VM202, a plasmid DNA that expresses two isoforms of hepatocyte growth factor, may elicit angiogenic effects that could benefit patients with critical limb ischemia (CLI). In a phase 2, double-blind trial in 52 CLI patients, we examined the safety and potential efficacy of intramuscular injections of low-dose (n=21) or high-dose (n=20) VM202 or placebo (n=11) in the affected limb (days 0, 14, 28 and 42). Adverse events and serious adverse events were similar among the groups; no malignancy or proliferative retinopathy was seen. In exploratory efficacy analyses, we found no differences in ankle or toe-brachial index, VAS, VascuQuol or amputation rate among the groups. Complete ulcer healing was significantly better in high-dose (8/13 ulcers; P<0.01) versus placebo (1/9) patients. Clinically meaningful reductions (>50%) in ulcer area occurred in high-dose (9/13 ulcers) and low-dose (19/27) groups versus placebo (1/9; P<0.05 and P<0.005, respectively). At 12 months, significant differences were seen in TcPO 2 between the high-dose and placebo groups (47.5±17.8 versus 36.6±24.0 mm Hg, respectively; P<0.05) and in the change from baseline among the groups (P<0.05). These data suggest that VM202 is safe and may provide therapeutic bioactivity in CLI patients.
Bibliographical noteFunding Information:
We acknowledge the dedicated collaboration with Emile R. Mohler, MD, Director of Vascular Medicine, University of Pennsylvania Health System; Tracie C. Collins, MD, MPH, Chair & Professor, Kansas Public Health Department; and J. Michael White, PhD at JM White Associates, who are DSMB members. Funded by ViroMed Co., Ltd, Seoul, Korea and supported by the Industrial Strategic Technology Development Program (grant no. 10031644, 'Clinical development of cardiovascular therapeutics (VM202) using novel hepatocyte growth factor gene in the US') funded by the Ministry of Trade, Industry & Energy (MI, Korea).
© 2016 Macmillan Publishers Limited.
All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Molecular Biology