Study of Hepatocyte Growth Factor (HGF) Via Plasmid Vector to Improve Perfusion in Critical Limb Ischemia Patients With Peripheral Ischemic Ulcers

Inclusion Criteria

• Subjects will have an appropriately sized peripheral ischemic ulcer(s).
• Subjects will have one or both of the following hemodynamic indicators of severe peripheral arterial occlusive disease:
• Ankle systolic pressure (in either the dorsalis pedis or posterior tibial arteries) of 2 weeks prior to treatment initiation are acceptable.
• Subjects who require a change in their hypertension medication (other than dosage change) as part of their standard of care within 4 weeks prior to treatment initiation.
• Subjects with deep ulcerations with bone or tendon exposure, or clinical evidence of invasive infection (e.g., cellulitis, osteomyelitis, etc.) uncontrollable by antibiotics.
• Subjects currently receiving immuno-suppressive medication, chemo or radiation therapy.
• Evidence or history of malignant neoplasm (clinical, laboratory or imaging), except for fully resolved basal cell carcinoma of the skin. Patient's who had successful tumor resection or radio-chemotherapy of breast cancer more than 10 years prior to inclusion in the study, and with no recurrence, may be enrolled in the study. Patient's who had successful tumor resection or radio-chemotherapy of all other tumor types more than 5 years prior to inclusion in the study, and with no recurrence, may be enrolled in the study.
• Subjects who have proliferative diabetic retinopathy, severe non-proliferative retinopathy, recent (within 6 months) retinal vein occlusion, macular degeneration with choroidal neovascularization, macular edema on fundus evaluation by ophthalmologist, or intraocular surgery within 3 months.
• Subjects with end stage renal disease (ESRD) defined as significant renal dysfunction evidenced by a creatinine of > 2.5 mg/dL, or receiving chronic hemodialysis therapy.
• Any co-morbid condition likely to interfere with assessment of safety or efficacy endpoints, acute cardiovascular events (i.e. cerebrovascular accident [CVA], myocardial infarction [MI], etc.) within 12 weeks of treatment, or non-cardiovascular diseases that in the opinion of the investigator may result in < 3 month subject mortality.
• A subject who has a history of hepatic cirrhosis, viral hepatitis, or HIV.
• Subjects with a clinically significant liver enzyme abnormality (i.e., AST or ALT more than two times the upper limit of normal and/or bilirubin more than 50% above the upper limit of normal).
• Subjects taking cilostazol (Pletal®) are eligible for inclusion, but the subject must have been taking the medication for at least 4 weeks prior to test material administration.
• Subject who received another investigational drug for peripheral arterial disease within 90 days of randomization, have previously received any gene transfer therapy or growth factor product not approved by the United States Food and Drug Administration (FDA) or received any investigational Drug Product in another clinical trial in the 30 days prior to administration of HGF.
• Unreliable or uncooperative subject or other severe concomitant disease(s), which the clinical investigator feels constitute(s) criteria for exclusion of a particular subject.