGantenerumab
    D.3.2Product code Ro 490-9832/F10-04
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNGANTENERUMAB
    D.3.9.2Current sponsor codeRo 490-9832/F10-04
    D.3.9.3Other descriptive nameGANTENERUMAB Ro 490-9832/F10-04
    D.3.9.4EV Substance CodeSUB190296
    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
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for injection
    D.8.4Route of administration of the placeboSubcutaneous use
    D.8 Placebo: 2
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for injection
    D.8.4Route of administration of the placeboSubcutaneous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Alzheimer's Disease (AD)
    Enfermedad de Alzheimer (EA)
    E.1.1.1Medical condition in easily understood language
    Alzheimer's disease is a progressive neurologic disorder that causes brain cells to die and leads to memory and thinking problems.
    La enfermedad de Alzheimer es un trastorno neurológico progresivo que hace que las células del cerebro mueran y conduce a problemas de memoria y pensamiento.
    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 20.0
    E.1.2Level HLT
    E.1.2Classification code 10001897
    E.1.2Term Alzheimer's disease (incl subtypes)
    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 evaluate the efficacy of gantenerumab compared with control on cognition
    ● Evaluar la eficacia de gantenerumab en comparación con el control sobre la capacidad cognitiva
    E.2.2Secondary objectives of the trial
    ● To evaluate the efficacy of gantenerumab compared with control on clinical progression based on time from randomization to clinical progression to mild cognitive impairment (MCI) or dementia and time to onset of confirmed clinical progression
    ● To evaluate the efficacy of gantenerumab compared with control on cognition and/or function
    ● To evaluate the safety of gantenerumab compared with placebo
    ● To evaluate biomarkers of pharmacodynamics of gantenerumab compared with control
    ● Evaluar la eficacia de gantenerumab en comparación con placebo de la progresión clínica según el tiempo desde la aleatorización hasta la progresión clínica hasta el deterioro cognitivo leve (DCL) o la demencia y el tiempo hasta el inicio de la progresión clínica confirmada.
    ● Evaluar la eficacia de gantenerumab en comparación con el control sobre la cognición o la función.
    ● Evaluar la seguridad de gantenerumab en comparación con el placebo
    ● Evaluar los biomarcadores de farmacodinámica de gantenerumab en comparación con el control
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Main Study
    ● Participants who:
    - Are age 60-80 years (inclusive) at the time of signing the ICF
    - Cognitively unimpaired with a screening Clinical Dementia Rating Global Score (CDR-GS) of 0, and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Delayed Memory Index (DMI) >=80
    - Show evidence of cerebral amyloid accumulation
    - Have an available person (referred to as a “study partner” throughout the protocol) who: a) Has frequent and sufficient contact with the participant, and is willing and able to provide accurate information regarding the participant’s cognitive and functional abilities, signs the necessary ICF(s), and has sufficient cognitive capacity to accurately report on the participant’s cognitive and functional abilities; b) Is in sufficiently good general health to have a high likelihood of maintaining the same level of interaction with the participant and participation in study procedures throughout the duration of the study; c) Is fluent in the language of the tests used at the study site; d) Every effort should be made to have same study partner participate throughout the duration of the study
    - Are fluent in the language of the tests used at the study site
    - Have adequate visual and auditory acuity, sufficient to perform neuropsychological testing
    - Have agreed not to donate blood or blood products for transfusion for the duration of the study and for 1 year after the final dose of study drug
    - Have agreed not to participate in other interventional research studies for the duration of this trial
    ● For women of childbearing potential:
    - Agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods during the treatment period and for at least 17 weeks after the final dose of study Treatment

    Optional Blood-Based Biomarker Prescreening Procedure
    ● Participants who:
    - Are age 60-80 years (inclusive) at the time of signing the Blood-Based Biomarker Prescreening Informed Consent Form (ICF)
    - Do not have a known clinical diagnosis of cognitive impairment, MCI, prodromal AD, or any form of dementia
    Estudio principal
    ● Participantes que:
    - Tengan entre 60 y 80 años (inclusive) en el momento de firmar el ICF
    - Cognitivamente intacto con un puntaje global de calificación de demencia clínica de detección (CDR-GS) de 0 y una batería repetible para la evaluación del estado neuropsicológico (RBANS), índice de memoria retardada (DMI)> = 80
    - Mostrar evidencia de acumulación de amiloide cerebral
    - Tener una persona disponible (a la que se hace referencia como "acompañante para el estudio" en todo el protocolo) que: a) Tiene contacto frecuente y suficiente con el participante, y está dispuesto y es capaz de proporcionar información precisa sobre las capacidades cognitivas y funcionales del participante, firma los ICF necesarios, y tiene suficiente capacidad cognitiva para informar con precisión sobre las habilidades cognitivas y funcionales del participante; b) Tiene una salud general lo suficientemente buena como para tener una alta probabilidad de mantener el mismo nivel de interacción con el participante y participación en los procedimientos del estudio a lo largo de la duración del estudio; c) Domina el idioma de las pruebas utilizadas en el lugar de estudio; d) Se debe hacer todo lo posible para que el mismo compañero de estudio participe durante la duración del estudio.
    - Domina el idioma de las pruebas utilizadas en el lugar de estudio.
    - Tener una agudeza visual y auditiva adecuada, suficiente para realizar pruebas neuropsicológicas
    - Han acordado no donar sangre o productos sanguíneos para transfusiones durante la duración del estudio y durante 1 año después de la dosis final del fármaco del estudio.
    - Haber aceptado no participar en otros estudios de investigación intervencionista durante la duración de este ensayo.
    ● Para mujeres en edad fértil:
    - Acuerdo para permanecer abstinente (abstenerse de tener relaciones heterosexuales) o utilizar métodos anticonceptivos durante el período de tratamiento y durante al menos 17 semanas después de la dosis final del tratamiento del estudio.
    Procedimiento opcional de preselección de biomarcadores basados ​​en sangre
    ● Participantes que:
    - Tengan entre 60 y 80 años (inclusive) en el momento de firmar el Formulario de consentimiento informado (ICF) para la preselección de biomarcadores en sangre
    - No tiene un diagnóstico clínico conocido de deterioro cognitivo, DCL, EA prodrómica o cualquier forma de demencia.
    E.4Principal exclusion criteria
    Exclusions Related to central nervous system (CNS) Disorders
    Participants who:
    - Show any evidence of an underlying neurological or neurodegenerative condition that may lead to cognitive impairment other than AD
    - Have a clinical diagnosis of MCI, prodromal AD, or any form of dementia
    - Have a history or presence of intracranial or intracerebral vascular malformations, aneurysm, subarachnoid hemorrhage, intracerebral macrohemorrhage, or posterior reversible encephalopathy syndrome
    - Have a history of ischemic stroke with clinical symptoms or an acute event that is consistent with a transient ischemic attack or severe, clinically significant CNS trauma
    - Have a history or presence of intracranial mass lesion that could potentially impair cognition or lead to progressive neurological deficits
    - Have infections that may affect brain function or a history of infections that resulted in neurologic sequelae
    - Have a history of major depression, schizophrenia, schizoaffective disorder, or bipolar disorder
    - Are at risk for suicide
    - Have had history of alcohol and/or substance abuse or dependence
    Exclusions Related to Imaging Findings
    Participants who:
    - According to the MRI central reader, show MRI evidence of any of the following:
    * >1 lacunar infarcts
    * Any territorial infarct >1 cm3
    * Any white matter lesion that corresponds to an Overall
    Fazekas score of 3
    - Have a combined number of microbleeds and areas of leptomeningeal hemosiderosis on the MRI of >5
    - Have a presence of any other significant cerebral abnormalities
    - Are not able to tolerate MRI procedures or have a contraindication to MRI
    Exclusions Related to Cardiovascular Disease
    Participants who:
    - Have a history or presence of clinically significant systemic vascular disease or atrial fibrillation
    - Experienced unstable or clinically significant cardiovascular disease
    - Have a history or presence of heart failure
    - Have had uncontrolled hypertension
    Exclusions Related to Hepatic and Renal Disorders
    Participants who:
    - Have chronic kidney disease or confirmed and unexplained impaired hepatic function
    Exclusions Related to Infections and Immune Disorders
    Participants who:
    - Have a history of, or are known to currently have an HIV infection, or hepatitis B or hepatitis C virus infection or spirochete infection of the CNS
    - Have a history or presence of systemic autoimmune disorders
    - Have systemic immunosuppression or immunomodulation
    - Have current COVID-19 infection
    Exclusions Related to Metabolic and Endocrine Disorders
    Participants who:
    - Have abnormal thyroid function
    - Show evidence of folic acid deficiency or vitamin B-12 deficiency
    - Have a screening hemoglobin A1c (HbA1c) >8% or poorly controlled insulin-dependent diabetes with hypoglycemic episodes
    Exclusions Related to Medications
    ● Any previous administration of:
    - Gantenerumab
    - Active immunotherapy (vaccine) that is being evaluated to prevent or postpone cognitive decline
    - Passive immunotherapy (Ig) or other long-acting biologic agent to prevent or postpone cognitive decline
    ● Any other investigational treatment within 5 half-lives or 6 months
    ● Any previous administration of sodium oligomannate (GV-971)
    ● Any previous treatment with medications specifically intended to treat symptoms related to Parkinson’s disease or any other neurodegenerative disorder
    ● Anticonvulsant medications, typical and atypical anti-psychotic or neuroleptic medications, anticoagulation medications
    ● Psychedelic drugs and substances, recreational cannabis and illicit use of opioids or ketamine
    ● Medical marijuana, chronic use of prescribed opiates or opioids for pain management and chronic use of prescribed benzodiazepines, barbiturates and hypnotic medications, medical food supplements are allowed if on a stable dose for at least 1 month prior to screening
    ● Nootropics and stimulant medications
    ● Any previous treatment with cholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists
    Additional Exclusions
    ● Participants who:
    - Are pregnant or breastfeeding, or intending to become pregnant
    - Have a deformity of the lumbosacral region of the spine, clinically significant abnormal screening blood, CSF or urine results, impaired coagulation, history of cancer, severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric, human, or humanized antibodies or fusion proteins, hypersensitivity to any gantenerumab excipients
    - Have any other severe or unstable medical conditions that could be expected to progress, recur, or change to such an extent that it could put the participant at special risk, interfere with the participant’s ability to complete the study assessments, or would require the equivalent of institutional or hospital care
    - Reside in a skilled nursing facility such as a convalescent home or long-term care facility
    ● Planned or recent exposure to ionizing radiation that exceeds recommended local guidelines
    Exclusión relac. con los trastornos del SNC.
    - Evidencia de condición neurológica o neurodegenerativa subyacente que pueda conducir a un deterioro cognitivo diferente a la EA
    - Diag. clínico de DCL, EA prodrómica o cualquier forma de demencia.
    - Antecedentes o presencia de malformaciones vasculares intracraneales o intracerebrales, aneurisma, hemorragia subaracnoidea, macrohemorragia intracerebral o síndrome de encefalopatía posterior reversible.
    - Antecedentes de ACV isquémico con síntomas clínicos o un evento agudo que es compatible con un ataque isquémico transitorio o un traumatismo grave del SNC clínicamente significativo.
    - Antecedentes o presencia de una masa de lesión intracraneal que potencialmente podría afectar la cognición o conducir a déficits neurológicos progresivos.
    - Infec. que pueden afectar la función cerebral o historial de infecciones que resultaron en secuelas neurológicas.
    - Antecedentesdepresión mayor, esquizofrenia, trastorno esquizoafectivo o trastorno bipolar.
    - Riesgo suicidio.
    - Antecedentes de abuso o dependencia de alcohol y / o sustancias.
    Exclusiones relacionadas con los resultados de las imágenes:
    - De acuerdo con el centro de lectura de MRI, muestren evidencia de MRI de:
    *> 1 infarto lacunar
    * Cualquier infarto territorial> 1 cm3
    * Cualquier lesión de la sustancia blanca que corresponda a Puntuación de Fazekas de 3
    - Tener número combinado de microhemorragias y áreas de hemosiderosis leptomeníngea en MRI de> 5
    - Presencia anomalía cerebral significativa.
    - No tolerar los procedimientos MRI o contraindicación
    Exclusiones relacionadas con ECV:
    - Antec. o presencia de enfermedad vascular sistémica clínicamente significativa o fibrilación auricular.
    - ECV inestable o clínicamente significativa
    - Antecedentes o presencia de insuficiencia cardíaca.
    - Hipertensión no controlada.
    Exclusiones relacionadas con los trastornos hepáticos y renales:
    - ECR o insuficiencia hepática confirmada e inexplicable.
    Exclusiones relacionadas con infecciones y trastornos inmunitarios:
    - Antecedentes o presencia conocida de infección VIH, o infección por el virus hepatitis B o C o infección por espiroquetas del SNC
    - Antecedentes o presencia de trastornos autoinmunes sistémicos.
    - Inmunosupresión o inmunomodulación sistémica
    - Infección actual por COVID-19
    Exclusiones relacionadas con trastornos metabólicos y endocrinos:
    - Función tiroidea anormal
    - Deficiencia de ácido fólico o deficiencia de vit B-12
    - Cribado de HbA1c> 8% o diabetes insulinodependiente mal controlada con episodios hipoglucémicos.
    Exclusiones relacionadas con los medicamentos
    ● Cualquier administración previa de:
    - Gantenerumab
    - Inmunoterapia activa (vacuna) que se está evaluando para prevenir o posponer el deterioro cognitivo
    - Inmunoterapia pasiva (Ig) u otro agente biológico de acción prolongada para prevenir o posponer el deterioro cognitivo
    ● Otro tto en investigación dentro de las 5 semividas o 6 meses.
    ● Admin. previa de oligomanato de sodio (GV-971)
    ● Tto. previo con medicamentos específicamente destinados a tratar los síntomas relacionados con la enfermedad de Parkinson o cualquier otro trastorno neurodegenerativo.
    ● Medic. anticonvulsivos, medic. antipsicóticos o neurolépticos típicos y atípicos, medicamentos anticoagulantes.
    ● Drogas y sustancias psicodélicas, cannabis recreativo y uso ilícito de opioides o ketamina
    ● Marihuana medicinal, uso crónico de opiáceos u opiáceos recetados para el manejo del dolor y uso crónico de benzodiazepinas, barbitúricos y medicamentos hipnóticos recetados, los complementos alimenticios médicos están permitidos si reciben una dosis estable durante al menos 1 mes antes de la evaluación
    ● Nootrópicos y medicamentos estimulantes.
    ● Tto previo con inhibidores de colinesterasa y antagonistas del receptor de N-metil-D-aspartato
    Exclusiones adicionales:
    - Este embarazada o amamantando, o con intención de quedar embarazada.
    - Tengan deformidad de la región lumbosacra de la columna vertebral, resultados anormales de detección de sangre, LCR u orina clínicamente significativos, alteración de la coagulación, antecedentes de cáncer, reacciones alérgicas graves, anafilácticas u otras reacciones de hipersensibilidad a anticuerpos o proteínas de fusión quiméricos, humanos o humanizados , hipersensibilidad a cualquier excipiente de gantenerumab
    - Tenga cualquier otra afección médica grave o inestable que podría esperarse que progrese, se repita o cambie hasta tal punto que pueda poner al participante en un riesgo especial, interferir con la capacidad del participante para completar las evaluaciones del estudio o requerir el equivalente. de atención institucional u hospitalaria
    - Residir en un centro de enfermería especializada, como un hogar de convalecientes o un centro de atención a largo plazo.
    ● Exposición planificada o reciente a radiación ionizante que excede las pautas locales recomendadas.
    E.5 End points
    E.5.1Primary end point(s)
    1. Change from baseline to Year 4 in the Preclinical Alzheimer’s Cognitive Composite-5 (PACC-5) score
    1. Cambio desde basal hasta el año 4 en la puntuación del compuesto cognitivo 5 compuesto preclínico de Alzheimer (PACC-5)
    E.5.1.1Timepoint(s) of evaluation of this end point
    1. Baseline to Year 4
    1. De basal a año 4
    E.5.2Secondary end point(s)
    1. Time from randomization to clinical progression to MCI or dementia due to AD based on the diagnosis of the independent Clinical Adjudication Committee (iCAC)
    2. Time to onset of confirmed clinical progression, defined as the time from randomization to the first occurrence of two consecutive visits (approximately 6 months apart) with a CDR-GS >0
    3. Change from baseline to Year 4 in the Amsterdam Instrumental Activities of Daily Living Questionnaire Short Version (A-IADL-Q-SV) and the Cognitive Function Instrument acute (CFIa)
    4. Change from baseline to Year 4 in the Clinical Dementia Rating Sum of Boxes (CDR-SB)
    5. Nature, frequency, severity, and timing of adverse events, serious adverse events, and adverse events of special interest
    6. Physical examinations (including neurological systems), vital signs, blood tests, electrocardiograms (ECGs), and Columbia-Suicide Severity Rating Scale (C-SSRS)
    7. Nature, frequency, severity, and timing of MRI findings: amyloid-related imaging abnormality-edema/effusion (ARIA-E) and amyloid-related imaging abnormality-hemosiderin deposition (ARIA-H)
    8. Nature, frequency, severity, and timing of injection-site reactions (ISRs)
    9. Presence of anti-drug antibodies (ADAs) during the study relative to the presence of ADAs at baseline
    10. Change in brain amyloid load over time, as measured by amyloid positron emission tomography (PET) in a subset of participants
    11. Change in brain tau load over time, as measured by tau PET in a subset of participants
    12. Change in cerebrospinal fluid (CSF) biomarkers, including, but not limited to, Aβ1-42, Aβ1-40, NfL, pTau, and tTau in a subset of participants
    13. Change in blood-based biomarkers biomarkers, including, but not limited to, Aβ1-42, Aβ1-40, NfL, pTau, and tTau in a subset of participants
    14. Change in magnetic resonance imaging (MRI)-derived measurements over time, including, but not limited to, volumetric changes in whole-brain, ventricles, hippocampus, or other structures in all participants
    1. Tiempo desde la aleatorización hasta la progresión clínica a DCL o demencia por EA según el diagnóstico del Comité de Adjudicación Clínica independiente (iCAC)
    2. Tiempo hasta el inicio de la progresión clínica confirmada, definido como el tiempo desde la aleatorización hasta la primera aparición de dos visitas consecutivas (aproximadamente con 6 meses de diferencia) con un CDR-GS> 0
    3. Cambio desde basal hasta el año 4 en la versión corta del cuestionario de actividades instrumentales de la vida diaria de Amsterdam (A-IADL-Q-SV) y en el instrumento de función cognitiva aguda (CFIa)
    4. Cambio desde basal hasta el año 4 en la suma de recuadros de calificación clínica de demencia (CDR-SB)
    5. Naturaleza, frecuencia, gravedad y momento de los eventos adversos, eventos adversos graves y eventos adversos de especial interés.
    6. Exámenes físicos (incluidos los sistemas neurológicos), signos vitales, análisis de sangre, electrocardiogramas (ECG) y escala Columbia-Suicide Severity Rating Scale (C-SSRS)
    7. Naturaleza, frecuencia, gravedad y momento de los hallazgos de la resonancia magnética: anomalía en la imagen relacionada con amiloide-edema / derrame (ARIA-E) y anomalía en la imagen relacionada con el amiloide-depósito de hemosiderina (ARIA-H)
    8. Naturaleza, frecuencia, gravedad y momento de las reacciones en el lugar de la inyección (ISR)
    9. Presencia de anticuerpos antidrogas (ADA) durante el estudio en relación con la presencia de ADA al inicio del estudio.
    10. Cambio en la carga de amiloide cerebral a lo largo del tiempo, medido por tomografía por emisión de positrones (PET) de amiloide en un subconjunto de participantes
    11. Cambio en la carga de tau cerebral a lo largo del tiempo, medido por tau PET en un subconjunto de participantes
    12. Cambio en los biomarcadores del líquido cefalorraquídeo (LCR), incluidos, entre otros, Aβ1-42, Aβ1-40, NfL, pTau y tTau en un subconjunto de participantes
    13. Cambio en los biomarcadores biomarcadores en sangre, incluidos, entre otros, Aβ1-42, Aβ1-40, NfL, pTau y tTau en un subconjunto de participantes
    14. Cambio en las mediciones derivadas de la resonancia magnética (MRI) a lo largo del tiempo, incluidos, entre otros, cambios volumétricos en todo el cerebro, los ventrículos, el hipocampo u otras estructuras en todos los participantes.
    E.5.2.1Timepoint(s) of evaluation of this end point
    1-4. Baseline to Year 4 (Week 211)
    5-9. Baseline to Week 227 (or 15 weeks after Early Term Visit) (Note: The primary comparison for safety will be between active gantenerumab and placebo)
    10-14. For CSF and PET: Baseline to week 211/For MRI: Baseline to Week 227 (or 15 weeks after Early Term Visit)
    1-4. Basal hasta el año 4 (semana 211)
    5-9. Basal hasta la semana 227 (o 15 semanas después de la visita de término temprano) (Nota: la comparación principal de seguridad será entre gantenerumab activo y placebo)
    10-14. Para LCR y PET: línea de base a la semana 211 / Para resonancia magnética: línea de base a la semana 227 (o 15 semanas después de la visita de término temprano)
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis Yes
    E.6.2Prophylaxis Yes
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    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) 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 Yes
    E.8.2.3.1Comparator description
    Control arm: pts randomized to pcb + pts randomised to pcb and starting active tx (ref protocol 4.1
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned6
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA60
    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
    Argentina
    Australia
    Belgium
    Canada
    France
    Germany
    Ireland
    Italy
    Japan
    Korea, Republic of
    Netherlands
    New Zealand
    Poland
    Russian Federation
    Spain
    Sweden
    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
    A participant is considered to have completed the study if he or she has completed all phases of the study, including the safety FU visit shown in the schedule of activities (see Section 1.3). The end of this study is defined as the date of the LPLV in the study or the date at which the last data point required for safety analyses or safety FU is received from the last participant, whichever occurs later. The end of the study is expected to occur 227 weeks after the last participant randomized.
    Se considera que participante ha completado el estudio si ha completado todas las fases, incluida visita seguridad y FU que se muestra en el programa de actividades (Sec 1.3). Final de estudio se define como la fecha de la LPLV en el estudio o la fecha en la que se recibe el último punto de datos requerido para análisis de seguridad o FU de seguridad del último participante, lo que ocurra más tarde. Se espera que el final del estudio ocurra 227 semanas después del último participante randomizado
    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 months5
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years6
    E.8.9.2In all countries concerned by the trial months5
    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: 900
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers Yes
    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 state80
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 410
    F.4.2.2In the whole clinical trial 1200
    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)
    The Sponsor will offer continued access to gantenerumab free of charge to eligible participants in accordance with the Roche Global Policy on Continued Access to Investigational Medicinal Product, as outlined in the Protocol section 6.6.
    El Promotor ofrecerá acceso continuado a gantenerumab sin cargo a los participantes elegibles de acuerdo con la Política global de Roche sobre acceso continuo a medicamentos en investigación, como se describe en la sección 6.6 del Protocolo.
    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 Decision2022-01-31
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2022-01-26
    P. End of Trial
    P.End of Trial StatusOngoing
    For support, visit the EMA Service Desk , log in using your EMA account and open a ticket specifying "EU CTR" in your request.
    If you do not have an account, please visit the EMA Account management page page click on "Create an EMA account" and follow the instructions.
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2023 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA