Investigating a new imaging agent for systemic amyloidosis

Phase 1 Study to Investigate the Dosimetry and Biodistribution of a Single Intravenous Administration of 99mTc-p5+14 Using SPECT/CT Imaging and Planar Gamma Scintigraphy in Healthy Volunteers and Patients With AL or ATTR Systemic Amyloidosis

This study is testing a new imaging agent to see if it can help find amyloid deposits in patients with systemic amyloidosis, especially those with heart issues.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 35 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Tennessee Graduate School of Medicine (Academic / other)
• Locations: 1 site (Knoxville, Tennessee)
• Trial ID: NCT05951816 on ClinicalTrials.gov

What this trial studies

This study evaluates 99mTc-p5+14, a synthetic peptide radiolabeled with technetium-99m, as a radiotracer for detecting amyloid deposits in patients with AL or ATTR systemic amyloidosis, particularly those with cardiac involvement. The research aims to assess the dosimetry and biodistribution of this radiotracer in patients compared to healthy volunteers. Utilizing advanced imaging techniques such as SPECT and PGS, the study seeks to improve diagnostic capabilities for systemic amyloidosis. The findings could enhance the understanding of amyloid distribution in affected tissues.

Who should consider this trial

Good fit: Ideal candidates for this study include adults over 18 years with a confirmed diagnosis of systemic AL amyloidosis.

Not a fit: Patients without a confirmed diagnosis of systemic amyloidosis or those under 18 years old may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved diagnostic imaging for patients with systemic amyloidosis, facilitating earlier and more accurate detection of the disease.

How similar studies have performed: Previous studies have shown promise with similar imaging approaches, but the specific use of 99mTc-p5+14 is novel.

Eligibility criteria

Inclusion Criteria:

PART 1

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) 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) Have one of the following:

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.

PART 4

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.

Exclusion Criteria:

PARTS 1-4

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.

Where this trial is running

Knoxville, Tennessee

• University of Tennessee Graduate School of Medicine — Knoxville, Tennessee, United States (Recruiting)

Study contacts

• Principal investigator: Jonathan S Wall, PhD — University of Tennessee Graduate School of Medicine
• Study coordinator: Emily B Martin, PhD

Conditions Systemic Amyloidosis; Amyloidosis; p5+14; SPECT imaging; iodine-124-evuzamitide