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Home > Vascular Annual Meeting^® > LB8. Safety and Efficacy of HGF Plasmid Gene Therapy...

LB8. Safety and Efficacy of HGF Plasmid Gene Therapy on Limb Perfusion and Wound Healing in Patients with Ischemic Lower Extremity Ulceration: Results of the HGF-0205 Trial

Richard J. Powell1, Pran Marrot2, Brian H. Annex3
1Dartmouth Hitchcock Medical Center, Lebanon, NH; 2AnGes Inc, Rockville, MD; 3University of Virginia Medical School, Charlottesville, VA

OBJECTIVES: We have previously reported the results of a dose finding Phase II trial showing that HGF angiogenic gene therapy can increase TcPO2 compared to placebo in patients with critical limb ischemia (CLI). The purpose of this randomized placebo controlled multi-center trial was to further assess the safety and clinical efficacy of a modified HGF gene delivery technique in patients with CLI and no revascularization options.

METHODS: Patients with tissue loss received 3 sets of 8 intra-muscular injections every two weeks of HGF plasmid under duplex ultrasound guidance. Injection locations were individualized for each patient based on arteriographically defined vascular anatomy.  Primary safety end-point was incidence of adverse events (AE) or serious adverse events (SAE). Clinical endpoints included change from baseline in toe brachial index (TBI), rest pain assessment by a 10 cm. visual analogue scale as well as wound healing, amputation, and survival at 3 and 6 months.

RESULTS: Randomization ratio was 4:1 HGF (n=21) vs Placebo (n=6). Mean age was 76+ 2 years, 56% male and 59% diabetic. There was no difference in demographics between groups.  There was no difference in AEs or SAEs which consisted mostly of transient injection site discomfort, worsening of CLI, and intercurrent illnesses. Change in TBI and rest pain significantly improved from baseline at 6 months in the HGF treated group compared to Placebo (See table). Complete ulcer healing at 12 months occurred in 31% HGF group and 0% Placebo (p=.21) There was no difference in amputation (HGF 19% vs Placebo 20%) or mortality (HGF 19% vs Placebo 13%) between groups.

CONCLUSIONS: HGF gene therapy using a patient vascular anatomy specific delivery technique appears safe, maintained limb perfusion and decreased rest pain in patients with CLI compared to placebo. A larger study to assess the efficacy of this therapy on more clinically relevant end-points is warranted.

 

AUTHOR DISCLOSURES: R.J. Powell, Consultant: Anges, Inc; P. Marrot, Employee: AnGes, Inc; B.H. Annex, Consultant: AnGes, Inc.