Study of Hepatocyte Growth Factor (HGF) Via Plasmid Vector to Improve Perfusion in Critical Limb Ischemia Patients With Peripheral Ischemic Ulcers

NCT00189540 | Completed Phase 2 Results FDA Drug

• 1 other identifier: AG-CLI-0205
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Arterial Occlusive Disease; Peripheral Vascular Disease; Ischemia; Ulcers

Keywords

Ischemic ulcers; Critical Limb Ischemia

Outcome Measures

Primary Outcomes (1)

• Wound Healing (Change in Total Wound Area of All Ischemic Ulcers)

  Wound healing measured by change in mean total wound area of all ischemic ulcers at Month 3 and Month 6

  Baseline, Month 3, Month 6

Secondary Outcomes (5)

• Percentage of Participants Where All Ulcers Healed

  Month 3 and Month 6

• Change in Pain at Rest as Measured on the Visual Analog Scale (VAS)

  Baseline, Month 3 and Month 6

• Number of Subjects Who Undergo a Major Amputation

  Month 3 and Month 6

• Change in Hemodynamic Measurements - Mean Change in Ankle Brachial Index (ABI)

  Baseline, Month 3, Month 6

• Change in Hemodynamic Measurements - Mean Change in Toe Brachial Index (TBI)

  Baseline, Month 3, Month 6

Study Arms (2)

Active Group

ACTIVE COMPARATOR

4.0 mg AMG0001 via intramuscular injections on days 0, 14, and 28

Genetic: HGF plasmid

Placebo Group

PLACEBO COMPARATOR

Placebo (saline) via intramuscular injections on days 0, 14, and 28

Genetic: Placebo

Interventions

HGF plasmid GENETIC

Intramuscular injections into the index leg on days 0, 14, and 28

Active Group

Placebo GENETIC

Intramuscular injections into the index leg on days 0, 14, and 28

Placebo Group

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects will have an appropriately sized peripheral ischemic ulcer(s).
• Subjects will have one or both of the following hemodynamic indicators of severe peripheral arterial occlusive disease:
• Ankle systolic pressure (in either the dorsalis pedis or posterior tibial arteries) of \< 70 mmHg
• 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.
• Subjects 40 years or older of either sex who have signed an informed consent form either directly or through a legally authorized representative.
• 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.
• If female, the subjects must be:
• at least one year post-menopausal, or
• surgically sterile, or
• 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.
• If female, the subject must not be breastfeeding for 30 days following administration of HGF.
• If subject is of reproductive potential, he or she must be using an accepted and effective (barrier) form of birth control during the study.

You may not qualify if:

• 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 (thromboangiitis 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 (completely occluded) for \>2 weeks prior to treatment initiation are acceptable.
• 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.
• Subjects with deep ulcerations with bone or tendon exposure, or clinical evidence of invasive infection (e.g., cellulitis, osteomyelitis, etc.) uncontrollable by antibiotics.
• Subjects currently receiving immuno-suppressive medication, chemo or radiation therapy.
• 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.
• 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.
• 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.
• A subject who has a history of hepatic cirrhosis, viral hepatitis, or HIV.
• 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).
• 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.

Sponsors & Collaborators

• AnGes USA, Inc.: lead

Study Sites (4)

Baptist Clinical Research

Pensacola, Florida, 32501, United States

Location

The Care Group, LLC

Indianapolis, Indiana, 46290, United States

Location

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

Dartmouth - Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Related Publications (1)

• Powell RJ, Goodney P, Mendelsohn FO, Moen EK, Annex BH; HGF-0205 Trial Investigators. Safety and efficacy of patient specific intramuscular injection of HGF plasmid gene therapy on limb perfusion and wound healing in patients with ischemic lower extremity ulceration: results of the HGF-0205 trial. J Vasc Surg. 2010 Dec;52(6):1525-30. doi: 10.1016/j.jvs.2010.07.044.

  PMID: 21146749 RESULT

MeSH Terms

Conditions

Arterial Occlusive Diseases; Peripheral Vascular Diseases; Ischemia; Ulcer; Chronic Limb-Threatening Ischemia

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Peripheral Arterial Disease; Atherosclerosis; Arteriosclerosis; Chronic Disease; Disease Attributes

Results Point of Contact

• Title: Director of Clinical Operations
• Organization: AnGes

information@anges-mg.com

240-780-9031

Study Officials

• Richard Powell, MD

  Dartmouth

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2005
• First Posted: September 19, 2005
• Study Start: August 1, 2005
• Primary Completion: July 1, 2008
• Study Completion: August 1, 2008
• Last Updated: October 28, 2021
• Results First Posted: August 19, 2011

Record last verified: 2021-10

Locations

US (4)