A Phase 3, Multicenter, Randomized, Double-blind, Placebo-Controlled Study of the Efficacy, Safety and Biomarker Effects of ALZ-801 in Subjects with Early Alzheimer's Disease and APOE4/4 Genotype

1. Male or female between the ages of 50 and 80 years (inclusive) at the
Screening - Part 1 Visit.
2. Clinical diagnosis of MCI or Mild Dementia due to AD consistent with the
NIA-AA Working Group Criteria
3. Homozygous for the *4 allele of the APOE gene (APOE4/4).
4. MMSE score of 22 to 30 (inclusive) at the Screening - Part 1 Visit.
5. CDR Global score at Screening of 0.5 or 1, and a CDR Memory Box score >= 0.5.
6. RBANS delayed memory index score <= 85.
7. Evidence of progressive memory loss over the last 12 months per investigator
assessment as captured on the diagnostic verification form.
8. Can complete the cognitive testing and all other required study procedures.
9. Has completed at least 6 years of formal education after age of 5 years, and
is able to read at minimum of 6th grade level or equivalent per investigator
assessment.
10. Lives at home independently, in a senior living facility, or in an assisted
living facility.
11. Has a body mass index (BMI) between 17-40 (inclusive).
12. Except for a diagnosis of AD and the presence of stable medical conditions,
is, in the opinion of the Investigator, in good general medical health based
upon the results of medical history, physical examination, laboratory tests,
vital signs, and ECG.
13. Has a reliable caregiver or study partner who is willing and able to sign
an ICF, to accompany the subject to study visits, and adhere to study
requirements (The caregiver or study partner, in the Investigator's opinion,
has adequate contact with the subject to be able to provide accurate
information about the participant's cognitive and functional ability).
See protocol for further inclusion criteria

1. Screening brain MRI indicative of significant abnormality per central
reader, other than AD related atrophy, including, but not limited to; prior
large vascular territorial infarct, > 2 lacunar infarcts (size > 1.5 cm)
outside the brain stem, severe white matter changes (deep white matter changes
Fazekas grade = 3), ventriculomegaly related to normal pressure hydrocephalus
(after clinical correlation), or aneurysm, subdural hematoma, abscess or brain
tumor (other than meningiomas or benign pituitary adenoma). 2. Diagnosis of a
neurodegenerative disorder other than AD. 3. Diagnosed with MDD according to
the criteria of the Diagnostic and Statistical Manual of Mental Disorders -
Fifth Edition (DSM-5), within one year prior to the Baseline Visit. A subject
who does not meet criteria for MDD and who is on stable doses of
antidepressants or mood stabilizers may be included in the study at the
discretion of the Investigator. 4. Currently taking memantine or has taken
memantine within 12 weeks prior to the Baseline Visit. 5. History of suicidal
behavior within one year prior to the Baseline Visit; or has ongoing suicidal
ideation with intent, with or without a specific plan or method (e.g., positive
response to C-SSRS items 4 or 5 during the past 6 months). 6. History of
seizures, excluding febrile seizures of childhood or a single distant seizure
(>= 5 years prior to the Baseline Visit). 7. Medically confirmed history of
recent cerebral infarct or transient ischemic attack within one year prior to
the Baseline Visit. 8. Medically confirmed history of recent myocardial
infarction or unstable, untreated coronary artery disease, or angina pectoris
(within 1 year prior to the Baseline Visit). 9. Lifetime history of
schizophrenia, schizoaffective disorder, or bipolar disorder. 10. History of,
or currently has, any clinically significant ECG finding, or a QT interval
corrected by Fridericia*s method (QTcF) of > 450 msec for males and > 470 msec
for females. 11. History of cancer, diagnosed and treated within the last 3
years prior to the Baseline Visit, with the exception of the following: (a)
treated basal cell carcinoma of the skin, (b) treated cutaneous squamous cell
carcinoma in situ, (c) treated in situ or Stage 1 prostate cancer, (d) treated
in situ cervical cancer, and (e) resected and cured early stage cutaneous
melanoma (all require approval by the Sponsor's Medical Officer). 12. Has
donated blood > 250 mL within 6 weeks prior to the Baseline Visit. 13. History
of alcohol or drug dependence or abuse according to the criteria of the DSM-5
within 2 years prior to the Baseline Visit. Note: A positive urine drug screen
does not automatically exclude subject, but requires review by Sponsor Medical
Officer. 14. Any significant medical condition or infection (e.g., uncontrolled
cardiovascular, GI, endocrinologic, hematologic, hepatic, immunologic,
metabolic, urologic, pulmonary, neurologic, dermatologic, renal, or other major
disease or malignancy) that is unstable and that would either: (a) place the
subject at undue risk from administration of study drug or from undergoing
study procedures, or (b) interfere with the interpretation of safety or
efficacy evaluations obtained in the course of the study. 15. Unable to swallow
ALZ-801 tablets or has a known intolerance or hypersensitivity to tramiprosate
or any of the excipients contained in the ALZ-801 tablets. 16. Except when
otherwise specified, has clinical laboratory tests outside normal limits per
the laboratory*s specification and considered clinically significant by the
investigator at the Screening - Part 2 Visit 17. Clinically relevant
abnormalities in serum thyroid-stimulating hormone (TSH) or calcium. If the
subject is taking thyroid hormone replacement therapy, corresponding Screening
test values must be considered not clinically significant by the investigator.
18. Serum vitamin B12 below the lower limit of normal at the Screening - Part 2
Visit. A subject can be treated with vitamin B12 replacement during screening
period, and enrolled if the value has normalized approximately four weeks
post-treatment. 19. Any clinical chemistry laboratory value greater than or
equal to Common Terminology Criteria for Adverse Events (CTCAE; version 5.0;
National Cancer Institute 2018) Grade 2, unless considered not clinically
relevant by the Investigator. 20. One or more of the following at the Screening
- Part 2 Visit: Alanine aminotransferase (ALT) > 3 × upper limit of normal
(ULN), Aspartate aminotransferase (AST) > 3 × ULN, or Total bilirubin (TBL) >
1.5 × ULN. (except for subjects with diagnosed Gilbert syndrome with isolated
hyperbilirubinemia). 21. Estimated glomerular filtration rate (eGFR) < 40
mL/min per 1.73 m2 according to the Modification of Diet in Renal Disease
(MDRD) formula [see National Institute of Diabetes and Digestive and Kidney
Diseases website for formula MDRD formula for eGFR (SI units)]. See protocol
for further exclusion criteria