Vascular Surgery Department of Xuan Wu Hospital, Institute of Vascular Surgery, Capital Medical University, Beijing, China.
J Gene Med. 2011 Nov;13(11):602-10. doi: 10.1002/jgm.1614.
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.
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.
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.
These results support the performance of a phase II randomized controlled trial with pCK-HGF-X7.
本Ⅰ期临床试验的目的是评估表达两种肝细胞生长因子（pCK-HGF-X7）同工型的裸 DNA 疗法在严重肢体缺血（CLI）患者中的安全性、耐受性和初步疗效。
21 例 CLI 患者连续接受递增剂量（队列 I：4mg；队列 II：8mg；队列 III：12mg；队列 IV：16mg）pCK-HGF-X7 治疗，分别于第 1 天和第 15 天在缺血小腿和/或大腿肌肉内给药。在 3 个月的随访期间，评估安全性和耐受性，使用视觉模拟评分（VAS）测量疼痛严重程度评分，评估溃疡状态、经皮氧分压（TcPO2）和踝肱指数（ABI）。
21 例患者在 3 个月的随访期间均未发生严重不良事件。治疗患者的疼痛显著减轻，平均 VAS 从 5.95 降至 1.64（p<0.001）。ABI 值在 3 个月随访时从 0.49 增至 0.63（p=0.026）。足底、前小腿和后小腿的平均 TcPO2 值分别从 28.25 增至 39.28mmHg（p=0.012）、从 22.00 增至 30.63mmHg（p=0.046）和从 32.05 增至 47.19mmHg（p=0.001）。在 9 例基线有溃疡的患者中，有 6 例观察到伤口愈合改善。
这些结果支持进行 pCK-HGF-X7 的Ⅱ期随机对照试验。
