We aimed to evaluate in a phase I dose-escalation study, the safety of intramuscular injections of a novel non-viral plasmid DNA expressing two isoforms of human hepatocyte growth factor (HGF) (VM202) in patients with critical limb ischemia (CLI). In total, 12 patients with CLI and unsuitable for revascularization were consecutively assigned to increasing doses (2 to 16 mg) of VM202 administered into the ischemic calf muscle at days 1 and 15. Patients were evaluated for safety and tolerability, changes in ankle-and toe brachial index (ABI and TBI), and pain severity score using a visual analog scale (VAS) throughout a 12-month follow-up period. Median age was 72 years and 53% of the patients were male. VM202 was safe and well tolerated with no death during the 12-month follow-up. Median ABI and TBI significantly increased from 0.35 to 0.52 (P0.005) and from 0.15 to 0.24 (P0.01) at 12 months follow-up. Median VAS decreased from 57.5 to 16.0 mm at 6 months follow-up (P0.03). In this first human clinical trial, VM202, which expresses two isoforms of human HGF, appear to be safe and well tolerated with encouraging clinical results and thus supports the performance of a phase II randomized controlled trial.
Bibliographical noteFunding Information:
We gratefully acknowledge the dedicated collaboration with Emile R Mohler III, MD, Director of Vascular Medicine, University of Pennsylvania Health System and Tracie C Collins, MD, MPH, Associate Professor, Department of Medicine, University of Minnesota, who are members of the DSMB. This study was funded by the ViroMed Co., Ltd, Seoul, Korea and was supported by grants from the Korean Ministry of Knowledge Economy (grant no. 10031644). We retain the sole responsibility for the data, statistical analysis and manuscript.
- angiogenesis-inducing agent
- hepatocyte growth factor
- peripheral vascular disease
- two isoforms