| Eligibility |
Inclusion Criteria:
1. Subjects will have an appropriately sized peripheral ischemic ulcer(s).
2. Subjects will have one or both of the following hemodynamic indicators of severe
peripheral arterial occlusive disease:
1. Ankle systolic pressure (in either the dorsalis pedis or posterior tibial
arteries) of < 70 mmHg
2. Toe systolic pressure < 50 mmHg
3. The subject is a poor candidate for standard revascularization treatment options for
peripheral arterial disease, based on inadequate bypass conduit, unfavorable anatomy,
or poor operative risk.
4. Subjects 40 years or older of either sex who have signed an informed consent form
either directly or through a legally authorized representative.
5. Subjects will be on a statin and an anti-platelet agent (e.g., clopidogrel,
ticlopidine, aspirin, etc.) as part of their standard of care, unless contraindicated.
Subjects for which these agents are contraindicated will have this restriction
recorded in their case report form (CRF). Subjects must be stable on these medical
regimens for at least 4 weeks prior to the start of treatment.
6. If female, the subjects must be:
1. at least one year post-menopausal, or
2. surgically sterile, or
3. if the subject is of child-bearing potential, she must have been practicing
adequate contraception for at least 12 weeks prior to entering the study and have
a negative urine pregnancy test result prior to study enrollment and agree to
periodic pregnancy screening tests during the study.
4. If female, the subject must not be breastfeeding for 30 days following
administration of HGF.
7. If subject is of reproductive potential, he or she must be using an accepted and
effective (barrier) form of birth control during the study.
Exclusion Criteria
1. Subjects who, in the opinion of the investigator, have a vascular disease prognosis
that indicates they would require a major amputation (at or above the ankle) within 4
weeks of start of treatment.
2. Subjects with a diagnosis of Buerger's disease (thromboangiitis obliterans).
3. Subjects with hemodynamically significant aorto-iliac occlusive disease.
4. Subjects who have had a revascularization procedure within 12 weeks prior to treatment
initiation that remains patent. Revascularization procedures that are evidenced to
have failed (completely occluded) for >2 weeks prior to treatment initiation are
acceptable.
5. 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.
6. Subjects with deep ulcerations with bone or tendon exposure, or clinical evidence of
invasive infection (e.g., cellulitis, osteomyelitis, etc.) uncontrollable by
antibiotics.
7. Subjects currently receiving immuno-suppressive medication, chemo or radiation
therapy.
8. 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.
9. 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.
10. 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.
11. 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.
12. A subject who has a history of hepatic cirrhosis, viral hepatitis, or HIV.
13. 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).
14. 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.
15. 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.
16. Unreliable or uncooperative subject or other severe concomitant disease(s), which the
clinical investigator feels constitute(s) criteria for exclusion of a particular
subject.
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