A Phase IIB Pilot Study of a Modified Dosage Regimen of AMG0001 in Subjects With Critical Limb Ischemia
Condition: Critical Limb Ischemia; Vascular Diseases; Peripheral Arterial Disease
MeSH terms: Peripheral Arterial Disease; Peripheral Vascular Diseases; Vascular Diseases; Chronic Limb-Threatening Ischemia; Ischemia
Intervention: HGF Plasmid
Intervention description: Intramuscular injection in the affected limb.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 40 Years
Maximum age: 90 Years
Healthy volunteers: No
Keywords: Peripheral Arterial Disease; Vascular Disease; CLI; Critical Limb Ischemia; PAD; AnGes; HGF Plasmid; HGF; Hepatocyte Growth Factor Plasmid; gene therapy

Summary:

      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)
    

Eligibility criteria:

        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.