Use of Ixmyelocel-T (Formerly Vascular Repair Cells [VRC]) in Patients With Peripheral Arterial Disease to Treat Critical Limb Ischemia

Study Overview
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Brief Summary
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This study is designed to evaluate the safety and efficacy of autologous Vascular Repair Cells (VRC) for patients with peripheral arterial disease as a treatment for critical limb ischemia. The double-blind study is expected to enroll 150 patients, randomized into two patient groups. The treatment group will receive intramuscular (IM) injections of the VRCs into the affected limb; the control group will receive intramuscular injections with an electrolyte solution (without cells). Both groups will receive the standard of care appropriate for their medical condition.

Detailed Description
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The study will assess the safety and ability of Aastrom TRC autologous bone marrow cells to restore peripheral blood flow affected by critical limb ischemia. Peripheral arterial disease (PAD), also known as Peripheral Vascular Disease (PVD), occurs when peripheral arteries are damaged by arterial hypertension and/or by the formation of atherosclerotic plaques. PAD is a chronic disease that progressively constricts arterial circulation of limbs. The term critical limb ischemia (CLI) is used for all patients with chronic ischemia rest pain, ulcers, or gangrene in limbs attributable to objectively proven PAD. These sequelae represent the end stage of PAD. PAD is associated with several other clinical conditions, i.e. hypertension, cardiovascular disease, hyperlipidemia, diabetes, tobacco use, obesity and stroke. The double-blind study is expected to enroll 150 patients, randomized into two patient groups. The treatment group will receive intramuscular injections of the TRC product into the affected limb; the control group will receive intramuscular injections with an electrolyte solution (without cells). Both groups will receive the standard of care appropriate for their medical condition.

Official Title
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Use of Ixmyelocel-T (Formerly TRC Autologous Bone Marrow Cells) in Patients With Peripheral Arterial Disease to Treat Critical Limb Ischemia

Conditions
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Peripheral Arterial Disease

Intervention / Treatment
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* Biological: Ixmyelocel-T
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females, 18-90 years of age Diagnosis of CLI Infrainguinal occlusive disease, without options for revascularization No surgical interventions planned Life expectancy of 2 years Normal organ and marrow function Patients with controlled blood pressure (≤ 180/110 mmHg) and established anti-hypertensive therapy Established anti-platelet therapy Exclusion Criteria: Poorly controlled diabetes mellitus (hemoglobin A1c [HbA1c] > 10%) Aortoiliac disease with > 50% stenosis Wounds with severity greater than Grade 3 on the Wagner Scale Any known failed ipsilateral revascularization within 2 weeks of enrollment Previous amputation of the talus, or above in the target limb Life-threatening ventricular arrhythmia; unstable angina; or, myocardial infarction within 4 weeks of enrollment Severe congestive heart failure (CHF) (i.e. New York Heart Association [NYHA] Stage IV) Receiving treatment with hematopoietic growth factors Infection of the involved extremity(ies) Active wet gangrenous tissue Require uninterruptible anticoagulation therapy Blood clotting disorder Cancer End stage renal disease requiring dialysis for more than 6 months prior to enrollment Pregnant or lactating Having received medication for thrombolytic therapy (e.g. rTPA or other enzymatic clot busters) within 30 days prior to enrollment Undergoing hyperbaric oxygen treatment within 2 weeks of enrollment Concomitant wound treatments with growth factors or tissue engineered products Receiving anti-angiogenic drugs

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ixmyelocel-T<br>The treatment arm of the study will receive injections of the study cellular product. | Biological: Ixmyelocel-T<br>* IM injection<br>|
| Placebo Comparator: Placebo<br>The control arm of the study will receive placebo injections. | Biological: Placebo<br>* IM Injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of TRCs in patients with CLI(key safety parameters include vital signs, physical exams, laboratory results, assessment of aspiration and injection sites, adverse events, major amputations, wounds presence(size and grading using the Wagner scale) |  | throughout trial | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite efficacy endpoint assessing time to treatment failure(failure defined as major amputation, doubling of wound size, and new gangrene) |  | Day 7 and Months 3, 6, 9, 12 | 
| Percentage of patients failing treatment |  | Day 7, and Months 3,6,9, and 12 | 
| Time to major amputation |  | Day 7 and Month 3, 6, 9, and 12 | 
| Percentage of patients undergoing major amputation |  | Day 7 and Months 3, 6, 9, 12 | 
| Incidence of revascularization interventions throughout duration of study |  | Day 7 and Months 3,6,9,12 | 
| Incidence of bypass surgery for patients throughout duration of study |  | Day 7 and Months 3,6,9,12 | 
| Healing of all wounds in the target limb |  | Day 7 and Months 3,6,9,12 | 
| Ankle and/or toe pressure and ankle brachial pressure index and/or toe brachial index |  | Day 7 and Months 3,6,9,12 | 
| Pain, as measured by visual analog scale(VAS) |  | Day 7 and Months 3,6,9,12 | 
| The King's College Vascular Quality of Life Questionnaire |  | Baseline and Months 6 and 12 | 
| Walking distance as measured by six-minute walk test(with or without walking device) |  | Baseline and Month 12 | 
| Concurrent Meds for trends |  | Day 7 and Months 3, 6, 9, 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Peripheral Arterial Disease, Critical Limb Ischemia, Ischemia, Peripheral Vascular Disease, ixmyelocel-T