DVC1-0101 to treat peripheral arterial disease: a Phase I/IIa open-label dose-escalation clinical trial.
DVC1-0101 to treat peripheral arterial disease: a Phase I/IIa open-label dose-escalation clinical trial.
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DOI：
10.1038/mt.2012.279
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发表时间：
2013-03
期刊：
影响因子：
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通讯作者：
Y. Yonemitsu;Takuya Matsumoto;H. Itoh;J. Okazaki;M. Uchiyama;Kumi Yoshida;M. Onimaru;T. Onohara;H. Inoguchi;R. Kyuragi;M. Shimokawa;H. Ban;Michiko Tanaka;M. Inoue;T. Shu;M. Hasegawa;Y. Nakanishi;Y. Maehara
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文献类型：
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作者：
Y. Yonemitsu;Takuya Matsumoto;H. Itoh;J. Okazaki;M. Uchiyama;Kumi Yoshida;M. Onimaru;T. Onohara;H. Inoguchi;R. Kyuragi;M. Shimokawa;H. Ban;Michiko Tanaka;M. Inoue;T. Shu;M. Hasegawa;Y. Nakanishi;Y. Maehara
我们报告了一项I/IIa期开放标签四剂量递增临床研究的结果，该研究评估了外周动脉疾病(PAD)患者单次肌肉注射DVC1-0101的安全性、耐受性和可能的疗效。DVC1-0101是一种基于表达人成纤维细胞生长因子-2基因(rSeV/DF-hFGF2)的不可传播的重组仙台病毒(RSeV)的新型基因转移载体。对12例静息性疼痛患者的12条肢体进行了基因转移，其中3例为缺血性溃疡(S)。在6个月的随访中，患者没有发现由基因转移引起的心血管或其他严重不良事件(SAE)。在研究期间，没有在任何患者身上检测到具有感染性的病毒颗粒，通过血凝活性进行评估。未见促炎细胞因子或血浆成纤维细胞生长因子-2的明显升高。在Rutherford分级、绝对跛行距离(ACD)和休息疼痛方面有显著且持续的改善(P<；0.05至0.01)。据我们所知，这是使用基于rSeV的基因转移载体的第一次临床试验。PAD患者单次肌肉注射DVC1-0101安全、耐受性好，肢体功能明显改善。作为下一步，有必要进行更大规模的关键研究。
We here report the results of a Phase I/IIa open-label four dose-escalation clinical study assessing the safety, tolerability, and possible therapeutic efficacy of a single intramuscular administration of DVC1-0101, a new gene transfer vector based on a nontransmissible recombinant Sendai virus (rSeV) expressing the human fibroblast growth factor-2 (FGF-2) gene (rSeV/dF-hFGF2), in patients with peripheral arterial disease (PAD). Gene transfer was done in 12 limbs of 12 patients with rest pain, and three of them had ischemic ulcer(s). No cardiovascular or other serious adverse events (SAEs) caused by gene transfer were detected in the patients over a 6-month follow-up. No infectious viral particles, as assessed by hemagglutination activity, were detected in any patient during the study. No representative elevation of proinflammatory cytokines or plasma FGF-2 was seen. Significant and continuous improvements in Rutherford category, absolute claudication distance (ACD), and rest pain were observed (P< 0.05 to 0.01). To the best of our knowledge, this is the first clinical trial of the use of a gene transfer vector based on rSeV. The single intramuscular administration of DVC1-0101 to PAD patients was safe and well tolerated, and resulted in significant improvements of limb function. Larger pivotal studies are warranted as a next step.