Safety and Efficacy of Autologous Concentrated Bone Marrow Aspirate for Critical Limb Ischemia - Continued Access

MarrOwStim™ PAD Kit for the Treatment of Critical LimB IschemIa (CLI) in Subjects With Severe Peripheral ArteriaL DiseasE (PAD) (MOBILE) - Continued Access

This study will continue to evaluate the performance of the MarrowStim™ PAD Kit to treat subjects with critical limb ischemia (CLI) caused by severe PAD.

This is a continued access enrollment intended for subjects with critical limb ischemia (CLI) that are unsuitable for revascularization. The investigational treatment utilizes autologous concentrated bone marrow aspirate (cBMA) at the point of care. The bone marrow aspirate is obtained from the subject's hip, concentrated with a bone marrow concentration device, and delivered intramuscularly to the affected limb. Subjects meeting the inclusion/exclusion criteria will be treated with the MarrowStim™ PAD Kit and followed for a total of five years. Information on subject outcomes, such as the occurrence of amputation and death, as well as measurements of rest pain, blood flow (ankle-brachial index, toe-brachial index), and quality of life will be collected. Safety information (via adverse event reporting) will also be collected.

Inclusion Criteria:

• Unilateral or bilateral lower extremity ischemia due to advanced peripheral arterial disease
• Unsuitable for revascularization
• Minor tissue loss (Rutherford Category 5) or ischemic rest pain (Rutherford Category 4)
• Competent to give consent
• No current malignancy or history of previous malignancy within the last five years, with the exception of adequately treated non-melanoma skin cancer (evidence of standard preventative cancer screenings required)

Exclusion Criteria:

• Major tissue loss (Rutherford Category 6)
• Diabetics with uncontrolled or untreated proliferative retinopathy
• Poorly controlled diabetes mellitus with HbA1C > 10%
• Uncompensated congestive heart failure and/or other conditions that preclude general anesthesia
• Myocardial infarction or stroke within last 90 days
• Elevated liver function tests (AST or ALT more than twice the upper limit of normal)
• Renal disease (creatinine > 2.5 mg/dl) or chronic hemodialysis
• White blood cell count < 3,000/µL or > 15,000/µL, platelet count < 100,000/µL, or hematocrit < 32%
• Topical growth hormone therapy within last 90 days, or injected growth hormone therapy within last 180 days
• Disease of central nervous system and/or other conditions that impair cognitive function
• Two or more episodes of pulmonary embolus with a documented DVT in index leg or history of DVT in index leg without evidence of clot resolution
• Current infection of index leg
• Pregnant women (negative urine pregnancy test required)
• Lower extremity venous disease with pitting edema in index leg
• Recent history (in the 6 months prior to screening) of bone marrow disease or treatment with any medication or procedure which adversely affects the bone marrow and would prohibit transplantation
• Current osteomyelitis in index leg
• Existing HIV diagnosis
• Organ transplant recipients
• Known terminal disease process with life expectancy less than one year
• Severe concomitant disease(s) or any additional condition(s) which the investigator feels constitute(s) criteria for exclusion of a particular subject
• Major amputation required within 30 days
• Inclusion in any other clinical study that may affect the outcome of this study
• Uncorrected stenosis(es) of greater than 50% in the common and/or external iliac artery and/or common femoral artery of the index leg.