REVEAL - Research With I-124 EVuzamitide to Elucidate Cardiac AmyLoidosis

NCT06788535 | Completed Phase 3 FDA Drug

• 1 other identifier: 2024P002136
• Study Type: interventional
• Target: 204
• Locations: 1 country
• Sites: 20

Brief Summary

The purpose of this multicenter, open-label, single-arm, single-dose study is to assess the sensitivity and specificity of I-124 evuzamitide for the diagnosis of cardiac amyloidosis compared to current clinical standards for diagnosis of cardiac amyloidosis. Participants will receive a positron emission tomography computed tomography (PET/CT) scan 4 hours (± 60 minutes) after administration of I-124 evuzamitide. The primary study hypotheses are that the sensitivity and specificity of I-124 evuzamitide PET/CT imaging of cardiac amyloidosis will be greater than 65% and 55%, respectively, in participants with suspected cardiac amyloidosis.

Conditions

Cardiac Amyloidosis

Keywords

Amyloid Light Chain (AL); Cardiac Amyloidosis; Amyloidosis; Amyloid Transthyretin (ATTR); Transthyretin (TTR); REVEAL; PET Imaging

Outcome Measures

Primary Outcomes (2)

• To evaluate the efficacy (sensitivity) of I-124 evuzamitide for diagnosing cardiac amyloidosis

  Assessment of the sensitivity of PET/CT imaging with I-124 evuzamitide for the diagnosis of cardiac amyloidosis based on visual scan interpretation.

  Up to 60 days after administration of I-124 evuzamitide

• To evaluate the efficacy (specificity) of I-124 evuzamitide for diagnosing cardiac amyloidosis

  Assessment of specificity of PET/CT imaging with I-124 evuzamitide for the diagnosis of cardiac amyloidosis based on visual scan interpretation.

  Up to 60 days after administration of I-124 evuzamitide

Secondary Outcomes (6)

• To evaluate the efficacy (sensitivity) of I-124 evuzamitide for diagnosing cardiac ATTR amyloidosis

  Up to 60 days after administration of I-124 evuzamitide

• To evaluate the efficacy (specificity) of I-124 evuzamitide for diagnosing cardiac ATTR amyloidosis

  Up to 60 days after administration of I-124 evuzamitide

• To evaluate the efficacy (sensitivity) of I-124 evuzamitide for diagnosing cardiac AL amyloidosis

  Up to 60 days after administration of I-124 evuzamitide

• To evaluate the efficacy (specificity) of I-124 evuzamitide for diagnosing cardiac AL amyloidosis

  Up to 60 days after administration of I-124 evuzamitide

• To evaluate the safety (treatment-emergent adverse events [AEs]) of a single intravenous administration of I-124 evuzamitide

  Up to 30 days after administration of I-124 evuzamitide

Study Arms (1)

Single dose, Open label

EXPERIMENTAL

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

Drug: I-124 evuzamitide

Interventions

I-124 evuzamitide DRUG

A single dose of 1 mCi (± 10%) I-124 evuzamitide administered intravenously.

Also known as: AT-01

Single dose, Open label

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Male or female ≥18 years of age.
• Is suspected of having cardiac amyloidosis and is undergoing or will undergo a diagnostic evaluation for cardiac amyloidosis (e.g., echocardiogram \[ECHO\], cardiac magnetic resonance imaging \[CMR\], bone-avid tracer cardiac single-photon emission computerized tomography (SPECT), extracardiac biopsy, or endomyocardial biopsy \[EMB\]). Participants may be enrolled before or during their diagnostic evaluation for cardiac amyloidosis.
• Able to undergo PET/CT imaging as part of the study, including ability to lie supine for approximately 1 hour.
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of \<1% per year during the treatment period and for at least 30 days after administration of I-124 evuzamitide.
• For men: agreement to remain abstinent or use contraceptive measures and agreement to refrain from donating sperm during the treatment period and for at least 120 days after the last dose of study intervention.

You may not qualify if:

• Established diagnosis of cardiac amyloidosis.
• Established diagnosis of systemic amyloidosis with known organ involvement (e.g., renal AL or ATTR peripheral neuropathy). Participants who are amyloid positive only from peripheral tissue, such as abdominal fat, carpal tunnel tissue, or laminectomy tissue, are allowed as long as they do not have other known organ involvement.
• Receiving therapy with an approved treatment (e.g., tafamadis) or in a clinical trial for treatment for ATTR cardiac amyloidosis at time of enrollment. For AL and ATTR amyloidosis: Patients may enter the screening period of a clinical trial for treatment after the ICF is signed and they are enrolled in this trial, but they may not receive an experimental therapy until after the Day 30 safety follow-up visit in this trial.
• Is pregnant or breast-feeding.
• Is mentally or legally incapacitated, has significant emotional problems at the time of the study, or has a history of psychosis.
• Has a known allergy to KI.
• Receiving hemodialysis or peritoneal dialysis.
• Estimated glomerular filtration rate (eGFR) less than 15 mL/min/1.73 m\^2.
• Myocardial infarction within 3 months of screening.
• Has severe claustrophobia or any condition, medical or otherwise, that would prevent completion of the study assessments.
• Has any illness that, in the opinion of the Investigator, might confound the results of the study or pose additional risk to the participant.
• Has received heparin or heparin analogs (e.g., enoxaparin, dalteparin, fondaparinux) within 7 days prior to I-124 evuzamitide administration.
• Known uncorrected thyroid disorders (other than mild elevation of thyroid stimulating hormone with normal thyroxine \[T4\]).

Sponsors & Collaborators

• Bayer: collaborator
• Sharmila Dorbala: lead

Study Sites (20)

Mayo Clinic

Scottsdale, Arizona, 85259, United States

Location

City of Hope - Duarte

Duarte, California, 91010, United States

Location

University of California

San Francisco, California, 94143, United States

Location

Yale Cardiovascular Medicine

New Haven, Connecticut, 06520, United States

Location

Cleveland Clinic

Weston, Florida, 33331, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Cook County Health

Chicago, Illinois, 60612, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

St. Lukes (CVIT) Saint Luke's Health System

Kansas City, Missouri, 64111, United States

Location

Washington University of St. Louis

St Louis, Missouri, 63110, United States

Location

Rutgers

New Brunswick, New Jersey, 08901, United States

Location

Columbia University

New York, New York, 10032, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Cone Health

Greensboro, North Carolina, 27401, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Houston Methodist

Houston, Texas, 77030, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (2)

• Wall JS, Martin EB, Lands R, Ramchandren R, Stuckey A, Heidel RE, Whittle B, Powell D, Richey T, Williams AD, Foster JS, Guthrie S, Kennel SJ. Cardiac Amyloid Detection by PET/CT Imaging of Iodine (124I) Evuzamitide (124I-p5+14): A Phase 1/2 Study. JACC Cardiovasc Imaging. 2023 Nov;16(11):1433-1448. doi: 10.1016/j.jcmg.2023.08.009.

  PMID: 37940323 BACKGROUND

• Clerc OF, Cuddy SAM, Robertson M, Vijayakumar S, Neri JC, Chemburkar V, Kijewski MF, Di Carli MF, Bianchi G, Falk RH, Dorbala S. Cardiac Amyloid Quantification Using 124I-Evuzamitide (124I-P5+14) Versus 18F-Florbetapir: A Pilot PET/CT Study. JACC Cardiovasc Imaging. 2023 Nov;16(11):1419-1432. doi: 10.1016/j.jcmg.2023.07.007. Epub 2023 Sep 6.

  PMID: 37676210 BACKGROUND

MeSH Terms

Conditions

Amyloid Neuropathies, Familial; Amyloidosis

Condition Hierarchy (Ancestors)

Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Nervous System Diseases; Amyloid Neuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Amyloidosis, Familial; Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases; Proteostasis Deficiencies

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Masking Details: I-124 evuzamitide PET/CT imaging will be evaluated by 3 independent readers who are blinded to all clinical data. The Clinical Adjudication Committee will not have access to I-124 evuzamitide PET/CT imaging.
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director Nuclear Cardiology

Study Record Dates

• First Submitted: December 23, 2024
• First Posted: January 23, 2025
• Study Start: January 14, 2025
• Primary Completion: April 8, 2026
• Study Completion: April 9, 2026
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (20)