Clinical trial NCT05635045: Evuzamitide in PET/CT to Measure Potential Therapeutic Response in ATTR
Official title: A Follow-Up Study to Monitor Therapeutic Response in Transthyretin Cardiac Amyloidosis Using Amyloid Reactive Peptide 124I-evuzamitide (AT01) PET/CT
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Transthyretin Amyloidosis
Keywords: 124I-evuzamitide
Positron Emission Tomography (PET)
ATTR-CM
Lead sponsor: Columbia University
Sponsor class: OTHER
Collaborators: name: Attralus, Inc.
First posted: 2022-12-02
Enrollment: 25
Sex: ALL
Minimum age (years): 50
Maximum age (years): 105
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: 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.

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:

Eligibility criteria: 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.

Primary outcomes:
measure: COV in subjects with heart failure and grade 1 PYP scans
timeFrame: Up to 1 month after scanning
measure: COV in subjects who are allele carriers with non-diagnostic PYP scans
timeFrame: Up to 1 month after scanning
measure: COV in subjects with ATTR-CM
timeFrame: Up to 1 month after scanning
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
Study officials:
affiliation: Columbia University
name: Mathew Maurer, MD
role: PRINCIPAL_INVESTIGATOR
References: