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

A Follow-Up Study to Monitor Therapeutic Response in Transthyretin Cardiac Amyloidosis Using Amyloid Reactive Peptide 124I-evuzamitide (AT01) PET/CT

This is 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 has elapsed since their original 124I-evuzamitide PET scan.

Ten previously scanned subjects will re-consent to undergo another 124I-evuzamitide PET scan. Demographic, clinical and phenotypic data will be collected to characterize potential changes since their previous scans.

Study Overview

• Status: Recruiting
• Conditions: Transthyretin Amyloidosis
• Intervention / Treatment: Drug: I 124-Evuzamitide

Detailed Description

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 want to use it to detect potential therapeutic changes in 10 subjects undergoing treatment for Transthyretin Amyloidosis:

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Mathew Maurer, MD; Phone Number: 212-932-4537; Email: msm10@cumc.columbia.edu
• Study Contact Backup: Name: Stephen Helmke, MPH; Phone Number: 212-932-4371; Email: sh2669@cumc.columbia.edu

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Irving Medical Center
      • Contact: Dia Smiley, DO; Phone Number: 419-902-5284; Email: ds4031@cumc.columbia.edu
      • Principal Investigator: Matthew Maurer, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 105 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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. New York Heart Association (NYHA) class I-III
3. Able to understand and sign the informed consent document after the nature of the study has been fully explained.

Cohort 1: Subjects with grade 1 Tc99-PYP scans who have clinical features suggestive of ATTR-CM or have grade 1 Tc99-PYP scans but endomyocardial biopsy evidence of TTR cardiac amyloidosis.

1. Heart failure with a preserved ejection fraction (EF>40%)
2. Grade 1 Tc99-PYP scan performed for clinical suspicion of ATTR-CM
3. No evidence of monoclonal proteins by assessment of serum kappa and lambda free light chain ratio and immunofixation of serum and urine.
4. Left ventricular septal OR inferolateral wall thickness ≥12 mm.

Cohort 2: Subjects with TTR variant such as Phe64Leu, late onset Val30Met, etc.) that are associated with cardiac amyloidosis but have PYP scans not diagnostic of ATTR-CM

1. Tc99-PYP scan performed for clinical suspicion of ATTR-CM that is not diagnostic of ATTR-CM
2. No evidence of monoclonal proteins by assessment of serum kappa and lambda free light chain ratio and immunofixation of serum and urine.
3. Left ventricular septal OR inferolateral wall thickness ≥12 mm with echocardiographic features of ATTR-CM (low tissue doppler velocities, preserved apical strain, elevated E/E') or CMR features of an infiltrative cardiomyopathy (increased wall thickness with delayed enhancement or difficulty nulling of the myocardium)

Cohort 3: Subjects with ATTR-CM from either ATTRwt or Val122Ile variant who have biopsy proven evidence of extra-cardiac TTR amyloidosis or clinical suspicion of extracardiac disease, including but not limited to peripheral neuropathy, carpal tunnel syndrome, spinal stenosis.

1. ATTR-CM defined by the following

   1. Amyloid deposits in cardiac or non-cardiac tissue confirmed by Congo Red (or equivalent) staining OR technetium scintigraphy with 99m Tc-pyrophosphate with Grade 2 or 3 cardiac uptake in the absence of abnormal light chains ratio,
   2. End-diastolic interventricular septum thickness of > 12 mm on previous echocardiogram
2. TTR genotype shown to be either Val122Ile or wild type.

Exclusion Criteria:

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.
13. Pregnancy or current lactational feeding of infants.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Subjects with grade 1 Tc99-PYP scans who have clinical features suggestive of ATTR-CM or have grade 1 Tc99-PYP scans but endomyocardial biopsy evidence of TTR cardiac amyloidosis will be administered single dose evuzamitide <1mCi.; Heart failure with a preserved ejection fraction (EF>40%); Grade 1 Tc99-PYP scan performed for clinical suspicion of ATTR-CM; No evidence of monoclonal proteins by assessment of serum kappa and lambda free light chain ratio and immunofixation of serum and urine.; Left ventricular septal OR inferolateral wall thickness ≥12 mm	Drug: I 124-Evuzamitide; Amyloid reactive protein used as imaging agent in whole body SPECT-CT imaging; Other Names: Attralus AT-01
Experimental: Cohort 2; Subjects with TTR variant such as Phe64Leu, late onset Val30Met, etc.) that are associated with cardiac amyloidosis but have PYP scans not diagnostic of ATTR-CM will be administered single dose evuzamitide <1mCi.; Tc99-PYP scan performed for clinical suspicion of ATTR-CM that is not diagnostic of ATTR-CM; No evidence of monoclonal proteins by assessment of serum kappa and lambda free light chain ratio and immunofixation of serum and urine.; Left ventricular septal OR inferolateral wall thickness ≥12 mm with echocardiographic features of ATTR-CM (low tissue doppler velocities, preserved apical strain, elevated E/E') or CMR features of an infiltrative cardiomyopathy (increased wall thickness with delayed enhancement or difficulty nulling of the myocardium)	Drug: I 124-Evuzamitide; Amyloid reactive protein used as imaging agent in whole body SPECT-CT imaging; Other Names: Attralus AT-01
Experimental: Cohort 3; Subjects with ATTR-CM from either ATTRwt or Val122Ile variant who have biopsy proven evidence of extra-cardiac TTR amyloidosis or clinical suspicion of extracardiac disease, including but not limited to peripheral neuropathy, carpal tunnel syndrome, spinal stenosis will be administered single dose evuzamitide <1mCi..; ATTR-CM defined by the followingAmyloid deposits in cardiac or non-cardiac tissue confirmed by Congo Red (or equivalent) staining OR technetium scintigraphy with 99m Tc-pyrophosphate with Grade 2 or 3 cardiac uptake in the absence of abnormal light chains ratio,End-diastolic interventricular septum thickness of > 12 mm on previous echocardiogram; TTR genotype shown to be either Val122Ile or wild type.	Drug: I 124-Evuzamitide; Amyloid reactive protein used as imaging agent in whole body SPECT-CT imaging; Other Names: Attralus AT-01

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
COV in subjects with heart failure and grade 1 PYP scans	Detection of TTR cardiac infiltration. To determine if 124I-evuzamitide PET scanning can detect cardiac TTR amyloidosis in subjects with heart failure, increased wall thickness but only grade 1 Tc99-PYP scans who are either not currently diagnosed with ATTR-CM or have endomyocardial biopsy evidence of ATTR-CM. The organ-specific radioactivity data will be expressed as the mean and standard deviation (SD) of three independent ROIs, unless otherwise noted. The coefficient of variation (COV) will be expressed as (SD/mean)*100.	Up to 1 month after scanning
COV in subjects who are allele carriers with non-diagnostic PYP scans	Detection of TTR cardiac infiltration. To determine if 124I-evuzamitide PET scanning can detect cardiac ATTR in allele carriers of TTR variants (Phe64Leu, late onset Val30Met) that are associated with cardiac amyloidosis but have PYP scans not diagnostic of ATTR-CM. The organ-specific radioactivity data will be expressed as the mean and standard deviation (SD) of three independent ROIs, unless otherwise noted. The coefficient of variation (COV) will be expressed as (SD/mean)*100.	Up to 1 month after scanning
COV in subjects with ATTR-CM	Detection of extra-cardiac TTR amyloidosis. To determine if 124I-evuzamitide PET scanning can identify and quantify extra-cardiac amyloidosis in subjects with ATTR-CM due to either ATTRwt or Val122Ile variant. The organ-specific radioactivity data will be expressed as the mean and standard deviation (SD) of three independent ROIs, unless otherwise noted. The coefficient of variation (COV) will be expressed as (SD/mean)*100.	Up to 1 month after scanning

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: Attralus, Inc.
• Investigators: Principal Investigator: Mathew Maurer, MD, Columbia University

Study record dates

Study Major Dates

• Study Start (Actual): July 8, 2022
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): September 1, 2024

Study Registration Dates

• First Submitted: November 23, 2022
• First Submitted That Met QC Criteria: November 23, 2022
• First Posted (Actual): December 2, 2022

Study Record Updates

• Last Update Posted (Estimated): February 6, 2024
• Last Update Submitted That Met QC Criteria: February 5, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Positron Emission Tomography (PET); ATTR-CM; 124I-evuzamitide
• Additional Relevant MeSH Terms: Metabolic Diseases; Proteostasis Deficiencies; Amyloidosis
• Other Study ID Numbers: AAAU0561

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