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 language | English |
|---|---|
| Pages (from-to) | 707-714 |
| Number of pages | 8 |
| Journal | Molecular Therapy |
| Volume | 21 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Jan 1 2013 |
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All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Molecular Biology
- Genetics
- Pharmacology
- Drug Discovery
Cite this
DVC1-0101 to treat peripheral arterial disease : A phase I/IIa open-label dose-escalation clinical trial. / Yonemitsu, Yoshikazu; matsumoto, takuya; Itoh, Hiroyuki; Okazaki, Jin; Uchiyama, Makiko; Yoshida, Kumi; Onimaru, Mitsuho; Onohara, Toshihiro; Inoguchi, Hiroyuki; Kyuragi, Ryoichi; Shimokawa, Mototsugu; Ban, Hiroshi; Tanaka, Michiko; Inoue, Makoto; Shu, Tsugumine; Hasegawa, Mamoru; Nakanishi, Yoichi; Maehara, Yoshihiko.
In: Molecular Therapy, Vol. 21, No. 3, 01.01.2013, p. 707-714.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - DVC1-0101 to treat peripheral arterial disease
T2 - A phase I/IIa open-label dose-escalation clinical trial
AU - Yonemitsu, Yoshikazu
AU - matsumoto, takuya
AU - Itoh, Hiroyuki
AU - Okazaki, Jin
AU - Uchiyama, Makiko
AU - Yoshida, Kumi
AU - Onimaru, Mitsuho
AU - Onohara, Toshihiro
AU - Inoguchi, Hiroyuki
AU - Kyuragi, Ryoichi
AU - Shimokawa, Mototsugu
AU - Ban, Hiroshi
AU - Tanaka, Michiko
AU - Inoue, Makoto
AU - Shu, Tsugumine
AU - Hasegawa, Mamoru
AU - Nakanishi, Yoichi
AU - Maehara, Yoshihiko
PY - 2013/1/1
Y1 - 2013/1/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84875230671&partnerID=8YFLogxK
U2 - 10.1038/mt.2012.279
DO - 10.1038/mt.2012.279
M3 - Article
VL - 21
SP - 707
EP - 714
JO - Molecular Therapy
JF - Molecular Therapy
SN - 1525-0016
IS - 3
ER -