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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate how effectively a special PET scan using 124I-evuzamitide (a radiotracer) can detect changes in individuals with ATTR amyloidosis undergoing treatment. ATTR amyloidosis involves the buildup of abnormal proteins in organs and tissues, impairing their function. Participants will undergo an additional scan to compare with their earlier one, allowing researchers to assess the treatment's impact. Suitable candidates have a specific genetic form of the condition and are already receiving certain treatments for ATTR. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants the opportunity to contribute to significant findings.

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 prior data suggests that 124I-evuzamitide PET scanning is safe for detecting therapeutic changes in amyloidosis?

Research has shown that I-124 evuzamitide is generally safe for people. In earlier studies, participants tolerated it well and did not experience serious side effects. They reported no major health problems after receiving the treatment. Safety checks revealed normal vital signs after administration. This imaging agent helps doctors visualize amyloid deposits in the body using a PET scan, a special type of imaging test. Overall, the safety data suggest that I-124 evuzamitide is a safe option for those considering joining the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the Evuzamitide Imaging for Amyloidosis trial because it aims to improve the way we detect amyloidosis, a condition often monitored using imaging techniques. Unlike existing imaging methods that might not effectively show changes over time, this trial uses I-124-Evuzamitide, a radioactive tracer that can provide detailed images of amyloid deposits in the body. This new approach could offer clearer insights into how treatments like tafamidis, vutrisiran, and others affect amyloid buildup, potentially leading to more personalized treatment plans. Overall, this study could revolutionize how we track the progress of amyloidosis and evaluate the effectiveness of different therapies.

What evidence suggests that this trial's treatments could be effective for amyloidosis?

Research has shown that 124I-evuzamitide effectively detects amyloidosis, a condition where proteins accumulate in the body, affecting the heart and other areas. It has proven to be 100% accurate, always correctly identifying the disease without mistakes. This imaging reveals amyloid deposits, the problematic proteins in amyloidosis. Studies have demonstrated its effectiveness in patients with heart-related amyloidosis, even before symptoms appear. This trial will compare different treatment arms, including those receiving stabilizers like tafamidis or silencers like vutrisiran, to assess changes in Evuzamitide uptake over time. This makes 124I-evuzamitide a promising option for tracking the disease and potentially aiding doctors in treatment decisions. ^{1 3 5 6 7}

Who Is on the Research Team?

Mathew Maurer, MD

Principal Investigator

Columbia University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Stabilizer Only Active Control 1 Intervention

Subjects treated with tafamidis selected to re-scan to determine the change over time in Evuzamitide uptake

Group II: Silencer Only Active Control 1 Intervention

Subjects treated with vutrisiran selected to re-scan to determine the change over time in Evuzamitide uptake

Group III: Stabilizer and Silencer (tafamidis + patisiran) Active Control 1 Intervention

Subjects treated with tafamidis and patisiran selected to re-scan to determine the change over time in Evuzamitide uptake

Group IV: Stabilizer and Silencer (vutrisiran + diflunisal) Active Control 1 Intervention

Subjects treated with vutrisiran and diflunisal selected to re-scan to determine the change over time in Evuzamitide uptake

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+

Published Research Related to This Trial

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]

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

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]

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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S1936878X2300414X

Cardiac Amyloid Detection by PET/CT Imaging of Iodine ... These data suggest that 124I-evuzamitide imaging can detect not only cardiac amyloidosis, but also extracardiac disease that may contribute to poor quality ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10758980/

Cardiac Amyloid Quantification Using 124I-Evuzamitide (124I ... 124 I-evuzamitide is a pan-amyloid imaging agent with visually apparent myocardial uptake in participants with cardiac amyloidosis.

3. attralus.com attralus.com/press-releases/attralus-presents-new-data-on-its-pan-amyloid-diagnostic-imaging-candidates-at-asnc-2025

Attralus Presents New Data on Its Pan-Amyloid Diagnostic ... 124I-evuzamitide, the first pan-amyloid diagnostic imaging agent, demonstrated 100% sensitivity and specificity for the diagnosis of cardiac ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06788535

Research With I-124 EVuzamitide to Elucidate Cardiac ... This Phase 3, open label, single dose study will evaluate the efficacy and safety of I-124 evuzamitide when administered as a single dose prior to a PET/CT scan ...

5. jacc.org jacc.org/doi/10.1016/j.jcmg.2023.09.002

Shining a Radiant Light on Cardiac Amyloidosis With ... Remarkably, abnormal 124I-evuzamitide cardiac uptake was observed in 6 patients with clinical diagnosis of ATTR amyloidosis but without signs of ...

6. attralus.com attralus.com/press-releases/attralus-announces-presentation-of-clinical-data-for-124i-evuzamitide-at-01-a-novel-amyloid-specific-pet-imaging-agent-at-the-28th-annual-scientific-session-of-the-american-society-of-nuclear-card

Attralus Announces Presentation of Clinical Data for 124I- ... AT-01 is a first-in-class pan-amyloid imaging agent capable of detecting diverse types of systemic amyloidosis in multiple organs.

7. jacc.org jacc.org/doi/10.1016/j.jcmg.2023.08.009

Cardiac Amyloid Detection by PET/CT Imaging of Iodine ... Safety assessments were performed before and after the infusion of 124I-evuzamitide. Vital signs were collected immediately prior to infusion of ...