Expanded Access Treatment of Subjects With Critical Limb Ischemia (CLI) With Minor Tissue Loss Who Are Unsuitable for Revascularization

Exclusion Criteria

• •1. Evidence of active localized osteomyelitis secondary to contiguous focus of infection, unless amputation is expected within 1 months post PLX-PAD administration. In case of osteomyelitis, patients must be treated with antibiotics during screening and PLX-PAD administration or as long as there is evidence of active infection.
• •2. Subject on renal replacement therapy or with eGFR \<15 mL/min.
• •3. Current treatment with high dose systemic steroids (prednisone equivalent \>7.5 mg/day) or topical steroids on the index leg.
• •4. History of autologous bone marrow transplantation (if not due to hematologic malignancy) or solid organ transplantation, clinically stable.
• •5. Immunocompromised subjects due to disease for any reason, including immunosuppressive therapy, at screening (for steroid therapy, refer to the criterion c)
• •6. CLI with major tissue loss (Rutherford Category 6) in the contralateral leg.
• •7. Diabetes mellitus with glycosylated hemoglobin (HbA1c) \>10% at Screening.
• •8. HIV controlled by antiretroviral therapy
• •9. Past drug or alcohol abuse.
• •1. Non-atherosclerotic PAD and vasculitis (e.g., Buerger's disease \[thromboangiitis obliterans\], Takayasu's arteritis, etc.).
• •2. CLI with major tissue loss (Rutherford Category 6) in the index leg. Ulcers from venous or neuropathic origin if not associated with at least one ulcer from arterial origin.
• •3. Evidence of active infection in either leg (e.g., cellulitis, myositis) except localized osteomyelitis secondary to contiguous focus of infection, under antibiotic treatment.
• •4. Subject having undergone surgical/endovascular revascularization or major/minor amputation, in either leg, less than 1 month prior to Screening.
• •5. Planned or potential need for major/minor amputation or any revascularization of either leg within 1 month of EAP entry upon physician's judgment.
• •6. Aortoiliac stenosis or common femoral artery stenosis or otherwise suspicion of inadequate inflow to the index leg at the time of Screening.
• •7. Current evidence or sign supporting an assessment of life expectancy of less than 6 months.
• •8. Stroke or acute myocardial infarction within 3 months prior to Screening.
• •9. Severe congestive heart failure symptoms (New York Heart Association \[NYHA\] Stage IV) at screening.
• •10. Life-threatening ventricular arrhythmia - except in subjects with an implantable cardiac defibrillator at screening.
• •11. Uncontrolled severe hypertension during Screening.
• •12. Current or history of proliferative retinopathy.
• •13. Known active Hepatitis B virus or Hepatitis C virus infections at Screening. Pluristem, Ltd Expanded Access Protocol
• •14. Acquired immunodeficiency syndrome (AIDS), severe uncontrolled inflammatory disease,or severe uncontrolled autoimmune disease (e.g., ulcerative colitis, Crohn's disease, etc.).
• •15. Subjects at an increased risk of blood clotting or bleeding according to the Physician's judgment.
• •16. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>3×ULN. Subjects with higher levels may be included if the condition associated with the increase in those liver enzymes is known and is considered clinically stable.
• •17. Current drug or alcohol abuse.
• •18. 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 (in which there is no IP administration).
• •19. Current use or use within 30 days prior to screening of wound dressing containing cells or growth factors like Apligraf®, or topical platelet derived growth factor.
• •20. Current use, planned use, or use within 15 days prior to treatment of hyperbaric oxygen therapy, spinal cord stimulation, or lumbar sympathectomy.
• •21. Exposure to allogeneic cell based therapy in the past or exposure to autologous cell therapy in the last 12 months before screening.
• •22. Known allergies to any of the following: dimethyl sulfoxide (DMSO), human serum albumin, bovine serum albumin.
• •23. History of allergic/hypersensitivity reaction to any substance having required hospitalization and/or treatment with intravenous steroids/epinephrine, known allergy to more than 3 allergens, or in the opinion of the Physician the subject is at high risk of developing severe allergic/hypersensitivity reactions.
• •24. History of severe atopic disease (including but not limited to chronic urticaria, respiratory allergy requiring oral steroids), or history of uncontrolled Asthma (Global Initiative for Asthma \[GINA\] III-IV).
• •1. Pulmonary disease requiring supplemental oxygen treatment on a daily basis.
• •2. History of acute transfusion reaction.
• •3. History of allogeneic bone marrow transplantation.
• •4. Active malignancy except for successfully resected skin basal cell carcinoma or not located on the index leg.
• •5. Pregnant or lactation women
• •6. Inability to understand and provide an informed consent.