Single Ascending-Dose Study of Selective ErbB4 Agonist JK07 in Heart Failure With Reduced Ejection Fraction

IF 8.4 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

JACC: Basic to Translational Science Pub Date : 2025-07-29 DOI:10.1016/j.jacbts.2025.101352

W.H. Wilson Tang MD , Johannes Steiner MD , Mahwash Kassi MD , Matthew T. Wheeler MD , Aferdita Spahillari MD, MPH , Nancy K. Sweitzer MD, PhD , Justin L. Grodin MD, MPH , Neal Solomon MD , Shalabh Singhal MD , Amanda M.G. McEwen MS , Samuel L. Murphy MD

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引用次数: 0

Abstract

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)

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选择性ErbB4激动剂JK07单次递增剂量治疗心力衰竭伴射血分数降低的研究

这项首次在人体进行的1期双盲安慰剂对照研究评估了选择性ErbB4激动剂JK07在心力衰竭伴射血分数降低（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。在这些接受最佳目标导向药物治疗的患者中，JK07在高达0.09 mg/kg的剂量水平下通常是安全且耐受性良好的。在最高剂量为0.27 mg/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的趋势。与之前的1期研究中短暂暴露于神经调节蛋白-1所观察到的长期效果一致，在输注后观察到左心室射血分数的改善持续长达180天。这些发现支持JK07在心力衰竭中的持续临床研究。JK07在心力衰竭伴射血分数降低患者中的应用研究NCT04210375)

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来源期刊

JACC: Basic to Translational Science CARDIAC & CARDIOVASCULAR SYSTEMS-

CiteScore

14.20

自引率

1.00%

发文量

161

审稿时长

16 weeks

期刊介绍： JACC: Basic to Translational Science is an open access journal that is part of the renowned Journal of the American College of Cardiology (JACC). It focuses on advancing the field of Translational Cardiovascular Medicine and aims to accelerate the translation of new scientific discoveries into therapies that improve outcomes for patients with or at risk for Cardiovascular Disease. The journal covers thematic areas such as pre-clinical research, clinical trials, personalized medicine, novel drugs, devices, and biologics, proteomics, genomics, and metabolomics, as well as early phase clinical trial methodology.