pUDK-HGF Gene Therapy to Relieve CLI Rest Pain and Ulcer: A Phase II, Double-Blind, Randomized Placebo-Controlled Trial
Yongquan Gu, Shijun Cui, Changjian Liu, Jichun Zhao, Ming Li, Yiqing Li, Xinglong Yang, Bonan Lv, Mingzhang Li, Wenguang Zhao, Wei Guo, Jianhua Huang, Wen Huang, Zhenming Qiu, Jun Zhao, Ping Yin, Tingting Qin, Dan Zhu, Wenjie Sun, Keyun Ren, Yuxin Lu, Xiaochen Cheng, Li Du, Fengjun Xiao, Qinglin Zhang, Chu-Tse Wu
Abstract
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 (n = 119) and patients with leg ulcers (n = 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 (p = 0.0148). More responders with >50% pain reduction were also observed in the pUDK-HGF groups than in the placebo groups (p = 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.