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

This is a single center prospective study evaluating 124I-evuzumitide in patients with systemic amyloidosis. The purpose of this study is to 1) Establish the diagnostic accuracy of 124I-evuzumitide in cardiac amyloidosis 2) Evaluate extracardiac uptake 3) identify and characterize the distribution and uptake of 124I-evuzumitide in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) and 4) 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.

Study Overview

• Status: Recruiting
• Conditions: Amyloidosis; Transthyretin Amyloidosis
• Intervention / Treatment: Diagnostic test: 124I-Evuzamitide

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ahmad Masri, MD; Phone Number: 503-418-1964; Email: masria@ohsu.edu

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health & Science University
      • Principal Investigator: Ahmad Masri, MD
      • Contact: Ahmad Masri, MD; Email: masria@ohsu.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 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
2. Patient willing to consent for the study and undergo the study procedures.

Exclusion Criteria:

1. Has severe claustrophobia or any medical condition that would prevent completion of the imaging protocol
2. Has a known allergy to potassium iodide treatment or to gadolinium.
3. Patients on dialysis or those with eGFR <30 cc/min/1.73 m2 will be excluded from undergoing gadolinium-enhanced cardiac MRI.
4. Has received heparin or heparin analogs (e.g., enoxaparin, dalteparin, fondaparinux) within 7 days prior to 124I-Evuzumitide administration

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• 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 with ATTR-CM; 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; Amyloid reactive protein used as imaging agent to detect systemic amyloidosis; Other Names: AT-01

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
I-124 evuzamitide diagnostic accuracy	To evaluate the efficacy of I-124 evuzamitide for diagnosing cardiac amyloidosis based on visual scan interpretation, compared to SoC site diagnosis. We will assess: The sensitivity of PET/MRI with 124I-evuzamitide PET/MRI for the diagnosis of cardiac amyloidosis.; The specificity of PET/MRI with 124I-evuzamitide for the diagnosis of cardiac amyloidosis.	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
Quantitative measures	To evaluate the efficacy of I-124 evuzamitide for diagnosing cardiac amyloidosis based on quantitative scan interpretation, compared to SoC site diagnosis. We will assess the sensitivity and specificity of various quantitative measures, and evaluate inter- and intra-reader agreement.	At baseline scan
To evaluate the safety of a single intravenous administration of I-124 evuzamitide.	Incidence of related treatment-emergent (S)AEs from time of study drug administration to Day 7	7 days from baseline scan

Collaborators and Investigators

• Sponsor: Oregon Health and Science University
• Collaborators: Bayer; Attralus, Inc.

Publications and helpful links

General Publications

• Wall JS, Martin EB, Endsley A, Stuckey AC, Williams AD, Powell D, Whittle B, Hall S, Lambeth TR, Julian RR, Stabin M, Lands RH, Kennel SJ. First in Human Evaluation and Dosimetry Calculations for Peptide 124I-p5+14-a Novel Radiotracer for the Detection of Systemic Amyloidosis Using PET/CT Imaging. Mol Imaging Biol. 2022 Jun;24(3):479-488. doi: 10.1007/s11307-021-01681-2. Epub 2021 Nov 16.

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2023
• Primary Completion (Estimated): December 10, 2027
• Study Completion (Estimated): March 10, 2028

Study Registration Dates

• First Submitted: January 25, 2023
• First Submitted That Met QC Criteria: February 24, 2023
• First Posted (Actual): March 7, 2023

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 6, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Proteostasis Deficiencies; Nutritional and Metabolic Diseases; Amyloidosis; Amyloidosis, Hereditary, Transthyretin-Related
• Other Study ID Numbers: 24299

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