Gu Yongquan, Cui Shijun, Liu Changjian, Zhao Jichun, Li Ming, Li Yiqing, Yang Xinglong, Lv Bonan, Li Mingzhang, Zhao Wenguang, Guo Wei, Huang Jianhua, Huang Wen, Qiu Zhenming, Zhao Jun, Yin Ping, Qin Tingting, Zhu Dan, Sun Wenjie, Ren Keyun, Lu Yuxin, Cheng Xiaochen, Du Li, Xiao Fengjun, Zhang Qinglin, Wu Zuze
Vascular Surgery Department, Xuan Wu Hospital, Capital Medical University, Beijing, China.
Vascular Surgery Department, Nanjin Drum Tower Hospital, Nanjing, China.
Hum Gene Ther. 2021 Aug;32(15-16):839-849. doi: 10.1089/hum.2020.290. Epub 2021 May 21.
This phase II clinical trial investigated the efficacy and safety of intramuscular injection of plasmid pUDK-HGF, which encodes the human hepatocyte growth factor gene in patients with critical limb ischemia. Resting pain patients ( = 119) and patients with leg ulcers ( = 121) were enrolled as two cohorts and randomized to receive pUDK-HGF treatment on days 0, 14, and 28. In the resting pain cohort, the proportion of patients with complete pain relief on day 180 after receiving pUDK-HGF injection, as the primary outcome, was significantly higher than that of the placebo group on the same day ( = 0.0148). More responders with >50% pain reduction were also observed in the pUDK-HGF groups than in the placebo groups ( = 0.0168). In the ulcer cohort of patients, pUDK-HGF treatment tended to be superior to the placebo in the percentage of patients with both complete ulcer healing and >50% ulcer healing. No significant differences in the incidence of adverse events (AEs) or serious AEs were observed among the groups. The mid-dose pUDK-HGF (6 mg) was the most efficacious, and is therefore an appropriate dose for use in a phase III clinical trial. This study was approved by the China Food and Drug Administration (2013L00637), China Clinical Trial Registry URL: www.chinadrugtrials.org.cn. Unique Identifier: 20130378.
这项II期临床试验研究了肌肉注射编码人肝细胞生长因子基因的质粒pUDK-HGF对严重肢体缺血患者的疗效和安全性。静息痛患者（n = 119）和腿部溃疡患者（n = 121）作为两个队列入组，并随机分配在第0、14和28天接受pUDK-HGF治疗。在静息痛队列中，以接受pUDK-HGF注射后第180天完全缓解疼痛的患者比例作为主要结局，该比例显著高于同日安慰剂组（P = 0.0148）。与安慰剂组相比，pUDK-HGF组中疼痛减轻>50%的缓解者也更多（P = 0.0168）。在溃疡患者队列中，pUDK-HGF治疗在溃疡完全愈合和溃疡愈合>50%的患者百分比方面往往优于安慰剂。各治疗组间不良事件（AE）或严重AE的发生率未观察到显著差异。中剂量pUDK-HGF（6mg）疗效最佳，因此是III期临床试验的合适剂量。本研究经中国食品药品监督管理总局批准（2013L00637），中国临床试验注册中心网址：www.chinadrugtrials.org.cn。唯一标识符：20130378。
