I-124 Evuzamitide for Cardiac Amyloidosis

(REVEAL Trial)

Recruiting at 22 trial locations

Overseen By Sharmila Dorbala, MD, MPH, MASNC

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Sharmila Dorbala

Must not be taking: Tafamadis, Heparin, others

Disqualifiers: Cardiac amyloidosis, Systemic amyloidosis, Pregnancy, Dialysis, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

200 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are receiving therapy for ATTR cardiac amyloidosis or have taken heparin or similar drugs within 7 days before the study.

What data supports the effectiveness of the drug I-124 evuzamitide for cardiac amyloidosis?

The research indicates that I-124 evuzamitide is a new type of imaging agent that can bind to amyloid deposits, which are harmful protein buildups in the heart. Although its ability to measure these deposits in cardiac amyloidosis hasn't been fully studied yet, it shows promise as a tool for better diagnosis and monitoring of the condition. ^{1 2 3 4 5}

What makes the drug I-124 evuzamitide unique for treating cardiac amyloidosis?

I-124 evuzamitide is unique because it is a novel radiotracer that directly binds to amyloid deposits, allowing for precise imaging and quantification of cardiac amyloid, which is not possible with current indirect imaging methods. ^{1 2 5 6 7}

What is the purpose of this trial?

The purpose of this Phase 3, open label, single dose imaging study is to evaluate the efficacy and safety of I-124 evuzamitide (radioactive dye) for diagnosing Cardiac Amyloidosis in participants with suspected Cardiac Amyloidosis. The imaging test that will be used in this study is a Positron Emission Tomography Computed Tomography (PET/CT) scan.

Research Team

Sharmila Dorbala, MD, MPH, MASNC

Principal Investigator

Brigham and Women's Hospital

Eligibility Criteria

This trial is for adults who may have cardiac amyloidosis and can lie still for an hour during a PET/CT scan. They must be able to consent, follow study rules, and use contraception if needed. People with known allergies to potassium iodide, recent heart attacks, severe claustrophobia, diagnosed cardiac or systemic amyloidosis without heart involvement, mental incapacity, certain medication usage within the last week (like heparin), pregnancy or breastfeeding status, dialysis treatment or severe kidney issues are excluded.

Inclusion Criteria

I can lie on my back for about an hour for a PET/CT scan.

Understands the study procedures and can give signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol

I agree to not have unprotected sex or donate sperm.

Exclusion Criteria

Has a known allergy to potassium iodide

I had a heart attack within the last 3 months.

Has severe claustrophobia or any medical condition that would prevent completion of the imaging protocol

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of I-124 evuzamitide followed by a PET/CT scan to diagnose cardiac amyloidosis

1 day

1 visit (in-person)

Follow-up

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

30 days

Extended Follow-up

Participants are monitored for additional safety and efficacy outcomes

Up to 60 days

Treatment Details

Interventions

• I-124 evuzamitide

Trial Overview The trial tests I-124 evuzamitide's effectiveness as a radioactive dye in diagnosing Cardiac Amyloidosis using PET/CT scans. It's an open-label Phase 3 study where participants receive a single dose of the dye to see how well it helps identify the disease.

Participant Groups

Group I: Single dose, Open label Experimental Treatment 1 Intervention

Open label use of I124-evuzamitide to diagnose cardiac amyloidosis.

Who Is Running the Clinical Trial?

Sharmila Dorbala

Lead Sponsor

Trials

1

Recruited

200+

Attralus, Inc.

Industry Sponsor

Trials

8

Recruited

670+

Findings from Research

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]

In a study of 153 previously treated patients with systemic AL amyloidosis, the combination of pomalidomide and dexamethasone led to a 44% rate of at least partial hematologic response after 6 treatment cycles, indicating its efficacy in this challenging patient population.

Patients who achieved at least a partial response had significantly improved overall survival (median 50 months) and progression-free survival (median 37 months), highlighting the importance of hematologic response in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pomalidomide and dexamethasone grant rapid haematologic responses in patients with relapsed and refractory AL amyloidosis: a European retrospective series of 153 patients. Milani, P., Sharpley, F., Schönland, SO., et al.[2021]

Cardiac magnetic resonance (CMR) imaging is revolutionizing the assessment of cardiac amyloidosis by providing more accurate evaluations of heart structure and function compared to traditional echocardiography, particularly in characterizing myocardial tissue.

New CMR techniques, such as T1 mapping, allow for precise measurement of amyloid burden and changes in heart tissue over time, which could enhance drug development and lead to improved treatment strategies and prognostic systems for patients with cardiac amyloidosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular magnetic resonance for amyloidosis. Fontana, M., Chung, R., Hawkins, PN., et al.[2022]

In a study of 75 patients with light-chain (AL) amyloidosis, left atrial volume and left ventricular global longitudinal strain (LVGLS) were found to be independent predictors of mortality, highlighting their importance in assessing patient prognosis.

A composite echocardiographic risk score combining left atrial volume and LVGLS demonstrated similar prognostic performance to the conventional Mayo staging system, suggesting that echocardiographic parameters can be effectively used alongside traditional cardiac biomarkers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel echocardiographic risk score for light-chain amyloidosis. Geenty, P., Sivapathan, S., Stefani, LD., et al.[2023]

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]

In a phase 2 trial involving 33 patients with previously treated AL amyloidosis, the combination of pomalidomide and dexamethasone showed a confirmed hematologic response rate of 48%, indicating its efficacy in this rare condition.

The treatment resulted in a median overall survival of 28 months and a progression-free survival of 14 months, suggesting that pomalidomide could be a valuable option for patients with limited treatment alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity of pomalidomide in patients with immunoglobulin light-chain amyloidosis. Dispenzieri, A., Buadi, F., Laumann, K., et al.[2022]

In a Phase I study involving 18 patients with AL amyloidosis, the antibody 11-1F4 showed significant uptake in various organs, including the liver and spleen, which could help in assessing disease extent.

The imaging results from PET/CT scans correlated well with traditional tissue biopsy findings, suggesting that the labeled antibody could be a useful tool for identifying patients suitable for passive immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radioimmunodetection of amyloid deposits in patients with AL amyloidosis. Wall, JS., Kennel, SJ., Stuckey, AC., et al.[2021]

References

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

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

2. England pubmed.ncbi.nlm.nih.gov

Pomalidomide and dexamethasone grant rapid haematologic responses in patients with relapsed and refractory AL amyloidosis: a European retrospective series of 153 patients. [2021]

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

Cardiovascular magnetic resonance for amyloidosis. [2022]

4. England pubmed.ncbi.nlm.nih.gov

A novel echocardiographic risk score for light-chain amyloidosis. [2023]

5. 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]

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

Activity of pomalidomide in patients with immunoglobulin light-chain amyloidosis. [2022]

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

Radioimmunodetection of amyloid deposits in patients with AL amyloidosis. [2021]