Proof-of-concept Study of New Imaging Diagnostic in Patients With Suspected Alzheimer's Disease

For healthy volunteers

1. 50-75 years old (inclusive)
2. Women of child-bearing potential must have a negative serum pregnancy test and agree to use highly effective contraception (hormonal or barrier method of birth control; abstinence) prior to study entry for the duration of the study and for 3 months after completion of dosing; men enrolled on this protocol must agree to use adequate contraception prior to study entry, for the duration of the study and for 3 months after completion of dosing; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
3. Signed informed consent prior to any study specific tests or procedures
4. Healthy, based on medical history, physical examination, electrocardiogram (ECG), and laboratory tests

For patients with amyloid plaques in PET:

1. 59-85 years old inclusive
2. Proven amyloid deposits in brain (amyloid PET)
3. Women of child-bearing potential must have a negative serum pregnancy test and agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry for the duration of the study and for 3 months after completion of dosing. Men enrolled on this protocol must agree to use adequate contraception prior to study entry and for 3 months after completion of dosing; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
4. Willing and able to provide written informed consent
5. The ability to provide consent determined and documented by a neurologist or psychiatrist.

Exclusion Criteria:

For healthy volunteers

1. Disturbances in fat metabolism [hyperlipemia, hyperlipoproteinemia or hypercholesterolemia (total cholesterol >260 mg/dL)]
2. History of allergic reactions attributed to any of the components of ADx-001, liposomes, other gadolinium contrast agents, or any other component of the formulation

3. Pathological liver function:

   1. Bilirubin > upper limit of normal, and/or
   2. AST (SGOT), ALT (SGPT) and Alkaline phosphatase > upper limit of normal
4. Calculated creatinine clearance \< 60 mL/min/1.73 m2 (CKD-EPI formula)
5. Heart rate at rest \<50 or >90 bpm
6. Systolic blood pressure \<100 or >140 mmHg
7. Diastolic blood pressure \<50 or >90 mmHg
8. Clinically relevant ECG findings, e.g., PQ >220 ms, QTc >450 ms, QRS >120 ms, branch bundle block, any sign of coronary heart disease
9. Unwillingness or inability to comply with procedures required in this protocol
10. Subjects who are currently receiving any other investigational agent, or who have received an investigational agent within the last 10 half-lives of the investigational agent
11. Having tested positive for COVID-19 within 4 weeks of inclusion
12. Any known disposition for allergic, anaphylactoid, hypersensitivity or idiosyncratic reactions, e.g. any history of clinical signs of hypersensitivity reaction to any agent (including, but not limited to, any allergen, food, drug, chemical, or contrast agent)
13. Use of systemic or topically active medication or herbal remedies, prescription or non-prescription, from screening to the first drug administration. Only use of contraceptives and occasional use of paracetamol, aspirin, or ibuprofen is permissible.
14. Any severe disease within the last 4 weeks prior to the first study drug administration
15. Any malignant tumor and history thereof within last 5 years
16. Any other medical condition which, at the discretion of the investigator, would make study participation unadvisable
17. Any clinically relevant finding at the physical examination
18. Blood donation or plasmapheresis within 4 weeks prior to screening
19. Women of child-bearing potential: pregnancy, positive pregnancy test, or lactation
20. Positive human immunodeficiency virus antibodies (HIV-1/2 Ab), hepatitis B virus surface antigen (HBsAg) or hepatitis C virus antibody (HCV-Ab) tests
21. Regular alcohol consumption equivalent to >20 g alcohol per day
22. Urine screen positive for any drug
23. Positive alcohol breath test
24. Subject is in custody by order of an authority or a court of law
25. Close affiliation with the investigational site; e.g. a close relative of the investigator, dependent person (e.g. employee or student of the investigational site) or employee of the sponsor
26. Criteria which, in the opinion of the investigator, preclude participation for scientific reasons, for reasons of compliance, or for reasons of the subject's safety

For patients with amyloid plaques in PET:

1. Disturbances in fat metabolism [hyperlipemia, hyperlipoproteinemia or hypercholesterolemia (total cholesterol >260 mg/dL)]
2. History of allergic reactions attributed to any of the components of ADx-001, liposomes, other gadolinium contrast agents, or any other component of the formulation
3. Patients with history of cancer treatment in the last 6 months or currently receiving cancer treatment
4. Major surgery within four weeks prior to Screening
5. History or presence of a neurological or psychiatric diagnosis other than AD (not limited to but including for example, stroke, traumatic brain injury, epilepsy, space occupying lesions, multiple sclerosis, Parkinson's disease, vascular dementia, transient ischemic attack, schizophrenia, major depression, brain tumors, etc.) that in the opinion of the investigator may limit compliance with study requirements, or compromise protocol objectives in the opinion of the investigator and/or the sponsor
6. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements or compromise protocol objectives in the opinion of the investigator and/or the sponsor
7. Unwillingness or inability to comply with procedures required in this protocol
8. Patients who are currently receiving any other investigational agent, or who have received an investigational agent within the last 10 half-lives of the investigational agent
9. Inability to undergo MRI
10. Pathological coagulation status (PT-INR/PTT >1.5 times the upper limit of normal)

11. Pathological hematologic status:

    • Granulocyte \< 1500 cells/mm3, and/or
    • Platelet count \< 150,000 (plt/mm3), and/or
    • Hemoglobin \< 10 g/dL

12. Pathological liver function:

    • Bilirubin > upper limit of normal, and/or
    • AST (SGOT), ALT (SGPT) and Alkaline phosphatase > upper limit of normal
13. Calculated creatinine clearance \< 60 mL/min/1.73 m2 (CKD-EPI formula)
14. Cannot tolerate the recommended pretreatment
15. Having tested positive for COVID-19 within 4 weeks of inclusion