Systemic Amyloidosis
Conditions
Keywords
systemic amyoidosis, p5+14, AT-01, PET/CT, evuzamitide
Brief summary
The goal of this research study is to determine whether changes in organ-specific uptake of 124I- AT-01 can be measured by PET/CT imaging and further, whether these values correlate with changes in a subject's disease status and thereby enable monitoring of disease response over time in terms of organ-specific amyloid load.
Detailed description
This is a single center, open label, prospective study using 124I-AT-01 PET/CT imaging to evaluate changes in amyloid load in patients with systemic amyloidosis who had undergone 124I-AT-01 imaging. Consented eligible patients will provide 3 tablespoons of blood for the following laboratory tests: complete blood count (CMP), complete blood count (CBC), C-reactive protein (CRP), Troponin, N-terminal fragment of prohormone brain natriuretic peptide (NT-proBNP), lactate dehydrogenase (LDH), Free Light Chain (FLC) and anti-drug antibody (ADA) analyses. A urine sample will also be collected to assess renal function. If required, a pregnancy test will be administered. Patients will then undergo a transthoracic echocardiographic examination and vital sign assessment before receiving an intravenous injection of no more than 2 mCi 124I-AT-01 followed, 5 h thereafter, by repeat vital sign measurements and PET/CT imaging from crown to thighs with a dynamic PET acquisition over the heart. Previously acquired 124I- AT-01 PET/CT images will be used as baseline values to determine quantitative changes in uptake of the radiotracer in the heart, liver, spleen, and kidney (and other organs deemed positive following visual inspection of the baseline and repeat imaging) as a measure of changes in amyloid load. Optionally, if the patients can return to the study site within \ 30 days post injection of 124I-AT-01, a second (post-injection) blood draw and ADA evaluation will be performed.
Interventions
DRUGInjection of peptide p5+14 radiolabeled with iodine-124 (124I-AT-01)
124I-AT-01 (124I-p5+14, iodine-124I evuzamitide) is a a novel iodine-124 (124I) labeled 45 L-amino acid peptide suitable for PET/CT imaging that has been shown to bind systemic amyloid deposits of diverse types in all organs, including the heart. The peptide binds amyloid through multivalent electrostatic interactions with the amyloid fibril and ubiquitous heparan sulfate proteoglycans.
Sponsors
University of Tennessee Graduate School of Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Must have given written informed consent (signed and dated) and any authorizations required by local law and be able to comply with all study requirements. * Must have a diagnosis of systemic amyloidosis based on the patient's medical record. * Must have undergone PET/CT imaging with 124I-AT-01 as part of the AMY1001 study (IND #132282) with visually positive uptake of radiotracer in at least one abdominothoracic organ. * Must have been imaged with 124I-AT-01 as part of the AMY1001 study (IND #132282) more than 12 months prior to repeat imaging. * Females: must be non-pregnant and non-lactating and either: surgically sterile (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy); post-menopausal (defined as 12 months of spontaneous amenorrhea in females \> 55 years of age or, in females ≤ 55 years, 12 months of spontaneous amenorrhea without an alternative medical cause and follicle-stimulating hormone (FSH) levels in the post-menopausal range for the laboratory involved).
Exclusion criteria
* Disabling dementia or other mental or behavioral disease. * Patients on dialysis. * Inability or unwillingness to comply with the study requirements. * Patients taking heparin, or heparin derivatives (e.g. low molecular weight heparins) for anticoagulation. * Other reason that would make the subject inappropriate for entry into this study. * Inability to lie still for 60 minutes on the PET/CT scanner. * History of iodine (potassium iodide) allergy. * Positive ADA finding defined as significantly higher than normal human serum mean values AND with a mean value at least five times greater than the mean value of the normal human serum control.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To Measure Visual Changes and Quantitative Changes in Organ-specific Uptake of 124I-AT-01 | Baseline PET/CT imaging from AMY1001 (NCT03678259) and repeat PET/CT imaging on Day 2 of the current study | The goal of this research study is to determine whether changes in organ-specific uptake of 124I- AT-01 can be measured by PET/CT imaging and further, whether these values correlate with changes in a subject's disease status and thereby enable monitoring of disease response over time in terms of organ-specific amyloid load. The specific aim of this study is to measure visual and quantitative changes in organ-specific uptake of 124I-AT-01 from baseline, in patients with systemic amyloidosis, using PET/CT imaging |
Countries
United States
Participant flow
Recruitment details
Data of participants diagnosed with systemic AL or ATTR amyloidosis who were previously imaged with 124I-AT-01 as part of the AMY1001 study (NCT03678259) and in whom there was visually positive uptake of radiotracer in at least one abdominothoracic organ.
Pre-assignment details
Prior to assignment, potential participants were screened to verify their medical records, including confirming that participants must have been imaged with 124I-AT-01 as part of the AMY1001 study more than 12 months prior to the repeat imaging.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 72 Years |
| Amyloid therapy at time of imaging of AL | 2 Participants |
| Amyloid therapy at time of imaging of ATTR Silencer only | 5 Participants |
| Amyloid therapy at time of imaging of ATTR Stabilizer and silencer | 4 Participants |
| Amyloid therapy at time of imaging of ATTR Stabilizer only | 1 Participants |
| Amyloid Type AL Kappa | 6 Participants |
| Amyloid Type AL Lambda | 3 Participants |
| Amyloid Type ATTR; Mutation type L58H | 3 Participants |
| Amyloid Type ATTR; Mutation type T60A | 5 Participants |
| Amyloid Type ATTR; Mutation type V30M and V122I | 1 Participants |
| Amyloid Type ATTR; Mutation type Wild type | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 18 Participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 11 Participants |
| Time Since baseline imaging in AMY1001 study (years) | 2.9 Years STANDARD_DEVIATION 0.9 |
| Time Since SA Diagnosis | 7 Years |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 19 |
| other Total, other adverse events | 1 / 19 |
| serious Total, serious adverse events | 0 / 19 |
Outcome results
None listed