| Eligibility |
Inclusion Criteria:
Inclusion Criteria for All Subjects:
1. Males or females aged 50 to 85 years, inclusive.
2. Female subjects must be documented by medical records or physician's note to be either
surgically sterile (by means of hysterectomy, bilateral oophorectomy, or tubal
ligation) or post-menopausal for at least 1 year (ie, 12 consecutive months with no
menses without an alternative medical cause) or, if they are of childbearing
potential, must commit to using a barrier contraception method or to abstinence for
the duration of the study and must have a negative pregnancy test.
3. Male subjects and their partners of childbearing potential must commit to the use of
two methods of contraception, one of which is a barrier method (ie, condom), or to
abstinence for the study duration.
4. Male subjects must not donate sperm for the study duration.
5. Willing and able to participate in all study procedures.
Additional Inclusion Criteria for Healthy Subjects:
1. Written informed consent must be obtained before any assessment is performed.
2. Medically healthy with no clinically relevant finding on physical examination,
laboratory profiles, VS, or ECG at screening and upon reporting for the [18F]APN-1607
Imaging Visit.
3. No cognitive impairment based on neuropsychological battery and as judged by the
Investigator.
4. No first-degree family history of early-onset AD or other neurodegenerative disease
associated with dementia (prior to age 65).
5. Has a clinical dementia rating (CDR) score of 0.
6. Has an MMSE score = 27.
7. The subject has an appropriate informant to accompany the subject to screening to
provide information for the CDR testing. In the event that the informant cannot
accompany the subject to screening, the interview may be performed via phone, at the
discretion of the site Investigator.
Additional Inclusion Criteria for Subjects with MDAD:
1. Written informed consent must be obtained before any assessment is performed.
2. Must meet all of the clinical criteria for MCI according to NIA-AA criteria, including
lack of functional impairment sufficient to warrant a diagnosis of dementia.
3. Has a CDR score = 0.5.
4. Has an MMSE score between 24 and 30, inclusive.
5. Has a positive amyloid PET scan obtained during screening or in the past 1 year.
6. Medications taken for symptomatic treatment of AD must have been stable for at least
30 days prior to screening and throughout the completion of the neuropsychological
battery.
7. The subject has an appropriate informant to provide information for the CDR and
accompany the subject for any visits, if required for subject or staff comfort or
safety.
Additional Inclusion Criteria for Subjects with AD Dementia:
1. Written informed consent must be obtained before any assessment is performed. If in
the Investigator's opinion the subject lacks capacity to consent, participation is
only possible if the subject has a legally authorized representative (LAR) or
responsible next-of-kin and that individual provides written informed consent in
accordance with local regulations and guidelines and the rules of the applicable
independent ethics committee (IEC)/institutional review board (IRB). When written
informed consent is provided by a LAR or responsible next of kin, the subject's assent
must also be obtained and documented. For subjects judged lacking capacity to consent,
next-of-kin consent in lieu of LAR consent is only allowed where permitted by local
laws and regulations.
2. Has a diagnosis of AD dementia according to NIA-AA criteria, including significant
impairment of activities of daily living.
3. Has a CDR score = 0.5 at screening.
4. Has an MMSE score between 10 and 26, inclusive.
5. Has a positive amyloid PET scan obtained during screening or in the past 1 year.
6. Medications taken for symptomatic treatment of AD must have been stable for 30 days
prior to screening and throughout the completion of the neuropsychological battery.
7. The subject has an appropriate informant to accompany the subject on all visits and
provide information for the CDR.
Exclusion Criteria for All Subjects:
1. Current or prior history (within the last 10 years) of alcohol or drug abuse.
2. Known hypersensitivity to [18F]APN-1607 or its excipients
3. Clinically significant active or unstable medical illness or planned surgical
procedures during the study period. History of cancer (other than non-melanoma skin
cancers or stable, local prostate cancer), unless without evidence of active disease
within the last 3 years and without ongoing medical or surgical therapy.
4. Laboratory tests with clinically significant abnormalities or a history or evidence of
clinically significant unstable medical illness.
5. Has received any investigational drug or device for any purpose within 30 days of
screening (or 5 halflives of the drug, whichever is longer), has received a
non-biologic investigational treatment (ie, small molecule) for AD or other cause of
dementia within the last 3 months (or 5 half-lives of the drug, whichever is longer),
or received a non-vaccine treatment (ie, monoclonal antibody) for the treatment of AD
or other cause of dementia within the last 6 months, or has ever received a vaccine
for the treatment of AD or other cause of dementia.
6. Prior participation in other research protocols or clinical care in the last year in
which the additional radiation exposure expected from participation in this clinical
study will together exceed local guidelines, eg, above an effective dose of 50 mSv in
the US.
7. Pregnant, lactating or breastfeeding.
8. Evidence of clinically significant gastrointestinal, cardiovascular, hepatic, renal,
hematological, neoplastic, endocrine, alternative neurological, immunodeficiency,
pulmonary, or other disorder or disease.
9. Unsuitable veins for repeated venipuncture.
10. MRI exclusion criteria include: Findings that may be responsible for the neurologic
status of the patient such as significant evidence of cerebrovascular disease (more
than two lacunar infarcts, any territorial infarct >1cm3, or deep white matter
abnormality corresponding to an overall Fazekas scale of 3 with at least one confluent
hyperintense lesion on the fluid-attenuated inversion recovery (FLAIR) sequence that
is =20 mm in any dimension), infectious disease, space-occupying lesions, normal
pressure hydrocephalus or any other abnormalities associated with central nervous
system (CNS) disease. For subjects with MDAD or AD dementia, there may be evidence of
atrophy compatible with AD.
11. Implants, such as implanted cardiac pacemakers or defibrillators, insulin pumps,
cochlear implants, metallic ocular foreign body, implanted neural stimulators, CNS
aneurysm clips and other medical implants that have not been certified for MRI, or
history of claustrophobia in MRI unless an acceptable MRI obtained in the 1 year prior
to participation in the study is used.
12. Signs or symptoms suggestive of active Coronavirus disease 2019 (COVID-19) and/or
confirmed diagnosis of COVID-19, or positive COVID-19 polymerase chain reaction (PCR)
test in the previous 2 weeks. These subjects should not be enrolled until 4 weeks
after full recovery and further assessment by the Investigator per institutional
guidelines. A subject with a known history of being exposed to someone who was
diagnosed of COVID-19, during the prior 4 weeks, should not be enrolled unless the
infection is excluded by local practice or institution.
Exclusion Criteria for Healthy Subjects:
1. Meets criteria for a diagnosis of MDAD or dementia or has ever had such a diagnosis.
2. Has ever received treatment with a drug for cognitive impairment or dementia.
Exclusion Criteria for Subjects with MDAD:
1. Meets criteria for a diagnosis of dementia due to AD.
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