ACTIVE_NOT_RECRUITING

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

Conditions

Chronic Limb-Threatening Ischemia Peripheral Arterial Disease Peripheral Vascular Disease

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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)

Quick Facts

Study Start:2016-06

Study Completion:2027-12

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT02805023

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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	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.

Inclusion Criteria

Exclusion 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

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.

Contacts and Locations

Principal Investigator

Shlomo J Baytner, MD

PRINCIPAL_INVESTIGATOR

Director of Vascular Surgery, Laniado Hospital, IL

Michael Conte, MD

PRINCIPAL_INVESTIGATOR

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

Edouard Aboian, MD

PRINCIPAL_INVESTIGATOR

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

Caitlin Hicks, MD

PRINCIPAL_INVESTIGATOR

Division of Vascular Surgery and Endovascular Therapy, Johns Hopkins Hospital

Tony Karram, MD

PRINCIPAL_INVESTIGATOR

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

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)

Moshe Halak, MD

PRINCIPAL_INVESTIGATOR

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

Igor Laskowski, MD

PRINCIPAL_INVESTIGATOR

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

Mark Wyers, MD

PRINCIPAL_INVESTIGATOR

Beth Israel Deaconess Medical Center (Harvard-Boston)

Alisha Oropallo, MD

PRINCIPAL_INVESTIGATOR

Northwell Health

Alexander Reyzelman, MD

PRINCIPAL_INVESTIGATOR

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

Study Locations (Sites)

University of San Francisco

San Francisco, California, 94143

United States

Yale University School of Medicine

New Haven, Connecticut, 06520-8039

United States

Johns Hopkins Hospital

Baltimore, Maryland, 21287

United States

Collaborators and Investigators

Sponsor: BioGenCell Ltd.

Shlomo J Baytner, MD, PRINCIPAL_INVESTIGATOR, Director of Vascular Surgery, Laniado Hospital, IL
Michael Conte, MD, PRINCIPAL_INVESTIGATOR, University of California, San Francisco - Division Vascular and Endovascular surgery
Edouard Aboian, MD, PRINCIPAL_INVESTIGATOR, Yale University School of Medicine- Division of Vascular Surgery, Department of Surgery
Caitlin Hicks, MD, PRINCIPAL_INVESTIGATOR, Division of Vascular Surgery and Endovascular Therapy, Johns Hopkins Hospital
Tony Karram, MD, PRINCIPAL_INVESTIGATOR, Director Department of Vascular Surgery & Transplantation Rambam Health Care Campus - IL
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)
Moshe Halak, MD, PRINCIPAL_INVESTIGATOR, The Sheba Fund for Health Services and Research, Sheba Medical Center at Tel HaShomer
Igor Laskowski, MD, PRINCIPAL_INVESTIGATOR, New York Medical College ("NYMC") and Westchester County Health Care Corporation, operator of Westchester Medical Center.
Mark Wyers, MD, PRINCIPAL_INVESTIGATOR, Beth Israel Deaconess Medical Center (Harvard-Boston)
Alisha Oropallo, MD, PRINCIPAL_INVESTIGATOR, Northwell Health
Alexander Reyzelman, MD, PRINCIPAL_INVESTIGATOR, Center for Clinical Research Castro Valley- Main site Post Street -Satellite site

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2016-06

Study Completion Date2027-12

Study Record Updates

Study Start Date2016-06

Study Completion Date2027-12

Terms related to this study

Additional Relevant MeSH Terms

Chronic Limb-Threatening Ischemia
Peripheral Arterial Disease
Peripheral Vascular Disease