An Efficacy and Safety Study of Ixmyelocel-T in Patients With Critical Limb Ischemia (CLI)

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