Phase 1/2 Open-label Dose-escalation Study of Plasmid DNA Expressing Two Isoforms of Hepatocyte Growth Factor in Patients With Painful Diabetic Peripheral Neuropathy
Phase 1/2 Open-label Dose-escalation Study of Plasmid DNA Expressing Two Isoforms of Hepatocyte Growth Factor in Patients With Painful Diabetic Peripheral Neuropathy
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DOI：
10.1038/mt.2013.69
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发表时间：
2013-06-01
影响因子：
12.4
通讯作者：
Kessler, John A.
中科院分区：
文献类型：
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作者：
Ajroud-Driss, Senda;Christiansen, Mark;Kessler, John A.
本研究旨在评价肌肉注射表达两种肝细胞生长因子（HGF）亚型的质粒DNA（VM 202）治疗疼痛性糖尿病周围神经病变（PDPN）受试者的安全性和初步疗效。三个组群（4、8和16 mg）中的12名患者接受两组VM 202注射，间隔两周。评价了安全性和耐受性，并在治疗后12个月内采用视觉模拟量表（VAS）、简明麦吉尔问卷（SF-MPQ）和糖尿病周围神经病变患者简明疼痛量表（BPI-DPN）测量疼痛水平。未观察到严重不良事件（AE）。治疗后6个月和12个月时，平均VAS较基线降低47.2%（P = 0.002）和44.1%（P = 0.005）。6个月随访时，4、8和16 mg剂量队列的VAS评分以剂量反应方式分别降低21%（P = 0.971）、53%（P = 0.014）和62%（P = 0.001）。BPI-DPN和SF-MPQ的结果显示与VAS评分相似的模式。总之，VM 202治疗似乎是安全的，耐受性良好，足以长期缓解PDPN患者的症状并改善其生活质量。
This study aimed to evaluate the safety and preliminary efficacy of intramuscular injections of plasmid DNA (VM202) expressing two isoforms of hepatocyte growth factor (HGF) in subjects with painful diabetic peripheral neuropathy (PDPN). Twelve patients in three cohorts (4, 8, and 16 mg) received two sets of VM202 injections separated by two weeks. Safety and tolerability were evaluated and the visual analog scale (VAS), the short form McGill questionnaire (SF-MPQ), and the brief pain inventory for patients with diabetic peripheral neuropathy (BPI-DPN) measured pain level throughout 12 months after treatment. No serious adverse events (AEs) were observed. The mean VAS was reduced from baseline by 47.2% (P = 0.002) at 6 months and by 44.1% (P = 0.005) at 12 months after treatment. The VAS scores for the 4, 8, and 16 mg dose cohorts at 6 months follow-up decreased in a dose-responsive manner, by 21% (P = 0.971), 53% (P = 0.014), and 62% (P = 0.001), respectively. The results with the BPI-DPN and SF-MPQ showed patterns similar to the VAS scores. In conclusion, VM202 treatment appeared to be safe, well tolerated, and sufficient to provide long term symptomatic relief and improvement in the quality of life in patients with PDPN.