BGC101 (EnEPC) Autologous Cell Therapy From Patient's Own Blood for Treatment of Critical Limb Ischemia (CLI)

Eligibility Criteria

• 1. Able to complete the study and comply with instructions.
• 2. Capable of understanding the purpose of the study and the contents of the informed consent form.
• 3. Aged at least 18 years.
• 4. Non-pregnant and non-lactating female patients.
• 5. Have the clinical indications diagnostic of CLI based on Rutherford category 4-5
• 6. Have at least one of the hemodynamic indicators of severe peripheral arterial occlusive disease (WIfI ischemia grade 2):
• * Toe pressure \< 40 mmHg
• * Ankle pressure \< 70 mmHg
• * TcPO2 \< 40mmHg
• 7. Meeting one of the following conditions:
• 1. Poor candidate for standard revascularization treatment for peripheral arterial disease due to unfavorable anatomy or high surgical/intervention risk based on the patient's underlying comorbidities.
• 2. After undergoing clinically ineffective revascularization. Six weeks or more after undergoing a prior index limb revascularization the patient demonstrates:
• * No improvement in clinical signs and symptoms of CLI as evidenced by lack of improvement in rest pain (when not under increased pain relief) and/or inadequate wound healing or progression of tissue loss despite adequate standard treatment.
• * Ongoing ischemia as defined above in the inclusion criterion 6.
• * The patient is no longer amenable to further interventional or surgical revascularization (see inclusion criterion 7c below).
• 3. Four weeks or more after a revascularization failure.
• * Technical Failure of the revascularization (inability to successfully cross or treat the intended target arterial path, thrombosis of the bypass graft or treated artery within 7 days of procedure)
• * Hemodynamic Failure of the revascularization (lack of improvement in toe pressure, ankle pressure, or TcPO2) post-procedure
• 1. Severe uncorrected aorto-iliac and/or common femoral artery disease, absent of femoral pulse or monophasic common femoral artery Doppler waveform.
• 2. Concurrent therapy that, in the Investigator's opinion, would interfere with the evaluation of the feasibility of the study medication.
• 3. Treatment with any investigational product within the last 6 months or enrollment in any active study involving the use of investigational devices or drugs.
• 4. Presence of any other condition or circumstance that, in the judgment of the investigator, might negatively impact the outcomes of the treatment under investigation.
• 5. Prognosis of a major amputation (below or above the knee), within 4 weeks after screening.
• 6. Severe wound (WIfI wound grade 2 or 3).
• 7. Significant ongoing infection (WIfI infection grade 2 or 3).
• 8. Relative or absolute contraindications for intramuscular injections at the intended treatment site, in cases such as severe skin lesions, severe edema or morbid obesity, based on clinician opinion.
• 9. Patient suffering from active vasculitis
• 10. Blood transfusions during the preceding 4 weeks (to exclude the potential of non-autologous cells in the harvested blood).
• 11. Hemoglobin (Hb) less than 9 g/dL.
• 12. Patient with HbA1C \> 8.5%
• 13. Myocardial infarction, cerebral infarction , uncontrolled myocardial ischemia or persistent severe heart failure (ejection fraction \[EF\] \< 25%) during the preceding 3 months.
• 14. Heart failure (New York Heart Association \[NYHA\] 3-4).
• 15. Significant valvular disease or less than 4 weeks after valve replacement or repair
• 16. Renal failure (estimated glomerular filtration rate \[eGFR\] \< 30 mL/min/1.73 m², chronic kidney damage stage 4-5).
• 17. Liver failure, Model for End-stage Liver Disease (MELD) scores 15 and higher.
• 18. Liver function tests more than three times normal upper limit (normal limits being defined in each local laboratory) (glutamic-oxaloacetic transaminase \[GOT\], glutamic-pyruvic transaminase \[GPT\], alkaline phosphatase \[AlkP\], gamma-glutamyl transferase \[GGT\], lactate dehydrogenase \[LDH\]).
• 19. Abnormal coagulation tests when not under warfarin (normalized prothrombin time \[PT INR\] \>2).
• 20. Pregnant or lactating women at entry of study.
• 21. People who are unwilling to agree to use acceptable methods of contraception during the study.
• 22. Malignancy within the preceding 3 years, except basal cell carcinoma.
• 23. Concurrent acute infectious disease with septicemia
• 24. Chronic infectious disease (human immunodeficiency virus-1 \[HIV-1\], human immunodeficiency virus-2 \[HIV-2\], hepatitis B virus \[HBV\], hepatitis C virus \[HCV\]).
• 25. Immunodeficiency syndrome.
• 26. Raynaud's syndrome
• 27. Systemic treatment with cytotoxic and/or immunosuppressive treatment.
• 28. Inability to communicate (that may interfere with the clinical evaluation of the patient).
• 29. Patient unlikely to be available for follow-up.