Safety Study of MultiGeneAngio in Patients With Chronic Critical Limb Ischemia

MultiGene Vascular Systems

Status and phase

Active, not recruiting

Phase 2

Phase 1

Conditions

Peripheral Vascular Disease

Critical Limb Ischemia

Peripheral Arterial Disease

Treatments

Biological: MultiGeneAngio

Study type

Interventional

Funder types

Industry

Identifiers

NCT00956332

MGVS-MGA 002

Details and patient eligibility

About

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.

Full description

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.

Enrollment

28 patients

Sex

All

Ages

50 to 90 years old

Volunteers

No Healthy Volunteers

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