Nine-year follow-up of patients receiving recombinant human hepatocyte growth factor nude plasmid DNA for critical limb ischemia: Updated safety and efficacy results

Abstract: CONTEXT: NL003 is a plasmid engineered to simultaneously express two isoforms of hepatocyte growth factor. The Phase II clinical trial shows that intramuscular injection of NL003 in the affected limb of patients with critical limb ischemia (CLI) is safe and could alleviate pain and promote ulcer healing. The purpose of this study was to evaluate the long-term safety and efficacy of NL003. METHODS: A total of 108 participants were evaluated: 32 in the placebo group and 76 in the NL003 group. The primary endpoint was 5-year amputation-free survival and the secondary endpoints were pain, ulcer, and adverse reactions. RESULTS: During a mean follow-up period of 10.4 years, the 5-year amputation-free survival rate was 67.1% (51/76) in the NL003 group and 37.5% (12/32) in the placebo group ( P < 0.05). The median amputation-free survival was 9.53 years in the NL003 group and 4.51 years in the placebo group. There was no significant difference in the rates of major amputation between the two groups (21.1% vs. 21.9%). Pain relief and ulcer healing tended to favor the NL003 group. No serious adverse reactions such as gene integration and tumor were found during the follow-up. CONCLUSIONS: NL003 has a favorable long-term safety profile and may provide long-term benefit for patients with CLI.