Clinical trial NCT00060892: Study of HGF Via Plasmid Vector to Improve Perfusion in Critical Limb Ischemia
Official title: A Phase II Double-Blind, Randomized, Placebo-Controlled Study to Assess the Safety and Efficacy of AMG0001 to Improve Perfusion in Critical Leg Ischemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Arterial Occlusive Disease
Peripheral Vascular Disease
Ischemia
Keywords: Critical Limb Ischemia
Lead sponsor: AnGes USA, Inc.
Sponsor class: INDUSTRY
First posted: 2003-05-16
Enrollment: 104
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: Tissue perfusion as measured by TcPO2
timeFrame: 6 months
Secondary outcomes:
measure: Ulcer healing
timeFrame: 6 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Cardiology, P.C.
state: Alabama
city: Little Rock
country: United States
facility: Central Arkansas Veteran's Healthcare System
state: Arkansas
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Stanford
country: United States
facility: Falk Cardiovascular Research Center
state: California
city: Washington
country: United States
facility: VA Medical Center Surgical Service (112)
state: District of Columbia
city: Pensacola
country: United States
facility: Basptist Hospital
state: Florida
city: Tampa
country: United States
facility: University of South Florida College of Medicine
state: Florida
city: Atlanta
country: United States
facility: American Cardiovascular Research Institute
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Hospitals
state: Illinois
city: Indianapolis
country: United States
facility: The Care Group, LLC
state: Indiana
city: Metairie
country: United States
facility: The Ochsner Heart and Vascular Institute
state: Louisiana
city: Minneapolis
country: United States
facility: Minneapolis Heart Institute Foundation
state: Minnesota
city: Lebanon
country: United States
facility: Dartmouth - Hitchcock Medical Center
state: New Hampshire
city: New York
country: United States
facility: Diabetes Foot and Ankle Center
state: New York
city: New York
country: United States
facility: NYPH-NY Weill Cornell Medical Center
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Greenville
country: United States
facility: Pitt County Memorial Hospital
state: North Carolina
city: Cincinnati
country: United States
facility: The Lindner Clinical Trial Center
state: Ohio
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Toledo
country: United States
facility: Jobst Vascular Center
state: Ohio
city: Toledo
country: United States
facility: Medical College of Ohio
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: San Antonio
country: United States
facility: Peripheral Vascular Associates
state: Texas
Study officials:
References:
citation: Powell RJ, Simons M, Mendelsohn FO, Daniel G, Henry TD, Koga M, Morishita R, Annex BH. Results of a double-blind, placebo-controlled study to assess the safety of intramuscular injection of hepatocyte growth factor plasmid to improve limb perfusion in patients with critical limb ischemia. Circulation. 2008 Jul 1;118(1):58-65. doi: 10.1161/CIRCULATIONAHA.107.727347. Epub 2008 Jun 16.