A Clinical Trial to Study the Efficacy and Safety of Different Doses of Bone Marrow Derived Mesenchymal Stem Cells in Patients With Critical Limb Ischemia Due to Buergers Disease

Study Overview
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Brief Summary
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This is an open label, non-randomized, dose ranging study to evaluate the safety and efficacy of different doses of Stempeucel in critical limb ischemia patients.

Official Title
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A Non-randomized, Open Label, Multicentric, Dose Ranging , Phase II Study Assessing the Efficacy and Safety of Intramuscular Administration of Stempeucel - CLI™ (ex Vivo Cultured Adult Bone Marrow Derived Allogeneic Mesenchymal Stem Cells) in Patients With Critical Limb Ischemia Due to Buerger's Disease

Conditions
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Critical Limb Ischemia, Buerger's Disease

Intervention / Treatment
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* Biological: Allogeneic Mesenchymal Stem Cells
* Biological: Allogeneic Mesenchymal Stem Cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Buerger's disease as diagnosed by Shionoya criteria Males or females (willing to use accepted methods of contraception during the course of the study) in the age group of 18-65 yrs Established CLI in the study limb, clinically and hemodynamically confirmed as per Rutherford- III-5 Patients in Rutherford- III-6 if gangrene extending maximally up to the head of metatarsal but limited to toes (Patients with wet gangrene must undergo wound debridement / amputation before screening) Patients having infrapopliteal occlusive disease with rest pain and ischemic ulcer/necrosis, who are not eligible for or have failed traditional revascularization treatment as per the investigators judgment (No option patients) Ankle Brachial Pressure Index (ABPI) ≤ 0.6 or ankle pressure ≤ 50 mm Hg or TcPO2 ≤ 40 mmHg in the foot of the study limb Patients who are able to understand the requirements of the study, and willing to provide voluntary written informed consent and video consent, abide by the study requirements, and agree to return for required follow-up visits Exclusion Criteria: Patients with CLI indicated for major amputation during screening Atherosclerotic PAD Ulcers with exposure of tendon and/bone in the shin region Previous above transmetatarsal amputation in study limb Any Lumbar sympathectomy procedure performed less than 90 days prior to the screening Patients with gait disturbance for reasons other than CLI Diagnosis of diabetes mellitus (type 1 or type 2) Patients having left ventricular ejection fraction < 35% Patients suffering from clinically relevant peripheral neuropathy History of Stroke or myocardial infarction Patients who are contraindicated for MRA Patients with deep vein thrombosis in any limb Patients who have clinically serious and/or unstable inter-current infection, medical illnesses or conditions that are uncontrolled or whose control, in the opinion of the Investigator, may be jeopardized by participation in this study or by the complications of this therapy Documented terminal illness or cancer or any concomitant disease process with a life expectancy of <1 year Patients already enrolled in another investigational drug trial or completed within 3 months or those who have participated in any stem cell clinical trial Patient with known hypersensitivity to the constituents of the IMP - dimethyl sulfoxide (DMSO) or human serum albumin (HSA) History of severe alcohol or drug abuse within 3 months of screening Hb% < 10 gm% for males, Hb% < 9 gm% for females, serum creatinine ≥ 2mg%, serum Total Bilirubin ≥2mg% Pregnant and lactating women Patients tested positive for HIV 1, HCV, HBV, CMV, RPR

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low dose<br>Stempeucel - CLI will be administered at the lowest dose | Biological: Allogeneic Mesenchymal Stem Cells<br>* Single intramuscular administration of low dose of stem cells<br>* Other names: Stempeucel - CLI;|
| Experimental: Intermediate dose<br>Stempeucel - CLI will be administered at intermediate dose | Biological: Allogeneic Mesenchymal Stem Cells<br>* Single intramuscular administration of intermediate dose of stem cells<br>* Other names: Stempeucel - CLI;|
| No Intervention: Control arm<br>Standard protocol of care alone | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relief of the rest pain | Rest pain will be measured using rest pain scale (0 to10) | 6 months | 
| Healing of ulcerations or reduction of ulcer area in the target limb | Complete ulcer healing defined as complete epithelisation of ulcer and partial ulcer healing as at least 30% decrease in ulcer size. | 6 months | 
| Relief of the rest pain | Rest pain will be measured using rest pain scale (0 to 10) | 24 months | 
| Healing of ulcerations or reduction of ulcer area in the target limb | Complete ulcer healing defined as complete epithelisation of ulcer and partial ulcer healing as at least 30% decrease in ulcer size. | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain free walking distance |  | 6 and 24 months | 
| Major amputation free survival |  | 6 and 24 months | 
| Ankle brachial pressure index (ABPI) - measured by Doppler |  | 6 and 24 months | 
| Increase in transcutaneous partial oxygen pressure (TcPO2) |  | 6 and 24 months | 
| Quality of life by King's College VascuQOL questionnaire |  | 6 and 24 months | 
| Angiogenesis - collateral blood vessels by Magnetic resonance angiogram (MRA) |  | 6 and 24 months | 
| The type of adverse events AE(s), number of AE(s) and proportion of patients with AE(s). |  | 6 and 24 months | 
| Assessment of clinical laboratory parameters |  | 6 and 24 months | 
| Physical examination findings and assessment of vital signs |  | 6 and 24 months | 
| Assessment of electrocardiogram (ECG) parameters |  | 6 and 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Critical limb ischemia, Buerger's disease, Critical limb ischemia due to Buerger's disease