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Men, and women of non-childbearing potential, 50-85 years of age inclusively, with a |
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diagnosis of mild to moderate Alzheimer's disease according to the 2011 NIA-AA |
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criteria and at least a 6 month decline in cognitive function documented in the |
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medical record. |
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i) Non-childbearing potential for women is defined as postmenopausal (last natural |
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menses greater than 24 months) or undergone a documented bilateral tubal ligation or |
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hysterectomy. If last natural menses less than 24 months, a serum FSH value confirming |
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post-menopausal status can be employed. |
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ii) Male participants who are sexually active with a woman of child-bearing potential |
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must agree to use condoms during the trial and for 3 months after last dose unless the |
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woman is using an acceptable means of birth control. Acceptable forms of birth control |
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include abstinence, birth control pills, or any double combination of: intrauterine |
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device (IUD), male or female condom, diaphragm, sponge, and cervical cap. |
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Diagnostic confirmation by amyloid PET with florbetaben or another approved amyloid |
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PET ligand. Previous amyloid imaging study with a positive result will be accepted. If |
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none is available, then amyloid PET will be conducted during screening. Diagnostic |
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confirmation by a CSF sample collected at the screening visit lumbar puncture in place |
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of amyloid PET will also be acceptable |
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Neuroimaging (MRI) obtained during screening consistent with the clinical diagnosis of |
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Alzheimer's disease and without findings of significant exclusionary abnormalities |
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(see exclusion criteria, number 4). An historical MRI, up to 1 year prior to |
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creening, may be used as long as there is no history of intervening neurologic |
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disease or clinical events (such as a stroke, head trauma etc.) and the subject is |
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without clinical symptoms or signs suggestive of such intervening events.). |
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MMSE 18-26 inclusive. |
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No active depression and a GDS \u22646 (see exclusion criteria number 6). |
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Modified Hachinski \u2264 4. |
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Formal education of eight or more years. |
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Subjects must have a caregiver/ study partner who in the opinion of the site principal |
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investigator, has contact with the study subject for a sufficient number of hours per |
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week to provide informative responses on the protocol assessments, oversee the |
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administration of study drug, and is willing and able to participate in all clinic |
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visits and some study assessments. The caregiver/ study partner must provide written |
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informed consent to participate in the study. |
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Subjects living at home or in the community (assisted living acceptable). |
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Ability to swallow CT1812 capsules. |
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Stable pharmacological treatment of any other chronic conditions for at least 30 days |
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prior to screening. |
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Subjects must be capable of providing written informed consent to the study procedures |
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and for use of protected health information [Health Insurance Portability and |
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Accountability Act (HIPAA), if applicable]. Written informed consent also shall be |
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obtained from the responsible caregiver. All consent processes must be undertaken in |
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the presence of a witness and prior to any study procedures. |
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Must consent to apolipoprotein E (ApoE) genotyping for data analysis stratification. |
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Subjects shall be generally healthy with mobility (ambulatory or ambulatory-aided, |
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i.e., walker or cane), vision and hearing (hearing aid permissible) sufficient for |
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compliance with testing procedures. |
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Must be able to complete all screening evaluations. |
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Participants will be excluded from the study if any of the following conditions apply:
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Hospitalization (except for planned procedures) or change of chronic concomitant
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medication within one month prior to screening.
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Subjects living in a continuous care nursing facility.
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Contraindication to the MRI examination for any reason.
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Screening MRI (or historical MRI, if applicable) of the brain indicative of
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ignificant abnormality, including, but not limited to, prior hemorrhage or infarct >1
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cm3, >3 lacunar infarcts, cerebral contusion, encephalomalacia, aneurysm, vascular
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malformation, subdural hematoma, hydrocephalus, space-occupying lesion (e.g. abscess
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or brain tumor such as meningioma). If a small incidental meningioma is observed, the
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medical monitor may be contacted to discuss eligibility..
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Clinical or laboratory findings consistent with:
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Other primary degenerative dementia, (dementia with Lewy bodies, fronto-temporal
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dementia, Huntington's disease, Creutzfeldt-Jakob Disease, Down syndrome, etc.).
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Other neurodegenerative condition (Parkinson's disease, amyotrophic lateral
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clerosis, etc.).
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Seizure disorder.
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Other infectious, metabolic or systemic diseases affecting the central nervous
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ystem (syphilis, present hypothyroidism, present vitamin B12 or folate
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deficiency, other laboratory values etc.).
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A current DSM-V diagnosis of active major depression, schizophrenia or bipolar
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disorder. Subjects with depressive symptoms successfully managed by a stable dose of
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an antidepressant are allowed entry.
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Clinically significant, advanced or unstable disease that may interfere with outcome
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evaluations, such as:
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Chronic liver disease, liver function test abnormalities or other signs of
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hepatic insufficiency (ALT, AST, alkaline phosphatase > 1.5 ULN, lactate
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dehydrogenase (LDH) > 1.5 x ULN).
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Respiratory insufficiency.
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Renal insufficiency eGFR < 50 mL/min based on the CKD\u2010EPI formula,
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https://www.mdcalc.com/ckd-epi-equations-glomerular-filtration-rate-gfr
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Heart disease (myocardial infarction, unstable angina, heart failure,
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cardiomyopathy within six months before screening).
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Bradycardia (<50/min.) or tachycardia (>100/min.).
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Poorly managed hypertension (systolic >160 mm Hg and/or diastolic >95 mm Hg) or
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hypotension (systolic <90 mm Hg and/or diastolic <60 mm Hg).
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Uncontrolled diabetes defined by HbA1c >7.5.
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History of cancer within 3 years of screening with the exception of fully excised
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non-melanoma skin cancers or non-metastatic prostate cancer that has been stable for
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at least 6 months.
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Seropositive for human immunodeficiency virus (HIV).
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History of acute/chronic hepatitis B or C and/or carriers of hepatitis B (seropositive
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for hepatitis B surface antigen [HbsAg] or anti-hepatitis C [HCV] antibody).
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Clinically significant abnormalities in screening laboratory tests, including:
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a. Hematocrit less than 35% for males and less than 32% for females, absolute
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neutrophil cell count of 1500/uL (with the exception of a documented history of a
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chronic benign neutropenia), or platelet cell count of < 120,000/uL; INR >1.4 or other
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coagulopathy, confirmed by repeat assessment of: i. Hematocrit ii. Neutrophil count
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iii. Platelet count
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Disability that may prevent the subject from completing all study requirements (e.g.
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blindness, deafness, severe language difficulty, etc.).
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Within 4 weeks of screening visit or during the course of the study, concurrent
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treatment with antipsychotic agents, antiepileptics, centrally active
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anti-hypertensive drugs (e.g., clonidine, l-methyl dopa, guanidine, guanfacine, etc.),
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edatives, opioids, mood stabilizers (e.g., valproate, lithium); or benzodiazepines,
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with the following exception:
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a. Low dose lorazepam may be used for sedation prior to MRI scan for those subjects
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requiring sedation. At the discretion of the investigator, 0.5 to 1 mg may be given
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orally prior to scan with a single repeat dose given if the first dose is ineffective.
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No more than a total of 2 mg lorazepam may be used for the MRI scan.
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Any disorder that could interfere with the absorption, distribution, metabolism or
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excretion of drugs (e.g. small bowel disease, Crohn's disease, celiac disease, or
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liver disease).
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Nootropic drugs except stable AD meds (acetylcholinesterase inhibitors and memantine.
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Suspected or known drug or alcohol abuse, i.e. more than approximately 60 g alcohol
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(approximately 1 liter of beer or 0.5 liter of wine) per day indicated by elevated MCV
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ignificantly above normal value at screening.
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Suspected or known allergy to any components of the study treatments.
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Enrollment in another investigational study or intake of investigational drug within
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the previous 30 days or five half lives of the investigational drug, whichever is
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longer.
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Intake of drugs or substances potentially involved in clinically significant induction
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or inhibition of CYP3A4 or P-gp mediated drug interactions with CT1812, within 4 weeks
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or five half-lives of the interacting drug prior to administration of CT1812 and
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throughout the course of the study. Grapefruit juice should be avoided in the two
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weeks prior to dosing and throughout the course of the study. See Appendix A for a
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complete list of prohibited substances.
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Exposure to immunomodulators, anti A\u03b2 vaccines, passive immunotherapies for AD (e.g.
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monoclonal antibodies) within the past 180 days and/or exposure to BACE inhibitors
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within the past 30 days.
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Anticipated use of nonsteroidal anti-inflammatory drugs (NSAIDs) on more than 14 days
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during the period from Baseline to Day 182.
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Contraindication to undergoing an LP including, but not limited to: inability to
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tolerate an appropriately flexed position for the time necessary to perform an LP;
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international normalized ratio (INR) > 1.4 or other coagulopathy; platelet count of <
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120,000/\u03bcL; infection at the desired lumbar puncture site; taking anti-coagulant
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medication within 90 days of screening (Note: low dose aspirin is permitted);
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degenerative arthritis of the lumbar spine; suspected non-communicating hydrocephalus
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or intracranial mass; prior history of spinal mass or trauma.
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Any condition, which in the opinion of the investigator or the sponsor makes the
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ubject unsuitable for inclusion.
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