an efficacy and safety study of ixmyelocel-t in patients with critical limb ischemia (cli)

Conditions: Critical Limb Ischemia

Summary: this study is designed to evaluate the efficacy and safety of ixmyelocel-t, a patient-specific expanded multicellular therapy, for the treatment of patients with critical limb ischemia (cli). the study is a randomized, vehicle controlled (placebo)study in cli patients who have no option for revascularization procedures. all patients randomized will undergo a small volume bone marrow aspiration in a 15-minute outpatient or in-office procedure. all patients will receive injections of either ixmyelocel-t or vehicle-control into their pre-identified index leg. patients will be followed for 18 months.


Eligibility criteria:
inclusion criteria: * males and nonpregnant, nonlactating females * ages 35 to 90 years of age * diagnosis of cli with tissue loss (corresponding to rutherford category 5; see appendix b) having an ulcer size of at least 0.5 cm2, a smaller sized ulcer penetrating into the subcutaneous tissue, and/or gangrene (dry). in addition, the subject must have one of the following documented at screening: * ankle systolic pressure \< 70 mm hg * toe systolic pressure \< 50 mm hg * tcpo2 \< 30 mm hg (in a supine position) * subjects must have no reasonable standard-of-care options for surgical or endovascular revascularization interventions * subjects must have the following: * a narrative documenting the reasons why the site vascular specialist considers the subject "no option". a vascular specialist will be the principal investigator (pi) or subinvestigator and is defined as: vascular surgeon, interventional cardiologist, certified vascular medicine specialist, or interventional radiologist; and * secondary confirmation by an independent eligibility review committee (erc; see section 8.1) after review of appropriate documents including, but not limited to: imaging results, medical records, surgical history, site vascular specialist narrative documenting reasons for "no option," and/or lab reports. * major amputation in the index leg or death is not anticipated within 3 months of screening in the opinion of the vascular specialist (who must be the pi or subinvestigator) * in the opinion of the investigator, the subject is controlled on medical therapy indicated for cli (unless there is a documented contraindication or intolerance) * subject is current with all age-appropriate american cancer society (acs) or similar (e.g., united states preventative service task force) screening guidelines * given medical history and concurrent medication, the subject is an acceptable candidate for bone marrow aspiration and intramuscular injection procedures in the opinion of the investigator * subject is willing and able to comply with the scheduled visits, aspiration/injection procedure, wound care instructions treatment plan, and other study procedures for the duration of the study * provide a personally-signed and dated informed consent document indicating that the subject (or a legally-acceptable representative, if permitted by the site's investigational review board \[irb\]) has been informed of all pertinent aspects of the study exclusion criteria: patients presenting with any of the following will not be randomized: disease-specific: * failed open surgical revascularization (on index leg) within 4 weeks of screening visit 1 * acute limb-threatening ischemia, trauma, known non-atherosclerotic vascular disease (e.g., temporal/giant cell arteritis, takayasu's arteritis, raynaud's occlusive disease, buerger's disease), embolic disease, aortoiliac disease with \> 50% stenosis, or history of hypercoagulable states * advanced cli (i.e., nonsalvageable) defined as rutherford category 6 * clinical evidence of invasive infection in index leg (e.g., cellulitis, osteomyelitis, wet gangrene) * at screening, non-heel wound size of \> 20 cm2 (excluding toe gangrene); or wounds on the heel \> 10 cm2 on the index leg as measured by the wound core lab (wcl) from photographs (and/or acetates) provided by the site * previous amputation at or above the talus in the index leg medical history * hemoglobin a1c (hba1c) ≥ 10% at screening * diabetic subjects with uncontrolled or untreated proliferative retinopathy as determined by dilated eye exam (by qualified eye care professional as per american diabetes association guidelines) * blood clotting disorder not caused by medication (e.g., thrombophilia) * active non-basal cell cutaneous malignancy requiring surgery, chemotherapy, and/or radiation in the past 12 months * current documented drug or alcohol abuse that would interfere with the subject's compliance with study procedures * known allergies to any equine, porcine, or bovine products * body mass index (bmi) ≥ 50 kg/m2 at screening * established chronic kidney disease (ckd) requiring dialysis (stage 5); estimated creatinine clearance \< 15 mg/ml/min at screening * systolic blood pressure (sbp) \> 200 mm hg or diastolic blood pressure (dbp) \> 120 mm hg or papilledema noted via ophthalmoscope at screening physical exam * within 3 months prior to screening, a clinically significant history of cardiac disease laboratory parameters: * abnormal laboratory values (performed at central lab) at screening: * platelets \< 50,000 μl * aspartate aminotransferase/alanine aminotransferase (ast/alt) \> 3 times the upper limit of normal (uln) * human immunodeficiency virus 1 (hiv 1), hiv 2, or syphilis positive (rapid plasma reagin \[rpr\]) * active hepatitis b surface antigen (hbsag) or hepatitis c virus (hcv); exclusionary procedures, devices, or medication * exposure to immunosuppressive therapy for oncologic or chronic non-oncologic reasons in the prior 12 months or expected requirement over the course of the study (e.g., chemotherapy, radiation therapy, methotrexate) * concurrent participation in another clinical trial or receiving experimental medication within 30 days of screening or having previously been exposed to aastrom's ixmyelocel t product \[previously known as tissue repair cells (trc), cardiac repair cells (crc), vascular repair cells (vrc)\] * on the index leg, use of concomitant wound treatments not currently approved for ischemic wound-healing within 30 days prior to screening or plans to initiate new, nonstandard-of-care treatments to the index leg during the study

Keywords: critical limb ischemia revive peripheral vascular disease cli pad msc stem cells cell therapy