DVC1-0101 to treat peripheral arterial disease: A phase I/IIa open-label dose-escalation clinical trial

Yoshikazu Yonemitsu, Takuya Matsumoto, Hiroyuki Itoh, Jin Okazaki, Makiko Uchiyama, Kumi Yoshida, Mitsuho Onimaru, Toshihiro Onohara, Hiroyuki Inoguchi, Ryoichi Kyuragi, Mototsugu Shimokawa, Hiroshi Ban, Michiko Tanaka, Makoto Inoue, Tsugumine Shu, Mamoru Hasegawa, Yoichi Nakanishi, Yoshihiko Maehara

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Abstract

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.

Original languageEnglish
Pages (from-to)707-714
Number of pages8
JournalMolecular Therapy
Volume21
Issue number3
DOIs
Publication statusPublished - Mar 2013

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All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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