A Phase IIB Pilot Study of a Modified Dosage Regimen of AMG0001 in Subjects With Critical Limb Ischemia

A Phase IIB Pilot Study to Confirm the Feasibility and Tolerability of a Modified Dosage Regimen of AMG0001 in Subjects With Critical Limb Ischemia

The purpose of the study is to confirm the feasibility of study procedures and the tolerability of a new dose regimen of AMG0001 in subjects with Critical Limb Ischemia (CLI)

The primary objectives of the study are:

1. To confirm the feasibility of study-related activities and the tolerability of a modified dosage regimen of AMG0001 in CLI
2. To evaluate safety of AMG0001

Inclusion Criteria:

• Subjects with stable CLI (Severe Rutherford 4 and Rutherford 5) who have no option for revascularization by endovascular intervention or surgical bypass or a poor option (high risk) for revascularization by surgery and no option for an endovascular intervention
• Subjects 40-90 years of either gender who have signed an informed consent
• Subjects currently are taking a statin and an anti-platelet agent
• If female, the subjects must not be of child bearing potential, e.g., post-menopausal or surgically sterile.
• 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.
• Subjects with a previous medical history of myocardial infarction and/or stroke should have adequate management of risk factors to prevent secondary occurrence.
• Subjects should have the ability to understand the requirements of the protocol and agree to return for the required study visits and assessments

Exclusion Criteria:

• Subjects whose CLI status is unstable (spontaneous marked improvement or marked worsening during the screening period).
• Subjects who may require a major amputation (amputation at or above the ankle) within 4 weeks of Day 0 (± 4 weeks of Day 0).
• 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).
• Subjects with purely neuropathic or venous ulcers.
• Subjects in Rutherford 6 class.
• 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.
• Subjects with a diagnosis of Buerger's disease (Thrombo-angiitis Obliterans).
• Subjects currently receiving immunosuppressive, chemo or radiation therapy.
• 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.
• 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.
• Subjects with severe renal disease defined as significant renal dysfunction evidenced by an estimated creatinine clearance of <30 mL/minute (calculated using the Cockcroft Gault formula), or receiving chronic hemodialysis therapy.
• A Stroke, TIA or MI within 3 months of entry into the study.
• Subjects with known liver disease (e.g., hepatitis B or C or cirrhosis of the liver).
• A subject with HIV, AIDS, or severe uncontrolled ulcerative colitis or Crohn's disease.
• Subjects with a current, uncorrected history of alcohol or substance abuse.
• Subjects that have been administered rhPDGF (e.g, becaplermin) or other growth factors locally within one month of randomization.
• 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.