Autologous Cell Therapy for Critical Limb Ischemia

(EnEPC-CLI Trial)

Recruiting at 4 trial locations

Overseen By Dvora Darky

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: BioGenCell Ltd.

Must not be taking: Cytotoxic, Immunosuppressive

Disqualifiers: Severe artery disease, Heart failure, Renal failure, Liver failure, others

Compensation: Varies

Number of Visits: 1

Duration: 1 day

40 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications, but it mentions that any concurrent therapy that might interfere with the study could be a concern. It's best to discuss your specific medications with the trial investigator.

What data supports the effectiveness of the treatment BGC101 for critical limb ischemia?

Research shows that using enriched circulating endothelial progenitor cells (EPCs) in patients with critical limb ischemia led to significant improvements in blood flow, pain relief, and wound healing. This suggests that similar cell-based therapies, like BGC101, could be effective for this condition. ^{1 2 3 4 5}

How is the treatment BGC101 different from other treatments for critical limb ischemia?

BGC101 is unique because it uses a patient's own cells (autologous cell therapy) to help improve blood flow and heal wounds in critical limb ischemia, offering an option for those who cannot undergo traditional surgeries. This approach is different from standard treatments as it involves using enriched cells from the patient's blood to promote healing and potentially avoid amputation. ^{2 3 4 5 6}

What is the purpose of this trial?

Evaluate the feasibility of an autologous cell preparation composed of a mixture of cells enriched for endothelial progenitor cells (EnEPCs) and multipotent adult hematopoietic stem/progenitor cells (HSPC) (BGC101), in the treatment of patients suffering from peripheral arterial disease (PAD) with critical limb ischemia (CLI) who have not responded to optimal pharmacological treatment or control of risk factors and/or had a revascularization failure, and do not have the option of further revascularization treatment.

Research Team

Alisha Oropallo, MD

Principal Investigator

Northwell Health

Paata Meshveliani, MD

Principal Investigator

West Georgia Medical Center (Kutaisi Hospital)

Moshe Halak, MD

Principal Investigator

The Sheba Fund for Health Services and Research, Sheba Medical Center at Tel HaShomer

Nathalie Moreels, MD

Principal Investigator

University Hospital Ghent-Thoracale en vasculaire heelkunde

Khanjan Nagarsheth, MD

Principal Investigator

University of Maryland

Mark Wyers, MD

Principal Investigator

Beth Israel Deaconess Medical Center (Harvard-Boston)

Jeffrey J Siracuse, MD

Principal Investigator

Boston Medical Center

Igor Laskowski, MD

Principal Investigator

New York Medical College ("NYMC") and Westchester County Health Care Corporation, operator of Westchester Medical Center.

Alexander Reyzelman, MD

Principal Investigator

Center for Clinical Research Castro Valley- Main site Post Street -Satellite site

Caitlin Hicks, MD

Principal Investigator

Division of Vascular Surgery and Endovascular Therapy, Johns Hopkins Hospital

Michael Conte, MD

Principal Investigator

University of California, San Francisco - Division Vascular and Endovascular surgery

Shlomo J Baytner, MD

Principal Investigator

Director of Vascular Surgery, Laniado Hospital, IL

Edouard Aboian, MD

Principal Investigator

Yale University School of Medicine- Division of Vascular Surgery, Department of Surgery

Tony Karram, MD

Principal Investigator

Director Department of Vascular Surgery & Transplantation Rambam Health Care Campus - IL

Eligibility Criteria

This trial is for adults with severe peripheral arterial disease and critical limb ischemia who haven't improved after standard treatments or can't have more surgery. They must not be pregnant, able to follow the study plan, and not have certain conditions like uncontrolled heart issues, recent major infections, liver failure, or a history of cancer within the last three years.

Inclusion Criteria

You have severe blockages in your leg arteries, as shown by specific low pressure measurements.

Have the time and ability to complete the study and comply with instructions.

Capable of understanding the purpose of the study and the contents of the informed consent form.

Exclusion Criteria

You have severe and untreated blockages in the major arteries in your legs.

You are at risk of having a major amputation of your leg within 4 weeks after screening.

You have conditions, like severe skin problems, extreme swelling, or severe obesity, that make it risky to get injections in the planned treatment area, according to your doctor's opinion.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose treatment of BGC101 or placebo by intramuscular injections into the affected leg

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including incidence of adverse events and major amputation rates

12 months

Treatment Details

Interventions

• BGC101

Trial Overview The trial tests BGC101 (EnEPC), a cell therapy made from patients' own blood designed to treat critical limb ischemia when other treatments fail. It's compared against a control medium in patients who meet specific criteria for severe artery blockages.

Participant Groups

Group I: BGC101 Experimental Treatment 1 Intervention

Intramuscular injection of BGC101 (autologous EnEPC preparation)

Group II: Placebo Placebo Group 1 Intervention

Intramuscular injection of control medium only

Who Is Running the Clinical Trial?

BioGenCell Ltd.

Lead Sponsor

Trials

1

Recruited

50+

Rabin Medical Center

Collaborator

Trials

423

Recruited

149,000+

Laniado Hospital

Collaborator

Trials

17

Recruited

3,800+

Findings from Research

The study successfully developed a second generation of pooled bone marrow-derived mesenchymal stromal cells (Stempeucel®-1A) that showed comparable angiogenic and immunomodulatory properties to the original Stempeucel®-1, indicating effective reproducibility in manufacturing.

In a preclinical model of hind limb ischemia, both Stempeucel®-1 and Stempeucel®-1A demonstrated significant tissue repair and improved limb function, achieving over 70% recovery of necrotic tissue, highlighting their potential efficacy in treating ischemic diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human bone marrow-derived, pooled, allogeneic mesenchymal stromal cells manufactured from multiple donors at different times show comparable biological functions in vitro, and in vivo to repair limb ischemia. Thej, C., Balasubramanian, S., Rengasamy, M., et al.[2021]

In a clinical trial involving 40 patients with critical limb ischemia, both enriched circulating endothelial progenitor cells (ECEPCs) and bone marrow mononuclear cells (BM-MNC) showed significant improvements in muscle perfusion and overall limb health after an average follow-up of 25 months.

The safety profiles of ECEPCs and BM-MNC treatments were similar, with both groups experiencing lower rates of death and major amputations compared to untreated patients, indicating that both therapies are safe and effective options for treating critical limb ischemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic Efficacy of Autologous Non-Mobilized Enriched Circulating Endothelial Progenitors in Patients With Critical Limb Ischemia - The SCELTA Trial. Liotta, F., Annunziato, F., Castellani, S., et al.[2022]

The JUVENTAS trial is a groundbreaking study involving 110 to 160 patients with critical limb ischemia (CLI) that aims to evaluate the efficacy of autologous bone marrow-derived cell therapy in preventing major amputations over a 6-month period.

This randomized, placebo-controlled, double-blinded trial is significant as it seeks to provide definitive evidence on whether bone marrow mononuclear cell infusion can serve as a new treatment option for CLI patients facing amputation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale and design of the JUVENTAS trial for repeated intra-arterial infusion of autologous bone marrow-derived mononuclear cells in patients with critical limb ischemia. Sprengers, RW., Moll, FL., Teraa, M., et al.[2022]

In a study of 62 patients with critical limb ischemia (CLI) who were not eligible for revascularization, those who experienced limb salvage and wound healing had higher counts of CD34(+) cells and total bone marrow mononuclear cells, indicating that these cell types are important for the therapy's effectiveness.

Younger patients with lower inflammation levels and higher oxygen pressure before treatment were more likely to benefit from autologous bone marrow cell therapy, suggesting that patient characteristics significantly influence treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characteristics of responders to autologous bone marrow cell therapy for no-option critical limb ischemia. Madaric, J., Klepanec, A., Valachovicova, M., et al.[2022]

In a study of 41 patients with critical limb ischemia (CLI), both intramuscular (IM) and intra-arterial (IA) delivery of bone marrow cells (BMCs) showed significant effectiveness, with a 73% limb salvage rate at 6 months and improvements in pain and quality of life.

Patients who responded well to BMC therapy had higher counts of CD34(+) cells and lower levels of inflammation markers, suggesting that these factors may enhance the therapeutic benefits of stem cell treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

No difference in intra-arterial and intramuscular delivery of autologous bone marrow cells in patients with advanced critical limb ischemia. Klepanec, A., Mistrik, M., Altaner, C., et al.[2013]

In a study involving nine patients with critical limb ischemia, autologous CD133+ cell implantation was safe and feasible, with no complications reported from the procedures.

The treatment successfully prevented limb amputation in seven out of nine patients, and significantly improved quality of life scores at 3 and 6 months, indicating potential benefits for patients facing severe vascular issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous peripheral blood CD133+ cell implantation for limb salvage in patients with critical limb ischemia. Burt, RK., Testori, A., Oyama, Y., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Human bone marrow-derived, pooled, allogeneic mesenchymal stromal cells manufactured from multiple donors at different times show comparable biological functions in vitro, and in vivo to repair limb ischemia. [2021]

2. Japan pubmed.ncbi.nlm.nih.gov

Therapeutic Efficacy of Autologous Non-Mobilized Enriched Circulating Endothelial Progenitors in Patients With Critical Limb Ischemia - The SCELTA Trial. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Rationale and design of the JUVENTAS trial for repeated intra-arterial infusion of autologous bone marrow-derived mononuclear cells in patients with critical limb ischemia. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Characteristics of responders to autologous bone marrow cell therapy for no-option critical limb ischemia. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

No difference in intra-arterial and intramuscular delivery of autologous bone marrow cells in patients with advanced critical limb ischemia. [2013]

6. England pubmed.ncbi.nlm.nih.gov

Autologous peripheral blood CD133+ cell implantation for limb salvage in patients with critical limb ischemia. [2021]