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Evuzamitide as SPECT/CT Imaging Agent for Diagnosis of Transthyretin Amyloidosis

Primary Purpose

Transthyretin Amyloidosis

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
I 124-Evuzamitide
Sponsored by
Columbia University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Transthyretin Amyloidosis focused on measuring 124I-evuzamitide, Positron Emission Tomography (PET), ATTR-CM

Eligibility Criteria

50 Years - 105 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: 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. New York Heart Association (NYHA) class I-III 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. 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. 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 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) 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. ATTR-CM defined by the following 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, End-diastolic interventricular septum thickness of > 12 mm on previous echocardiogram TTR genotype shown to be either Val122Ile or wild type. Exclusion Criteria: Primary amyloidosis (AL) or secondary amyloidosis (AA). Active malignancy or non-amyloid disease with expected survival of less than 1 year. Heart failure, in the opinion of the investigator, primarily caused by something other than amyloidosis. Ventricular assist device. Impairment from stroke, injury or other medical disorder that precludes participation in the study. Disabling dementia or other mental or behavioral disease. Enrollment in a clinical trial not approved for co-enrollment. Continuous intravenous inotropic therapy. Inability or unwillingness to comply with the study requirements. Chronic kidney disease requiring hemodialysis or peritoneal dialysis. Patients taking heparin, or heparin derivatives (e.g. low molecular weight heparins) for anticoagulation. Other reason that would make the subject inappropriate for entry into this study. Pregnancy or current lactational feeding of infants.

Sites / Locations

  • Columbia University Irving Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Cohort 1

Cohort 2

Cohort 3

Arm Description

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

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)

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 following 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, End-diastolic interventricular septum thickness of > 12 mm on previous echocardiogram TTR genotype shown to be either Val122Ile or wild type.

Outcomes

Primary Outcome Measures

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.
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.
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.

Secondary Outcome Measures

Full Information

First Posted
November 23, 2022
Last Updated
August 29, 2023
Sponsor
Columbia University
Collaborators
Attralus, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05635045
Brief Title
Evuzamitide as SPECT/CT Imaging Agent for Diagnosis of Transthyretin Amyloidosis
Official Title
A Pilot Study Using Amyloid Reactive Peptide AT-01(124I-evuzamitide) in Transthyretin Cardiac Amyloidosis for Early Detection, Assessment of Cardiac Involvement in Rare Variants and Quantification of Extra-Cardiac Amyloidosis
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 8, 2022 (Actual)
Primary Completion Date
January 1, 2024 (Anticipated)
Study Completion Date
March 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Columbia University
Collaborators
Attralus, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a single center, prospective cohort study that is evaluating the ability of 124I-evuzamitide PET scanning to: (1) identify extra-cardiac amyloid deposits in patients with ATTRwt-CA and the Val122Ile variant; (2) to detect cardiac TTR amyloidosis in subjects with heart failure, increased wall thickness but only grade 1 Tc99PYP scans who are not currently diagnosed with ATTR-CA; and (3) to 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. If 124I-evuzamitide PET scanning is shown to be valuable in any of these three cohorts, it would address critical unmet needs regarding the diagnosis and extent of disease in ATTR-CM. Consented eligible patients will undergo a single 124I-evuzamitide PET scan. Clinically available demographic, clinical and phenotypic data that is collected as part of routine clinical care will be used to characterize the type, severity, and stage of ATTR-CM.
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. A new radiation compound, evuzamitide, has been shown to detect amyloidosis in the heart, liver, spleen, kidney, bone marrow and even in the peripheral nerves. So, the investigators want to use it to detect Transthyretin Amyloidosis: In people who have a type of Amyloidosis which normally deposits in the heart, but in which PYP Scintigraphy didn't find it in there; In people who have a type of Amyloidosis which normally deposits outside the heart, to see if this compound can detect it in the heart; and In people who have proven Amyloid deposits in the heart, to see if this compound can detect them outside the heart.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Transthyretin Amyloidosis
Keywords
124I-evuzamitide, Positron Emission Tomography (PET), ATTR-CM

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
25 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1
Arm Type
Experimental
Arm Description
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
Arm Title
Cohort 2
Arm Type
Experimental
Arm Description
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)
Arm Title
Cohort 3
Arm Type
Experimental
Arm Description
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 following 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, End-diastolic interventricular septum thickness of > 12 mm on previous echocardiogram TTR genotype shown to be either Val122Ile or wild type.
Intervention Type
Drug
Intervention Name(s)
I 124-Evuzamitide
Other Intervention Name(s)
Attralus AT-01
Intervention Description
Amyloid reactive protein used as imaging agent in whole body SPECT-CT imaging
Primary Outcome Measure Information:
Title
COV in subjects with heart failure and grade 1 PYP scans
Description
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.
Time Frame
Up to 1 month after scanning
Title
COV in subjects who are allele carriers with non-diagnostic PYP scans
Description
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.
Time Frame
Up to 1 month after scanning
Title
COV in subjects with ATTR-CM
Description
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.
Time Frame
Up to 1 month after scanning

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
105 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 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. New York Heart Association (NYHA) class I-III 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. 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. 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 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) 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. ATTR-CM defined by the following 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, End-diastolic interventricular septum thickness of > 12 mm on previous echocardiogram TTR genotype shown to be either Val122Ile or wild type. Exclusion Criteria: Primary amyloidosis (AL) or secondary amyloidosis (AA). Active malignancy or non-amyloid disease with expected survival of less than 1 year. Heart failure, in the opinion of the investigator, primarily caused by something other than amyloidosis. Ventricular assist device. Impairment from stroke, injury or other medical disorder that precludes participation in the study. Disabling dementia or other mental or behavioral disease. Enrollment in a clinical trial not approved for co-enrollment. Continuous intravenous inotropic therapy. Inability or unwillingness to comply with the study requirements. Chronic kidney disease requiring hemodialysis or peritoneal dialysis. Patients taking heparin, or heparin derivatives (e.g. low molecular weight heparins) for anticoagulation. Other reason that would make the subject inappropriate for entry into this study. Pregnancy or current lactational feeding of infants.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Mathew Maurer, MD
Phone
212-932-4537
Email
msm10@cumc.columbia.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Stephen Helmke, MPH
Phone
212-932-4371
Email
sh2669@cumc.columbia.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mathew Maurer, MD
Organizational Affiliation
Columbia University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Columbia University Irving Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dia Smiley, DO
Phone
419-902-5284
Email
ds4031@cumc.columbia.edu
First Name & Middle Initial & Last Name & Degree
Matthew Maurer, MD

12. IPD Sharing Statement

Plan to Share IPD
No

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Evuzamitide as SPECT/CT Imaging Agent for Diagnosis of Transthyretin Amyloidosis

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