Use of Ixmyelocel-T (Formerly Vascular Repair Cells [VRC]) in Patients With Peripheral Arterial Disease to Treat Critical Limb Ischemia

Use of Ixmyelocel-T (Formerly TRC Autologous Bone Marrow Cells) in Patients With Peripheral Arterial Disease to Treat Critical Limb Ischemia

This study is designed to evaluate the safety and efficacy of autologous Vascular Repair Cells (VRC) for patients with peripheral arterial disease as a treatment for critical limb ischemia.

The double-blind study is expected to enroll 150 patients, randomized into two patient groups. The treatment group will receive intramuscular (IM) injections of the VRCs into the affected limb; the control group will receive intramuscular injections with an electrolyte solution (without cells). Both groups will receive the standard of care appropriate for their medical condition.

The study will assess the safety and ability of Aastrom TRC autologous bone marrow cells to restore peripheral blood flow affected by critical limb ischemia.

Peripheral arterial disease (PAD), also known as Peripheral Vascular Disease (PVD), occurs when peripheral arteries are damaged by arterial hypertension and/or by the formation of atherosclerotic plaques. PAD is a chronic disease that progressively constricts arterial circulation of limbs. The term critical limb ischemia (CLI) is used for all patients with chronic ischemia rest pain, ulcers, or gangrene in limbs attributable to objectively proven PAD. These sequelae represent the end stage of PAD. PAD is associated with several other clinical conditions, i.e. hypertension, cardiovascular disease, hyperlipidemia, diabetes, tobacco use, obesity and stroke.

The double-blind study is expected to enroll 150 patients, randomized into two patient groups. The treatment group will receive intramuscular injections of the TRC product into the affected limb; the control group will receive intramuscular injections with an electrolyte solution (without cells). Both groups will receive the standard of care appropriate for their medical condition.

Inclusion Criteria:

• Males and females, 18-90 years of age
• Diagnosis of CLI
• Infrainguinal occlusive disease, without options for revascularization
• No surgical interventions planned
• Life expectancy of 2 years
• Normal organ and marrow function
• Patients with controlled blood pressure (≤ 180/110 mmHg) and established anti-hypertensive therapy
• Established anti-platelet therapy

Exclusion Criteria:

• Poorly controlled diabetes mellitus (hemoglobin A1c [HbA1c] > 10%)
• Aortoiliac disease with > 50% stenosis
• Wounds with severity greater than Grade 3 on the Wagner Scale
• Any known failed ipsilateral revascularization within 2 weeks of enrollment
• Previous amputation of the talus, or above in the target limb
• Life-threatening ventricular arrhythmia; unstable angina; or, myocardial infarction within 4 weeks of enrollment
• Severe congestive heart failure (CHF) (i.e. New York Heart Association [NYHA] Stage IV)
• Receiving treatment with hematopoietic growth factors
• Infection of the involved extremity(ies)
• Active wet gangrenous tissue
• Require uninterruptible anticoagulation therapy
• Blood clotting disorder
• Cancer
• End stage renal disease requiring dialysis for more than 6 months prior to enrollment
• Pregnant or lactating
• Having received medication for thrombolytic therapy (e.g. rTPA or other enzymatic clot busters) within 30 days prior to enrollment
• Undergoing hyperbaric oxygen treatment within 2 weeks of enrollment
• Concomitant wound treatments with growth factors or tissue engineered products
• Receiving anti-angiogenic drugs