Repeat PET/CT Imaging of Patients With Amyloid 124I-AT-01 to Measure Changes in Organ-specific Amyloid Load

Repeat PET/CT Imaging of Patients With Systemic Amyloidosis Using Amyloid Reactive Peptide 124I-AT-01 (124I-p5+14, Iodine-124I-evuzamitide) to Measure Changes in Organ-specific Amyloid Load

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.

Study Overview

• Status: Completed
• Conditions: Systemic Amyloidosis
• Intervention / Treatment: Drug: Injection of peptide p5+14 radiolabeled with iodine-124 (124I-AT-01)

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.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • University of Tennessee Graduate School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Patients will receive a single IV injection of 124I-AT-01 radiotracer and PET/CT imaging; 124I-AT-01 (124I-p5+14, iodine-124I evuzamitide) is an iodine-124 (124I) labeled 45 L-amino acid peptide suitable for PET/CT imaging. The peptide binds many forms of amyloid through multivalent electrostatic interactions with the amyloid fibril and ubiquitous heparan sulfate proteoglycans. 124I-AT-01 has been evaluated previously in an open-label Phase 1/2 clinical trial, AMY1001, performed at the University of Tennessee Medical Center (IND# 132282; NCT T03678259). In this repeat imaging study, patients previously enrolled in the AMY1001 study, in whom positive PET/CT imaging findings were observed will undergo repeat imaging to assess changes in radiotracer uptake in the liver, spleen, heart and kidneys.

Drug: Injection 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.; Other Names: 124I-p5+14; iodine-124-evuzamitide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To Measure Visual Changes and Quantitative Changes in Organ-specific Uptake of 124I-AT-01	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	Baseline PET/CT imaging from AMY1001 (NCT03678259) and repeat PET/CT imaging on Day 2 of the current study

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure of Interest	Compare changes, when possible, in radiotracer distribution from baseline based on analysis dynamic PET data.	From enrollment to the end of the study is 8 days
Measure of Interest	Compare changes, when possible, in ejection fraction from baseline based on analysis dynamic PET data.	From enrollment to the end of the study is 8 days
Measures of Interest	For AL, ATTR and all patients, we will correlate visual and quantitative changes in 124I- AT-01 uptake, from baseline, in the heart, liver and kidney with echocardiographic parameters (including left ventricular wall thickness (cm), intraventricular wall thickness (cm), and global logitudinal strain (%)) and serum biomarker levels (including NTproBNP, eGFR, creatinine, AST and ALT) assessed prior to imaging and from data recorded in the patients' medical record.	Baseline (assessed during previous study NCT03678259) and Repeat Assessment (Day 1 to Day 2 of current study)
Measure of Interest	For AL, ATTR and all patients, we will correlate visual and quantitative changes in organ-specific 124I-AT-01 uptake (percent change in radiotracer uptake from baseline) with change in disease status (progression, response, or stable state) when this can be established from data (serum biomarkers and cardiac imaging parameters) in the patients' medical record or collected during the AMY1001 trial. Disease status is categorized based on NTproBNP, creatinine, blood urea nitrogen or alkaline phosphatase compared to baseline values taken at the original scan time or noted in the medical record based on a sum of clinical findings. Progression is defined as a ≥30% increase; Response is defined as a ≥30% decrease; and Stable disease is defined as a <30% increase or decrease.	From enrollment to the end of the study is 8 days
Measure of Interest	For AL patients, correlate visual and quantitative changes in organ-specific 124I-AT-01 uptake (percent change in radiotracer uptake from baseline) with change in serum free light chains over the period between imaging studies, when available in the medical record. Baseline assessments reflect the values assessed during the previous study (NCT03678259). Repeat assessments reflect the values assessed during this current study. The 'change in' values are calculated as the repeat value from this current study minus the baseline value from the previous study (NCT03678259).	Baseline (assessed during previous study NCT03678259) and Repeat Assessment (Day 1 to Day 2 of current study)

Collaborators and Investigators

• Sponsor: University of Tennessee Graduate School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): December 7, 2022
• Primary Completion (Actual): August 1, 2023
• Study Completion (Actual): September 1, 2023

Study Registration Dates

• First Submitted: June 30, 2023
• First Submitted That Met QC Criteria: July 28, 2023
• First Posted (Actual): August 1, 2023

Study Record Updates

• Last Update Posted (Actual): September 2, 2026
• Last Update Submitted That Met QC Criteria: August 10, 2026
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: PET/CT; p5+14; systemic amyoidosis; AT-01; evuzamitide
• Additional Relevant MeSH Terms: Neoplasms; Metabolic Diseases; Immune System Diseases; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Paraproteinemias; Proteostasis Deficiencies; Amyloidosis; Nutritional and Metabolic Diseases; Immunoglobulin Light-chain Amyloidosis; Anti-Infective Agents; Physiological Effects of Drugs; Trace Elements; Micronutrients; Anti-Infective Agents, Local; Iodine-124
• Other Study ID Numbers: UTMC-AT01-163117

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No