Study to Assess the Efficacy and Safety of CLBS12 in Patients With Critical Limb Ischemia (CLI)

Study Overview
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Brief Summary
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A prospective, open label, controlled, randomized, double arm, multi-center study to assess the efficacy and safety of CLBS12 in patients with critical limb ischemia (CLI) due to arteriosclerosis obliterans (ASO) with a single arm sub-study to assess the safety and potential efficacy of CLBS12 in patients with CLI due to Buerger's Disease (BD).

Detailed Description
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Main ASO Study: This study will compare safety and efficacy of intramuscular transplantation of autologous CD34+ cells (CLBS12) plus standard of care (SOC) pharmacotherapy (cell treatment arm) versus SOC pharmacotherapy alone (e.g., antiplatelets, anticoagulants, and vasodilators including prostanoids) (control arm) in subjects with CLI categorized as Rutherford score 4 or 5 due to ASO aged 20 to 85 years and with no endovascular or surgical revascularization options. Subjects assigned to the cell treatment arm will continue SOC pharmacotherapy and will also receive subcutaneous injections of GRAN® 5 ug/kg/day for 5 days and undergo apheresis on the last day of GRAN® administration. Then each subject in the cell treatment arm will receive intramuscular injections of autologous CD34+ cells. Subjects assigned to the control arm will continue to receive SOC pharmacotherapy alone with the possibility of receiving cell treatment via the rescue option. BD Substudy: A single arm substudy is included to assess the safety and efficacy of intramuscular transplantation of CLBS12 in patients (N= 5) with CLI categorized as 4 or 5 Rutherford score due to BD aged 20 to 85 years. Subjects who give informed consent will be screened for eligibility within 28 days before registration. Subjects will continue SOC pharmacotherapy and will also receive subcutaneous injections of GRAN® 5 µg/kg/day for 5 days (Pretreatment Days 1 5) to mobilize CD34+ cells into the peripheral blood and undergo apheresis on pretreatment Day 5 to collect CD34+ cells. The choice of pharmacotherapy will be made by the investigators. Each subject in a cell treatment arm will receive intramuscular injections of up to 1 × 10^6 autologous CD34+ cells/kg/limb. All subjects will be evaluated for efficacy and safety assessments during approximately 12 months. Efficacy assessments include CLI free status, AFS, PFS, ABI, TBI, SPP, TcPO2, ICD, VAS, and AQA.

Official Title
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A Prospective, Open Label, Controlled, Randomized, Multicenter Study to Assess the Efficacy and Safety of CLBS12 in Patients With Critical Limb Ischemia (CLI) Due to Arteriosclerosis Obliterans (ASO) With a Single-arm Substudy to Assess the Safety and Potential Efficacy of CLBS12 in Patients With CLI Due to Buerger's Disease (BD)

Conditions
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Critical Limb Ischemia, Buerger Disease, Thromboangiitis Obliterans, Atherosclerosis Obliterans

Intervention / Treatment
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* Biological: CLBS12
* Drug: SOC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: subject has CLI caused by ASO or BD Exclusion Criteria: < 20 years old

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CLI Due to ASO with CLBS12 + SOC<br>This group of subjects with CLI due to ASO will be administered with CLBS12 + SOC for collecting efficacy and safety data. | Biological: CLBS12<br>* Intramuscular transfusion of CLBS12.<br>* Other names: CD34+ cells;Drug: SOC<br>* Standard of care (SOC) is defined as pharmacotherapy with approved drugs (e.g., antiplatelets, anticoagulants, and vasodilators including prostanoids).<br>* Other names: Standard of care;|
| Active Comparator: CLI Due to ASO with SOC<br>This group of subjects with CLI due to ASO will be administered with SOC only. | Drug: SOC<br>* Standard of care (SOC) is defined as pharmacotherapy with approved drugs (e.g., antiplatelets, anticoagulants, and vasodilators including prostanoids).<br>* Other names: Standard of care;|
| Experimental: CLI Due to BD with CLBS12<br>CLBS12 will be administered to patients with CLI due to BD for collecting safety and efficacy data. | Biological: CLBS12<br>* Intramuscular transfusion of CLBS12.<br>* Other names: CD34+ cells;Drug: SOC<br>* Standard of care (SOC) is defined as pharmacotherapy with approved drugs (e.g., antiplatelets, anticoagulants, and vasodilators including prostanoids).<br>* Other names: Standard of care;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to continuous CLI-free status | CLI-free is determined by assessing the Rutherford score (</=3) by the investigator and a central adjudication committee. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CLI, ASO, TAO