Safety Study of MultiGeneAngio in Patients With Chronic Critical Limb Ischemia

Phase I/IIa Safety, Two-dose Study of MultiGeneAngio in Patients With Chronic Critical Limb Ischemia

The purpose of this study is to evaluate the safety and activity of two doses of MultiGeneAngio, a cell therapy product produced from the patient's own cells, as potential treatment for patients with chronic critical limb ischemia.

Approximately 16 million patients worldwide (1 in 20 people over the age of 50) suffer from peripheral arterial disease(PAD). PAD is characterized by narrowing or occlusion of vessels supplying blood to the lower limbs, most often due to atherosclerosis. Symptoms of PAD include claudication that may progress to critical limb ischemia manifested by rest pain, tissue loss and gangrene, which eventually may necessitate amputation.

MultiGeneAngio is a cell therapy-based product developed for treatment of patients with chronic critical limb ischemia due to narrow or blocked leg arteries. MultiGeneAngio is composed of endothelial and smooth muscle cells that are isolated from a short vein segment harvested from the patient's arm. After isolation the cells are expanded, characterized, and gene modified by transfer of angiogenic genes.

MultiGeneAngio is a clear cell suspension injected intra-arterially at the site of blockage using a standard diagnostic catheter, in order to create and expand new collateral arteries, and thereby improve blood flow to an ischemic limb.

Comprehensive pre-clinical studies, as well as clinical experience with PAD patients suffering from claudication showed that production and administration of MultiGeneAngio was feasible and safe, as no apparent drug-related adverse events have been observed. Moreover, follow-up data of peak walking times imply a beneficial trend of this efficacy end-point. Additional follow-up data will continue to be collected to help evaluate the safety and efficacy of MultiGeneAngio.

Inclusion Criteria:

• Men and women 50 years of age or older
• Ischemic rest pain (Rutherford category 4) and/or
• Non-healing wounds (Rutherford category 5)
• ABI of 0.5 or less, or TBI of 0.3 or less
• Ankle systolic pressure of 70 mm Hg or less, or toe systolic pressure of 50 mm Hg or less
• Poor or no option for conventional revascularization

Exclusion Criteria:

• Life expectancy of less than one year
• Presence of significant inflow disease (>50% stenosis) in the distal aorta, common or external iliac
• Advanced CLI, characterized by extensive tissue loss or gangrene (Rutherford category 6)
• Previous major amputation on the leg to be treated or planned major amputation within a month from enrollment
• Evidence of osteomyelitis
• Ischemic wounds with uncontrolled infectious symptoms
• Heart angioplasty or CABG within 3 months prior to enrollment
• Severe congestive heart failure (New York Heart Association stage IV)
• Acute cardiovascular event within 3 months prior to enrollment
• Uncontrolled blood pressure: SBP≥ 180 mmHg or DBP ≥110 mmHg
• Known Buerger's disease
• History of bleeding diathesis (e.g., hemophilia due to Factor VIII or IX deficiency)
• Renal failure defined as a serum creatinine >2.5mg/dL
• Significant hepatic disease:>3-fold elevation in ALT/AST, HBV or HCV carriers
• Severe pulmonary disease
• Active proliferative retinopathy and/or severe macular oedema
• Intra-ocular surgery within 6 months prior to enrollment
• Immunodeficient states (e.g. known HIV positivity, or organ transplant recipient) or subject receiving immunosuppressive medication
• History of malignant neoplasm (except curable non-melanoma skin malignancies) within 5 years prior to enrollment
• Pregnant or lactating women
• Previous treatment with angiogenic growth factors or stem cells
• No demonstrable venous access
• Known hypersensitivity to VEGF, Angiopoietin-1, or heparin