A Study to Evaluate the Efficacy and Safety of Gantenerumab in Participants at Risk for or at the Earliest Stages of Alzheimer's Disease (AD)

• Status: Recruiting
• Trial end date: 2028-10-13
• Target enrollment: 0
• Participant gender: All

Summary

A study to evaluate the efficacy and safety of gantenerumab in amyloid-positive, cognitively unimpaired participants at risk for or at the earliest stages of AD. The planned number of participants for this study is approximately 1200 participants randomized in a 1:1 ratio to receive either gantenerumab or placebo (600 participants randomized to gantenerumab and 600 participants randomized to placebo).

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Hoffmann-La Roche

Criteria

Key Inclusion Criteria:

• Willing and able 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 positron emission tomography (PET) imaging].

• Cognitively unimpaired with a screening clinical dementia rating global score (CDR-GS) of 0, and Repeatable Battery for the Assessment of Neuropsychological Status Delayed Memory Index (RBANS DMI) >=80.

• Evidence of cerebral amyloid accumulation.

• Participants who have an available person (referred to as a "study partner").

• Fluent in the language of the tests used at the study site.

• Adequate visual and auditory acuity, sufficient to perform neuropsychological testing (eye glasses and hearing aids are permitted).

• 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 <1% per year during the treatment period and for at least 17 weeks after the final dose of study treatment.

Key Exclusion Criteria:

• Any evidence of an underlying neurological or neurodegenerative condition that may lead to cognitive impairment other than AD.

• Clinical diagnosis of mild cognitive impairment (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) central nervous system (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., human immunodeficiency virus (HIV), syphilis, neuroborreliosis, and viral or bacterial meningitis and encephalitis].

• History of major depression, schizophrenia, schizoaffective disorder, or bipolar disorder.

• At risk for suicide.

• History of alcohol and/or substance abuse or dependence.

• History or presence of clinically significant systemic vascular disease, atrial fibrillation or heart failure.

• Within the last year, experienced unstable or clinically significant cardiovascular disease (e.g., myocardial infarction).

• Uncontrolled hypertension.

• Chronic kidney disease, indicated by creatinine clearance <30 mL/min.

• Confirmed and unexplained impaired hepatic function.

• History of, or are known to currently have an HIV infection, or hepatitis B or hepatitis C virus infection that has not been adequately treated.

• History or presence of systemic autoimmune disorders that may lead to progressive neurological impairment with associated cognitive deficits.

• Systemic immunosuppression or immunomodulation due to the continuing effects of immunosuppressant or immunomodulating medications.

• Current COVID-19 infection.

• Evidence of folic acid or vitamin B-12 deficiency.

• Any passive immunotherapy (Ig) or other long-acting biologic agent to prevent or postpone cognitive decline within 1 year of screening.

• Any other investigational treatment within 5 half-lives or 6 months (whichever is longer) prior to screening.

• Typical/Atypical anti-psychotic medications or neuroleptic medications.

• Anticoagulation medications within 3 months of screening with no plans to initiate any prior to randomization.

• Any previous treatment with cholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists are exclusionary at screening.

• Pregnant or breastfeeding, or intending to become pregnant during the study or within 17 weeks after the final dose of gantenerumab.

• Impaired coagulation.

• Known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric, human, or humanized antibodies or fusion proteins, including gantenerumab and gantenerumab excipients.

• Participants who reside in a skilled nursing facility such as a convalescent home or long-term care facility.

• Participants who require residence in such facilities during the study may continue in the study and be followed for efficacy and safety, provided that they have a study partner who meets the study partner requirements.