Seltoplasmid promotes ulcer healing versus placebo for treating patients with chronic limb-threatening ischemia: HOPE CLTI-2 trial.

IF 12.1 1区医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Molecular Therapy Pub Date : 2025-04-11 DOI:10.1016/j.ymthe.2025.04.009

Xiao Di,Changwei Liu,Siqiao Sun,Jinbao Qin,Xueli Guo,Yikuan Chen,Xin Li,Hongkun Zhang,Ming Liu,Liu Yang,Hui Zhao,Shaoying Lu,Jingyong Huang,Yunfeng Zhang,Jun Li,Xiaolei Lin,Kai Yao,Jingdong Tang,Jian Wang,Zhanfeng Gao,Jinjun Wang,Xiaojin Huang,Songshan Xu,Yue Liu,Wei Han,Leng Ni,Wei Ye,Yuehong Zheng,Yuexin Chen,Bao Liu

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引用次数: 0

Abstract

Intramuscular injection of donaperminogene seltoplasmid (recombinant human hepatocyte growth factor plasmids) represents a gene therapy that treat patients with chronic limb-threatening ischemia (CLTI). The HOPE CLTI-2 trial was a Phase 3, multicenter, double-blind, placebo-controlled study aimed to evaluate the efficacy and safety of seltoplasmid in patients with Rutherford class 5 CLTI. This study did not require participants to be ineligible for revascularization, allowing enrollment of patients with CLTI caused by either atherosclerosis (ASO) or Buerger's disease (TAO). The primary endpoint was the complete ulcer healing rate at 6 months. A total of 242 participants (53.3% ASO versus 46.7% TAO) were enrolled, with 161 receiving seltoplasmid and 81 receiving placebo. Complete ulcer healing was achieved in 70 patients in the seltoplasmid group compared to 15 patients in the placebo group, resulting in an adjusted healing rate difference of 26.1% (95% confidence interval [CI]: 15.1-37.0%; P < 0.001). The hazard ratio for healing was 2.31 (95% CI: 1.32-4.05; P = 0.004). The benefits of seltoplasmid on ulcer healing persisted in both TAO and ASO subgroups. Serious adverse events were rare. Our study demonstrated that seltoplasmid significantly improved ulcer healing rates in patients with Rutherford class 5 CLTI compared to placebo.

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Seltoplasmid 与安慰剂相比，可促进慢性肢体缺血患者的溃疡愈合：HOPE CLTI-2 试验。

肌内注射donaperminogene自质粒（重组人肝细胞生长因子质粒）是治疗慢性肢体缺血（CLTI）患者的一种基因疗法。HOPE CLTI-2试验是一项3期、多中心、双盲、安慰剂对照研究，旨在评估self质粒在卢瑟福5级CLTI患者中的疗效和安全性。本研究不要求参与者不符合血运重建术的条件，允许由动脉粥样硬化（ASO）或伯格氏病（TAO）引起的CLTI患者入组。主要终点是6个月时溃疡完全愈合率。共有242名参与者（53.3% ASO vs 46.7% TAO）入组，其中161人接受自质粒治疗，81人接受安慰剂治疗。与安慰剂组15例患者相比，自质粒组70例患者溃疡完全愈合，调整后的治愈率差异为26.1%(95%置信区间[CI]: 15.1-37.0%；P < 0.001)。愈合的危险比为2.31 (95% CI: 1.32-4.05；P = 0.004)。自质粒对溃疡愈合的益处在TAO和ASO亚组中持续存在。严重的不良事件很少发生。我们的研究表明，与安慰剂相比，自质粒显著提高了卢瑟福5级CLTI患者的溃疡愈合率。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Therapy 医学-生物工程与应用微生物

CiteScore

19.20

自引率

3.20%

发文量

357

审稿时长

3 months

期刊介绍： Molecular Therapy is the leading journal for research in gene transfer, vector development, stem cell manipulation, and therapeutic interventions. It covers a broad spectrum of topics including genetic and acquired disease correction, vaccine development, pre-clinical validation, safety/efficacy studies, and clinical trials. With a focus on advancing genetics, medicine, and biotechnology, Molecular Therapy publishes peer-reviewed research, reviews, and commentaries to showcase the latest advancements in the field. With an impressive impact factor of 12.4 in 2022, it continues to attract top-tier contributions.