PMID- 33726499 OWN - NLM STAT- MEDLINE DCOM- 20220131 LR - 20220131 IS - 1557-7422 (Electronic) IS - 1043-0342 (Linking) VI - 32 IP - 15-16 DP - 2021 Aug TI - pUDK-HGF Gene Therapy to Relieve CLI Rest Pain and Ulcer: A Phase II, Double-Blind, Randomized Placebo-Controlled Trial. PG - 839-849 LID - 10.1089/hum.2020.290 [doi] AB - 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. FAU - Gu, Yongquan AU - Gu Y AD - Vascular Surgery Department, Xuan Wu Hospital, Capital Medical University, Beijing, China. FAU - Cui, Shijun AU - Cui S AD - Vascular Surgery Department, Xuan Wu Hospital, Capital Medical University, Beijing, China. FAU - Liu, Changjian AU - Liu C AD - Vascular Surgery Department, Nanjin Drum Tower Hospital, Nanjing, China. FAU - Zhao, Jichun AU - Zhao J AD - Vascular Surgery Department, West China Hospital, Sichuan University, Chengdu, China. FAU - Li, Ming AU - Li M AD - Vascular Surgery Department, The First Affiliated Hospital of Medical School of Zhejiang University, Hangzhou, China. FAU - Li, Yiqing AU - Li Y AD - Vascular Surgery Department, Wuhan Union Hospital, Wuhan, China. FAU - Yang, Xinglong AU - Yang X AD - General Surgery Department, The First Affiliated Hospital of Nanchang University, Nanchang, China. FAU - Lv, Bonan AU - Lv B AD - General Surgery Department, Hebei General Hospital, Shijiazhuang, China. FAU - Li, Mingzhang AU - Li M AD - General Surgery Department, Baotou Central Hospital, Baotou, China. FAU - Zhao, Wenguang AU - Zhao W AD - Vascular Surgery Department, The First Bethune Hospital of Jilin University, Changchun, China. FAU - Guo, Wei AU - Guo W AD - Vascular Surgery Department, Chinese PLA General Hospital, Beijing, China. FAU - Huang, Jianhua AU - Huang J AD - Vascular Surgery Department, Xiangya Hospital Central South University, Changsha, China. FAU - Huang, Wen AU - Huang W AD - Vascular Surgery Department, The First Affiliated Hospital of Chongqin Medical University, Chongqing, China. FAU - Qiu, Zhenming AU - Qiu Z AD - General Surgery Department, Taizhou Hospital of Zhejiang Province, Linhai, China. FAU - Zhao, Jun AU - Zhao J AD - General Surgery Department, Shanghai Sixth People's Hospital Affiliated to Shanghai JiaoTong University, Shanghai, China. FAU - Yin, Ping AU - Yin P AD - School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Qin, Tingting AU - Qin T AD - School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Zhu, Dan AU - Zhu D AD - Humanwell Healthcare (Group) Co. Ltd., Wuhan, China. FAU - Sun, Wenjie AU - Sun W AD - Humanwell Healthcare (Group) Co. Ltd., Wuhan, China. FAU - Ren, Keyun AU - Ren K AD - Humanwell Healthcare (Group) Co. Ltd., Wuhan, China. FAU - Lu, Yuxin AU - Lu Y AD - Department of Experimental Hematology and Biochemistry, Beijing Institute of Radiation Medicine, Beijing, China. FAU - Cheng, Xiaochen AU - Cheng X AD - Department of Experimental Hematology and Biochemistry, Beijing Institute of Radiation Medicine, Beijing, China. FAU - Du, Li AU - Du L AD - Department of Experimental Hematology and Biochemistry, Beijing Institute of Radiation Medicine, Beijing, China. FAU - Xiao, Fengjun AU - Xiao F AD - Department of Experimental Hematology and Biochemistry, Beijing Institute of Radiation Medicine, Beijing, China. FAU - Zhang, Qinglin AU - Zhang Q AUID- ORCID: 0000-0003-4023-2212 AD - Department of Experimental Hematology and Biochemistry, Beijing Institute of Radiation Medicine, Beijing, China. FAU - Wu, Zuze AU - Wu Z AD - Department of Experimental Hematology and Biochemistry, Beijing Institute of Radiation Medicine, Beijing, China. LA - eng PT - Clinical Trial, Phase II PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20210521 PL - United States TA - Hum Gene Ther JT - Human gene therapy JID - 9008950 RN - 0 (HGF protein, human) RN - 67256-21-7 (Hepatocyte Growth Factor) SB - IM MH - Chronic Limb-Threatening Ischemia MH - Genetic Therapy MH - *Hepatocyte Growth Factor/genetics MH - Humans MH - Ischemia/therapy MH - Pain MH - *Ulcer OTO - NOTNLM OT - critical limb ischemia OT - gene therapy OT - hepatocyte growth factor OT - pUDK-HGF OT - peripheral arterial disease OT - phase II clinical trial EDAT- 2021/03/18 06:00 MHDA- 2022/02/01 06:00 CRDT- 2021/03/17 05:33 PHST- 2021/03/18 06:00 [pubmed] PHST- 2022/02/01 06:00 [medline] PHST- 2021/03/17 05:33 [entrez] AID - 10.1089/hum.2020.290 [doi] PST - ppublish SO - Hum Gene Ther. 2021 Aug;32(15-16):839-849. doi: 10.1089/hum.2020.290. Epub 2021 May 21.