Rationale and Design of CARDIO-TTRansform, a Phase 3 Trial of Eplontersen in Transthyretin Amyloid Cardiomyopathy

作者：Ahmad Masri, F. Cappelli, M. K. Davis, M. Fontana, P. García-Pavía, J. Gillmore, M. Hanna, L. Obici, S. Solomon, B. Sperry, N. Tahara, Márcia Waddington-Cruz, A. Kristen, Rodney H. Falk, Sanjiv J. Shah, Jose Nativi-Nicolau, Nicholas J. Viney, Qing-Qing Yang, Jersey Chen, S. Tsimikas, Mathew S. Maurer · 发表于：Circulation: Heart Failure · 年份：2026 · DOI：10.1161/circheartfailure.126.014205 · 被引用次数：2 · 研究领域：Medicine

Background Transthyretin amyloidosis with cardiomyopathy (ATTR-CM) is a progressive, fatal disease characterized by deposition of extracellular misfolded transthyretin (TTR) in the myocardium. Eplontersen is an N-acetylgalactosamine (GalNAc) ligand-conjugated antisense oligonucleotide targeting hepatocyte TTR messenger ribonucleic acid mRNA to reduce production of circulating TTR. Methods CARDIO-TTRansform is a Phase 3, randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of eplontersen in ATTR-CM. Key inclusion criteria include: histological evidence of amyloid deposits or grade 2–3 cardiac uptake on cardiac scintigraphy in the absence of plasma cell dyscrasia, New York Heart Association class I–III, and end-diastolic interventricular septum thickness >12 millimeters. Participants were randomized 1:1 to receive eplontersen 45 mg or placebo, administered subcutaneously every 4 weeks up to 140 weeks, followed by a 20-week post-treatment evaluation period or open-label extension. Participants received locally available standard of care, including unrestricted use of TTR stabilizers. The primary endpoint is a composite of cardiovascular mortality and recurrent clinical cardiovascular events through 140 weeks. Secondary endpoints, in order of testing hierarchy, include changes from baseline in 6-minute walk distance and Kansas City Cardiomyopathy Questionnaire overall summary score, recurrent cardiovascular events, all-cause mortality, the primary ...