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

This study has been completed.
Sponsor:
Information provided by:
AnGes
ClinicalTrials.gov Identifier:
NCT00060892
First received: May 15, 2003
Last updated: January 9, 2008
Last verified: January 2008
  Purpose

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 Intervention Phase
Arterial Occlusive Disease
Peripheral Vascular Disease
Ischemia
Genetic: HGF plasmid
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by AnGes:

Primary Outcome Measures:
  • Tissue perfusion as measured by TcPO2 [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Ulcer healing [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Enrollment: 104
Study Start Date: April 2003
Study Completion Date: January 2007
Primary Completion Date: May 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00060892

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Sponsors and Collaborators
AnGes
  More Information

Additional Information:
No publications provided by AnGes

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Prannath Marrott, M.D., AnGes Inc
ClinicalTrials.gov Identifier: NCT00060892     History of Changes
Other Study ID Numbers: AG-CLI-0202
Study First Received: May 15, 2003
Last Updated: January 9, 2008
Health Authority: United States: Food and Drug Administration

Keywords provided by AnGes:
Critical Limb Ischemia

Additional relevant MeSH terms:
Arterial Occlusive Diseases
Ischemia
Vascular Diseases
Peripheral Vascular Diseases
Peripheral Arterial Disease
Cardiovascular Diseases
Pathologic Processes
Atherosclerosis
Arteriosclerosis

ClinicalTrials.gov processed this record on August 28, 2014