Efficacy and Safety of AMG0001 in Subjects With Critical Limb Ischemia

This is a double-blind, randomized, placebo-controlled, phase 3, multinational, multicenter
study of AMG0001 (HGF plasmid) in subjects with Critical Limb Ischemia (CLI).

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 an
endovascular intervention (see Section 3.1 Study Population for full definition
for appropriate inclusions).

2. Subjects 40-90 years of either gender who have signed an informed consent form either
directly 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 their
standard of care, unless contraindicated. Subjects for whom these agents are
contraindicated will have the reason for contraindication recorded in their case
report form (CRF).

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

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

6. Subjects with a previous medical history of myocardial infarction and/or stroke
should have 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 and
agree 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. Entry
requirements apply to the index leg. The index leg may also be referred to as
the treated leg or affected leg in the text of this protocol or other study
documents. If the subject has two legs that have the same Rutherford
classification (severe Rutherford 4 or Rutherford 5) and are both eligible for
treatment, the leg with greater disease severity (based on more extensive
necrosis or more extensive/deeper ulceration(s), difference in ABI or TBI ≥ 0.1,
and/or more extensive vascular disease based on the angiogram) will be chosen as
the index leg. If there is no clinical, hemodynamic or angiographic or other
evidence to determine which leg has greater disease severity, the subject will
be excluded from the study.

- These entry criteria will be enforced (prior to randomization) by the Sponsor,
as well as an Entry Committee who will review all relevant clinical data
including but 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 marked
worsening during the screening period) or who have excessive tissue necrosis that is
unlikely to benefit from medication, or those poor option subjects requiring
immediate revascularization by surgery. Stability of the CLI status will be confirmed
by the Principal Investigator prior to randomization and retrospectively reviewed by
the Adjudication 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
infection or with the largest ulcer that is greater than 20 cm2 in area (>10 cm2 area
if on the heel).

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
for successfully excised basal cell or squamous cell carcinoma, or successfully
excised early melanoma of the skin. Subjects, who had successful tumor resection or
radio-chemotherapy of breast cancer more than 10 years prior to inclusion in the
study, and with no recurrence, may be enrolled in the study. Subjects, who had
successful tumor resection or radio-chemotherapy of all other tumor types and have
been in remission for more than 5 years prior to inclusion in the study, and with no
recurrence, may be enrolled in the study. A dermatological exam will have ruled out
any skin cancer.

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

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

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

13. Any co-morbid condition likely to interfere with assessment of safety or efficacy
endpoints, acute cardiovascular events (i.e., CVA, MI, etc.) within 3 months of
treatment, or any disease that in the 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 severe
uncontrolled autoimmune disease (e.g., ulcerative colitis, Crohn's disease, etc).

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

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
factors locally within one month of randomization.

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