Safety and efficacy of plasmid DNA expressing two isoforms of hepatocyte growth factor in patients with critical limb ischemia

M. R. Kibbe, A. T. Hirsch, F. O. Mendelsohn, M. G. Davies, H. Pham, J. Saucedo, W. Marston, W. B. Pyun, S. K. Min, B. G. Peterson, A. Comerota, D. Choi, J. Ballard, R. A. Bartow, D. W. Losordo, W. Sherman, V. Driver, E. C. Perin

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Abstract

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.

Original languageEnglish
Pages (from-to)306-312
Number of pages7
JournalGene Therapy
Volume23
Issue number3
DOIs
Publication statusPublished - 2016 Mar 1

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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    Kibbe, M. R., Hirsch, A. T., Mendelsohn, F. O., Davies, M. G., Pham, H., Saucedo, J., Marston, W., Pyun, W. B., Min, S. K., Peterson, B. G., Comerota, A., Choi, D., Ballard, J., Bartow, R. A., Losordo, D. W., Sherman, W., Driver, V., & Perin, E. C. (2016). Safety and efficacy of plasmid DNA expressing two isoforms of hepatocyte growth factor in patients with critical limb ischemia. Gene Therapy, 23(3), 306-312. https://doi.org/10.1038/gt.2015.110