AV-1959R Vaccine in Individuals With Preclinical Alzheimer's Disease

Prior treatment

• Contraindication to MRI. Serious illness requiring systemic treatment and/or hospitalization within 4 weeks before study entry.
• Participation in another investigational drug study or use of an investigational drug within 30 days or 5 half-lives, whichever is longer, before dosing.
• Prior amyloid-beta or tau immunotherapy, including vaccine or monoclonal antibody, within 1 year before screening.

Other illness

• Clinically relevant cardiovascular, respiratory, gastrointestinal, endocrine, immunologic, hematologic, neurologic, or other systemic disease that could interfere with participation or follow-up.
• Pre-existing autoimmune disease. History of seizure disorder, except protocol-permitted use of certain antiepileptic medications for chronic pain.
• Any medical, psychological, or social condition that may interfere with participation, compliance, or safety.
• History of severe local or systemic vaccine reactions or significant allergic reactions.

Lab values

• Insulin-dependent diabetes. Clinically significant ECG abnormalities, including protocol-defined conduction abnormalities or QTc abnormalities.
• Clinically significant laboratory abnormalities at screening. Positive testing for HIV-1/2, hepatitis B surface antigen, or hepatitis C virus.

Other

• Screening MRI showing clinically significant abnormalities, including protocol-defined infarcts, excessive microbleeds, leptomeningeal hemosiderosis, superficial siderosis, or ARIA-E.
• Recent use of protocol-defined immunomodulatory or growth-stimulating agents. Chronic use of protocol-defined anticoagulants or antiplatelet agents; aspirin is permitted.
• Parenteral use of immunoglobulin preparations, blood products, or plasma derivatives.

• Male or female participants 55 to 80 years of age, inclusive, at screening. Signed informed consent before initiation of study-related procedures.
• Cognitively unimpaired participants with preclinical Alzheimer's disease meeting all of the following:
• CDR global score = 0 at screening. MMSE score ≥26 at screening, with education adjustment. WMS-R LM2 score ≥ 6 Plasma p-tau217/Aβ1-42 ratio ≥0.00738. Brain amyloid burden ≥ 20CL. Vision and hearing sufficient to comply with study procedures, in the investigator's judgment.
• Stable concomitant medications for management of existing medical conditions, as appropriate.
• Women must be of non-childbearing potential as defined in the protocol. Men must meet protocol-defined contraception and sperm donation requirements. Ability, in the investigator's opinion, to understand the study and comply with study requirements.