Inclusion Criteria:
1. Has the ability to understand and sign the written ICF and local medical privacy
authorization forms, which must be obtained prior to the conduct of any study related
procedures.
2. Female subjects of non-childbearing potential must be either surgically sterile
(hysterectomy, bilateral tubal ligation, salpingectomy, and/or bilateral oophorectomy
at least 26 weeks before the Screening Visit) or postmenopausal, defined as
spontaneous amenorrhea for at least 2 years, with follicle-stimulating hormone (FSH)
in the postmenopausal range at screening, based on the local laboratory's defined
ranges.
3. Female subjects of childbearing potential (i.e., ovulating, premenopausal, and not
surgically sterile) and all male subjects must agree to practice abstinence from
sexual intercourse or use a medically accepted contraceptive regimen (including
hormonal contraceptives) during their participation in the study and for 90 days
(males) or 6 months (females) after Day 1. Medically accepted contraceptive methods
are defined as those with 90% or greater efficacy and are as follows:
1. Male subjects: condoms or surgical sterilization of subject at least 26 weeks
before the Screening Visit (i.e., vasectomy).
2. Female subjects:
1. Surgical sterilization at least 26 weeks before the Screening Visit
(includes hysterectomy or bilateral tubal ligation, bilateral oophorectomy,
or salpingectomy);
2. Intrauterine device or diaphragm with spermicide for at least 12 weeks
before the Screening Visit; or. 3. Hormonal contraception (oral, implant, injection, ring, or patch) for at
least 12 weeks before the Screening Visit.
4. If male, subjects must agree to abstain from sperm donation through 90 days after the
Day 1 Visit.
5. Female subjects may not be pregnant, lactating, or breastfeeding.
6. Female subjects of childbearing potential must have negative result for pregnancy test
at Screening and Check-in.
7. Subjects must have an estimated glomerular filtration rate (eGFR) of >45 mL/min/1.73m2
at Screening.
8. C-reactive protein level ≤10 mg/dL.
9. Subjects must be willing and able to abide by all study requirements and restrictions.
Inclusion Criteria Specific to ALS Subjects:
10. Adult (Age 18 to 80, inclusive) at the Screening Visit. 11. Sporadic or familial ALS diagnosed as possible, laboratory-supported probable,
probable, or definite as defined by the modified El Escorial criteria.
12. Forced vital capacity (FVC) of ≥50%; or if in the opinion of the investigator can lay
flat for up to 90 minutes. If FVC has been performed within the past 6 months, this
data may be used at the discretion of the investigator.
13. For ALS subjects, medication changes within 30 days prior to the Screening Visit
should be discussed with the Medical Monitor.
Inclusion Criteria Specific to AD Subjects. 14. Adult (Age 40 to 80, inclusive) at the Screening Visit. 15. Clinical diagnosis of early stage dementia, Alzheimer type, plus positive Aβ and tau
PET imaging, cerebrospinal fluid (CSF) and/or plasma biomarkers consistent with 2018
NIA-AA criteria. 16. MMSE score >20 at Screening. 17. AD medication changes within 30 days prior to the Screening Visit should be discussed
with the Medical Monitor.
Inclusion Criteria Specific to MS Subjects:
18. Adult (Age 18 to 70, inclusive) at the Screening Visit. 19. MS medication changes within 30 days prior to the Screening Visit should be discussed
with the Medical Monitor.
Inclusion criteria specific to subjects with RRMS:
20. Diagnosis of RRMS based on 2017 McDonald criteria. 21. If not newly diagnosed, subjects should have at least 1 documented relapse in the last
24 months.
22. "Active disease" subjects should have at least 1 Gadolinium-enhancing (Gd+)
T1-weighted brain or spinal cord lesion at Screening MRI.
23. "Disease in remission" subjects should have no Gd+ T1-weighted brain or spinal cord
lesions at Screening MRI and stable clinical symptoms for at least 3 months prior to
Day 1.
24. EDSS score between 2.0 and 5.5 inclusive at Screening. Inclusion criteria specific to subjects with progressive MS:
25. Diagnosis of PPMS or SPMS based on 2017 McDonald criteria. 26. EDSS score between 3.0 and 6.5 inclusive at Screening. 27. No evidence of relapse in the prior 6 months. 28. Neurological exam and symptom stability for ≥30 days prior to Day 1. 29. Documented evidence of disability progression in the past 24 months not temporally
related to a relapse. Inclusion Criteria Specific to PD Subjects:
30. Adult (Age 55 to 80, inclusive) at the Screening Visit. 31. Diagnosis of definite, idiopathic Parkinson's disease according to UK Parkinson's
Society Brain Bank diagnostic criteria. 32. PD medication changes within 30 days prior to the Screening Visit should be discussed
with the Medical Monitor.
Overall Exclusion Criteria
- - For All Subjects:
Subjects meeting any of the following criteria will be excluded from this study:
1.
Body weight >120 kg. 2. Evidence of clinically significant or past medical history of hematologic, renal,
endocrine, pulmonary, cardiac, gastrointestinal, hepatic, psychiatric, neurologic,
immunologic, allergic disease (including multiple or clinically significant drug
allergies) or any other condition that, in the opinion of the Investigator, might
significantly interfere with the absorption, distribution, metabolism or excretion of
study drug or place the subject at an unacceptable risk as a participant in this study. 3. History of recurrent kidney or liver malignancy. 4. Pacemaker or defibrillator or any non-removable metallic foreign objects in the body
not compatible with MRI. 5. Inability to lie in a PET/CT or PET/MRI scanner for up to 90 minutes at a time. 6. Laboratory results (serum chemistry, hematology, coagulation and urinalysis) outside
the normal range at Screening and Check-In and considered clinically significant in
the opinion of the Investigator. Any elevation of aspartate transaminase (AST) and
alanine transaminase (ALT) more than 3 times above the upper limit of normal at
screening and/or check-in is exclusionary. One retest of an exclusionary laboratory
result is allowed at the discretion of the Investigator and with approval from the
Medical Monitor.
7. Resolved acute illness considered clinically significant by the Investigator within 10
days prior to Screening. 8. History of alcoholism or drug abuse within 2 years prior to Screening. No cannabinoid
drug use for at least 10 days prior to Day 1.
9. Positive urine drug test, marijuana test or cotinine test at Screening or Check-In. 10. Any immunizations within the 28 days prior to screening. 11. Received any other investigational medicinal product within 30 days or 5 half-lives
(whichever is longer) prior to Day 1. 12. Corticosteroid treatment (e.g., prednisone, solumedrol) within 30 days of Baseline. 13. Treatment with any of the following classes of nonsteroidal anti-inflammatory drugs
(NSAIDS): carboxylic acids, enolic acids, cyclooxygenase (COX) II inhibitors within 14
days of Day 1. 14. Lost or donated >450 mL of whole blood or blood products within 30 days prior to
Screening. 15. MRI
exclusion criteria:
findings that may interfere with interpretation of the PET
imaging, including but not limited to significant cortical/subcortical cerebrovascular
disease, infectious disease, space-occupying lesions, hydrocephalus or other
abnormalities associated with CNS disease not related to ALS, AD, MS or PD. 16. CT exclusion criteria include any medical device or metallic implant that may
interfere with image acquisition or affect image reconstruction (e.g., CT attenuation
correction).
17. Investigator has reason to believe that the subject may be unable to fulfill the
protocol visit schedule or requirements. 18. Has any finding that, in the view of the Investigator and Medical Monitor, would
compromise the subject's safety in the trial. Exclusion Criteria Specific to MS Subjects:
19. Clinical signs or laboratory findings suggestive of neuromyelitis optica (NMO)
spectrum disorders or myelin oligodendrocyte glycoprotein (MOG)-associated
encephalomyelitis (i.e., presence of anti-NMO [aquaporin-4] antibodies or anti-MOG
antibodies)
20. Diagnosis of progressive multifocal leukoencephalopathy (PML)
Exclusion Criteria Specific to PD Subjects:
21. Secondary, atypical, or genetic parkinsonism. Exclusion Criteria Specific to HV Subjects:
22. Clinically relevant finding on physical examination at Screening. 23. Family history of neurological disease that may confound interpretation of imaging
results. 24. History of any central nervous system disorder or brain trauma that could cause
imaging abnormalities in the opinion of the Principal Investigator and Medical Monitor
