부산대학교 도서관

Background:Transthyretin (TTR) amyloidosis (ATTR) is an under-diagnosed cause of heart failure driven by TTR destabilization due to pathogenic mutations and/or aging. AG10 is a small molecule TTR stabilizer under development for the treatment of ATTR. In a randomized, double-blind Phase 2 study in patients with symptomatic ATTR cardiomyopathy (ATTR-CM), AG10 was well tolerated, demonstrated near-complete stabilization of TTR, and increased serum TTR levels to normal in all treated subjects. Serum TTR levels have been reported to be predictive of survival in ATTR-CM, and treatment with TTR stabilizers increases serum TTR levels to an extent that is correlated with their ability to increase stability of tetrameric TTR ex vivo.Methods:ATTRibute-CM is designed to enroll approximately 510 patients with symptomatic ATTR-CM, including those with either wild-type or mutant TTR, with New York Heart Association Class I-III symptoms. Participants will be randomized 2:1 to AG10 800 mg or placebo twice daily and followed for 30 months. After 12 months, change in six-minute walk distance (6MWD), the primary endpoint, will be compared between treatment and placebo groups using mixed model repeated measures as an early assessment of functional clinical benefit. Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) quality-of-life scale will be a key secondary endpoint at this stage. At 30 months, the primary analysis will be the hierarchical combination of all-cause mortality and frequency of cardiovascular-related hospitalizations compared between AG10 and placebo using the Finkelstein-Schoenfeld method.Conclusions:ATTRibute-CM is a prospective, randomized, double-blind, placebo-controlled, global Phase 3 clinical trial in patients with ATTR-CM designed to evaluate AG10?s ability to slow or halt progression of ATTR-CM as measured by function (6MWD), quality of life (KCCQ), and a hierarchical combination of all-cause mortality and frequency of cardiovascular-related hospitalizations.