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

Who can take part

• Able to complete the study and comply with instructions
• Capable of understanding the purpose of the study and the contents of the informed consent form
• Aged at least 18 years
• Non-pregnant and non-lactating female patients
• Have the clinical indications diagnostic of CLI based on Rutherford category 4-5
• 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
• Meeting one of the following conditions:; 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; 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); 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

Who cannot take part

• Concurrent therapy that, in the Investigator's opinion, would interfere with the evaluation of the feasibility of the study medication
• Treatment with any investigational product within the last 6 months or enrollment in any active study involving the use of investigational devices or drugs
• Concurrent acute infectious disease with septicemia
• Systemic treatment with cytotoxic and/or immunosuppressive treatment
• Severe uncorrected aorto-iliac and/or common femoral artery disease, absent of femoral pulse or monophasic common femoral artery Doppler waveform
• Presence of any other condition or circumstance that, in the judgment of the investigator, might negatively impact the outcomes of the treatment under investigation
• Significant ongoing infection (WIfI infection grade 2 or 3)
• Heart failure (New York Heart Association [NYHA] 3-4)
• Significant valvular disease or less than 4 weeks after valve replacement or repair
• Liver failure, Model for End-stage Liver Disease (MELD) scores 15 and higher
• Malignancy within the preceding 3 years, except basal cell carcinoma
• Chronic infectious disease (human immunodeficiency virus-1 [HIV-1], human immunodeficiency virus-2 [HIV-2], hepatitis B virus [HBV], hepatitis C virus [HCV])
• Immunodeficiency syndrome
• Raynaud's syndrome
• Hemoglobin (Hb) less than 9 g/dL
• Patient with HbA1C > 8.5%
• Myocardial infarction, cerebral infarction , uncontrolled myocardial ischemia or persistent severe heart failure (ejection fraction [EF] < 25%) during the preceding 3 months
• Renal failure (estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73 m², chronic kidney damage stage 4-5)
• 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])
• Abnormal coagulation tests when not under warfarin (normalized prothrombin time [PT INR] >2)
• Prognosis of a major amputation (below or above the knee), within 4 weeks after screening
• Severe wound (WIfI wound grade 2 or 3)
• 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
• Patient suffering from active vasculitis
• Blood transfusions during the preceding 4 weeks (to exclude the potential of non-autologous cells in the harvested blood)
• Pregnant or lactating women at entry of study
• People who are unwilling to agree to use acceptable methods of contraception during the study
• Inability to communicate (that may interfere with the clinical evaluation of the patient)
• Patient unlikely to be available for follow-up