The primary purpose of this study is to assess the overall safety of different dose regimens of AMG0001 as well as evaluate the improvement of blood perfusion in subjects with critical limb ischemia (CLI). This study will also evaluate the improvement in wound healing without adverse effects on the quality of life, as well as the potential reduction of amputation, mortality and rest pain in the CLI population.

Condition	Treatment or Intervention	Phase
Arterial Occlusive Disease Peripheral Vascular Disease Ischemia	Gene Transfer: HGF transferred via plasmid vector	Phase II

The primary goal of this study is to assess the safety of AMG0001, detect potential angiogenesis response to AMG0001 treatment and to correlate these changes to clinical endpoints dependent upon improvement in tissue perfusion for relief of CLI complications. The objectives of this study are: Assess the overall safety of different exposure regimens of AMG0001 in the CLI subject population. Evaluate the potential effect of angiogenesis associated with different doses and dose regimens of AMG0001 as measured by improvement in tissue perfusion. Evaluate the activity of different exposure regimens of AMG0001 to benefit clinical outcomes of reduction of amputation and mortality, wound healing, rest-pain reduction and improvement in subject’s ability to function without adverse consequences on quality of life.

Ages Eligible for Study:  40 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• Subjects will have one or more clinical indications diagnostic of CLI such as: distal extremity pain at rest that requires the subject to use analgesics for >2 weeks; or peripheral ischemic ulcer(s); or areas of gangrene.
• The subject will have a TcPO2 of </= 40 mmHg.
• Subjects will have one or both of the following hemodynamic indicators of severe peripheral arterial occlusive disease: A. Ankle systolic pressure of </= 70 mmHg B. Toe systolic pressure </= 50 mmHg.
• The subject is a poor candidate for standard revascularization treatment options for peripheral arterial disease, based on inadequate bypass conduit, unfavorable anatomy, or poor operative risk.
• Subject has signed an informed consent form either directly or through a legally authorized representative
• If female, the subject must be (a) at least one year post-menopausal, or (b) surgically sterile, or (c) if the subject is of child-bearing potential, she must have been practicing contraception for at least 12 weeks prior to entering the study.
• If subject is of reproductive potential, he or she must be using an accepted and effective (barrier) form of birth control during the study.
• Subjects will be on a statin and an anti-platelet agent as part of their standard of care and must be stable on these regimens for at least 4 weeks prior to treatment.

Exclusion Criteria:

• Subjects, who in the opinion of the investigator, have a vascular disease prognosis that indicates they would require a major amputation (at or above the ankle) within 4 weeks of start of treatment.
• Subjects with a diagnosis of Buerger's disease (Thromboangitis Obliterans).
• Subjects with hemodynamically significant aorto-iliac occlusive disease.
• Subjects who have had a revascularization procedure within 12 weeks prior to treatment initiation that remains patent. Revascularization procedures that are evidenced to have failed for >2 weeks prior to treatment initiation are acceptable.
• Subjects who require a change in their hypertension medication as part of their standard of care within 4 weeks prior to treatment.
• Evidence or history of malignant neoplasm (clinical, laboratory or imaging), except for basal cell carcinoma of the skin.
• Subjects who have proliferative diabetic retinopathy or severe, non-proliferative retinopathy
• Subjects with end stage renal disease (ESRD) defined as significant renal dysfunction evidenced by a creatinine of > 2.5, or receiving chronic hemodialysis therapy.
• A subject who has hepatic cirrhosis, viral hepatitis, or is HIV positive.
• Subjects with a clinically significant liver enzyme abnormality (i.e., AST or ALT more than two times the upper limit of normal and/or bilirubin more than 50% the upper limit of normal).
• Subjects requiring the use of hyperbaric oxygen treatment for wound healing during the screening and 6 month follow-up period.

Andrew Hinson      301-990-1660 X4131    ahinson@anges-mg.com
Jeffrey Carey      301-990-1660 X4154    jcarey@anges-mg.com

Alabama
      Cardiology, P.C., Birmingham,  Alabama,  35211,  United States; Recruiting
Arkansas
      Central Arkansas Veteran's Healthcare System, Little Rock,  Arkansas,  72205,  United States; Recruiting
California
      Cedars-Sinai Medical Center, Los Angeles,  California,  90048,  United States; Recruiting
      Falk Cardiovascular Research Center, Stanford,  California,  94305,  United States; Recruiting
District of Columbia
      VA Medical Center Surgical Service (112), Washington,  District of Columbia,  20422,  United States; Recruiting
Florida
      Basptist Hospital, Pensacola,  Florida,  32501,  United States; Recruiting
      University of South Florida College of Medicine, Tampa,  Florida,  33606,  United States; Recruiting
Georgia
      American Cardiovascular Research Institute, Atlanta,  Georgia,  30342,  United States; Recruiting
Illinois
      University of Chicago Hospitals, Chicago,  Illinois,  60637,  United States; Recruiting
Indiana
      The Care Group, LLC, Indianapolis,  Indiana,  46290,  United States; Recruiting
Louisiana
      The Ochsner Heart and Vascular Institute, Metairie,  Louisiana,  70002,  United States; Recruiting
Minnesota
      Minneapolis Heart Institute Foundation, Minneapolis,  Minnesota,  55407,  United States; Recruiting
New Hampshire
      Dartmouth - Hitchcock Medical Center, Lebanon,  New Hampshire,  03756,  United States; Recruiting
New York
      University of Rochester, Rochester,  New York,  14642,  United States; Recruiting
      NYPH-NY Weill Cornell Medical Center, New York,  New York,  10021,  United States; Recruiting
      Diabetes Foot and Ankle Center, New York,  New York,  10003,  United States; Recruiting
North Carolina
      Pitt County Memorial Hospital, Greenville,  North Carolina,  27834,  United States; Recruiting
Ohio
      Jobst Vascular Center, Toledo,  Ohio,  43606,  United States; Recruiting
      Medical College of Ohio, Toledo,  Ohio,  43614,  United States; Recruiting
      The Lindner Clinical Trial Center, Cincinnati,  Ohio,  45219,  United States; Recruiting
      The Cleveland Clinic Foundation, Cleveland,  Ohio,  44195,  United States; Recruiting
Oklahoma
      University of Oklahoma Health Sciences Center, Oklahoma City,  Oklahoma,  73104,  United States; Recruiting
Tennessee
      University of Tennessee-Knoxville, Knoxville,  Tennessee,  37920,  United States; Recruiting
Texas
      Baylor College of Medicine, Houston,  Texas,  77030,  United States; Recruiting
      Peripheral Vascular Associates, San Antonio,  Texas,  78215,  United States; Recruiting

Study ID Numbers:  AG-CLI-0202
Record last reviewed:  September 2004
Record first received:  May 15, 2003
ClinicalTrials.gov Identifier:  NCT00060892
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2004-11-10