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A Randomized, Double-Blind, Placebo-Controlled Phase II Study of Hepatocyte Growth Factor in the Treatment of Critical Limb Ischemia.
Mol Ther 2019; 27(12):2158-2165MT

Abstract

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.

Authors+Show Affiliations

Vascular Surgery Department, Xuan Wu Hospital, Capital Medical University, Beijing, China. Electronic address: 15901598209@163.com.Vascular Surgery Department, Xuan Wu Hospital, Capital Medical University, Beijing, China.Vascular Surgery Department, First Hospital, Jilin University, Changchun, China.Vascular Surgery Department, Nanjing Drum Tower Hospital, Nanjing, China.Vascular Surgery Department, Wuhan Union Hospital, Wuhan, China.Vascular Surgery Department, Chinese PLA General Hospital, Beijing, China.Vascular Surgery Department, Peking Union Medical College Hospital, Beijing, China.Diabetic Foot Treatment Center, Second Hospital of Dalian Medical University, Dalian, China.Vascular Surgery Department, Second Xiang Ya Hospital, Central South University, Changsha, China.Vascular Surgery Department, Shi Ji Tan Hospital, Capital Medical University, Beijing, China.R&D Center of Beijing Northland Biotech. Co., Ltd., China.R&D Center of Beijing Northland Biotech. Co., Ltd., China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31805256

Citation

Gu, Yongquan, et al. "A Randomized, Double-Blind, Placebo-Controlled Phase II Study of Hepatocyte Growth Factor in the Treatment of Critical Limb Ischemia." Molecular Therapy : the Journal of the American Society of Gene Therapy, vol. 27, no. 12, 2019, pp. 2158-2165.
Gu Y, Cui S, Wang Q, et al. A Randomized, Double-Blind, Placebo-Controlled Phase II Study of Hepatocyte Growth Factor in the Treatment of Critical Limb Ischemia. Mol Ther. 2019;27(12):2158-2165.
Gu, Y., Cui, S., Wang, Q., Liu, C., Jin, B., Guo, W., ... Liu, Y. (2019). A Randomized, Double-Blind, Placebo-Controlled Phase II Study of Hepatocyte Growth Factor in the Treatment of Critical Limb Ischemia. Molecular Therapy : the Journal of the American Society of Gene Therapy, 27(12), pp. 2158-2165. doi:10.1016/j.ymthe.2019.10.017.
Gu Y, et al. A Randomized, Double-Blind, Placebo-Controlled Phase II Study of Hepatocyte Growth Factor in the Treatment of Critical Limb Ischemia. Mol Ther. 2019 12 4;27(12):2158-2165. PubMed PMID: 31805256.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A Randomized, Double-Blind, Placebo-Controlled Phase II Study of Hepatocyte Growth Factor in the Treatment of Critical Limb Ischemia. AU - Gu,Yongquan, AU - Cui,Shijun, AU - Wang,Qi, AU - Liu,Changjian, AU - Jin,Bi, AU - Guo,Wei, AU - Liu,Changwei, AU - Chu,Tongbin, AU - Shu,Chang, AU - Zhang,Fuxian, AU - Han,Chengquan, AU - Liu,Yue, Y1 - 2019/10/31/ PY - 2018/11/26/received PY - 2019/10/24/revised PY - 2019/10/28/accepted PY - 2020/12/04/pmc-release PY - 2019/12/6/entrez PY - 2019/12/6/pubmed PY - 2019/12/6/medline KW - HGF KW - NL003 KW - angiogenesis KW - critical limb ischemia KW - gene therapy KW - hepatocyte growth factor KW - naked plasmid KW - peripheral arterial disease SP - 2158 EP - 2165 JF - Molecular therapy : the journal of the American Society of Gene Therapy JO - Mol. Ther. VL - 27 IS - 12 N2 - 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. SN - 1525-0024 UR - https://www.unboundmedicine.com/medline/citation/31805256/A_Randomized,_Double-Blind,_Placebo-Controlled_Phase_II_Study_of_Hepatocyte_Growth_Factor_in_the_Treatment_of_Critical_Limb_Ischemia L2 - https://linkinghub.elsevier.com/retrieve/pii/S1525-0016(19)30493-9 DB - PRIME DP - Unbound Medicine ER -