Tang W H Wilson, Steiner Johannes, Kassi Mahwash, Wheeler Matthew T, Spahillari Aferdita, Sweitzer Nancy K, Grodin Justin L, Solomon Neal, Singhal Shalabh, McEwen Amanda M G, Murphy Samuel L
Department of Cardiovascular Medicine, Heart Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Knight Cardiovascular Institute, Oregon Health Sciences University, Portland, Oregon, USA.
JACC Basic Transl Sci. 2025 Jul 29;10(9):101352. doi: 10.1016/j.jacbts.2025.101352.
This first-in-human, phase 1, double-blind, placebo-controlled study evaluated the safety, tolerability, immunogenicity, pharmacokinetics, and exploratory efficacy of a selective ErbB4 agonist, JK07, in patients with heart failure with reduced ejection fraction (HFrEF). In these patients on optimal goal-directed medical therapy, JK07 was generally safe and well tolerated at dose levels up to 0.09 mg/kg. There was a trend toward increased incidence and severity of treatment-emergent adverse events observed at the highest dose of 0.27 mg/kg. Consistent with prolonged effects seen with transient exposure to neuregulin-1 in previous phase 1 investigations, improvements in left ventricular ejection fraction lasting up to 180 days after infusion were observed. These findings support continued clinical investigation of JK07 in heart failure. (Study of JK07 in Subjects With Heart Failure With Reduced Ejection Fraction; NCT04210375).
这项首次人体、1期、双盲、安慰剂对照研究评估了选择性表皮生长因子受体4（ErbB4）激动剂JK07在射血分数降低的心力衰竭（HFrEF）患者中的安全性、耐受性、免疫原性、药代动力学和探索性疗效。在接受最佳目标导向药物治疗的这些患者中，JK07在剂量水平高达0.09mg/kg时总体安全且耐受性良好。在最高剂量0.27mg/kg时观察到治疗中出现的不良事件的发生率和严重程度有增加趋势。与先前1期研究中短暂暴露于神经调节蛋白-1所见的延长效应一致，观察到输注后左心室射血分数改善持续长达180天。这些发现支持对JK07在心力衰竭中的持续临床研究。（射血分数降低的心力衰竭患者中JK07的研究；NCT04210375）
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