A Study to Evaluate the Safety and Efficacy of CT1812 in Subjects With Mild to Moderate Alzheimer's Disease.

• Status: Active, not recruiting
• Trial end date: 2020-07-31
• Target enrollment: 0
• Participant gender: All

Summary

This is a multi-center, randomized, double-blind, placebo-controlled, parallel group 36 week multicenter Phase 2 study of two doses of CT1812 in adults with mild to moderate Alzheimer's Disease (AD).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Cognition Therapeutics

Criteria

1. Men, and women of non-childbearing potential, 50-85 years of age inclusively, with a diagnosis of mild to moderate Alzheimer's disease according to the 2011 NIA-AA criteria and at least a 6 month decline in cognitive function documented in the medical record.

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

ii) Male participants who are sexually active with a woman of child-bearing potential must agree to use condoms during the trial and for 3 months after last dose unless the woman 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 condom, diaphragm, sponge, and cervical cap.

2. Diagnostic confirmation by amyloid PET with florbetaben or another approved amyloid PET ligand. Previous amyloid imaging study with a positive result will be accepted. If none is available, then amyloid PET will be conducted during screening. Diagnostic confirmation by a CSF sample collected at the screening visit lumbar puncture in place of amyloid PET will also be acceptable

3. Neuroimaging (MRI) obtained during screening consistent with the clinical diagnosis of Alzheimer's disease and without findings of significant exclusionary abnormalities (see exclusion criteria, number 4). An historical MRI, up to 1 year prior to screening, may be used as long as there is no history of intervening neurologic disease or clinical events (such as a stroke, head trauma etc.) and the subject is without clinical symptoms or signs suggestive of such intervening events.).

4. MMSE 18-26 inclusive.

5. No active depression and a GDS ≤6 (see exclusion criteria number 6).

6. Modified Hachinski ≤ 4.

7. Formal education of eight or more years.

8. Subjects must have a caregiver/ study partner who in the opinion of the site principal investigator, has contact with the study subject 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 clinic visits and some study assessments. The caregiver/ study partner must provide written informed consent to participate in the study.

9. Subjects living at home or in the community (assisted living acceptable).

10. Ability to swallow CT1812 capsules.

11. Stable pharmacological treatment of any other chronic conditions for at least 30 days prior to screening.

12. Subjects must be capable of providing written informed consent to the study procedures and for use of protected health information [Health Insurance Portability and Accountability Act (HIPAA), if applicable]. Written informed consent also shall be obtained from the responsible caregiver. All consent processes must be undertaken in the presence of a witness and prior to any study procedures.

13. Must consent to apolipoprotein E (ApoE) genotyping for data analysis stratification.

14. Subjects shall be generally healthy with mobility (ambulatory or ambulatory-aided, i.e., walker or cane), vision and hearing (hearing aid permissible) sufficient for compliance with testing procedures.

15. Must be able to complete all screening evaluations.

EXCLUSION CRITERIA:

Participants will be excluded from the study if any of the following conditions apply:

1. Hospitalization (except for planned procedures) or change of chronic concomitant medication within one month prior to screening.

2. Subjects living in a continuous care nursing facility.

3. Contraindication to the MRI examination for any reason.

4. 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 (e.g. abscess or brain tumor such as meningioma). If a small incidental meningioma is observed, the medical monitor may be contacted to discuss eligibility..

5. 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. Seizure disorder.

4. Other infectious, metabolic or systemic diseases affecting the central nervous system (syphilis, present hypothyroidism, present vitamin B12 or folate deficiency, other laboratory values etc.).

6. A current DSM-V diagnosis of active major depression, schizophrenia or bipolar disorder. Subjects with depressive symptoms successfully managed by a stable dose of an antidepressant are allowed entry.

7. 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.

8. 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.

9. Seropositive for human immunodeficiency virus (HIV).

10. 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).

11. Clinically significant abnormalities in screening laboratory tests, including:

a. Hematocrit less than 35% for males and less than 32% for females, absolute neutrophil cell count of 1500/uL (with the exception of a documented history of a chronic benign neutropenia), or platelet cell count of < 120,000/uL; INR >1.4 or other coagulopathy, confirmed by repeat assessment of: i. Hematocrit ii. Neutrophil count iii. Platelet count

12. Disability that may prevent the subject from completing all study requirements (e.g. blindness, deafness, severe language difficulty, etc.).

13. Within 4 weeks of screening visit or during the course of the study, concurrent treatment with antipsychotic agents, antiepileptics, centrally active anti-hypertensive drugs (e.g., clonidine, l-methyl dopa, guanidine, guanfacine, etc.), sedatives, opioids, mood stabilizers (e.g., valproate, lithium); or benzodiazepines, with the following exception:

a. Low dose lorazepam may be used for sedation prior to MRI scan for those subjects requiring sedation. At the discretion of the investigator, 0.5 to 1 mg may be given orally prior to scan with a single repeat dose given if the first dose is ineffective. No more than a total of 2 mg lorazepam may be used for the MRI scan.

14. Any disorder that could interfere with the absorption, distribution, metabolism or excretion of drugs (e.g. small bowel disease, Crohn's disease, celiac disease, or liver disease).

15. Nootropic drugs except stable AD meds (acetylcholinesterase inhibitors and memantine.

16. Suspected or known drug or alcohol abuse, i.e. more than approximately 60 g alcohol (approximately 1 liter of beer or 0.5 liter of wine) per day indicated by elevated MCV significantly above normal value at screening.

17. Suspected or known allergy to any components of the study treatments.

18. 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.

19. Intake of drugs or substances potentially involved in clinically significant induction or inhibition of CYP3A4 or P-gp mediated drug interactions with CT1812, within 4 weeks or five half-lives of the interacting drug prior to administration of CT1812 and throughout the course of the study. Grapefruit juice should be avoided in the two weeks prior to dosing and throughout the course of the study. See Appendix A for a complete list of prohibited substances.

20. Exposure to immunomodulators, anti Aβ vaccines, passive immunotherapies for AD (e.g. monoclonal antibodies) within the past 180 days and/or exposure to BACE inhibitors within the past 30 days.

21. Anticipated use of nonsteroidal anti-inflammatory drugs (NSAIDs) on more than 14 days during the period from Baseline to Day 182.

22. 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 screening (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.

23. Any condition, which in the opinion of the investigator or the sponsor makes the subject unsuitable for inclusion.