A Study to Evaluate the Safety and Efficacy of CT1812 in Early Alzheimer's Disease

This is an interventional treatment trial for Early Alzheimer's Disease focused on measuring Alzheimer's Disease Read More

Inclusion Criteria:

1. Documentation of the participant's informed consent to study procedures (including ApoE genotyping) and for the use of PHI (HIPAA Authorization, if applicable).
2. Ages 50-85 years.

3. Persons with female biological sex, must be of non-childbearing potential. Persons with male biological sex who are sexually active must agree to use acceptable contraceptives during the trial and for 3 months after their last dose unless their partner is using an acceptable means of birth control or is of non-childbearing potential.

   i) Persons with female biological sex will be considered of childbearing potential unless they are postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age range, and without other known or suspected cause) or have been sterilized surgically (i.e., bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 90 days before Screening). In women under the age of 60, post-menopausal status will be confirmed with follicle stimulating hormone (FSH).

   ii) Persons with male biological sex who are sexually active with a female of child-bearing potential must agree to use condoms during the trial and for 3 months after the last dose unless the female is using an acceptable means of birth control. Acceptable forms of birth control include abstinence, birth control pills, or any double combination of: intrauterine device (IUD), male or female condoms, diaphragm, sponge, and cervical cap.

4. Ability to swallow CT1812 capsules.

5. Diagnosis of either MCI due to AD or mild AD dementia, defined as meeting all of the following requirements at screening:

   1. At least 6 months of decline in cognitive function
   2. Abnormal memory function documented by scoring within the education adjusted ranges on the Logical Memory II (Delayed Paragraph Recall) from the Wechsler Memory Scale - Revised:

   i. ≤8 for 16 or more years of education

   ii. ≤4 for 8-15 years of education

   iii. ≤2 for 0-7 years of education

   c. Global CDR score of 0.5 (for MCI due to AD) and 0.5 to 1 (for mild AD), where Memory Box score ≥0.5.

6. MMSE 20-30 (inclusive).
7. Amyloid PET scan of the brain or CSF biomarkers consistent with AD.
8. Neuroimaging (MRI) obtained during screening consistent with the clinical diagnosis of Alzheimer's disease, as based on central read.
9. Stable dose of permitted medications for 30 days prior to screening.
10. Resides at home or in the community (assisted living acceptable).
11. In the opinion of the site PI, has a study partner able and willing to provide accurate information about the participant, oversee the administration of study drug, and participate in study visits and informant-based assessments (usually requires at least 5 hours of contact per week).
12. As assessed by the site PI, participant is likely to be able to comply with the protocol, including completion of all screening evaluations, and has adequate vision, hearing (hearing aid permitted), and literacy in English or Spanish sufficient for compliance with required testing procedures.

13 Must complete all screening evaluations as outlined in the Schedule of Activities (SoA).

Exclusion Criteria:

1. Prior or current treatment with a prohibited medication.
2. Prior treatment with CT1812. NOTE: If a participant was previously involved in a CT1812 study, inclusion in this study is permitted only if it can be confirmed the participant received placebo in the previous CT1812 study.
3. Enrollment in another investigational study or intake of investigational drug within the previous 30 days or five half lives of the investigational drug, whichever is longer.
4. Suspected or known allergic reactions, adverse reactions, or hypersensitivity to any components of the study treatments (CT1812 or placebo).
5. Hospitalization within 30 days prior to screening or baseline.
6. For participants undergoing an LP for eligibility purposes or as part of the optional longitudinal CSF biomarker sub-study, contraindication to undergoing an LP including, but not limited to: inability to tolerate an appropriately flexed position for the time necessary to perform an LP; international normalized ratio (INR) > 1.4 or other coagulopathy; platelet count of < 120,000/μL; infection at the desired lumbar puncture site; taking anti-coagulant medication within 90 days of LP (Note: low dose aspirin is permitted); degenerative arthritis of the lumbar spine; suspected non-communicating hydrocephalus or intracranial mass; prior history of spinal mass or trauma.
7. Screening MRI of the brain indicative of significant abnormality, including, but not limited to, prior lobar hemorrhage or infarct >1 cm3, >3 lacunar infarcts, cerebral contusion or encephalomalacia >1 cm, aneurysm, high flow vascular malformation, subdural hematoma, hydrocephalus, space-occupying lesion (e.g. abscess or intraaxial brain tumor).

8. Clinically significant abnormalities in screening laboratory tests, including, but not limited to:

   1. hematocrit less than 35% for those with male biological sex and less than 32% for those with female biological sex
   2. absolute neutrophil cell count of 1500/uL (with the exception of a chronic benign neutropenia)
   3. absolute lymphocyte count <900/uL,
   4. platelet cell count of <120000/uL
   5. INR >1.4 or other coagulopathy, confirmed by repeat

9. Clinical or laboratory findings consistent with:

   1. Other primary degenerative dementia, (dementia with Lewy bodies, fronto-temporal dementia, Huntington's disease, Creutzfeldt-Jakob Disease, Down syndrome, etc.).
   2. Other neurodegenerative condition (Parkinson's disease, amyotrophic lateral sclerosis, etc.).
   3. Other infectious, metabolic or systemic diseases affecting the central nervous system (syphilis, present hypothyroidism, present vitamin B12 or folate deficiency, other laboratory values etc.).

10. Clinically significant, advanced or unstable disease that may interfere with outcome evaluations, such as:

    1. Chronic liver disease, liver function test abnormalities or other signs of hepatic insufficiency (ALT, AST, alkaline phosphatase > 1.5 ULN, lactate dehydrogenase (LDH) > 1.5 x ULN).
    2. Respiratory insufficiency.
    3. Renal insufficiency eGFR < 50 mL/min based on the CKD-EPI formula, https://www.mdcalc.com/ckd-epi-equations-glomerular-filtration-rate-gfr
    4. Heart disease (myocardial infarction, unstable angina, heart failure, cardiomyopathy within six months before screening).
    5. Bradycardia (<50/min.) or tachycardia (>100/min.).
    6. Poorly managed hypertension (systolic >160 mm Hg and/or diastolic >95 mm Hg) or hypotension (systolic <90 mm Hg and/or diastolic <60 mm Hg).
    7. Uncontrolled diabetes defined by HbA1c >7.5.
11. History of cancer within 3 years of screening with the exception of fully excised non-melanoma skin cancers or non-metastatic prostate cancer that has been stable for at least 6 months.
12. Seropositive for human immunodeficiency virus (HIV).
13. History of acute/chronic hepatitis B or C and/or carriers of hepatitis B (seropositive for hepatitis B surface antigen [HbsAg] or anti-hepatitis C [HCV] antibody).
14. Suspected or known drug or alcohol abuse

15. A current DSM-V diagnosis of active major depression or GDS > 6, (unless the site PI does not consider participant clinically depressed), schizophrenia, or bipolar disorder.

    NOTE: Participants with depressive symptoms successfully managed by a stable dose of an antidepressant are considered eligible.

16. Any condition, which in the opinion of the site PI, Data and Coordinating Center, regulatory sponsor, or Protocol PI, makes the participant unsuitable for inclusion.