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Study of HGF Via Plasmid Vector to Improve Perfusion in Critical Limb Ischemia

Phase 2
Completed
Conditions
Arterial Occlusive Disease
Peripheral Vascular Disease
Ischemia
Interventions
Genetic: HGF plasmid
Registration Number
NCT00060892
Lead Sponsor
AnGes USA, Inc.
Brief Summary

The primary purpose of this study was to assess the overall safety of different dose regimens of AMG0001 (HGF transferred via plasmid vector) as well as evaluate the improvement of blood perfusion in subjects with critical limb ischemia (CLI). This study also evaluated 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.

Detailed Description

The primary goal of this study was 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 were to:

* 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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
104
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
4HGF plasmidPlacebo (saline) on days 0, 14, and 28
2HGF plasmid4.0 mg AMG0001 on days 0, 14, and 28
1HGF plasmid0.4 mg AMG0001 on days 0, 14, and 28
3HGF plasmid4.0 mg AMG0001 on days 0 and 28; placebo on day 14
Primary Outcome Measures
NameTimeMethod
Tissue perfusion as measured by TcPO26 months
Secondary Outcome Measures
NameTimeMethod
Ulcer healing6 months

Trial Locations

Locations (24)

The Ochsner Heart and Vascular Institute

🇺🇸

Metairie, Louisiana, United States

University of South Florida College of Medicine

🇺🇸

Tampa, Florida, United States

Cardiology, P.C.

🇺🇸

Birmingham, Alabama, United States

Diabetes Foot and Ankle Center

🇺🇸

New York, New York, United States

Central Arkansas Veteran's Healthcare System

🇺🇸

Little Rock, Arkansas, United States

VA Medical Center Surgical Service (112)

🇺🇸

Washington, District of Columbia, United States

Basptist Hospital

🇺🇸

Pensacola, Florida, United States

Minneapolis Heart Institute Foundation

🇺🇸

Minneapolis, Minnesota, United States

University of Chicago Hospitals

🇺🇸

Chicago, Illinois, United States

Medical College of Ohio

🇺🇸

Toledo, Ohio, United States

NYPH-NY Weill Cornell Medical Center

🇺🇸

New York, New York, United States

Cedars-Sinai Medical Center

🇺🇸

Los Angeles, California, United States

The Cleveland Clinic Foundation

🇺🇸

Cleveland, Ohio, United States

Baylor College of Medicine

🇺🇸

Houston, Texas, United States

American Cardiovascular Research Institute

🇺🇸

Atlanta, Georgia, United States

Falk Cardiovascular Research Center

🇺🇸

Stanford, California, United States

The Lindner Clinical Trial Center

🇺🇸

Cincinnati, Ohio, United States

University of Rochester

🇺🇸

Rochester, New York, United States

The Care Group, LLC

🇺🇸

Indianapolis, Indiana, United States

Peripheral Vascular Associates

🇺🇸

San Antonio, Texas, United States

Dartmouth - Hitchcock Medical Center

🇺🇸

Lebanon, New Hampshire, United States

Jobst Vascular Center

🇺🇸

Toledo, Ohio, United States

University of Oklahoma Health Sciences Center

🇺🇸

Oklahoma City, Oklahoma, United States

Pitt County Memorial Hospital

🇺🇸

Greenville, North Carolina, United States

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