Efficacy, Tolerability and Safety of Intramuscular Injections of PLX PAD for the Treatment of Subjects With Critical Limb Ischemia (CLI) With Minor Tissue Loss Who Are Unsuitable for Revascularization

Inclusion criteria

• Adult male or female subjects between ages 45-99 years of age.
• CLI, with minor tissue loss up to the ankle level (Rutherford Category 5)
• Ankle pressure (AP) ≤70 mmHg or TP ≤50 mmHg in the index leg. (If a subject has ABI >1.4 and TP is not measureable, inclusion may be based on TcPO2 ≤30 mmHg)
• Subject unsuitable for revascularization (by any method) in the index leg.
• Ischemic lesions in the index leg stable for at least 2 weeks.
• Ischemic ulcers in the index leg without tendon or bone exposure (unless secondary to a minor amputation).
• Under treatment for cardiovascular risk factors: hypertension, hyperlipidemia, diabetes, in accordance with applicable guidelines. Concomitant therapy with a statin and an anti-platelet agent for at least 2 weeks prior to randomization.
• Women of childbearing potential must have a negative serum pregnancy test at screening and must be willing to use at least one highly effective birth control method throughout the study.
• Subject understood, agreed and provided informed consent. Patients must give written informed consent before any assessment is performed .

Exclusion criteria

• Non-atherosclerotic PAD (e.g. Buerger's disease).
• CLI with major tissue loss (Rutherford Category 6) in either leg.
• Evidence of active infection (e.g., cellulitis, osteomyelitis).
• Subject having undergone surgical revascularization or major amputation less than 1 month prior to screening, or endovascular revascularization or minor amputation less than 2 weeks prior to screening.
• Planned or potential need for major/minor amputation or any revascularization within 1 month of study entry upon investigator's judgment.
• Aorto-iliac stenosis or common femoral artery stenosis ≥70%, or otherwise suspicion of inadequate inflow to the leg.
• Life expectancy of less than 6 months.
• Stroke or acute myocardial infarction/unstable angina within 3 months prior to screening.
• Severe congestive heart failure symptoms (New York Heart Association [NYHA] class III-IV).
• Uncontrolled severe hypertension.
• Diabetes mellitus with HbA1c >10%.
• Current or history of proliferative retinopathy.
• Known Hepatitis B virus or Hepatitis C virus or acquired immunodeficiency syndrome (AIDS) infections.
• Subjects with international normalized ratio (INR) >2.
• Subject on renal replacement therapy or planned to start renal replacement therapy within 3 months of first screening visit.
• Subject is currently enrolled in, or has not yet completed a period of at least 30 days since ending another investigational device or drug trial(s), unless in long-term follow-up phase.
• Use of hyperbaric oxygen therapy, prostanoids, spinal cord stimulation, lumbar sympathectomy, wound dressing containing cells or growth factors, or topical platelet derived growth factor.
• Known allergies to any of the following: DMSO, human serum albumin, bovine serum albumin.
• History of allergic/hypersensitivity reaction to any substance having required hospitalization and/or treatment with IV steroids/epinephrine.
• Pulmonary disease requiring supplemental oxygen treatment on a daily basis.
• Active malignancy or history of malignancy within 5 years prior to study entry.
• In the opinion of the investigator, the subject is unsuitable for participating in the study.
• Chronic liver disease Child Pugh class B\\C