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

Inclusion Criteria

PART 1

• Understand the study procedures and agree to participate in the study by giving written informed consent..

• 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.

• 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.

• Be a healthy volunteer (n=3) or have a confirmed diagnosis of systemic amyloidosis (n=2) 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.

• Healthy volunteers must also meet inclusion criteria for Part 3. PART 2

• Understand the study procedures and agree to participate in the study by giving written informed consent.
• Be male or female >18 years of age.
• 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.
• 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.
• Have one of the following:

• 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.
• 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.
• Have a diagnosis of cardiac amyloidosis within 4 years of screening, or longer if contemporaneous clinical data indicates the persistent presence of cardiac amyloidosis.

PART 3

• Understand the study procedures and agree to participate in the study by giving written informed consent.
• Be male or female >18 years of age.
• 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.
• 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.
• 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.
• 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.

PART 4

• Understand the study procedures and agree to participate in the study by giving written informed consent.
• Be male or female >18 years of age.
• 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.
• 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.
• 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.
• Has a diagnosis of cardiac amyloidosis within 4 years of screening, or longer if contemporaneous clinical data indicates the persistent presence of cardiac amyloidosis.
• Has a negative 99mTc-PYP imaging study.

Exclusion Criteria

PARTS 1-4

• 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.
• Is pregnant or breast-feeding.
• Is mentally or legally incapacitated, has significant emotional problems at the time of the study, or has a history of psychosis.
• Receiving hemodialysis or peritoneal dialysis.
• Has severe claustrophobia or any medical condition that would prevent completion of the imaging protocol.
• Has any illness that, in the opinion of the Investigator, might confound the results of the study or pose additional risk to the subject.
• Has received heparin or heparin analogs (e.g., enoxaparin, dalteparin, fondaparinux) within seven (7) days prior to 99mTc-p5+14 administration.
• Have previously received any dose of p5+14, in any form.
• 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.
• 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.
• Have a QTc interval, using Bazett's formula (QTcB) of >530 ms, measured within six months prior to enrollment, or assessed prior to injection.