NL003 is a plasmid engineered to simultaneously express two isoforms of hepatocyte growth factor. This phase II study was performed to assess the clinical safety and efficacy of intramuscular injection of NL003 in critical limb ischemia (CLI) patients for 6 months. Two hundred patients (Rutherford scale 4-5) were randomly assigned: placebo (n = 50), low-dose NL003 (n = 50), middle-dose NL003 (n = 50), or high-dose NL003 (n = 50). The drug was administered in the affected limb of 197 patients on days 0, 14, and 28. No significant differences in the incidence of adverse events (AEs) or serious AEs were found among the groups. At 6 months, pain severity was significantly reduced in all NL003 groups, but not in the placebo group (p < 0.05). The proportion of patients with complete ulcer healing in the high-dose group was significantly higher than that of the placebo group (p = 0.0095). There were no statistically significant differences in transcutaneous oxygen pressure (TcPO2), ankle-brachial index (ABI), or toe-brachial index (TBI) value among the four groups throughout the study period. These results provide the first effective evidence of significant improvements in total healing of ulcers in treated legs, complete pain relief without analgesics, and safety for NL003 in patients with Rutherford stage 4-5.

中文翻译：

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肝细胞生长因子治疗严重肢体缺血的随机、双盲、安慰剂对照 II 期研究。


NL003 是一种经工程改造可同时表达肝细胞生长因子两种亚型的质粒。这项II期研究旨在评估严重肢体缺血（CLI）患者肌肉注射NL003 6个月的临床安全性和有效性。 200 名患者（卢瑟福量表 4-5）被随机分配：安慰剂 (n = 50)、低剂量 NL003 (n = 50)、中剂量 NL003 (n = 50) 或高剂量 NL003 (n = 50) ）。该药物在第 0、14 和 28 天对 197 名患者的受影响肢体进行了给药。各组之间未发现不良事件 (AE) 或严重 AE 的发生率存在显着差异。 6 个月时，所有 NL003 组的疼痛严重程度均显着降低，但安慰剂组则不然 (p < 0.05)。高剂量组溃疡完全愈合的患者比例显着高于安慰剂组（p = 0.0095）。在整个研究期间，四组之间的经皮氧分压（TcPO2）、踝臂指数（ABI）或趾臂指数（TBI）值没有统计学上的显着差异。这些结果提供了第一个有效证据，证明 NL003 在卢瑟福 4-5 期患者中的治疗腿部溃疡的完全愈合显着改善，无需镇痛药即可完全缓解疼痛，并且安全。