title: Safety of a non-viral plasmid-encoding dual isoforms of hepatocyte growth factor in critical limb ischemia patients: a phase I study.
abstract: 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 (P=0.005) and from 0.15 to 0.24 (P=0.01) at 12 months follow-up. Median VAS decreased from 57.5 to 16.0 mm at 6 months follow-up (P=0.03). 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.
authors: Minneapolis Heart Institute Foundation at Abbott Northwestern Hospital, Minneapolis, MN, USA. henry003@umn.edu
authors: T D
authors: TD
authors: Henry
authors: A T
authors: AT
authors: Hirsch
authors: J
authors: J
authors: Goldman
authors: Y L
authors: YL
authors: Wang
authors: D L
authors: DL
authors: Lips
authors: W D
authors: WD
authors: McMillan
authors: S
authors: S
authors: Duval
authors: T A
authors: TA
authors: Biggs
authors: H H
authors: HH
authors: Keo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D043925:Angiogenesis Inducing Agents / Q000627:therapeutic use; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000009:adverse effects* / Q000379:methods; D017228:Hepatocyte Growth Factor / Q000097:blood / Q000235:genetics*; D006801:Humans; D007273:Injections, Intramuscular; D007511:Ischemia / Q000628:therapy; D007866:Leg / Q000098:blood supply*; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement; D058729:Peripheral Arterial Disease / Q000628:therapy*; D010957:Plasmids; D020033:Protein Isoforms / Q000235:genetics
chemical_list: D043925:Angiogenesis Inducing Agents; C066855:HGF protein, human; D020033:Protein Isoforms; D017228:Hepatocyte Growth Factor