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

NCT ID: NCT00060892

Last Updated: 2008-01-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 104 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-04-30
• Study Completion Date: 2007-01-31

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.

Conditions

Arterial Occlusive Disease; Peripheral Vascular Disease; Ischemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

1

0.4 mg AMG0001 on days 0, 14, and 28

Group Type: ACTIVE_COMPARATOR

HGF plasmid

Intervention Type: GENETIC

Intramuscular injections into index leg on Days 0, 14, and 28

2

4.0 mg AMG0001 on days 0, 14, and 28

Group Type: ACTIVE_COMPARATOR

HGF plasmid

Intervention Type: GENETIC

Intramuscular injections into index leg on Days 0, 14, and 28

3

4.0 mg AMG0001 on days 0 and 28; placebo on day 14

Group Type: ACTIVE_COMPARATOR

HGF plasmid

Intervention Type: GENETIC

Intramuscular injections into index leg on Days 0, 14, and 28

4

Placebo (saline) on days 0, 14, and 28

Group Type: PLACEBO_COMPARATOR

HGF plasmid

Intervention Type: GENETIC

Intramuscular injections into index leg on Days 0, 14, and 28

Interventions

HGF plasmid

Intramuscular injections into index leg on Days 0, 14, and 28

Intervention Type: GENETIC

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.

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AnGes USA, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

AnGes Inc

Locations

Cardiology, P.C.

Birmingham, Alabama, United States

Central Arkansas Veteran's Healthcare System

Little Rock, Arkansas, United States

Cedars-Sinai Medical Center

Los Angeles, California, United States

Falk Cardiovascular Research Center

Stanford, California, United States

VA Medical Center Surgical Service (112)

Washington D.C., District of Columbia, United States

Basptist Hospital

Pensacola, Florida, United States

University of South Florida College of Medicine

Tampa, Florida, United States

American Cardiovascular Research Institute

Atlanta, Georgia, United States

University of Chicago Hospitals

Chicago, Illinois, United States

The Care Group, LLC

Indianapolis, Indiana, United States

The Ochsner Heart and Vascular Institute

Metairie, Louisiana, United States

Minneapolis Heart Institute Foundation

Minneapolis, Minnesota, United States

Dartmouth - Hitchcock Medical Center

Lebanon, New Hampshire, United States

Diabetes Foot and Ankle Center

New York, New York, United States

NYPH-NY Weill Cornell Medical Center

New York, New York, United States

University of Rochester

Rochester, New York, United States

Pitt County Memorial Hospital

Greenville, North Carolina, United States

The Lindner Clinical Trial Center

Cincinnati, Ohio, United States

The Cleveland Clinic Foundation

Cleveland, Ohio, United States

Jobst Vascular Center

Toledo, Ohio, United States

Medical College of Ohio

Toledo, Ohio, United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Baylor College of Medicine

Houston, Texas, United States

Peripheral Vascular Associates

San Antonio, Texas, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 18559703 (View on PubMed)

Other Identifiers

AG-CLI-0202

Identifier Type: -

Identifier Source: org_study_id