Efficacy and Safety of the PET Imaging Agent [18F]NAV4694 in Subjects With Probable Alzheimer's Disease

Inclusion Criteria:

All participants:

- is able to provide informed consent or assent, and exhibits adequate visual,
auditory, and communication capabilities to enable compliance with study procedures

- should be able to perform the psychometric testing

- has a modified Hachinski score ((Hachinski, et al., 2012; Rosen, et al., 1980) ≤ 4 at
screening

- possesses a general health that permits adequate compliance with all study procedures
as ascertained by a detailed review of the medical history, surgical history,
laboratory and physical examination findings, which must be performed within 56 days
prior to administration of [18F]NAV4694

- informed consent has been signed and dated by the subject and/or the subject's
legally authorized representative (LAR; for probable AD subjects)

Healthy Volunteers Only

- is male or female and is between the age of 18 and 40 years (for younger HVs) or 55
to 85 years of age (for older HVs)

- if female does not have childbearing potential: must be confirmed by either:
post-menopausal status; or history of surgical sterilization or of hysterectomy

- if female has childbearing potential: must demonstrate a negative serum beta-HCG
level at screening and a negative urine pregnancy test on the day of injection (prior
to injection) consistent with a non-gravid state and agree to use two acceptable
forms of birth control

- has no evidence of cognitive impairment as indicated by a clinical dementia rating
(CDR) (Morris, 1993) score of 0 (zero) and a score of ≥ 28 in the Mini-Mental State
Examination (MMSE) (Folstein, et al., 1975)

- has MRI brain scan that has been judged as "normal (age-appropriate)" supporting the
lack of cerebrovascular disease (e.g., a white matter lesion score of 0, 1, or 2 and
a basal ganglia score of 0 to 1 on the ARWMC scale)

Probable Alzheimer's Disease Subjects Only

- is male or female and is ≥ 55 of age, whereby females must be without childbearing
potential (confirmed by either:post-menopausal status; or history of surgical
sterilization or of hysterectomy)

- presents with positive assessment for dementia of Alzheimer's type in accordance with
the DSM-IV-TR and probable AD according to the NINCDS-ADRDA criteria and fulfills
none of the exclusion criteria of either

- does not fulfill the International Consensus Criteria (ICC) for probable diffuse Lewy
body disease (DLBD), the NINDS-AIREN for probable vascular dementia, or the Neary
criteria for frontotemporal dementia (FTD) [Neary et al. 1998]

- has a MMSE score between 16 and 23

- has a CDR (Morris, 1993) score of 1 to 2

- has a Cornell Scale for Depression in Dementia (CSDD; (Alexopoulos, et al., 1988))
score less than or equal to 18 (definite major depression)

- MRI brain scan findings that do not reveal changes indicative of stroke and/or
generalized cerebrovascular disease changes (limited to: a white matter lesion score
of 0, 1, or 2 and a basal ganglia score of 0 or 1 on the ARWMC scale)

- has a caregiver who is willing and able to attend study visits and perform the
psychometric tests requiring the presence of a caregiver

Exclusion Criteria:

- has any contraindication to MRI examination, e.g., metal implants or phobia

- is not able to lie down flat in the MRI and PET scanners

- is scheduled for surgery and/or another invasive procedure within the time period of
up to 10 days after [18F]NAV4694 application

- is medically unstable and whose clinical course during the observation period is
unpredictable, e.g., subjects within 14 days of myocardial infarction or stroke,
unstable subjects with previous surgery (within 7 days), subjects with advanced heart
insufficiency (NYHA stage IV), or with acute renal failure

- has a history of exposure to any radiation > 30 mSv in the last year (e.g.,
occupational, diagnostic imaging, or radiation therapy)

- is receiving drug therapy or other treatment that is known to lead to greatly
fluctuating values of the hematological or chemical laboratory parameters or to
severe side effects (e.g., chemotherapy)

- has received anti-amyloid immunotherapy

- has been previously enrolled in this study and received [18F]NAV4694 or participated
in a clinical study involving an investigational pharmaceutical product within 30
days prior to screening, and/or any radiopharmaceutical within 10 radioactive
half-lives prior to [18F]NAV4694 administration

- has a brain tumor or other intracranial lesion, a disturbance of cerebrospinal fluid
(CSF) circulation (e.g., normal pressure hydrocephalus) and/or a history of serious
head trauma or brain surgery

- has a history, physical, laboratory, or imaging findings indicative of a significant
neurological or psychiatric illness (other than AD for the subjects with probable AD)

- has another untreated disease that can cause disturbance of brain function (e.g.
vitamin B12 or folic acid deficiency, disturbed thyroid function, anemia)

- has a history of alcohol abuse or drug dependency in the 3 years prior to study entry
or is an alcoholic or drug addict as determined by the investigator