Using patients' own blood cells to treat critical limb ischemia

Phase 1/2, Open Label & Double Blind Randomized Placebo-controlled Study to Assess the Feasibility of BGC101 (EnEPC) in the Treatment of Peripheral Arterial Disease (PAD) With Critical Limb Ischemia (CLI)

This study is testing a new treatment using patients' own blood cells to see if it can help people with critical limb ischemia who haven't found relief from other treatments.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: BioGenCell Ltd. (industry)
• Locations: 5 sites (San Francisco, California and 4 other locations)
• Trial ID: NCT02805023 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the feasibility of BGC101, an autologous cell therapy derived from patients' own blood, to treat individuals suffering from critical limb ischemia (CLI) who have not responded to standard treatments. The study involves a double-blind, randomized controlled trial with two arms: one receiving the BGC101 treatment and the other receiving a placebo. The treatment consists of a single dose of personalized cells injected into the affected leg, with the preparation process taking less than a day. The trial aims to assess both the safety and efficacy of this innovative approach in a population with severe peripheral arterial disease.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with critical limb ischemia who are poor candidates for revascularization or have experienced ineffective revascularization.

Not a fit: Patients who are not diagnosed with critical limb ischemia or who are not eligible for the study criteria will not benefit from this treatment.

Why it matters

Potential benefit: If successful, this therapy could provide a new treatment option for patients with critical limb ischemia who have limited alternatives.

How similar studies have performed: While this approach is innovative, similar studies using autologous cell therapies have shown promise in treating other vascular conditions, indicating potential for success.

Eligibility criteria

Inclusion 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

Exclusion criteria:

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.

Where this trial is running

San Francisco, California and 4 other locations

• University of San Francisco — San Francisco, California, United States (RECRUITING)
• Yale University School of Medicine — New Haven, Connecticut, United States (RECRUITING)
• Johns Hopkins Hospital — Baltimore, Maryland, United States (RECRUITING)
• Rambam Health Care Campus — Haifa, Israel (RECRUITING)
• Laniado Hospital — Netanya, Israel (RECRUITING)

Study contacts

• Principal investigator: Shlomo J Baytner, MD — Director of Vascular Surgery, Laniado Hospital, IL
• Study coordinator: Dvora Darky

Conditions: Chronic Limb-Threatening Ischemia, Peripheral Arterial Disease, Peripheral Vascular Disease