Safety and Efficacy Study Using Gene Therapy for Critical Limb Ischemia

Inclusion Criteria

• Male or female, between 18 and 90 years of age;
• Diagnosis of critical limb ischemia (Rutherford Class 4 or 5), including:
• A resting ankle systolic pressure (in either the dorsalis pedis or posterior tibial arteries) of ≤ 70 mmHg in the affected limb; or
• A resting toe systolic pressure of ≤ 50 mmHg in the affected limb; or
• For patients in which measurement of ankle systolic pressure is not feasible (e.g. vessel calcification and non-compressibility); TcPO2 ≤ 30 mmHg;
• Poor or suboptimal candidate for bypass graft surgery or percutaneous angioplasty;
• Pain at rest, and/or ischemic ulcers, and/or focal gangrene ( 30 days
• Be capable of understanding and complying with the protocol and signing the informed consent document prior to being subjected to any study related procedures;
• Women who are surgically sterile or at least 1 year postmenopausal or who have been practicing adequate contraception for at least 12 weeks prior to entering the study. If the subject is of child-bearing potential, she must have a negative urine pregnancy test result prior to study enrollment and must agree to repeat pregnancy screening tests during the study. If the subject or the subject's partner(s) is of child bearing potential, the subject and the subject's partner(s) must agree to use a "double barrier" method of birth control while participating in this study.

Exclusion Criteria

• Subjects who have undergone a successful revascularization procedure or sympathectomy within 12 weeks prior to study entry. A clinically unsuccessful revascularization procedure is defined as one in which:
• the target vessel re-occludes (≥50%, as verified by a second angiogram. Duplex ultrasonography can be used to determine vessel patency if the patient cannot tolerate a second angiogram), or
• the target vessel remains patent, but there is no resolution of symptoms 6 weeks after the procedure (e.g. no evidence of ulcer healing, no improvement in pressures, no reduction in resting pain);
• Subjects that will require an amputation in the target leg within 4 weeks of randomization;
• Subjects with evidence of active infection (e.g., cellulitis, osteomyelitis) or deep ulceration exposing bone or tendon in the extremity planned for treatment;
• Heart Failure with a NYHA classification of III or IV;
• Stroke (NIH scale >2) or myocardial infarction within last 3 months;
• Unstable angina
• Uncontrolled hypertension defined as sustained systolic blood pressure (SBP) > 200 mmHg or diastolic BP (DBP) > 110 mmHg at baseline/screening evaluation;
• Ophthalmologic conditions pertinent to proliferative retinopathy or conditions that preclude standard ophthalmologic examination;
• Inflammatory disorder of the blood vessels (inflammatory angiopathy, such as Buerger's disease);
• Subjects with advanced liver disease including decompensated cirrhosis, jaundice, ascites or bleeding varices;
• Subjects currently receiving immunosuppressive medications chemotherapy, or radiation therapy;
• Positive HIV or HTLV at screening;
• Active Hepatitis B or C infection as determined by Hepatitis B surface antibody (HBsAb), Hepatitis B core antibody (IgG and IgM; HBcAb), Hepatitis B surface antigen (HBsAg) and Hepatitis C antibodies (Anti-HCV), at Screening;
• Specific laboratory values at Screening including: Hemoglobin 3 times the upper limit of normal or any other clinically significant lab abnormality which in the opinion of the investigator should be exclusionary;
• Patients with a recent history ( 81 mg daily of acetylsalicylic acid; If > 81 mg are taken at screening, subjects may be enrolled if willing/able to switch to another medication;
• Subjects requiring regular COX-2 inhibitor drug(s) or high dose steroids (excepting inhaled steroids);
• Major psychiatric disorder in past 6 months;
• History of drug or alcohol abuse / dependence in the past 2 years;
• Use of an investigational drug or treatment in past 12 months; concurrent participation in inves