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. Copyright © 2011 John Wiley & Sons, Ltd.