A Clinical Trial to Study the Efficacy and Safety of Stempeucel® in Patients With CLI Due to Buergers Disease

Study Overview
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Brief Summary
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This study is being conducted as an extension of the phase II clinical trial SRPL/CLI/10-11/001 (NCT01484574). The CDSCO has recommended flexibility for continued clinical study in consultation with ICMR, as per recommendation of Cellular biology based therapeutic drug evaluation committee (CBBTDEC).

Detailed Description
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This study will evaluate the safety and efficacy of intramuscular injection of stempeucel(R) (Ex vivo cultured adult bone marrow derived allogeneic mesenchymal stem cells) in Critical Limb Ischemia due to Buerger's Disease

Official Title
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A Single Arm, Open Label, Multicentric, Clinical Study Assessing the Efficacy and Safety of Stempeucel® (ex Vivo Cultured Adult Bone Marrow Derived Allogeneic Mesenchymal Stem Cells) in Patients With CLI Due to Buerger's Disease

Conditions
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Critical Limb Ischemia Due to Buerger's Disease

Intervention / Treatment
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* Biological: Stempeucel(R)


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 (patients should have at least one measureable ulcer), who are not eligible for or have failed traditional revascularization treatment as per the investigators judgment (No option patients) . ABPI ≤ 0.6 or ankle pressure ≤ 50 mm Hg. 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 trans metatarsal 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 DVT 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 received stem cells in the past Patient with known hypersensitivity to the constituents of the stempeucel®- 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 & 2, HCV, HBV, CMV, RPR antibodies and for HBsAg antigen

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Stem cells<br>Patients will receive intramuscular and local injection of stempeucel(R) in addition to standard protocol of care | Biological: Stempeucel(R)<br>* Ex vivo cultured adult bone marrow derived allogeneic mesenchymal stem cells<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relief of the rest pain |  | 6 months | 
| Reduction of ulcer area in the target limb |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total walking distance |  | 6 months and 24 months | 
| Major amputation free survival |  | 6 months and 24 months | 
| Ankle brachial pressure index (ABPI) - measured by Doppler |  | 6 months and 24 months | 
| Quality of life (QOL) by King's College VascuQOL questionnaire |  | 6 months and 24 months | 
| Angiogenesis - collateral blood vessels by Magnetic resonance angiogram (MRA) |  | 6 months and 24 months |