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    Summary
    EudraCT Number:2021-001184-25
    Sponsor's Protocol Code Number:WN42444
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2022-02-23
    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 ConcernedItaly - Italian Medicines Agency
    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
    STUDIO DI FASE III, MULTICENTRICO, RANDOMIZZATO, A GRUPPI PARALLELI, IN DOPPIO CIECO E CONTROLLATO CON PLACEBO VOLTO A VALUTARE L’EFFICACIA E LA SICUREZZA DI GANTENERUMAB IN PARTECIPANTI A RISCHIO DI MALATTIA DI ALZHEIMER O NEGLI STADI INIZIALI DELLA MALATTIA
    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
    Uno studio per valutare l'efficacia e la sicurezza di Gantenerumab in partecipanti a rischio o nelle prime fasi della malattia di Alzheimer
    A.3.2Name or abbreviated title of the trial where available
    na
    na
    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 SponsorF. 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. Hoffman-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.5.4Telephone number000000
    B.5.5Fax number000000
    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 nameGantenerumab
    D.3.2Product code [Ro 490-9832/F10-03]
    D.3.4Pharmaceutical form Solution for injection/infusion
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy 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/infusion
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy 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/infusion
    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/infusion
    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)
    Morbo di Alzheimer
    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.
    Il morbo di Alzheimer è un disordine neurologico progressivo che causa la morte delle cellule cerebrali e porta a problemi di memoria e di pensiero.
    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
    Per valutare l'efficacia di gantenerumab rispetto al controllo su cognizione
    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
    Valutare l'efficacia di gantenerumab rispetto al controllo sulla progressione clinica sulla base del tempo dalla randomizzazione alla alla progressione clinica verso il deterioramento cognitivo lieve (MCI) o la demenza e il tempo all'inizio della progressione clinica confermata
    Valutare l'efficacia di gantenerumab rispetto al controllo su cognizione e/o funzione
    Valutare la sicurezza di gantenerumab rispetto al placebo
    Valutare i biomarcatori della farmacodinamica di gantenerumab rispetto al controllo
    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
    Studio principale
    Partecipanti che:
    - Hanno un'età di 60-80 anni (inclusi) al momento della firma dell'ICF
    - Cognitivamente non compromessi con un Clinical Dementia Rating Globale (CDR-GS) di 0, e Batteria Ripetibile per la Valutazione dello stato neuropsicologico (RBANS) Indice di memoria ritardata (DMI) >=80
    - Mostrare evidenza di accumulo di amiloide cerebrale
    - Avere una persona disponibile (indicata come "partner di studio" in tutto il protocollo) che: a) abbia contatti frequenti e sufficienti con il partecipante ed è disposta e in grado di fornire informazioni accurate informazioni accurate sulle capacità cognitive e funzionali del partecipante, firmi il/i ICF necessario, e ha una capacità cognitiva sufficiente per riferire accuratamente capacità cognitive e funzionali del partecipante; b) è in salute generale sufficientemente buona da avere un'alta probabilità di mantenere lo stesso livello di interazione con il partecipante e di partecipazione alle alle procedure di studio per tutta la durata dello studio; c) Parla correntemente la lingua dei test utilizzati nel sito dello studio; d) deve essere fatto ogni sforzo per fare in modo che lo stesso partner partecipi per tutta la durata dello studio
    - parlare correntemente la lingua dei test utilizzati nel sito dello studio
    - avere un'adeguata acutezza visiva e uditiva, sufficiente per eseguire test neuropsicologici
    - Hanno accettato di non donare sangue o prodotti sanguigni per la trasfusione per la durata dello studio e per 1 anno dopo l'ultima dose del farmaco in studio
    - Hanno accettato di non partecipare ad altri studi di ricerca interventistica per la durata di questo studio
    Per le donne in età fertile:
    - Accordo di rimanere in astinenza (astenersi da rapporti eterosessuali) o usare metodi contraccettivi durante il periodo di trattamento e per almeno almeno 17 settimane dopo l'ultima dose del trattamento di studio

    Procedura opzionale di pre-selezione dei biomarcatori basati sul sangue
    Partecipanti che:
    - Hanno un'età compresa tra i 60 e gli 80 anni (inclusi) al momento della firma del Blood-Based pre-selezione dei biomarcatori su base ematica Modulo di consenso informato (ICF)
    - Non hanno una diagnosi clinica nota di deterioramento cognitivo, MCI, AD prodromico, o qualsiasi forma di demenza
    E.4Principal exclusion criteria
    Related to CNS Disorders:
    Neurological/neurodegenerative condition that may lead to cognitive impairment other than AD
    Clinical diagnosis of MCI/prodromal AD/any form of dementia
    Infections that may affect brain function or history of infections with neurologic sequelae
    Risk for suicide
    •History/presence of:
    -Intracranial/intracerebral vascular malformations, aneurysm, subarachnoid hemorrhage, intracerebral macrohemorrhage, or posterior reversible encephalopathy syndrome
    -Intracranial mass lesion that could impair cognition or lead to progressive neurological deficits
    History of:
    -Ischemic stroke with clinical symptoms/acute event that is consistent with a transient ischemic attack/severe, clinically significant CNS trauma
    -Major depression, schizophrenia, schizoaffective disorder, or bipolar disorder
    -Alcohol/substance abuse or dependence
    Related to Imaging Findings
    MRI evidence of any of the following:
    ->1 lacunar infarcts
    -Territorial infarct >1 cm3
    -White matter lesion corresponding to Fazekas score of 3
    •Combined number of microbleeds and areas of leptomeningeal hemosiderosis on the MRI of >5
    •Other significant cerebral abnormalities
    •No tolerance for MRI procedures or contraindication to MRI
    Related to Cardiovascular Disease
    •History/presence of clinically significant systemic vascular disease or atrial fibrillation
    •Unstable/clinically significant cardiovascular disease
    •History/presence of heart failure
    •Uncontrolled hypertension
    Related to Hepatic and Renal Disorders
    •Chronic kidney disease/confirmed, unexplained impaired hepatic function
    Related to Infections and Immune Disorders
    •History/known HIV, hepatitis B or C virus infection, or spirochete infection of the CNS
    •History/presence of systemic autoimmune disorders
    •Systemic immunosuppression/immunomodulation
    •Current COVID-19 infection
    Related to Metabolic and Endocrine Disorders
    ¿Abnormal thyroid function
    ¿Folic acid/vitamin B-12 deficiency
    ¿Screening hemoglobin A1c (HbA1c) >8%/poorly controlled insulin-dependent diabetes with hypoglycemic episodes
    Related to Medications
    ¿Previous administration of:
    -Gantenerumab
    -Active immunotherapy that is being evaluated to prevent or postpone cognitive decline
    -Passive immunotherapy or other long-acting biologic agent to prevent or postpone cognitive decline
    ¿Other investigational treatment within 5 half-lives or 6 months
    ¿Previous administration of sodium oligomannate (GV-971)
    ¿Previous treatment with medications specifically intended to treat symptoms related to Parkinson’s disease or other neurodegenerative disorders
    ¿Anticonvulsant, typical and atypical anti-psychotic or neuroleptic, anticoagulation medications
    ¿Psychedelic drugs/substances, recreational cannabis and illicit use of opioids or ketamine
    ¿Medical marijuana/chronic use of prescribed opiates or opioids for pain management/chronic use of prescribed benzodiazepines, barbiturates and hypnotic medications; Medical food supplements are allowed if on a stable dose for = 1 month prior to screening
    ¿Nootropics and stimulant medications
    ¿Previous treatment with cholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists
    Additional Exclusions
    ¿Pregnant/breastfeeding/intending to become pregnant
    ¿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 gantenerumab excipients
    ¿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
    ¿Residence in a skilled nursing facility
    ¿Planned or recent exposure to ionizing radiation that exceeds recommended local guidelines
    Relat ai dist. del SNC
    Cond. neurologica/neurodegenerativa che può portare a un deterioramento cognitivo diverso da MA
    Diagn. clinica di MCI/prodromica di AD/qualsiasi forma di demenza
    Inf. che possono influenzare le funz. cerebrali o st. di inf. con sequele neurologiche
    Rischio di suicidio
    St.presenza di:
    Malfor. vascolari intracraniche/intracerebrali,aneurisma,emorragia subaracnoidea,macroemorragia intracerebrale o sindrome da encefalopatia reversibile posteriore
    Les. intracranica di massa che potrebbe compromettere la cognizione o portare a deficit neurologici progressivi
    St. di:
    Ictus ischemico con sintomi clinici/evento acuto coerente con un attacco ischemico transitorio/trauma grave e clinicamente significativo del SNC
    Depress. maggiore,schizofrenia,dist. schizoaffettivo/dist. bipolare
    Abuso o dipendenza da alcol/sostanze
    Relat ai risul. di imaging
    Evidenza MRI di uno dei seguenti elementi:
    >1 infarto lacunare
    Infarto territoriale >1 cm3
    Les. della materia bianca corrispondente al punteggio di Fazekas di 3
    Num combinato di microbleeds e aree di emosiderosi leptomeningea sulla MRI di >5
    Altre anomalie cerebrali significative
    Nessuna tolleranza alle procedure MRI o controindicazione alla MRI
    Correlato a malat. cardiovascolare
    St./presenza di malat. vascolare sistemica clinicamente significativa o fibrillazione atriale
    Malat. cardiovascolare instabile/clinicamente significativa
    St./presenza di insufficienza cardiaca
    Ipertens. non controllata
    Relat a dist. epatici e renali
    Malat. renale cronica/confermata,inspiegabile alterazione della funzione epatica
    In relaz. a inf. e dist. immunitari
    St./conosciuta di HIV,infezione da virus dell'epatite B o C o infezione da spirochete del SNC
    St./presenza di dist. autoimmuni sistemici
    Immunosoppressione/immunomodulazione sistemica
    Inf. attuale da COVID-19
    Correlato a dist. metabolici ed endocrini
    Funz. tiroidea anormale
    Carenza di acido folico/vitamina B-12
    Screening dell'emoglobina A1c (HbA1c) >8%/ diabete insulino-dipendente scarsamente controllato con episodi ipoglicemici
    Relat ai farmaci
    Precedenti somm. di:
    Gantenerumab
    Immunot. attiva che viene valutata per prevenire o posticipare il declino cognitivo
    Immunot. passiva o altro agente biologico a lunga durata d'azione per prevenire o posticipare il declino cognitivo
    Altro trat. sperim. entro 5 emivite o 6 mesi
    Preced. somm. di oligomannato di sodio (GV-971)
    Preced. tratt. con farmaci specificamente destinati al tratt. dei sintomi legati al morbo di Parkinson o ad altri dist. neurodegenerativi
    Farm. anticonvulsivanti,antipsicotici o neurolettici tipici e atipici,far.ci anticoagulanti
    Droghe/sostanze psichedeliche,cannabis ricreativa e uso illecito di oppioidi o ketamina
    Marijuana medica/uso cronico di oppiacei o oppioidi prescritti per la gestione del dolore/uso cronico di benzodiazepine,barbiturici e farmaci ipnotici prescritti;gli integr alim medici sono consentiti se la dose è stabile da = 1 mese prima dello screening
    Nootropici e far.ci stimolanti
    Trat. precedente con inibitori della colinesterasi e antagonisti del recettore N-metil-D-aspartato
    Ult. esclus.
    Gravid/allattam/intenzione di gravid
    Deformità della regione lombosacrale della colonna vertebrale/ris. anormali clinicamente significativi dello screening del sangue,del liquor o delle urine/coagulazione alterata/st. di cancro/gravi reazioni allergiche,anafilattiche o altre reazioni di ipersensibilità agli anticorpi chimerici, umani o umanizzati o alle proteine di fusione/ipersensibilità agli eccipienti di gantenerumab
    Altre cond. Med. gravi o instabili che potrebbero progredire,ripetersi o cambiare in misura tale da mettere il pt. a rischio speciale,interferire con la capacità del partecipante di completare le valutazioni dello studio o richiedere l'equivalente delle cure istituzionali o ospedaliere
    Resid. in una struttura infermieristica qualificata
    Esposiz. pianificata o recente a radiazioni ionizzanti che superano le linee guida locali raccomandate
    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. Cambiamento dal basale all'anno 4 nel punteggio Preclinical Alzheimer's Cognitive Composite-5 (PACC-5)
    E.5.1.1Timepoint(s) of evaluation of this end point
    1. Baseline to Year 4
    1. Dalla linea di base all'anno 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, Aß1-42, Aß1-40, NfL, pTau, and tTau in a subset of participants
    13. Change in blood-based biomarkers biomarkers, including, but not limited to, Aß1-42, Aß1-40, 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. Tempo dalla randomizzazione alla progressione clinica verso l'MCI o la demenza dovuta all'AD in base alla diagnosi del Comitato indipendente di valutazione clinica (iCAC)
    2. Tempo di insorgenza della progressione clinica confermata, definito come il tempo dalla randomizzazione al primo verificarsi di due visite consecutive (a distanza di circa 6 mesi) con un CDR-GS >0
    3. Cambiamento dal basale al 4° anno nell'Amsterdam Instrumental Activities of Daily Living Questionnaire Short Version (A-IADL-Q-SV) e nel Cognitive Function Instrument acute (CFIa)
    4. Cambiamento dal basale all'anno 4 nel Clinical Dementia Rating Sum of Boxes (CDR-SB)
    5. Natura, frequenza, gravità e tempi degli eventi avversi, eventi avversi gravi ed eventi avversi di particolare interesse
    6. Esami fisici (compresi i sistemi neurologici), segni vitali, esami del sangue, elettrocardiogrammi (ECG), e Columbia-Suicide Severity Rating Scale (C-SSRS)
    7. Natura, frequenza, gravità e tempistica dei risultati della risonanza magnetica: anormalità di imaging legata all'amiloide-edema/effusione (ARIA-E) e anormalità di imaging legata all'amiloide-deposizione di emosiderina (ARIA-H)
    8. Natura, frequenza, gravità e tempistica delle reazioni al sito di iniezione (PVR)
    9. Presenza di anticorpi anti-farmaco (ADA) durante lo studio rispetto alla presenza di ADA al basale
    10. Cambiamento del carico di amiloide nel cervello nel tempo, come misurato dalla tomografia ad emissione di positroni (PET) in un sottogruppo di partecipanti
    11. Cambiamento del carico di tau nel cervello nel tempo, come misurato da tau PET in un sottoinsieme di partecipanti
    12. Cambiamento nei biomarcatori del liquido cerebrospinale (CSF), compresi, ma non limitati a, Aß1-42, Aß1-40, NfL, pTau, e tTau in un sottogruppo di partecipanti
    13. Cambiamento nei biomarcatori basati sul sangue, compresi, ma non limitati a, Aß1-42, Aß1-40, NfL, pTau, e tTau in un sottoinsieme di partecipanti
    14. Cambiamento nelle misure derivate dalla risonanza magnetica (MRI) nel tempo, inclusi, ma non limitati a, cambiamenti volumetrici nel cervello intero, ventricoli, ippocampo, o altre strutture in tutti i partecipanti
    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. Dalla linea di base all' anno 4 (settimana 211)
    5-9. Dal basale alla settimana 227 (o 15 settimane dopo la visita iniziale) (Nota: il confronto primario per la sicurezza sarà tra gantenerumab attivo e placebo)
    10-14. Per CSF e PET: dal basale alla settimana 211/For MRI: dal basale alla settimana 227 (o 15 settimane dopo la visita iniziale)
    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
    Braccio di controllo: pazienti randomizzati a pcb + pazienti randomizzati a pcb e che iniziano il tx
    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 concerned11
    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 Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    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.
    Si considera che un part.te ha complet. lo st.io se ha complet. tutte le fasi di st.io,compresa visita FU di sicur.za indicata nel progr. delle attività(vedi sez1.3).La fine di questo st.io è def.ta come la data di LPLV dello st.io o la data in cui l'ultimo punto di dati richiesto per le analisi di sicurezza o l'UFC di sicurezza viene ricevuto dall'ultimo part.te,a seconda di quale delle 2 date si verifichi dopo.La fine dello st.io dovrebbe avvenire 227 sett.ne dopo l'ultimo part.te randomizzato
    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 days0
    E.8.9.2In all countries concerned by the trial years6
    E.8.9.2In all countries concerned by the trial months5
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 300
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 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 state55
    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.
    Lo sponsor offrirà l'accesso continuato a gantenerumab gratuitamente ai partecipanti idonei in conformità alla politica globale di Roche sull'accesso continuato al prodotto medicinale in fase di sperimentazione, come indicato nella sezione 6.6 del protocollo.
    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 Decision2022-04-14
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2022-03-10
    P. End of Trial
    P.End of Trial StatusOngoing
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