Pilot Clinical Study of CT1812 in Mild to Moderate Alzheimer's Disease Using EEG

Inclusion Criteria

• Women of non-childbearing potential and men, aged 50 to 85 years, inclusive, with a diagnosis of mild to moderate Alzheimer's disease according to the 2018 NIA-AA criteria and at least a 6-month history of decline in cognitive function documented in the medical record.

i) Non-childbearing potential for women is defined as postmenopausal (last menses greater than 24 months) or undergone a documented bilateral tubal ligation or hysterectomy. If last menses less than 24 months, a serum follicle stimulating hormone (FSH) value confirming post-menopausal status may be used.

ii) Male participants who are sexually active with a woman of child-bearing potential must agree to use condoms during the study and for 3 months after last dose. Female partners should also consider using an acceptable means of birth control, though it is not mandatory. Acceptable forms of birth control include abstinence, birth control pills, or any double combination of: intrauterine device (IUD), male or female condom, diaphragm, sponge, and cervical cap.

• CSF positive for amyloid beta (as defined in the study manual). Historical CSF results will be considered provided the results are consistent with the CSF amyloid beta threshold required for inclusion and following discussion with the medical monitor; however, an LP is still required as part of screening procedures
• Neuroimaging (MRI) consistent with the clinical diagnosis of Alzheimer's disease and without findings of significant exclusionary abnormalities (see Section 9.3 exclusion criteria no. 4). An historical MRI, up to 1 year prior to screening, may be used as long as there have been no interval clinical neurologic events that may suggest a change in the MRI scan.
• MMSE 18-26 inclusive.
• Geriatric Depression Scale (GDS) ≤ 6 with no active depression (see Section 9.3 exclusion criteria no. 6).
• Formal education of 8 or more years.
• Participants must have a caregiver/study partner who in the opinion of the site's Principal Investigator, has contact with the study participant for a sufficient number of hours per week to provide informative responses on the protocol assessments, oversee the administration of study drug, and is willing and able to participate in all study site visits and some study assessments. The caregiver/ study partner must provide written informed consent to participate in the study.
• Participants living at home or in the community (assisted living acceptable).
• Participants must have no known history of difficulty swallowing capsules.
• Stable pharmacological treatment of any other chronic conditions for at least 30 days prior to screening.
• Must consent to apolipoprotein E (APOE) genotyping.
• Participants shall be generally healthy with mobility (ambulatory or ambulatory-aided, ie, walker or cane), vision and hearing (hearing aid permissible) sufficient for compliance with testing procedures.
• Must be able to complete all screening evaluations.

Exclusion Criteria

• Hospitalization (except for planned procedures) or change of chronic concomitant medication within 1 month prior to screening.
• Participants living in a continuous care nursing facility.
• Contraindications to the MRI examination for any reason.
• Screening MRI (or historical MRI, if applicable) of the brain indicative of significant abnormality, including, but not limited to, prior hemorrhage or infarct > 1 cm3, > 3 lacunar infarcts, cerebral contusion, encephalomalacia, aneurysm, vascular malformation, subdural hematoma, hydrocephalus, space-occupying lesion (eg, abscess or brain tumor such as meningioma).
• Clinical or laboratory findings consistent with:
• Other primary degenerative dementia, (dementia with Lewy bodies, fronto-temporal dementia, Huntington's disease, Creutzfeldt-Jakob Disease, Down syndrome, etc).
• Other neurodegenerative condition (Parkinson's disease, amyotrophic lateral sclerosis, etc).
• Seizure disorder.
• Other infectious, meta