Study of Hepatocyte Growth Factor (HGF) Via Plasmid Vector to Improve Perfusion in Critical Limb Ischemia Patients With Peripheral Ischemic Ulcers
Condition: Arterial Occlusive Disease; Peripheral Vascular Disease; Ischemia; Ulcers
MeSH terms: Vascular Diseases; Chronic Limb-Threatening Ischemia; Peripheral Vascular Diseases; Peripheral Arterial Disease; Arterial Occlusive Diseases; Ischemia; Ulcer
Intervention: HGF plasmid; Placebo
Intervention description: Intramuscular injections into the index leg on days 0, 14, and 28; Intramuscular injections into the index leg on days 0, 14, and 28
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 27.0
Sex: All
Minimum age: 40 Years
Healthy volunteers: No
Keywords: Ischemic ulcers; Critical Limb Ischemia

Summary:

      The objective of this study is to test the hypothesis that AMG0001 treatment is safe and
      induces angiogenesis as detected by improved wound healing, reduction in amputation, improved
      pain at rest and hemodynamic measurement and to assess the effectiveness of the
      administrative method.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Subjects will have an appropriately sized peripheral ischemic ulcer(s).

          2. Subjects will have one or both of the following hemodynamic indicators of severe
             peripheral arterial occlusive disease:

               1. Ankle systolic pressure (in either the dorsalis pedis or posterior tibial
                  arteries) of < 70 mmHg

               2. Toe systolic pressure < 50 mmHg

          3. 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.

          4. Subjects 40 years or older of either sex who have signed an informed consent form
             either directly or through a legally authorized representative.

          5. Subjects will be on a statin and an anti-platelet agent (e.g., clopidogrel,
             ticlopidine, aspirin, etc.) as part of their standard of care, unless contraindicated.
             Subjects for which these agents are contraindicated will have this restriction
             recorded in their case report form (CRF). Subjects must be stable on these medical
             regimens for at least 4 weeks prior to the start of treatment.

          6. If female, the subjects must be:

               1. at least one year post-menopausal, or

               2. surgically sterile, or

               3. if the subject is of child-bearing potential, she must have been practicing
                  adequate contraception for at least 12 weeks prior to entering the study and have
                  a negative urine pregnancy test result prior to study enrollment and agree to
                  periodic pregnancy screening tests during the study.

               4. If female, the subject must not be breastfeeding for 30 days following
                  administration of HGF.

          7. If subject is of reproductive potential, he or she must be using an accepted and
             effective (barrier) form of birth control during the study.

        Exclusion Criteria

          1. 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.

          2. Subjects with a diagnosis of Buerger's disease (thromboangiitis obliterans).

          3. Subjects with hemodynamically significant aorto-iliac occlusive disease.

          4. 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 (completely occluded) for >2 weeks prior to treatment initiation are
             acceptable.

          5. Subjects who require a change in their hypertension medication (other than dosage
             change) as part of their standard of care within 4 weeks prior to treatment
             initiation.

          6. Subjects with deep ulcerations with bone or tendon exposure, or clinical evidence of
             invasive infection (e.g., cellulitis, osteomyelitis, etc.) uncontrollable by
             antibiotics.

          7. Subjects currently receiving immuno-suppressive medication, chemo or radiation
             therapy.

          8. Evidence or history of malignant neoplasm (clinical, laboratory or imaging), except
             for fully resolved basal cell carcinoma of the skin. Patient's 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.
             Patient's who had successful tumor resection or radio-chemotherapy of all other tumor
             types more than 5 years prior to inclusion in the study, and with no recurrence, may
             be enrolled in the study.

          9. Subjects who have proliferative diabetic retinopathy, severe non-proliferative
             retinopathy, recent (within 6 months) retinal vein occlusion, macular degeneration
             with choroidal neovascularization, macular edema on fundus evaluation by
             ophthalmologist, or intraocular surgery within 3 months.

         10. Subjects with end stage renal disease (ESRD) defined as significant renal dysfunction
             evidenced by a creatinine of > 2.5 mg/dL, or receiving chronic hemodialysis therapy.

         11. Any co-morbid condition likely to interfere with assessment of safety or efficacy
             endpoints, acute cardiovascular events (i.e. cerebrovascular accident [CVA],
             myocardial infarction [MI], etc.) within 12 weeks of treatment, or non-cardiovascular
             diseases that in the opinion of the investigator may result in < 3 month subject
             mortality.

         12. A subject who has a history of hepatic cirrhosis, viral hepatitis, or HIV.

         13. 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% above the
             upper limit of normal).

         14. Subjects taking cilostazol (Pletal®) are eligible for inclusion, but the subject must
             have been taking the medication for at least 4 weeks prior to test material
             administration.

         15. Subject who received another investigational drug for peripheral arterial disease
             within 90 days of randomization, have previously received any gene transfer therapy or
             growth factor product not approved by the United States Food and Drug Administration
             (FDA) or received any investigational Drug Product in another clinical trial in the 30
             days prior to administration of HGF.

         16. Unreliable or uncooperative subject or other severe concomitant disease(s), which the
             clinical investigator feels constitute(s) criteria for exclusion of a particular
             subject.