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

Sponsor

AnGes USA, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT00060892

Collaborator

(none)

104

Enrollment

Locations

Arms

Duration (Months)

4.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Arterial Occlusive Disease Peripheral Vascular Disease Ischemia	Genetic: HGF plasmid	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

104 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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 Start Date :

Apr 1, 2003

Actual Primary Completion Date :

May 1, 2006

Actual Study Completion Date :

Jan 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1 0.4 mg AMG0001 on days 0, 14, and 28	Genetic: HGF plasmid Intramuscular injections into index leg on Days 0, 14, and 28
Active Comparator: 2 4.0 mg AMG0001 on days 0, 14, and 28	Genetic: HGF plasmid Intramuscular injections into index leg on Days 0, 14, and 28
Active Comparator: 3 4.0 mg AMG0001 on days 0 and 28; placebo on day 14	Genetic: HGF plasmid Intramuscular injections into index leg on Days 0, 14, and 28
Placebo Comparator: 4 Placebo (saline) on days 0, 14, and 28	Genetic: HGF plasmid Intramuscular injections into index leg on Days 0, 14, and 28

Outcome Measures

Primary Outcome Measures

Tissue perfusion as measured by TcPO2 [6 months]

Secondary Outcome Measures

Ulcer healing [6 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cardiology, P.C.	Birmingham	Alabama	United States	35211
2	Central Arkansas Veteran's Healthcare System	Little Rock	Arkansas	United States	72205
3	Cedars-Sinai Medical Center	Los Angeles	California	United States	90048
4	Falk Cardiovascular Research Center	Stanford	California	United States	94305
5	VA Medical Center Surgical Service (112)	Washington	District of Columbia	United States	20422
6	Basptist Hospital	Pensacola	Florida	United States	32501
7	University of South Florida College of Medicine	Tampa	Florida	United States	33606
8	American Cardiovascular Research Institute	Atlanta	Georgia	United States	30342
9	University of Chicago Hospitals	Chicago	Illinois	United States	60637
10	The Care Group, LLC	Indianapolis	Indiana	United States	46290
11	The Ochsner Heart and Vascular Institute	Metairie	Louisiana	United States	70002
12	Minneapolis Heart Institute Foundation	Minneapolis	Minnesota	United States	55407
13	Dartmouth - Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
14	Diabetes Foot and Ankle Center	New York	New York	United States	10003
15	NYPH-NY Weill Cornell Medical Center	New York	New York	United States	10021
16	University of Rochester	Rochester	New York	United States	14642
17	Pitt County Memorial Hospital	Greenville	North Carolina	United States	27834
18	The Lindner Clinical Trial Center	Cincinnati	Ohio	United States	45219
19	The Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
20	Jobst Vascular Center	Toledo	Ohio	United States	43606
21	Medical College of Ohio	Toledo	Ohio	United States	43614
22	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
23	Baylor College of Medicine	Houston	Texas	United States	77030
24	Peripheral Vascular Associates	San Antonio	Texas	United States	78215