Evuzamitide Imaging for Amyloidosis

Overseen By Stephen Helmke, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Columbia University

Must not be taking: Heparin

Disqualifiers: Primary amyloidosis, Active malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 1 month

25 Participants Needed

Trial Summary

Do I need to stop my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are taking heparin or heparin derivatives for anticoagulation, you cannot participate in the study.

What data supports the effectiveness of the treatment I 124-Evuzamitide for amyloidosis?

Research shows that the treatment I 124-Evuzamitide, also known as 124I-p5+14, is effective in detecting amyloid deposits in patients with various types of systemic amyloidosis using PET/CT imaging. This treatment has demonstrated the ability to bind to amyloid deposits in multiple organs, aiding in the early and accurate diagnosis of the disease. ^{1 2 3 4 5}

Is I 124-Evuzamitide safe for humans?

In a first-in-human study, the safety of I 124-Evuzamitide (also known as 124I-p5+14) was evaluated in patients with systemic amyloidosis, focusing on how the body processes the radiotracer. While specific safety outcomes are not detailed, the study's completion suggests it was considered safe enough to proceed with human testing. ^{1 2 4 6 7}

How does the drug Evuzamitide differ from other treatments for amyloidosis?

Evuzamitide is unique because it is a radiotracer that can bind to amyloid deposits from multiple types of amyloid proteins, allowing for non-invasive imaging and quantification of amyloid in the body using PET/CT scans. This approach is novel as it provides a way to detect and monitor amyloidosis early and accurately, which is challenging with current methods. ^{1 2 4 5 8}

What is the purpose of this trial?

This trial uses a special imaging technique to look for changes in the hearts of patients with a specific heart condition after treatment. The scan helps doctors see harmful protein deposits in the heart, which can indicate if the treatment is working.

Research Team

Mathew Maurer, MD

Principal Investigator

Columbia University

Eligibility Criteria

This trial is for adults with thickened heart walls and signs of cardiac amyloidosis, who can consent to the study. It's not for those with primary or secondary amyloidosis unrelated to transthyretin, pregnant women, patients on certain blood thinners, or anyone with a life expectancy under one year due to other diseases.

Inclusion Criteria

Your heart's interventricular septum is thicker than 12 mm on a recent echocardiogram.

My genetic test shows I have the Val122Ile mutation or no mutation.

My heart has thick walls and signs of a specific type of heart disease.

Exclusion Criteria

I have a serious illness with a life expectancy of less than 1 year.

You have a ventricular assist device.

My heart failure is not mainly due to amyloidosis.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of 124I-evuzamitide and undergo PET/CT scanning to detect potential therapeutic changes in ATTR

1 month

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the PET/CT scan

1 month

Treatment Details

Interventions

• I 124-Evuzamitide

Trial Overview The trial tests I 124-Evuzamitide as a PET scan imaging agent in detecting cardiac and extra-cardiac amyloid deposits in patients suspected of having ATTR-CM but have inconclusive standard scans. It aims to improve diagnosis accuracy for specific genetic variants associated with this condition.

Participant Groups

Group I: Cohort 3 Experimental Treatment 1 Intervention

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.. 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.

Group II: Cohort 2 Experimental Treatment 1 Intervention

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. 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)

Group III: Cohort 1 Experimental Treatment 1 Intervention

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. 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

Who Is Running the Clinical Trial?

Columbia University

Lead Sponsor

Trials

1,529

Recruited

2,832,000+

Attralus, Inc.

Industry Sponsor

Trials

8

Recruited

670+

Findings from Research

The first-in-human study of the iodine-124 labeled peptide 124I-p5+14 demonstrated that it is well tolerated and rapidly accumulates in organs commonly affected by amyloidosis, such as the heart, kidneys, and liver, indicating its potential for effective imaging of amyloid deposits.

Dosimetry estimates for 124I-p5+14 were found to be acceptable for whole-body PET/CT imaging, with a low effective radiation dose of 0.23 mSv/MBq, suggesting that this imaging technique could be a safe and non-invasive method for diagnosing systemic AL amyloidosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Wall, JS., Martin, EB., Endsley, A., et al.[2022]

The Tc-99m labeled peptide p5 + 14 was successfully developed as a radiotracer for SPECT imaging of systemic peripheral amyloidosis, showing a high radiochemical yield of 75% and over 90% purity, indicating its potential effectiveness for clinical use.

In mouse models, [(99m)Tc]p5 + 14 demonstrated specific uptake in amyloid-laden organs, with levels approximately five times higher than in healthy tissues, confirming its ability to accurately visualize amyloid deposits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tc-99m Radiolabeled Peptide p5 + 14 is an Effective Probe for SPECT Imaging of Systemic Amyloidosis. Kennel, SJ., Stuckey, A., McWilliams-Koeppen, HP., et al.[2019]

A new synthetic peptide, p5+14, has been developed as a radiotracer for noninvasive imaging of amyloidosis, which could help in evaluating the whole-body amyloid load in patients.

The study supports moving forward to a phase 1 clinical trial using this radiotracer labeled with iodine-124 for positron emission tomography (PET) imaging in patients with systemic amyloidosis, potentially improving diagnosis and management of this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dual-Energy SPECT and the Development of Peptide p5+14 for Imaging Amyloidosis. Wall, JS., Kennel, SJ., Martin, EB.[2020]

The novel radiotracer 124I-evuzamitide effectively quantifies cardiac amyloid deposits, showing significant differences in uptake between amyloid cardiomyopathy (CMP) patients and control subjects, which could enhance early diagnosis and treatment monitoring.

In patients with wild-type transthyretin (ATTRwt) CMP, 124I-evuzamitide demonstrated superior performance in detecting cardiac amyloid compared to the existing radiotracer 18F-florbetapir, indicating its potential as a more effective diagnostic tool.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac Amyloid Quantification Using&#160;124I-Evuzamitide (124I-P5+14) Versus 18F-Florbetapir: A Pilot PET/CT Study. Clerc, OF., Cuddy, SAM., Robertson, M., et al.[2023]

The peptide p5+14 can non-invasively detect all types of systemic amyloidosis by binding to amyloid deposits, which is crucial for early diagnosis and better patient outcomes.

In a Phase 1/2 clinical trial involving 8 patients with different types of amyloidosis, PET/CT imaging showed that the iodine-124-labeled p5+14 effectively localized amyloid deposits in affected organs, confirming its potential as a diagnostic tool.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Confirmation of Pan-Amyloid Reactivity of Radioiodinated Peptide 124I-p5+14 (AT-01) in Patients with Diverse Types of Systemic Amyloidosis Demonstrated by PET/CT Imaging. Martin, EB., Stuckey, A., Powell, D., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

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. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Tc-99m Radiolabeled Peptide p5 + 14 is an Effective Probe for SPECT Imaging of Systemic Amyloidosis. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Dual-Energy SPECT and the Development of Peptide p5+14 for Imaging Amyloidosis. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Cardiac Amyloid Quantification Using&#160;124I-Evuzamitide (124I-P5+14) Versus 18F-Florbetapir: A Pilot PET/CT Study. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical Confirmation of Pan-Amyloid Reactivity of Radioiodinated Peptide 124I-p5+14 (AT-01) in Patients with Diverse Types of Systemic Amyloidosis Demonstrated by PET/CT Imaging. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Role of (99m)Tc-DPD scintigraphy in diagnosis and prognosis of hereditary transthyretin-related cardiac amyloidosis. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

SPECT and PET myocardial perfusion imaging in Austria, Germany, and Switzerland results of the first joint survey of 2021. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Radioimaging of light chain amyloid with a fibril-reactive monoclonal antibody. [2018]