Efficacy and Safety of AMG0001 in Subjects With Critical Limb Ischemia

Inclusion Criteria:

1. Subjects with CLI (Severe Rutherford 4 and Rutherford 5) who have:

• No option for revascularization by endovascular intervention or surgical bypass or

• Poor option (high risk) for revascularization by surgery and no option for anendovascular intervention (see Section 3.1 Study Population for full definitionfor appropriate inclusions).

2. Subjects 40-90 years of either gender who have signed an informed consent form eitherdirectly or through a legally authorized representative.

3. Subjects currently are taking a statin and an anti-platelet agent (e.g., clopidogrel,ticlopidine, aspirin, etc.) for 2 weeks or more prior to Day 0 as part of theirstandard of care, unless contraindicated. Subjects for whom these agents arecontraindicated will have the reason for contraindication recorded in their casereport form (CRF).

4. If female, the subjects must not be of child bearing potential, e.g., post-menopausalor surgically sterile.

5. If a male subject is of reproductive potential, he must agree to use an accepted andeffective (barrier) form of birth control starting with the first dose of studyproduct and continue for 12 weeks from the last dose of study product. This applies toboth courses of treatment.

6. Subjects with a previous medical history of myocardial infarction and/or stroke shouldhave adequate management of risk factors to prevent secondary occurrence. (See Section 4.2 Medical History for guidelines on appropriate secondary prevention.)

7. Subjects should have the ability to understand the requirements of the protocol andagree to return for the required study visits, assessments and follow up.

• The index leg will be the leg with the greater severity of CLI disease. Entryrequirements apply to the index leg. The index leg may also be referred to as thetreated leg or affected leg in the text of this protocol or other studydocuments. If the subject has two legs that have the same Rutherfordclassification (severe Rutherford 4 or Rutherford 5) and are both eligible fortreatment, the leg with greater disease severity (based on more extensivenecrosis or more extensive/deeper ulceration(s), difference in ABI (anklebrachial index) or TBI (toe brachial index) ≥ 0.1, and/or more extensive vasculardisease based on the angiogram) will be chosen as the index leg. If there is noclinical, hemodynamic or angiographic or other evidence to determine which leghas greater disease severity, the subject will be excluded from the study.

• These entry criteria will be enforced (prior to randomization) by the Sponsor, aswell as an Entry Committee who will review all relevant clinical data includingbut not limited to medical illness, CLI status, the findings of an angiogram,ulcer photographs and measurements and hemodynamic data.

Exclusion Criteria:

1. Subjects whose CLI status is unstable (spontaneous marked improvement or markedworsening during the screening period) or who have excessive tissue necrosis that isunlikely to benefit from medication, or those poor option subjects requiring immediaterevascularization by surgery. Stability of the CLI status will be confirmed by thePrincipal Investigator prior to randomization and retrospectively reviewed by theAdjudication Committee.

2. Subjects who may require a major amputation (amputation at or above the ankle) within 4 weeks of Day 0 (± 4 weeks of Day 0).

3. Subjects with ulcers with exposure of tendons, osteomyelitis or uncontrolled infectionor with the largest ulcer that is greater than 20 cm2 in area (>10 cm2 area if on theheel).

4. Subjects with purely neuropathic, or with venous ulcers.

5. Subjects in Rutherford 6 class.

6. Subjects who have had revascularization by surgery or angioplasty within 3 months,unless the procedure has failed based on the anatomy or the hemodynamic measurements.

7. Subjects with a diagnosis of Buerger's disease (Thrombo-angiitis Obliterans).

8. Subjects currently receiving immunosuppressive, chemo or radiation therapy.

9. Evidence or history of malignant neoplasm (clinical, laboratory or imaging) except forsuccessfully excised basal cell or squamous cell carcinoma, or successfully excisedearly melanoma of the skin. Subjects, who had successful tumor resection orradio-chemotherapy of breast cancer more than 10 years prior to inclusion in thestudy, and with no recurrence, may be enrolled in the study. Subjects, who hadsuccessful tumor resection or radio-chemotherapy of all other tumor types and havebeen in remission for more than 5 years prior to inclusion in the study, and with norecurrence, may be enrolled in the study. A dermatological exam will have ruled outany skin cancer.

10. Subjects who have proliferative retinopathy, or moderate or severe non-proliferativeretinopathy, from any cause (ETDRS Score > 35), clinically significant macular oedemaor previous panretinal photocoagulation therapy (Results from the Early TreatmentDiabetic Retinopathy Study. Ophthalmology May 1991 Supplement 98: 823-833).

11. Females of child-bearing potential defined as subjects that are not surgically sterileor post-menopausal.

12. Subjects with severe renal disease defined as significant renal dysfunction evidencedby an estimated creatinine clearance of <30 mL/minute (calculated using the CockcroftGault formula), or receiving chronic hemodialysis therapy.

13. Any co-morbid condition likely to interfere with assessment of safety or efficacyendpoints, acute cardiovascular events (i.e., CVA (cardiovascular accident), MI (myocardial infarction), etc.) within 3 months of treatment, or any disease that inthe opinion of the Investigator may result in subject mortality in less than 3 months.

14. Subjects with known liver disease (e.g., hepatitis B or C or cirrhosis of the liver).

15. A subject with HIV, AIDS, severe uncontrolled inflammatory disease or severeuncontrolled autoimmune disease (e.g., ulcerative colitis, Crohn's disease, etc).

16. Subjects who have a significant psychiatric disorder or mental disability that couldinterfere with the subject's ability to provide informed consent or comply with studyprocedures.

17. Subjects with a current, uncorrected history of alcohol or substance abuse.

18. Diabetic subjects with an uncorrected HbA1c > 9.0% during the screening period.

19. Subjects that have been administered rhPDGF (e.g, becaplermin) or other growth factorslocally within one month of randomization.

20. Subjects who have received another investigational drug within 30 days ofrandomization or have previously received any gene transfer therapy within 3 years ofentering the study.