A Phase 1 Study of 99mTc-p5+14 in Healthy Volunteers and Patients With AL or ATTR Systemic Amyloidosis

Eligibility Criteria

• 1. Understand the study procedures and agree to participate in the study by giving written informed consent as described in Section 10.1 - Appendix 1.
• 2. Be male or female \>18 years of age.
• 3. Women of child-bearing potential (WOCBP) (those who have not been surgically sterilized, are not postmenopausal \[i.e., last menstrual period \>2 years ago without pharmaceutical intervention\], and women who are fertile) must have a negative pregnancy test prior within 24 h prior to infusion.
• 4. WOCBP who are not exclusively in same-sex relationships and male participants with female sexual partners who are WOCBP must agree to use adequate contraceptive methods, defined as use of a condom by the male partner combined with use of a highly effective method of contraception by the female partner, for at least 2.5 days after injection of 99mTc-p5+14.
• 5. Have a confirmed diagnosis of systemic AL amyloidosis based on either a histologic confirmation with a biopsy containing deposits of apple-green birefringent, Congophilic material with aberrant organ-specific biomarkers indicating amyloid involvement, physical examination, or imaging study.
• 6. Have a diagnosis of cardiac amyloidosis within 2 years of screening. PART 2
• 1. a confirmed diagnosis of systemic AL amyloidosis, based on either a histologic confirmation of a cardiac or extracardiac biopsy containing deposits of apple-green birefringent, Congophilic material AND imaging parameters (ECHO or CMR) indicative of cardiac involvement.
• 2. a confirmed diagnosis of systemic ATTR amyloidosis, based on either a histologic confirmation of a cardiac biopsy containing deposits of apple-green birefringent, Congophilic material or extracardiac biopsy and imaging parameters (ECHO or CMR or 99mTc-PYP) indicative of cardiac involvement, with no evidence of abnormal serum free light chains.
• 3. Have a diagnosis of cardiac amyloidosis within 2 years of screening. PART 3
• 1. Understand the study procedures and agree to participate in the study by giving written informed consent as described in Section 10.1 - Appendix 1.
• 2. Be male or female \>18 years of age.
• 3. WOCBP (those who have not been surgically sterilized, are not postmenopausal \[i.e., last menstrual period \> 2 years ago without pharmaceutical intervention\], and women who are fertile) must have a negative pregnancy test prior within 24 h prior to infusion.
• 4. WOCBP who are not exclusively in same-sex relationships and male participants with female sexual partners who are WOCBP must agree to use adequate contraceptive methods, defined as use of a condom by the male partner combined with use of a highly effective method of contraception by the female partner, for at least 2.5 days after injection of 99mTc-p5+14.
• 5. Be in good general health, as determined by no clinically significant findings (including Type 2 diabetes mellitus) in the opinion of the Investigator from review of the medical history.
• 6. Does not have a diagnosis of amyloidosis nor has a first- or second-degree relative (parent, sibling, child, aunt, uncle, niece, nephew) with confirmed or suspected familial amyloidosis.
• 1. Understand the study procedures and agree to participate in the study by giving written informed consent as described in Section 10.1 - Appendix 1.
• 2. Be male or female \>18 years of age.
• 3. Women of child-bearing potential (those who have not been surgically sterilized, are not postmenopausal \[i.e., last menstrual period \>2 years ago without pharmaceutical intervention\], and women who are fertile) must have a negative pregnancy test prior within 24 h prior to infusion.
• 4. WOCBP who are not exclusively in same-sex relationships and male participants with female sexual partners who are WOCBP must agree to use adequate contraceptive methods, defined as use of a condom by the male partner combined with use of a highly effective method of contraception by the female partner, for at least 2.5 days after injection of 99mTc-p5+14..
• 5. Has a confirmed diagnosis of systemic ATTR amyloidosis, based on either a histologic confirmation of a cardiac biopsy containing deposits of apple-green birefringent, Congophilic material or extracardiac biopsy and imaging parameters (ECHO or CMR), or abnormal serum biomarkers indicative of cardiac involvement, with no evidence of abnormal serum free light chains.
• 6. Has a diagnosis of cardiac amyloidosis within 2 years of screening.
• 7. Has a negative 99mTc-PYP imaging study.
• 1. Due to annual dosimetry limitations, patients who have participated in another nuclear medicine amyloid imaging clinical trial protocol and received tracer injection in the last 6 months.
• 2. Is pregnant or breast-feeding.
• 3. Is mentally or legally incapacitated, has significant emotional problems at the time of the study, or has a history of psychosis.
• 4. Has a known allergy to potassium iodide.
• 5. Receiving hemodialysis or peritoneal dialysis.
• 6. Has severe claustrophobia or any medical condition that would prevent completion of the imaging protocol.
• 7. Has any illness that, in the opinion of the Investigator, might confound the results of the study or pose additional risk to the subject.
• 8. Has received heparin or heparin analogs (e.g., enoxaparin, dalteparin, fondaparinux) within seven (7) days prior to 99mTc-p5+14 administration.
• 9. Have previously received any dose of p5+14, in any form.
• 10. Have a QTc interval, using Bazett's formula (QTcB) of \>480 ms, measured within six months prior to enrollment, or assessed prior to injection.
• 11. Have a serum AST \>2x the upper limit of normal or 80 IU/L AND total bilirubin \> 1.5x the upper limit of normal or 1.8 mg/dL within the previous six months of enrollment.
• 12. Have a serum ALT \>2x the upper limit of normal or 64 IU/L AND total bilirubin \> 1.5x the upper limit of normal or 1.8 mg/dL within the previous six months of enrollment.