Evuzamitide in PET/CT to Measure Potential Therapeutic Response in ATTR

Columbia University10 enrolled

Overview

This was a single center, prospective cohort study that is evaluating the ability of 124I-evuzamitide PET scanning to detect potential therapeutic changes in subjects under treatment for ATTR after one year had elapsed since their original 124I-evuzamitide PET scan. Ten previously scanned subjects re-consented to undergo another 124I-evuzamitide PET scan. Demographic, clinical and phenotypic data were collected to characterize potential changes since their previous scans.

Transthyretin cardiac amyloidosis (ATTR-CA) causes progressive heart disease that is often overlooked. It harms the heart muscle because the unstable, unfurled amyloid proteins fold up into large pieces that get caught in between layers of heart tissue, causing amyloid deposits. The earlier it is detected, the better for the patient. There is a need to improve the early diagnosis of this disease because echocardiography (sonograms of the heart) and cardiac MRI are not useful enough for this. There is an X-ray of the heart using a compound called PYP that can detect amyloid deposits earlier than ultrasound images or clinical signs, but it's not clear how early it does so. Also, it can't detect amyloid deposits outside the heart, which causes lots of pain and suffering in people with this disease. In the first phase of this study the radiation compound, evuzamitide, was shown to detect amyloidosis in the heart of selected subjects. So, the investigators used it to detect potential therapeutic changes in 10 subjects undergoing treatment for Transthyretin Amyloidosis. Changes in the uptake of evuzamitide were compared between subjects treated on stabilizer only, subjects treated on silencer only and subjects treated with two different combinations of stabilizer plus silencer

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

DIAGNOSTIC

Masking

NONE

Enrollment

Conditions

Transthyretin Amyloidosis

Interventions

I 124-EvuzamitideDRUG

Amyloid reactive protein used as imaging agent in whole body SPECT-CT imaging

Eligibility

Sex: ALLMin age: 50 YearsMax age: 105 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: 1. 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. 2. Were enrolled in the initial pilot using 124I-Evuzamitide, on ATTR stabilizer and/or silencer therapy. Able to understand and sign the informed consent document after the nature of the study has been fully explained. 3. TTR genotype shown to be either Val122Ile or wild type. Exclusion Criteria: Overall Inclusion Criteria: 1. 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. 2. Were enrolled in the initial pilot using 124I-Evuzamitide, on ATTR stabilizer and/or silencer therapy. Able to understand and sign the informed consent document after the nature of the study has been fully explained. 3. TTR genotype shown to be either Val122Ile or wild type. The presence of any of the following excludes eligibility for enrollment in this study: 1. Primary amyloidosis (AL) or secondary amyloidosis (AA). 2. Active malignancy or non-amyloid disease with expected survival of less than 1 year. 3. Heart failure, in the opinion of the investigator, primarily caused by something other than amyloidosis. 4. Ventricular assist device. 5. Impairment from stroke, injury or other medical disorder that precludes participation in the study. 6. Disabling dementia or other mental or behavioral disease. 7. Enrollment in a clinical trial not approved for co-enrollment. 8. Continuous intravenous inotropic therapy. 9. Inability or unwillingness to comply with the study requirements. 10. Chronic kidney disease requiring hemodialysis or peritoneal dialysis. 11. Patients taking heparin, or heparin derivatives (e.g. low molecular weight heparins) for anticoagulation. 12. Other reason that would make the subject inappropriate for entry into this study.

Locations (1)

Columbia University Irving Medical Center

New York, New York, United States

Outcomes

Primary Outcomes

Median of Uptake of Evuzamitide as Measured by Volume of Interest in Milliliters

Volumes of interest (VOIs) were manually traced on PET emission images fused with CT images to define the left ventricular (LV) and right ventricular (RV) contours, including cavity blood pool. Blood pool activity concentration was measured in a 10-mm-diameter left atrial spherical VOI. For 124I-evuzamitide, we used a threshold of mean + 2 standard deviations of blood pool activity concentration.

Time frame: Up to one month after imaging

Median of Change in Evuzamitide Uptake as Measured by Percentage Change in Injected Dose (%ID)

Median percentage change in injected dose (%ID), calculated as VOI mean activity concentration x VOI volume/injected activity.

Time frame: Up to one month after imaging

Median of Uptake of Evuzamitide as Measured by Cardiac Amyloid Activity (CAA) in Grams

Cardiac amyloid activity (CAA) in grams is measured as VOI mean standardized uptake value times VOI volume. Standardized uptake value was defined as mean or maximal VOI activity concentration/(injected activity/bodyweight), while target-to-background ratio was considered VOI mean activity concentration/blood pool mean activity concentration. VOI volume was manually traced on PET emission images fused with CT images.

Time frame: Up to one month after imaging

Data from ClinicalTrials.gov

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