title: DVC1-0101 to treat peripheral arterial disease: a Phase I/IIa open-label dose-escalation clinical trial.
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.
authors: Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan. yonemitu@med.kyushu-u.ac.jp
authors: Yoshikazu
authors: Y
authors: Yonemitsu
authors: Takuya
authors: T
authors: Matsumoto
authors: Hiroyuki
authors: H
authors: Itoh
authors: Jin
authors: J
authors: Okazaki
authors: Makiko
authors: M
authors: Uchiyama
authors: Kumi
authors: K
authors: Yoshida
authors: Mitsuho
authors: M
authors: Onimaru
authors: Toshihiro
authors: T
authors: Onohara
authors: Hiroyuki
authors: H
authors: Inoguchi
authors: Ryoichi
authors: R
authors: Kyuragi
authors: Mototsugu
authors: M
authors: Shimokawa
authors: Hiroshi
authors: H
authors: Ban
authors: Michiko
authors: M
authors: Tanaka
authors: Makoto
authors: M
authors: Inoue
authors: Tsugumine
authors: T
authors: Shu
authors: Mamoru
authors: M
authors: Hasegawa
authors: Yoichi
authors: Y
authors: Nakanishi
authors: Yoshihiko
authors: Y
authors: Maehara
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016207:Cytokines / Q000378:metabolism; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D008875:Middle Aged; D058729:Peripheral Arterial Disease / Q000235:genetics / Q000628:therapy*; D029082:Sendai virus / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D016207:Cytokines; D016222:Fibroblast Growth Factor 2