Rationale and Design of CARDIO-TTRansform, a Phase 3 Trial of Eplontersen in Transthyretin Amyloid Cardiomyopathy.
Ahmad, M., Francesco, C., K, D.M., Marianna, F., Pablo, G.P., D, G.J., Mazen, H., Laura, O., D, S.S., W, S.B., Nobuhiro, T., Marcia, W.C., V, K.A., H, F.R., J, S.S., Jose, N.N., J, V.N., Qingqing, Y., Jersey, C., . . . S, M.M. (2026). Rationale and Design of CARDIO-TTRansform, a Phase 3 Trial of Eplontersen in Transthyretin Amyloid Cardiomyopathy.. Circ Heart Fail. https://doi.org/10.1161/CIRCHEARTFAILURE.126.014205
Ahmad M, Francesco C, K DM, Marianna F, Pablo GP, D GJ, et al. Rationale and Design of CARDIO-TTRansform, a Phase 3 Trial of Eplontersen in Transthyretin Amyloid Cardiomyopathy.. Circ Heart Fail. 2026; doi: 10.1161/CIRCHEARTFAILURE.126.014205
Ahmad M, Francesco C, K DM, et al. Rationale and Design of CARDIO-TTRansform, a Phase 3 Trial of Eplontersen in Transthyretin Amyloid Cardiomyopathy.[J]. Circ Heart Fail. 2026. DOI: 10.1161/CIRCHEARTFAILURE.126.014205.
@article{ahmad2026,
author = {Masri Ahmad and Cappelli Francesco and Davis Margot K and Fontana Marianna and Garcia-Pavia Pablo and Gillmore Julian D and Hanna Mazen and Obici Laura and Solomon Scott D and Sperry Brett W and Tahara Nobuhiro and Waddington-Cruz Marcia and Kristen Arnt V and Falk Rodney H and Shah Sanjiv J and Nativi-Nicolau Jose and Viney Nicholas J and Yang Qingqing and Chen Jersey and Tsimikas Sotirios and Maurer Mathew S},
title = {Rationale and Design of CARDIO-TTRansform, a Phase 3 Trial of Eplontersen in Transthyretin Amyloid Cardiomyopathy.},
journal = {Circ Heart Fail},
year = {2026},
doi = {10.1161/CIRCHEARTFAILURE.126.014205},
note = {PMID: 42104840},
}
TY - JOUR AU - Masri Ahmad AU - Cappelli Francesco AU - Davis Margot K AU - Fontana Marianna AU - Garcia-Pavia Pablo AU - Gillmore Julian D AU - Hanna Mazen AU - Obici Laura AU - Solomon Scott D AU - Sperry Brett W AU - Tahara Nobuhiro AU - Waddington-Cruz Marcia AU - Kristen Arnt V AU - Falk Rodney H AU - Shah Sanjiv J AU - Nativi-Nicolau Jose AU - Viney Nicholas J AU - Yang Qingqing AU - Chen Jersey AU - Tsimikas Sotirios AU - Maurer Mathew S TI - Rationale and Design of CARDIO-TTRansform, a Phase 3 Trial of Eplontersen in Transthyretin Amyloid Cardiomyopathy. T2 - Circ Heart Fail PY - 2026 DO - 10.1161/CIRCHEARTFAILURE.126.014205 AN - PMID:42104840 ER -
Transthyretin amyloidosis with cardiomyopathy is a progressive, fatal disease characterized by deposition of extracellular misfolded transthyretin (TTR) in the myocardium. Eplontersen is an N-acetylgalactosamine ligand-conjugated antisense oligonucleotide targeting hepatocyte TTR messenger RNA to reduce the production of circulating TTR. CARDIO-TTRansform is a Phase 3, randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of eplontersen in transthyretin amyloidosis with cardiomyopathy. Key inclusion criteria include histological evidence of amyloid deposits or grade 2 to 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 for 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 end point is a composite of cardiovascular mortality and recurrent clinical cardiovascular events through 140 weeks. Secondary end points, 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 end point in the patient subgroup receiving stabilizers at baseline, and cardiovascular mortality. Echocardiography was performed in all participants, with cardiovascular magnetic resonance imaging and technetium scintigraphy in a subset. CARDIO-TTRansform is fully enrolled, with 1432 randomized participants who were dosed with study drug or placebo. As the largest transthyretin amyloidosis with cardiomyopathy study to date, it will evaluate whether eplontersen improves cardiovascular outcomes in patients receiving locally available standard of care, including TTR stabilizers. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04136171. URL: http://ClinicalTrialsRegister.eu; Unique identifier: EudraCT number 2019-002835-27.