Neurologisch
Conditions
Interventions
The treatment period consists of a dose escalation period and a study dose
period.
Dose escalation (approximately 9 months):
During dose escalation (approximately 9 months), the subject receives
in
QW or Q2W according to schedule.
The dose escalation after progression is followed by a maintenance dose with
the target dose and will not extend the total time in the treatment period
(approximatel
Sponsors
Roche Nederland B.V.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: * Ability to provide written informed consent and has signed the Informed Consent Form * Age 60-80 years old (inclusive) at time of signing the Informed Consent Form * Willingness and ability to comply with the study protocol, and complete all aspects of the study (including cognitive and functional assessments, physical and neurological examinations, MRI, CSF collection, genotyping, and PET imaging) * Cognitively unimpaired with a screening CDR-GS of 0, MoCA score 26 or > 26 and RBANS DMI 85 -115 * Evidence of cerebral amyloid accumulation, as confirmed by a combined measure of quantitative and qualitative amyloid PET or CSF pTau/A(-42 ratio * Availability of a person ("study partner* throughout the study) in the investigator's judgment - Participants who are fluent in the language of the tests used at the study site - Participants who have adequate visual and auditory acuity, sufficient to perform neuropsychological testing (eye glasses and hearing aids are permitted) - Participants who 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 - Participants who 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 that result in a failure rate of
Exclusion criteria
Exclusion criteria: - Exclusions Related to CNS Disorders: - Any evidence of an underlying neurological or neurodegenerative condition that may lead to cognitive impairment other than AD, including, but not limited to, frontotemporal dementia, dementia with Lewy bodies, vascular dementia, Parkinson*s disease, corticobasal syndrome, Creutzfeldt-Jakob disease, progressive supranuclear palsy, frontotemporal lobar degeneration, Huntington disease, normal pressure hydrocephalus, seizure disorder, delirium, hypoxia, or encephalopathy related to prior COVID-19 infection - Clinical diagnosis of MCI, prodromal AD, or any form of dementia - History or presence of intracranial or intracerebral vascular malformations, aneurysm, subarachnoid hemorrhage, or intracerebral macrohemorrhage - History or presence of posterior reversible encephalopathy syndrome - History of ischemic stroke with clinical symptoms or an acute event that is consistent with a transient ischemic attack within 12 months of screening - History of severe, clinically significant (i.e., resulting in persistent neurologic deficit or structural brain damage) CNS trauma (e.g., cerebral contusion) - History or presence of intracranial mass lesion (e.g., glioma, meningioma) that could potentially impair cognition or lead to progressive neurological deficits - Infections that may affect brain function or a history of infections that resulted in neurologic sequelae (e.g., HIV, syphilis, neuroborreliosis, and viral or bacterial meningitis and encephalitis) - History of major depression, schizophrenia, schizoaffective disorder, or bipolar disorder History or presence of major depression is acceptable if the participant is considered to be in remission or depression is controlled by treatment and the participant has had no episode of major depression within 12 months of screening. - At risk for suicide - History of alcohol and/or substance abuse or dependence (according to the criteria specified in the Diagnostic and Statistical Manual of Mental Disorders, Version 5) within 2 years of screening - Exclusions Related to Imaging Related Criteria - Exclusions Related to Cardiovascular Disorders - Exclusions Related to Hepatic and Renal Disorders - Exclusions Related to Infections and Immune Disorders - Exclusions Related to Metabolic and Endocrine Disorders - Exclusions Related to Medications - Other Exclusions
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary objective: To evaluate the efficacy of gantenerumab compared with control on cognition Primary endpoint: Change from baseline to Year 4 in the Preclinical Alzheimer's Cognitive Composite-5 (PACC-5) score | — |
Secondary
| Measure | Time frame |
|---|---|
| Secundary objectives: * 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 Secundary endpoints: 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 ta | — |
Countries
Netherlands
Outcome results
None listed