AHEAD 3-45 Study: A Study to Evaluate Efficacy and Safety of Treatment With Lecanemab in Participants With Preclinical Alzheimer's Disease and Elevated Amyloid and Also in Participants With Early Preclinical Alzheimer's Disease and Intermediate Amyloid

Exclusion Criteria

• •Participants who meet any of the following criteria will be excluded from this study:
• •1. Females who are breastfeeding or pregnant at screening or baseline
• •2. Females of childbearing potential who:
• •• Within 28 days before study entry, did not use a highly effective method of contraception For sites outside of Europe, it is permissible that if a highly effective method of contraception is not appropriate or acceptable to the participant, then the participant must agree to use a medically acceptable method of contraception
• •3. History of transient ischemic attacks (TIA), stroke, or seizures within 12 months of screening
• •4. Current or history within the past 2 years of psychiatric diagnosis or symptoms that, in the opinion of the investigator, could interfere with study procedures
• •5. Contraindications to 3 Tesla magnetic resonance imaging (MRI) scanning, including cardiac pacemaker/defibrillator, ferromagnetic metal implants (example, in-skull and cardiac devices other than those approved as safe for use in MRI scanners), or exhibit other significant pathological findings on brain MRI at Screening
• •6. Hypersensitivity to any monoclonal antibody treatment
• •7. Any immunological disease which is not adequately controlled, or which requires treatment with immunoglobulins, systemic monoclonal antibodies (or derivatives of monoclonal antibodies), systemic immunosuppressants, or plasmapheresis during the study
• •8. Bleeding disorder that is not under adequate control (including a platelet count \<50,000 or international normalized ratio \[INR\] \>1.5) at screening
• •9. Results of laboratory tests conducted during screening that are outside the following limits:
• •* Thyroid stimulating hormone (TSH) above normal range
• •* Abnormally low (below lower limit of normal \[LLN\]) serum vitamin B12 levels for the testing laboratory (if participant is taking vitamin B12 injections, level should be at or above the LLN for the testing laboratory). A low vitamin B12 is exclusionary, unless the required follow-up labs (homocysteine and methylmalonic acid \[MMA\]) indicate that it is not physiologically significant
• •10. Known to be human immunodeficiency virus (HIV) positive
• •11. Any other clinically significant abnormalities that in the opinion of the investigator require further investigation or treatment or may interfere with study procedures or safety
• •12. Malignant neoplasms within 3 years of screening (except for basal or squamous cell carcinoma in situ of the skin, or localized prostate cancer in male participants with treatment cycles completed at least 6 months before screening). Participants who had malignant neoplasms but who have had at least 3 years of documented uninterrupted remission before screening need not be excluded
• •13. Answer "yes" to Columbia-Suicide Severity Rating Scale (C-SSRS) suicidal ideation Type 4 or 5, or any suicidal behavior assessment within 6 months before screening, at screening, or at baseline, or has been hospitalized or treated for suicidal behavior in the past 5 years before screening
• •14. Known or suspected history of drug or alcohol abuse or dependence within 2 years before screening or a positive urine drug test at screening. Participants who test positive for benzodiazepines, opioids, or tetrahydrocannabinol (THC) in urine drug testing need not be excluded unless in the clinical opinion of the investigator this is due to potential drug abuse
• •15. Taking prohibited medications
• •16. Participation in a clinical study involving:
• •* Any anti-amyloid plaque lowering immunotherapy (example, therapeutic monoclonal antibody or active anti-amyloid vaccine) at any time, unless it can be documented that the participant was randomized to placebo or never received study drug
• •* Any immunoglobulin therapy, or vaccine within 6 months before Screening, unless it can be documented that the participant was randomized to placebo or never received study drug
• •* Lecanemab
• •* Any new chemical entities or investigational drug for AD within 6 months before randomization unless it can be documented that the participant received only placebo
• •* Any other investigational medication or device study in the 8 weeks or 5 half-lives (whichever is longer) of the medication before randomization unless it can be documented that the participant was in a placebo treatment arm
• •17. Planned surgery during the pre-randomization phase or within 3 months of randomization, which requires general anesthesia
• •For extension phase:
• •1. Discontinued from the Core Study or from study treatment
• •2. Under study drug interruption due to ARIA or other AE at the time of transition to the extension phase