Systemic Amyloidosis
Conditions
Keywords
Amyloidosis, p5+14, SPECT imaging, iodine-124-evuzamitide
Brief summary
This study will investigate 99mTc-p5+14, an amyloid-reactive synthetic peptide, p5+14, radiolabeled with technetium-99m, as a radiotracer for detecting paamyloid deposits in patients with AL or ATTR-associated systemic amyloidosis, notably with cardiac involvement.
Detailed description
The University of Tennessee Graduate School of Medicine (UTGSM) is investigating 99mTc-p5+14, an amyloid-reactive synthetic peptide, p5+14, radiolabeled with technetium-99m, as a radiotracer for planar gamma scintigraphy (PGS), single photon emission computed tomography (SPECT) or SPECT with x-ray computed tomography (SPECT/CT) for the diagnosis of systemic amyloidosis, notably with cardiac involvement. Based on nonclinical data and clinical data of 124I-p5+14 from Study AMY1001, peptide p5+14 binds many types of human amyloid and is rapidly cleared from the central compartment. When radiolabeled with 99mTc, p5+14 may enable visualization of amyloid laden tissues and organs by SPECT/CT imaging or PGS. Thus, this study has been designed to evaluate the dosimetry and biodistribution of 99mTc-p5+14 in patients with systemic amyloidosis compared with the biodistribution in healthy volunteers.
Interventions
DRUG99mTc-p5+14 is an amyloid reactive peptide labeled with technetium-99m.
Peptide p5+14 is a pan-amyloid reactive, synthetic 45 L-amino acid polypeptide with a net +12 positive charge that can bind two major components of all extracellular amyloid deposits: (i) hypersulfated heparan sulfate glycosaminoglycans (proteoglycans) and (ii) amyloid fibrils. The polypeptide, labeled with iodine-124, has been shown (study AMY1001) to bind amyloid in all organs including the heart. This study will evaluate a Tc-99m-labeled version of the peptide for gamma imaging.
DRUG99mTc-Pyrophosphate
99mTc-PYP is an FDA-approved, commercially available bone-seeking radiotracer used routinely in nuclear medicine. 99mTC-PYP imaging is used clinically for the diagnosis of cardiac ATTR amyloidosis.
Sponsors
University of Tennessee Graduate School of Medicine
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
PART 1 1\) Understand the study procedures and agree to participate in the study by giving written informed consent.. 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\) 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. 6\) Healthy volunteers must also meet inclusion criteria for Part 3. PART 2 1. Understand the study procedures and agree to participate in the study by giving written informed consent. 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. 6. 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 1. Understand the study procedures and agree to participate in the study by giving written informed consent. 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. 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 4 years of screening, or longer if contemporaneous clinical data indicates the persistent presence of cardiac amyloidosis. 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. Receiving hemodialysis or peritoneal dialysis. 5. Has severe claustrophobia or any medical condition that would prevent completion of the imaging protocol. 6. Has any illness that, in the opinion of the Investigator, might confound the results of the study or pose additional risk to the subject. 7. Has received heparin or heparin analogs (e.g., enoxaparin, dalteparin, fondaparinux) within seven (7) days prior to 99mTc-p5+14 administration. 8. Have previously received any dose of p5+14, in any form. 9. 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. 10. 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. 11. Have a QTc interval, using Bazett's formula (QTcB) of \>530 ms, measured within six months prior to enrollment, or assessed prior to injection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Whole body effective dosimetry measurement | From enrollment to the end of study is 8 days | Whole body effective radiation dose assessed from analysis of organ-specific radioactivity uptake in planar and SPECT images. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Measure cardiac uptake of 99mTc-p5+14 radioactivity from planar and SPECT/CT images in comparison to 99mTc-PYP uptake | From enrollment to the end of study is 8 days | Measurement of 99mTc-p5+14 uptake in the heart of healthy volunteers and patients with systemic AL or ATTR amyloidosis and comparison with contemporaneous 99mTc-PYP cardiac radioactivity. |
| Measure uptake of 99mTc-p5+14 radioactivity in extracardiac tissues from planar and SPECT/CT images | From enrollment to the end of study is 8 days | Measurement of 99mTc-p5+14 radioactivity in abdominothoracic organs of healthy volunteers and patients with systemic AL or ATTR amyloidosis from planar and SPECT/CT images. |
Countries
United States
Contacts
CONTACTEmily B Martin, PhD
PRINCIPAL_INVESTIGATORJonathan S Wall, PhD
University of Tennessee Graduate School of Medicine
Outcome results
None listed