| Eligibility |
INCLUSION CRITERIA:
Subjects may be included in the study only if they meet all of the following criteria:
1. Men, and women of non-childbearing potential, 50-85 years of age inclusively, with a
diagnosis of mild to moderate Probable Alzheimer's Disease Dementia according to the
2011 NIA-AA criteria and at least a 6 month decline in cognitive function documented
in the medical record.
1. a. Non-childbearing potential for women is defined as postmenopausal [last
natural menses greater than 24 months; in women under age 55, menopausal status
will be documented with serum follicle stimulating hormone (FSH) test] or
undergone a documented bilateral tubal ligation or hysterectomy
2. b. Male participants who are sexually active with a woman of childbearing
potential must agree to use condoms during the trial 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. Neuromaging (MRI) obtained during screening consistent with the clinical diagnosis of
Alzheimer's disease and without findings of significant exclusionary abnormalities
(see exclusion criteria, number 3).
3. MMSE 18-26 inclusive. Subjects must, in the opinion of the investigator, be able to
comply with study procedures and must understand the consent process. The investigator
will use his or her clinical judgment in conjunction with the cognitive screening
assessments to determine whether the subject meets these criteria in a manner that is
consistent with local clinical practice and standards. Subjects with borderline low
MMSE at screening may undergo repeat MMSE administration if extenuating circumstances
were present at original assessment.
4. A positive amyloid scan (florbetaben F18, florbetapir F18, or flutametamol F18) at
screening or within prior 12 months, as read by the certified, site-designated PET
scan reader.
5. Must consent to apolipoprotein E (ApoE) genotyping.
6. Subjects must have a caregiver or study partner who can participate in all clinic
visits.
7. Patients living at home or in the community (assisted living acceptable).
8. Able to swallow CT1812 capsules.
9. Stable pharmacological treatment of any other chronic conditions for at least 30 days
prior to screening.
10. Subjects must be capable of providing either written informed consent to the study
procedures and for use of protected health information [Health Insurance Portability
and Accountability Act (HIPAA) Authorization, if applicable]. Written informed consent
also shall be obtained from the responsible caregiver or study partner. All consent
processes must be undertaken in the presence of a witness and prior to any study
procedures.
11. 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.
12. Must be able to complete all screening evaluations.
EXCLUSION CRITERIA:
Subjects will be excluded from the study if any of the following conditions apply:
1. Hospitalization or change of chronic concomitant medication within one month prior to
screening.
2. Patients living in a continuous care nursing facility
3. Screening MRI 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.
4. Clinical or laboratory findings consistent with:
1. Other primary degenerative dementia, (dementia with Lewy bodies, fronto-temporal
dementia, Huntington's disease, Jacob-Creutzfeld Disease, Down syndrome, etc.);
2. Other neurodegenerative condition (Parkinson's disease, amyotrophic lateral
sclerosis, etc.);
3. Seizure disorder; or
4. Other infectious, metabolic or systemic diseases affecting the central nervous
system (syphilis, present hypothyroidism.) Present vitamin B12 or folate
deficiency or other laboratory abnormalities of possible clinical significance
should be discussed with medical monitor to determine eligibility.
5. A current DSM-V diagnosis that would interfere with the subject's ability to
participate in the study. Patients with depressive symptoms successfully managed by a
stable dose of an antidepressant are allowed entry.
6. Any prior history of suicidal thoughts or behavior that are believed by the
investigator to represent a current safety risk.
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, > 1.5 ULN);
2. Respiratory insufficiency;
3. Renal insufficiency, defined as eGFR <40 mL/min based on the CKD-EPI (Chronic
Kidney Disease Epidemiology Collaboration) formula,
https://www.mdcalc.com/ckd-epi-equations-glomerular-filtration-rate-gfr Heart
disease (myocardial infarction, unstable angina, heart failure, cardiomyopathy
within six months before screening). If a subject has a history of heart disease
of questionable clinical significance, the medical monitor may be contacted to
discuss eligibility.
4. Bradycardia (<50 beats/min.) or tachycardia (>100 beats/min.). Otherwise healthy
subjects with borderline bradycardia may be discussed with the medical monitor to
determine eligibility.
5. 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); or
6. 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. 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).
10. Clinically significant abnormalities in screening laboratory tests, including:
1. hematocrit less than 35% for males and less than 32% for females
2. platelet cell count of < 120,000/uL,
3. INR >1.4 or other coagulopathy, confirmed by repeat analysis, or
4. lymphocyte count less than 1200/ul
11. Disability that may prevent the patient from completing all study requirements (e.g.
blindness, deafness, severe language difficulty, etc.).
12. 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 exceptions:
1. benzodiazepines must not be administered within 5 half-lives of cognitive
testing;
2. administration of selective serotonin re-uptake inhibitors (SSRI) may be
continued if doses have been stable for 60 days prior to Screening;
3. low dose lorazepam may be used for sedation prior to MRI scan for those patients
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.
13. 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.)
14. Nootropic drugs except for AD meds (acetylcholinesterase inhibitors and memantine)
stable for at least 30 days
15. 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.
16. Suspected or known allergy to any components of the study treatments.
17. 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.
18. Intake of drugs or substances potentially involved in clinically significant
inhibition or induction 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. See Appendix A and Appendix B for a complete list of
prohibited substances.
19. Previous exposure to anti Aß vaccines.
20. Exposure to passive immunotherapies for AD (e.g. monoclonal antibodies) within the
previous 180 days to dosing, or BACE inhibitors within the previous 30 days to
dosing..
21. 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.
22. Positive assay for Lyme disease if a screening lumbar puncture is conducted and
includes this measurement.
23. Any condition, which in the opinion of the investigator or the sponsor makes the
patient unsuitable for inclusion.
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