Design and rationale of the Research with EVuzamitide to Evaluate for cardiac AmyLoidosis (REVEAL) positron emission...

The objective of this study is to describe the rationale and design of the multicenter phase 3 Research with EVuzamitide to Evaluate for cardiac AmyLoidosis (REVEAL) trial evaluating the diagnostic performance of ¹²⁴I-evuzamitide positron emission tomography/computed tomography (PET/CT) for detection of cardiac amyloidosis (CA) in patients undergoing evaluation for suspected disease. ¹²⁴I-evuzamitide is a novel fibril-targeting positron-emitting radiotracer that binds hypersulfated heparan sulfate glycans in amyloid fibrils across multiple amyloid subtypes.

This open-label, single-arm study, enrolled adults with suspected CA at 18 USA centers. Participants with previously diagnosed CA or systemic amyloidosis with known organ involvement, precursor protein targeted therapy use, estimated glomerular filtration rate less than 15 mL/min/1.73 m², recent myocardial infarction, or recent heparin exposure were excluded. Cardiac and partial-body static PET/CT imaging was performed 4 ± 1 hour after intravenous administration of ¹²⁴I-evuzamitide (1.0 ± 0.1 mCi). Potassium iodide was administered to reduce thyroid uptake of free radioiodine. Three blinded expert physicians independently assessed myocardial tracer uptake visually on PET/CT scans. Separately, three blinded amyloidosis experts adjudicated the presence or absence of CA using standard-of-care clinical, laboratory, biopsy, genetic, electrocardiographic, echocardiographic, cardiac magnetic resonance, and bone-avid tracer cardiac scintigraphy data. The primary endpoints were the sensitivity and specificity of visually interpreted ¹²⁴I-evuzamitide PET/CT for the diagnosis of CA compared with the adjudicated standard-of-care diagnosis.

REVEAL is the first multicenter phase 3 study evaluating a fibril-targeted PET radiotracer for the diagnosis of CA and may establish a noninvasive molecular imaging approach for detecting cardiac and systemic amyloid deposition across multiple amyloid subtypes.