Study of AV-1959D, an Amyloid Beta Vaccine

Exclusion Criteria

• •1. Participation in another investigational drug or device study or treated with an investigational drug within 30 days or 5 half-lives, whichever is longer, before dosing.
• •2. Prior administration of any amyloid-beta or tau immunotherapy (vaccine, antibody)
• •3. Magnetic resonance imaging (MRI) showing evidence of any of the following:
• •* More than 1 lacunar infarct greater than 1.5 cm
• •* Any territorial infarct, including acute or chronic, greater than 1.5 cm
• •* Subjects who have a combined number of microbleeds and areas of leptomeningeal hemosiderosis (i.e., cumulative ARIA-H) on the MRI of \> 5 (and should not include any disseminated leptomeningeal hemosiderosis)
• •* Subjects who have a presence of any other significant cerebral abnormalities, including ARIA-E, as assessed in the screening MRI scan.
• •4. Contraindications for MRI scanning, including implanted metallic devices (e.g., non-MRI-safe cardiac pacemaker or neurostimulator; some artificial joints metal pins; surgical clips; or other implanted metal parts), or claustrophobia or discomfort in confined spaces.
• •5. Use of immunomodulatory or growth-stimulating factors such as systemic corticosteroids, cyclosporine, methotrexate, azathioprine, anti-CD25 antibody, GM-CSF, C-CSF, interferon (IFN), or interleukin-2 (IL-2) within 30 days prior to study entry.
• •6. Concurrent use of warfarin or other coumarin derivatives or a combination of acetylsalicylic acid and an anti-platelet agent (e.g., clopidogrel). Low dose of acetylsalicylic acid (≤81 mg per day) is allowed.
• •7. Parenteral use of immunoglobulin preparations, blood products, plasma derivatives.
• •8. Any serious illness requiring systemic treatment and/or hospitalization within 4 weeks prior to study entry.
• •9. Any major or unstable illness, including unstable ischemic cardiovascular disease, or require use of excluded medications.
• •10. History/evidence of clinically relevant pathology related to cardiovascular system, respiratory tract, gastrointestinal tract, endocrinology, immunology, hematology, or any other systemic disorder/major surgeries that in the opinion of the Investigator would confound the subject's participation and follow-up in the clinical study.
• •11. Subjects with insulin-dependent diabetes.
• •12. Cardiac arrhythmias or palpitations \[e.g., supraventricular tachycardia, atrial fibrillation, frequent ectopy, or sinus bradycardia\]. Cardiac conduction abnormalities to be specified including prolonged QT interval and bundle branch blocks.
• •13. Subjects with pre-existing autoimmune diseases.
• •14. A medical condition that in the opinion of the Investigator might be a contributing cause of cognitive impairment.
• •15. History/evidence of severe local or systemic reactions to vaccination or significant allergic reactions.
• •16. History of seizure disorder.
• •17. Any other medical, psychological, social condition or diagnostic test which, in the opinion of the Investigator and Medical Monitor may lead to screen failure or prevent the subject from fully participating in the study, represent a concern for study compliance, or constitute a safety concern to the subject.