A phase I clinical study of naked DNA expressing two isoforms of hepatocyte growth factor to treat patients with critical limb ischemia

J Gene Med. 2011 Nov;13(11):602-10. doi: 10.1002/jgm.1614.

Abstract

Background: The purpose of the present phase I clinical trial was to evaluate the safety, tolerability, and preliminary efficacy of naked DNA therapy expressing two isoforms of hepatocyte growth factor (pCK-HGF-X7) in critical limb ischemia (CLI) patients.

Materials and methods: Twenty-one patients with CLI were consecutively assigned to receive increasing doses (cohort I: 4 mg; cohort II: 8 mg; cohort III: 12 mg; and cohort IV: 16 mg) of pCK-HGF-X7, which was administered into the ischemic calf and/or thigh muscle at days 1 and 15. A safety and tolerability evaluation and measurement of pain severity score using a visual analog scale (VAS), ulcer status, transcutaneous oxygen (TcPO(2) ) and ankle-brachial index (ABI) were performed throughout a 3-month follow-up period.

Results: No serious adverse events were observed in any of the 21 patients for the 3-month follow-up period. A significant reduction in pain was observed in the treated patients, with the mean VAS decreasing from 5.95-1.64 (p < 0.001). The mean ABI value increased from 0.49-0.63 (p = 0.026) at 3-month follow-up. The mean TcPO(2) value on the dorsum of the foot, the anterior calf and posterior calf significantly increased from 28.25-39.28 mmHg (p = 0.012), from 22.00-30.63 mmHg (p = 0.046) and 32.05-47.19 mmHg (p = 0.001) at 3-month follow-up, respectively. Wound healing improvement was observed in the six of nine patients that had an ulcer at baseline.

Conclusions: These results support the performance of a phase II randomized controlled trial with pCK-HGF-X7.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Ankle Brachial Index
  • Blood Gas Monitoring, Transcutaneous / methods
  • Diabetic Foot / therapy*
  • Female
  • Follow-Up Studies
  • Gene Transfer Techniques
  • Genetic Therapy / methods*
  • Hepatocyte Growth Factor / administration & dosage
  • Hepatocyte Growth Factor / genetics
  • Hepatocyte Growth Factor / therapeutic use*
  • Humans
  • Injections, Intramuscular
  • Ischemia / therapy*
  • Male
  • Middle Aged
  • Neovascularization, Pathologic / therapy
  • Peripheral Arterial Disease / therapy
  • Protein Isoforms / administration & dosage
  • Protein Isoforms / genetics
  • Protein Isoforms / therapeutic use
  • Wound Healing
  • Young Adult

Substances

  • HGF protein, human
  • Protein Isoforms
  • Hepatocyte Growth Factor