Phase 3, Double-blind, Randomized, Placebo-controlled Trial to Evaluate the Efficacy and Safety of AR1001 in Participants With Early Alzheimer's Disease (Polaris-AD)

This AR1001-ADP3-US01 protocol is a double-blind, randomized, placebo-controlled, multi- center, parallel-group comparison pivotal Phase 3 study to evaluate the efficacy and safety of AR1001 for the treatment of participants with early AD.

Inclusion Criteria:

1. Male or female participants aged 55 to 80 years of age at the time of signing the informed consent form
2. Mild cognitive impairment or mild dementia consistent with AD defined by stages 3 to 4 according to the NIA AA at Screening
3. Participants with a history of subjective cognitive and memory decline with onset within 3 years before Screening, confirmed by study partner.
4. Participants who have a MMSE Score greater than or equal to 20
5. Participants with a CDR global rating of 0.5 or 1
6. Participants with a RBANS score less than or equal to 85 based on the Delayed Memory Index (DMI) score
7. Participants who have had a magnetic resonance imaging (MRI) or computer tomography (CT) scan performed after onset of symptoms and within 2 years prior to screening with findings consistent with the diagnosis of AD and without any other clinically significant comorbid pathologies
8. Confirmed amyloid beta pathology by cerebrospinal fluid (CSF) analysis

Exclusion Criteria:

1. Participants who are female and are either pregnant, nursing, or of childbearing potential and not practicing effective contraception
2. Participants who have signs of delirium
3. Participants who have any diagnosis of dementia or cognitive decline other than that related to Alzheimer's disease, including, but not limited to concomitant history of significant head trauma, alcohol abuse, frontotemporal dementia, Huntington Disease, and Parkinsonism (e.g., Parkinson's disease, Dementia with Lewy Bodies, etc.)
4. Participants with any current psychiatric diagnosis if, in the judgment of the investigator, the psychiatric disorder (e.g., schizophrenia) or symptom is likely to confound interpretation of drug effect, affect cognitive assessments, or affect the participant's ability to complete the study
5. Participants with vascular dementia and/or a Hachinski Ischemic Scale (HIS) score ≥7
6. Participants with a recent MRI with evidence of central nervous system (CNS) infection, cerebrovascular (CBV) disease, or other neurological disease thought to interfere with the evaluations in this study
7. Participants with a history of myocardial infarction, unstable angina, coronary artery disease, or New York Heart Association (NYHA) class III or IV heart failure within the last 12 months
8. Participants with uncontrolled hypertension (systolic blood pressure >160 mmHg or diastolic blood pressure > 95 mmHg) or hypotension (systolic blood pressure <90 mmHg or diastolic blood pressure <50 mmHg). Participants may undergo repeated testing to ensure that accurate blood pressure readings are obtained
9. Participants with a body mass index (BMI) > 35 kg/m2
10. Participants who have any other clinically significant abnormal laboratory tests such as elevated aspartate aminotransferase (AST), alanine transaminase (ALT), or total bilirubin levels, or abnormally low vitamin B12, high TSH levels, or evidence of folic acid deficiency, as determined by the Investigator
11. Participants who have history of cancer or malignant tumor within 5 years prior to screening with the exception of:
12. Basal or squamous cell carcinoma of the skin or cervical dysplasia, which has been adequately treated
13. In situ Grade 1 cervical cancer, fully treated at least 2 years prior to screening, and without recurrence.
14. Prostate cancer, confined to the prostate gland, which has been adequately treated (surgery and/or radiation) with normal or low and stable PSA levels for 2 years prior to Screening
15. Adequately treated non-metastatic breast cancer
16. Participants who have history of untreated thyroid disorder
17. Participants with inherited degenerative retinal disease
18. Participants who have an undiagnosed or uncontrolled seizure disorder (and/or an epileptic syndrome), which has or could lead to cognitive impairment either from repeated seizures or the medications used to control the seizure disorder
19. Participants who are being treated, or likely to require treatment during the study, with any medications prohibited by the study protocol

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