| Eligibility |
Inclusion Criteria:
1. Male or female aged 55 to 80 years old (inclusive)
2. Diagnosis of probable AD dementia based on National Institute on Aging and Alzheimer's
Association (NIA/AA) AD Dementia diagnostic criteria
3. Mild AD as assessed by Mini Mental State Examination (MMSE) score between 18 to 26 at
Screening Visit (inclusive)
4. Tau positive as evaluated by Tau PET using 18F-PI-2620 and assessment of tracer uptake
in the medial temporal lobe and any cortical regions associated with Alzheimer's
disease.
5. Geriatric Depression Scale score of = 6 (on the staff administered short form)
6. Magnetic resonance imaging (MRI) or computerized tomography (CT) scan performed within
the past 2 years that has confirmed no findings inconsistent with a diagnosis of AD
7. Subjects or his/her caregiver and/or legally authorized representative must have
signed and dated an Institutional Review Board (IRB)/Independent Ethics Committee
(IEC) approved written Informed Consent Form (ICF)
8. Subjects must be willing and able to comply with scheduled visits, treatment schedule,
laboratory tests, and other requirements of the study
9. Must have one caregiver who, in the investigator's judgment, has frequent and
sufficient contact with the subject (at least 10 hours/week) and is able to provide
accurate information about the subject's cognitive and functional abilities; the
caregiver must agree to, accompany the subject to clinic visits and/or be available by
phone at designated times to provide information to the investigator and study staff
about the subject, attend in person clinic visits that require partner input for scale
completion, and must agree to monitor the subject's administration of any prescribed
medications
10. Female must either be post menopausal (no menstrual period for >1 year), or surgically
sterilized (by hysterectomy, bilateral oophorectomy, or bilateral tubal ligation).
11. Males who are sexually active and whose partners are females of childbearing potential
must agree to use condoms from screening through 90 days after administration of the
last dose of IMP; their partners must be willing to use a medically acceptable method
of contraception (a barrier method, intrauterine device, or hormonal contraception)
from screening through 90 days after administration of the last dose of IMP
12. Must consent to Apolipoprotein E (ApoE) genotyping; the subject's ApoE status may be
disclosed to him/her at the investigator's discretion -
Exclusion Criteria:
1. Meets National Institute of Neurological Disorders and Stroke/Association
Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS/AIREN)
criteria for vascular dementia
2. Has current serious or unstable illnesses including cardiovascular, hepatic, renal,
gastroenterological, respiratory, endocrinologic, neurologic (other than AD),
psychiatric, immunologic, or hematologic disease and other conditions that, in the
investigator's opinion, could interfere with the analyses of safety and pharmacologic
effect in this study; or has a life expectancy of < 2 years
3. Has had a history within the last 5 years of a serious infectious disease affecting
the brain or head trauma resulting in protracted loss of consciousness
4. Has a history within the last 5 years of a primary or recurrent malignant disease with
the exception of resected cutaneous squamous cell carcinoma in situ, basal cell
carcinoma, cervical carcinoma in situ, or in situ prostate cancer with a normal
prostate specific antigen post treatment
5. Has a known history of human immunodeficiency virus (HIV), clinically significant
multiple or severe drug allergies, or severe post treatment hypersensitivity reactions
6. Has a "yes" answer to Columbia Suicide Severity Rating Scale (C-SSRS) suicidal
ideation item 4 or 5, or any suicidal behavior assessment within 6 months of
Screening, or has been hospitalized or treated for suicidal behavior in the past 5
years before Screening
7. Has received acetylcholinesterase inhibitor (AChEIs), memantine, and/or other AD
therapy for less than 4 months or has less than 2 months of stable therapy on these
treatments
8. Has not been stable on medications that affect the Central nervous system (CNS), for
at least 4 weeks (including antidepressants, hypnotics, antipsychotics, etc.) except
occasional use of benzodiazepine (definition of occasional use - not more than twice
in a week or three times in a month during the past 3 months).
9. Has a history of chronic alcohol or drug abuse/dependence within the past 5 years
10. Any medical or neurological/neurodegenerative condition (other than AD) that, in the
opinion of the investigator, might be a contributing cause to the subject's cognitive
impairment (e.g., current history of substance abuse, uncontrolled vitamin B12
deficiency or abnormal thyroid function, stroke or other cerebrovascular condition,
Parkinson's disease, Lewy body dementia, or frontotemporal dementia)
11. Transient ischemic attack or stroke or any unexplained loss of consciousness within 1
year prior to Screening Visit
12. History of bleeding disorder or predisposing conditions, blood clotting, or clinically
significant abnormal results on coagulation profile at Screening, as determined by the
investigator
13. History of unstable angina, myocardial infarction, chronic heart failure (New York
Heart Association Class III or IV), or clinically significant conduction abnormalities
(e.g., unstable atrial fibrillation) within 1 year prior to Screening Visit
14. Clinically significant 12 lead Electrocardiogram (ECG) abnormalities, as determined by
the investigator
15. Indication of impaired liver function as shown by an abnormal liver function profile
at Screening (e.g., repeated values of Aspartate aminotransferase (AST) and Alanine
aminotransferase (ALT) = 2 × the upper limit of normal [ULN]) and/or indication of
impaired renal function at Screening (e.g., repeated values of creatinine and blood
urea nitrogen [BUN] = 1.5 × Upper limit of normal (ULN) or estimated glomerular
filtration rate < 45 mL/minute/1.73 m2 and corroborating medical history and physical
examination)
16. Contraindications to having a brain Magnetic resonance imaging (MRI) (e.g., MRI
incompatible pacemaker; MRI incompatible aneurysm clips, artificial heart valves, or
other metal foreign body; claustrophobia that cannot be medically managed); if the MRI
compatibility of implanted devices is unknown, the subject must be excluded from the
study
17. Contraindication to having a PET brain scan (e.g., inability to lie flat or still for
the duration of the scan) or intolerance to previous PET scans (i.e., previous
hypersensitivity reactions to any PET ligand or imaging agent, failure to participate
in and comply with previous PET scans)
18. Contraindication to having an FDG PET scan, including uncontrollable glucose levels,
inability to fast for the prescribed number of hours prior to the FDG PET scan,
inability to withhold all insulin and oral diabetic medication after midnight prior to
the PET scan
19. Inability to refrain from using sleep medication for the 24 hours prior to each FDG
PET scan or to refrain from use of antipsychotics, sedatives, or other strong acting
neuropsychiatric medication on the day of each PET scan prior to the scan
20. Current or recent participation (within 12 months before screening) in any procedures
involving radioactive agents such that radiation exposure of the, in the judgement of
the investigator (upon review of medical history), subject in any given year would
exceed the whole-body limits of annual and total dose commitment of 5 rems set forth
in the US Code of Federal Regulations (CFR) Title 21 section 361.1.
21. Any contraindications to lumbar puncture (LP), e.g., increased bleeding risk (platelet
count <100,000/µL, coagulopathies, anticoagulant drugs), lumbar spine deformity that
might interfere with the procedure evidence on MRI contraindicating LP, risk for
cerebral herniation, space occupying lesion with mass effect, abnormal intracranial
pressure due to increased CSF pressure, Arnold Chiari malformation, local infections
at the puncture site and patient fear of LP; abnormalities in the screening CSF
profile that are considered by the Investigator to be clinically significant are
exclusionary
22. Any major surgery within 12 weeks of Screening Visit or during the Screening Period
23. Has active ocular condition that in the opinion of the investigator may alter visual
acuity during the course of the study.
24. Use of any drugs that are strong inhibitors of Cytochrome (CYP)450 (2D6 or 2C19)
within 7 days or 5 half lives of the inhibitor (whichever is longer), prior to
administration of the first dose of Investigational medicinal product (IMP) and/or
plan to use throughout the study
25. Participation within the 12 months prior to Screening Visit in a study of any agent(s)
with a purported disease modifying effect in AD (e.g., anti beta amyloid, ß secretase
inhibitors, ? secretase inhibitors), unless documentation of receipt of placebo is
available
26. Has taken other investigational drugs or participated in any clinical study within 30
days or 5 half lives (if known) of the investigational drug, whichever is longer,
prior to first dose of IMP in this study or is currently participating in another
clinical study
27. Other unspecified reasons that, in the opinion of the investigator or Samus, and/or
its delegated medical monitor, make the subject unsuitable for the study
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