GenePHIT phase 2 study design: a double blind, placebo-controlled trial to assess efficacy, safety, and tolerability of AB-1002 gene therapy in adults with heart failure

作者：Timothy D. Henry, Eugene Chung, M.F. Alvisi, Farah Sethna, Lothar Roessig, Lisa Roberts, Sandeep K. Reddy, Leigh Ervin, Sameh Mikhail, Chen Jiang, Jude Samulski, Evangelia G. Kranias, Anna Tretiakova, Roger J. Hajjar · 发表于：European Heart Journal · 年份：2024 · DOI：10.1093/eurheartj/ehae666.3642 · 被引用次数：3 · 研究领域：CRISPR and Genetic Engineering、Pluripotent Stem Cells Research、CAR-T cell therapy research

Abstract Introduction Heart failure (HF) is associated with substantial morbidity and mortality, highlighting a critical need for novel therapies. AB-1002, an engineered adeno-associated virus (AAV) vector gene therapy candidate, delivers a constitutively active form of protein phosphatase inhibitor (I-1c) to restore cardiomyocyte intracellular calcium homeostasis. Preliminary results from an ongoing Phase (Ph) 1 trial (NCT04179643) of AB-1002 showed favourable safety and tolerability. Here we describe the design of AB-1002 Ph 2 trial (GenePHIT; NCT05598333) to evaluate efficacy, safety, and tolerability. Methods This phase 2 adaptive, double-blind, placebo-controlled, randomised, multi-centre trial (currently United States; European sites planned) includes a 52-week observation and 4-year follow-up period. Eligible patients are ≥18 years of age with non-ischaemic cardiomyopathy and New York Health Association (NYHA) Class III heart failure symptoms (Figure). Patients will be randomised 1:1:1 (n=30–50/treatment arm), including a single dose of AB-1002 administered via antegrade intracoronary infusion at 1 of 2 different doses, or placebo, all in addition to standard of care. The primary endpoint will evaluate efficacy at 52 weeks based on the composite endpoint by modified win ratio, which includes cardiovascular-related death, change in NYHA classification, and for the responders, improvements in left ventricular ejection fraction (LVEF) (≥5%), peak oxygen uptake (pVO2) ≥1.5...