Autologous Cell Therapy for Critical Limb Ischemia

(EnEPC-CLI Trial)

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new cell therapy, BGC101, for individuals with critical limb ischemia (CLI). CLI occurs when blood flow to the legs is severely reduced, often due to peripheral arterial disease (PAD), causing pain and potential tissue damage. The trial aims to determine if BGC101 can improve blood flow for those who have not found success with other treatments, such as medication or surgery. Suitable candidates for this trial have experienced persistent leg pain or poor wound healing despite previous treatments. As a Phase 1 trial, this research focuses on understanding how BGC101 works in people, offering participants the chance to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that BGC101 is likely to be safe for humans?

Research shows that BGC101, a treatment using a person's own cells, is being tested for safety in individuals with critical limb ischemia (CLI), a severe condition affecting blood flow in the legs. Early results suggest it is generally safe. In past studies, participants who received BGC101 did not experience major side effects. This therapy uses a combination of cells taken from the patient, including those that help form blood vessels and those that can become different types of blood cells. Since the treatment uses the patient's own cells, the risk of rejection is low. However, the trial remains in the early stages, so further research is needed to fully confirm its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for critical limb ischemia?

Unlike the standard treatments for critical limb ischemia, which typically include medication to improve blood flow or surgical interventions like angioplasty and bypass surgery, BGC101 offers a novel approach. Researchers are excited about BGC101 because it involves autologous cell therapy, using a patient's own endothelial progenitor cells (EnEPCs) to promote blood vessel growth and repair. This innovative treatment is delivered via intramuscular injection, potentially enhancing tissue regeneration and improving blood circulation in a more targeted and natural way. By harnessing the body's own repair mechanisms, BGC101 represents a promising alternative that could lead to better outcomes for patients with this challenging condition.

What evidence suggests that BGC101 might be an effective treatment for critical limb ischemia?

Research has shown that BGC101, a treatment using a patient's own cells, may help treat severe leg artery blockages in people with poor blood flow. In this trial, some participants will receive BGC101, which early results suggest can improve circulation and might save limbs in patients who haven't benefited from other treatments. One study found that all patients survived, and more than 80% retained their limbs after 12 months. This treatment uses special cells to repair and grow new blood vessels, which is vital for those with serious blood flow problems. While more research is needed, these early findings offer hope for new treatment options. ^{1 2 4 5 6}

Who Is on the Research Team?

Alisha Oropallo, MD

Principal Investigator

Northwell Health

Alexander Reyzelman, MD

Principal Investigator

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

Moshe Halak, MD

Principal Investigator

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

Mark Wyers, MD

Principal Investigator

Beth Israel Deaconess Medical Center (Harvard-Boston)

Igor Laskowski, MD

Principal Investigator

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

Nathalie Moreels, MD

Principal Investigator

University Hospital Ghent-Thoracale en vasculaire heelkunde

Jeffrey J Siracuse, MD

Principal Investigator

Boston Medical Center

Khanjan Nagarsheth, MD

Principal Investigator

University of Maryland

Paata Meshveliani, MD

Principal Investigator

West Georgia Medical Center (Kutaisi Hospital)

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

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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 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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02805023

NCT02805023 | BGC101 (EnEPC) Autologous Cell ... BGC101 is designed to treat peripheral vascular disease in patients suffering from Critical Leg Ischemia (CLI) also referred to as chronic limb threatening ...

2. clinicaltrials.eu clinicaltrials.eu/trial/study-on-bgc101-for-treating-peripheral-arterial-disease-with-critical-limb-ischemia-in-patients-not-responding-to-standard-treatments/

Study on BGC101 for Treating Peripheral Arterial Disease ... This clinical trial studies the safety and effectiveness of BGC101, a cell therapy, for treating Peripheral Arterial Disease and Critical ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1465324925001227

ENEPC-CLI-01- A PHASE 2 DOUBLE BLIND PLACEBO ... A pilot, single site, open-label study with BGC101 in 5 patients with CLTI (including 3 diabetics) who had not responded to standard pharmacological treatment, ...

4. biogencell.net biogencell.net/clinical-trials/

Clinical Trials Double blind randomized placebo controlled study to assess the feasibility of BGC101(EnEPC) in treating Critical Limb Ischemia.

5. veithsymposium.org veithsymposium.org/2024/abstracts/vei/690.pdf

Presenter Disclosure Information A Phase II Double Blind ... (PAD) with critical limb ischemia (CLI). U.S. FDA IND NCT02805023 ... Efficacy Results: BGC101 achieved 100% survival and >80% at 12 ...

6. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/vascular-disease

UCSF Vascular Disease Clinical Trials for 2025 BGC101 (EnEPC) Autologous Cell Therapy From Patient's Own Blood for Treatment of Critical Limb Ischemia (CLI) ... safety, efficacy, and ...