Autologous Cell Therapy for Critical Limb Ischemia
(EnEPC-CLI Trial)
Recruiting in Palo Alto (17 mi)
+4 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: BioGenCell Ltd.
Must not be taking: Cytotoxic, Immunosuppressive
Disqualifiers: Severe artery disease, Heart failure, Renal failure, Liver failure, others
Trial Summary
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.
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.
12345How 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.
23456Eligibility 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.
+4 more
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.
+26 more
Trial 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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: BGC101Experimental Treatment1 Intervention
Intramuscular injection of BGC101 (autologous EnEPC preparation)
Group II: PlaceboPlacebo Group1 Intervention
Intramuscular injection of control medium only
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Yale University School of MedicineNew Haven, CT
University of San FranciscoSan Francisco, CA
Johns Hopkins HospitalBaltimore, MD
Loading ...
Who Is Running the Clinical Trial?
BioGenCell Ltd.Lead Sponsor
Rabin Medical CenterCollaborator
Laniado HospitalCollaborator
References
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]We have previously demonstrated that a pooled population of bone marrow-derived, allogeneic mesenchymal stromal cells (BMMSC), Stempeucel®-1, produced under good manufacturing practices (GMP) conditions, showed clinical efficacy and safety in patients suffering from critical limb ischemia (CLI) due to Buerger's disease. While Stempeucel®-1 is currently used for CLI and other clinical indications, we wanted to ensure that the product's continuity is addressed by developing and characterizing a second generation of pooled product (Stempeucel®-1A), manufactured identically from second BM aspirates of the same three donors after a 2-year interval.
Therapeutic Efficacy of Autologous Non-Mobilized Enriched Circulating Endothelial Progenitors in Patients With Critical Limb Ischemia - The SCELTA Trial. [2022]Label="BACKGROUND">The therapeutic efficacy of bone marrow mononuclear cells (BM-MNC) autotransplantation in critical limb ischemia (CLI) has been reported. Variable proportions of circulating monocytes express low levels of CD34 (CD14+CD34lowcells) and behave in vitro as endothelial progenitor cells (EPCs). The aim of the present randomized clinical trial was to compare the safety and therapeutic effects of enriched circulating EPCs (ECEPCs) with BM-MNC administration.Methods and Results:ECEPCs (obtained from non-mobilized peripheral blood by immunomagnetic selection of CD14+and CD34+cells) or BM-MNC were injected into the gastrocnemius of the affected limb in 23 and 17 patients, respectively. After a mean of 25.2±18.6-month follow-up, both groups showed significant and progressive improvement in muscle perfusion (primary endpoint), rest pain, consumption of analgesics, pain-free walking distance, wound healing, quality of life, ankle-brachial index, toe-brachial index, and transcutaneous PO2. In ECEPC-treated patients, there was a positive correlation between injected CD14+CD34lowcell counts and the increase in muscle perfusion. The safety profile was comparable between the ECEPC and BM-MNC treatment arms. In both groups, the number of deaths and major amputations was lower compared with eligible untreated patients and historical reference patients.
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]Critical limb ischemia (CLI) continues to form a substantial burden on Western healthcare. Many patients still face amputation as a last treatment option. Autologous bone marrow (BM)-derived cell administration has emerged as a potential new treatment, but proof for sustainable clinical effects of BM-derived cell therapy in CLI is still lacking. The JUVENTAS (reJUVenating ENdothelial progenitor cells via Transcutaneous intra-Arterial Supplementation) trial is the first randomized, placebo-controlled, double-blinded clinical trial on repeated intra-arterial BM mononuclear cell (MNC) infusion in 110 to 160 CLI patients, designed to provide definite proof for the efficacy of stem cell therapy. Primary outcome is the incidence of major amputation at 6 months. Inclusion of patients is well underway. If BM-MNC cells therapy is beneficial, it could become a novel treatment to prevent amputation in patients with CLI.
Characteristics of responders to autologous bone marrow cell therapy for no-option critical limb ischemia. [2022]The present study investigated factors associated with therapeutic benefits after autologous bone marrow cell (BMC) therapy in patients with "no-option" critical limb ischemia (CLI).
No difference in intra-arterial and intramuscular delivery of autologous bone marrow cells in patients with advanced critical limb ischemia. [2013]Stem cell therapy has been proposed to be an alternative therapy in patients with critical limb ischemia (CLI), not eligible for endovascular or surgical revascularization. We compared the therapeutic effects of intramuscular (IM) and intra-arterial (IA) delivery of bone marrow cells (BMCs) and investigated the factors associated with therapeutic benefits. Forty-one patients (mean age, 66 ± 10 years; 35 males) with advanced CLI (Rutherford category, 5 and 6) not eligible for revascularization were randomized to treatment with 40 ml BMCs using local IM (n = 21) or selective IA infusion (n = 20). Primary endpoints were limb salvage and wound healing. Secondary endpoints were changes in transcutaneous oxygen pressure (tcpO(2)), quality-of-life questionnaire (EQ5D), ankle-brachial index (ABI), and pain scale (0-10). Patients with limb salvage and wound healing were considered to be responders to BMC therapy. At 6-month follow-up, overall limb salvage was 73% (27/37) and 10 subjects underwent major amputation. Four patients died unrelated to stem cell therapy. There was significant improvement in tcpO(2) (15 ± 10 to 29 ± 13 mmHg, p
Autologous peripheral blood CD133+ cell implantation for limb salvage in patients with critical limb ischemia. [2021]We report the safety and feasibility of autologous CD133+ cell implantation into the lower extremity muscles of patients with critical limb ischemia, whose only other option was limb amputation. Nine patients participated in the study: seven patients suffering from arteriosclerosis obliterans, one with thromboangiitis obliterans (Buerger's disease) and one with thromboembolic disorder. Autologous PBSC were collected after the administration of G-CSF (10 mcg/kg/day). CD133+ cells were selected using the CLINIMACS cell separation device and were injected i.m. without earlier cryopreservation using a 22-gauge needle into multiple sites 3 cm apart in the gastrocnemius/soleus muscle, or depending on clinical circumstances, in the foot or quadriceps muscle, or both, of the involved leg. There were no complications from either leukapheresis or injection. Stem cell injection prevented leg amputation in seven of the nine patients. In this small cohort of patients with end-stage critical limb ischemia, quality of life (Short Form-36) physical component score improved significantly at 3 (P=0.02) and 6 (P=0.01) months, but not at 1 year (P=0.08). There was a trend towards the improvement in pain-free treadmill walking time (P=0.13) and exercise capacity (P=0.16) at 1 year. Lower extremity limb salvage was achieved for seven of the nine treated patients.