Characterizing Iodine-124 Evuzumitide (AT-01) in Systemic Amyloidosis

Study Overview
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Brief Summary
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This is a single center prospective study evaluating 124I-evuzumitide in patients with systemic amyloidosis. The purpose of this study is to 1)identify and characterize the distribution and uptake of 124I-evuzumitide in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) and 2) Correlate the uptake with the structure and function of different organs, including the heart. To achieve these goals, eligible patients will undergo primarily hybrid positron emission tomography and magnetic resonance imaging (PET/MRI). In a subgroup of patients who are unable to undergo PET/MR, computed tomography will be used instead of MRI (i.e. PET/CT). In a subgroup of patients, repeat imaging with the same modality will be done at a interval of 6-12 months. Clinically available data (demographics, phenotype, imaging, laboratory) will also be collected to characterize the disease in each patient.

Official Title
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Characterizing Iodine-124 Evuzumitide (AT-01) in Systemic Amyloidosis

Conditions
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Amyloidosis, Transthyretin Amyloidosis

Intervention / Treatment
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* Diagnostic Test: 124I-Evuzamitide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects will at least have one of the following conditions: systemic amyloidosis with known organ involvement, carrier of a known pathogenic mutation in the transthyretin gene, multiple myeloma, and monoclonal gammopathy of undetermined significance Patient willing to consent for the study and undergo the study procedures. Exclusion Criteria: Has severe claustrophobia or any medical condition that would prevent completion of the imaging protocol Has a known allergy to potassium iodide treatment or to gadolinium. Patients on dialysis or those with eGFR <30 cc/min/1.73 m2 will be excluded from undergoing gadolinium-enhanced cardiac MRI. Has received heparin or heparin analogs (e.g., enoxaparin, dalteparin, fondaparinux) within 7 days prior to 124I-Evuzumitide administration

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients with ATTR-CM<br>Patients with ATTR-CM will undergo hybrid 124I-Evuzamitide PET/MRI imaging (or PET/CT) at baseline and in a subgroup, repeat imaging will be performed at an interval of 6-12 months. | Diagnostic Test: 124I-Evuzamitide<br>* Amyloid reactive protein used as imaging agent to detect systemic amyloidosis<br>* Other names: AT-01;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between ECV and 124I-Evuzamitide cardiac uptake and distribution | Pearson Correlation Coefficient of ECV (%) and SUV (124I-Evuzamitide) globally and at a per segment basis | At baseline scan | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between clinical cardiac biomarkers (i.e. stage of amyloidosis) and myocardial 124I-Evuzamitide uptake | Pearson Correlation Coefficient of stage of amyloidosis (Mayo Staging System) and SUV (124I-Evuzamitide) | At baseline scan | 
| Correlation between Kansas City Cardiomyopathy Questionnaire overall summary score (KCCQ-OS) and myocardial 124I-Evuzamitide |  | During baseline scan and follow up scan | 
| Correlation between New York Heart Association (NYHA) class and 124I-Evuzamitide uptake |  | During baseline scan and follow up scan | 
| Correlation between liver and spleen ECV and their respective 124I-Evuzamitide uptake |  | During baseline scan and follow up scan | 
| Proportion of patients with ATTR-CM and MGUS or smoldering myeloma who are correctly classified as ATTR-CM based on 124I-Evuzamitide distribution and uptake |  | During baseline scan |