PMID- 31805256
OWN - NLM
STAT- MEDLINE
DCOM- 20200626
LR  - 20201207
IS  - 1525-0024 (Electronic)
IS  - 1525-0016 (Print)
IS  - 1525-0016 (Linking)
VI  - 27
IP  - 12
DP  - 2019 Dec 4
TI  - A Randomized, Double-Blind, Placebo-Controlled Phase II Study of Hepatocyte 
      Growth Factor in the Treatment of Critical Limb Ischemia.
PG  - 2158-2165
LID - S1525-0016(19)30493-9 [pii]
LID - 10.1016/j.ymthe.2019.10.017 [doi]
AB  - 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 (TcPO(2)), 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.
CI  - Copyright (c) 2019. Published by Elsevier Inc.
FAU - Gu, Yongquan
AU  - Gu Y
AD  - Vascular Surgery Department, Xuan Wu Hospital, Capital Medical University, 
      Beijing, China. Electronic address: 15901598209@163.com.
FAU - Cui, Shijun
AU  - Cui S
AD  - Vascular Surgery Department, Xuan Wu Hospital, Capital Medical University, 
      Beijing, China.
FAU - Wang, Qi
AU  - Wang Q
AD  - Vascular Surgery Department, First Hospital, Jilin University, Changchun, China.
FAU - Liu, Changjian
AU  - Liu C
AD  - Vascular Surgery Department, Nanjing Drum Tower Hospital, Nanjing, China.
FAU - Jin, Bi
AU  - Jin B
AD  - Vascular Surgery Department, Wuhan Union Hospital, Wuhan, China.
FAU - Guo, Wei
AU  - Guo W
AD  - Vascular Surgery Department, Chinese PLA General Hospital, Beijing, China.
FAU - Liu, Changwei
AU  - Liu C
AD  - Vascular Surgery Department, Peking Union Medical College Hospital, Beijing, 
      China.
FAU - Chu, Tongbin
AU  - Chu T
AD  - Diabetic Foot Treatment Center, Second Hospital of Dalian Medical University, 
      Dalian, China.
FAU - Shu, Chang
AU  - Shu C
AD  - Vascular Surgery Department, Second Xiang Ya Hospital, Central South University, 
      Changsha, China.
FAU - Zhang, Fuxian
AU  - Zhang F
AD  - Vascular Surgery Department, Shi Ji Tan Hospital, Capital Medical University, 
      Beijing, China.
FAU - Han, Chengquan
AU  - Han C
AD  - R&D Center of Beijing Northland Biotech. Co., Ltd., China.
FAU - Liu, Yue
AU  - Liu Y
AD  - R&D Center of Beijing Northland Biotech. Co., Ltd., China.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20191031
PL  - United States
TA  - Mol Ther
JT  - Molecular therapy : the journal of the American Society of Gene Therapy
JID - 100890581
RN  - 67256-21-7 (Hepatocyte Growth Factor)
SB  - IM
CIN - Mol Ther. 2019 Dec 4;27(12):2053. PMID: 31732297
MH  - Double-Blind Method
MH  - Female
MH  - Follow-Up Studies
MH  - Genetic Therapy/*methods
MH  - Hepatocyte Growth Factor/*administration & dosage/genetics
MH  - Humans
MH  - Injections, Intramuscular
MH  - Ischemia/genetics/pathology/*therapy
MH  - Leg/*blood supply
MH  - Male
MH  - Middle Aged
MH  - Plasmids/*administration & dosage/genetics
MH  - Prognosis
PMC - PMC6904746
OTO - NOTNLM
OT  - HGF
OT  - NL003
OT  - angiogenesis
OT  - critical limb ischemia
OT  - gene therapy
OT  - hepatocyte growth factor
OT  - naked plasmid
OT  - peripheral arterial disease
EDAT- 2019/12/06 06:00
MHDA- 2020/06/27 06:00
PMCR- 2020/12/04
CRDT- 2019/12/06 06:00
PHST- 2018/11/26 00:00 [received]
PHST- 2019/10/24 00:00 [revised]
PHST- 2019/10/28 00:00 [accepted]
PHST- 2019/12/06 06:00 [entrez]
PHST- 2019/12/06 06:00 [pubmed]
PHST- 2020/06/27 06:00 [medline]
PHST- 2020/12/04 00:00 [pmc-release]
AID - S1525-0016(19)30493-9 [pii]
AID - 10.1016/j.ymthe.2019.10.017 [doi]
PST - ppublish
SO  - Mol Ther. 2019 Dec 4;27(12):2158-2165. doi: 10.1016/j.ymthe.2019.10.017. Epub 
      2019 Oct 31.