Adenoviral-mediated gene transfer of vascular endothelial growth factor in critical limb ischemia: safety results from a phase I trial.
| Publication Type | Academic Article |
| Authors | Mohler E, Rajagopalan S, Olin J, Trachtenberg J, Rasmussen H, Pak R, Crystal R |
| Journal | Vasc Med |
| Volume | 8 |
| Issue | 1 |
| Pagination | 9-13 |
| Date Published | 01/01/2003 |
| ISSN | 1358-863X |
| Keywords | Adenoviridae, Angiogenesis Inducing Agents, Angiogenic Proteins, Endothelial Growth Factors, Gene Transfer Techniques, Ischemia, Lower Extremity, Lymphokines, Peripheral Vascular Diseases, Vascular Endothelial Growth Factor A |
| Abstract | Critical limb ischemia (CLI) is typified by rest pain and/or tissue necrosis secondary to advanced peripheral arterial disease (PAD) and is characterized by diminution in limb perfusion at rest. We tested the safety of an angiogenic strategy with CI-1023 (Ad(GV)VEGF121.10), a replication-deficient adenovirus encoding human vascular endothelial growth factor isoform 121 in patients with CLI as part of a phase I trial. Fifteen subjects >35 years of age with CLI and angiographic disease involving the infra-inguinal vessels underwent intramuscular injection of CI-1023 (4 x 10(8) to 4 x 10(10) particle units, n = 13) or placebo (n = 2). All of the patients tolerated the injection well and there were no serious complications related to the procedure. Transient edema was noted in one patient. A total of 79 adverse events were reported over the course of one year. One death (day 136) and one malignancy (day 332) occurred in the CI-1023 group. CI-1023 appears to be well tolerated and safe for single-dose administration in patients with critical limb ischemia due to PAD. Further studies are needed to determine the efficacy of this form of therapeutic angiogenesis. |
| DOI | 10.1191/1358863x03vm460oa |
| PubMed ID | 12866606 |