title: Adenoviral-mediated gene transfer of vascular endothelial growth factor in critical limb ischemia: safety results from a phase I trial.
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.
authors.affiliation: Department of Internal Medicine, Section of Vascular Medicine, Division of Cardiology, University of Pennsylvania Health System, Philadelphia, PA, USA. mohlere@uphs.upenn.edu
authors.forename: Emile R
authors.initials: ER
authors.lastname: Mohler
authors.forename: Sanjay
authors.initials: S
authors.lastname: Rajagopalan
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Olin
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Trachtenberg
authors.forename: Henrik
authors.initials: H
authors.lastname: Rasmussen
authors.forename: Raphael
authors.initials: R
authors.lastname: Pak
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Crystal
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D043925:Angiogenesis Inducing Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D042501:Angiogenic Proteins / Q000008:administration & dosage / Q000235:genetics* / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D016228:Endothelial Growth Factors / Q000008:administration & dosage / Q000235:genetics* / Q000627:therapeutic use*; D005260:Female; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics / Q000627:therapeutic use; D006801:Humans; D007511:Ischemia / Q000188:drug therapy* / Q000235:genetics*; D035002:Lower Extremity / Q000098:blood supply*; D008222:Lymphokines / Q000008:administration & dosage / Q000235:genetics* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D016491:Peripheral Vascular Diseases / Q000188:drug therapy* / Q000235:genetics*; D020033:Protein Isoforms / Q000008:administration & dosage / Q000235:genetics / Q000627:therapeutic use; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage / Q000235:genetics* / Q000627:therapeutic use*
chemical_list: C437806:AdGVVEGF121.10; D043925:Angiogenesis Inducing Agents; D042501:Angiogenic Proteins; D016228:Endothelial Growth Factors; D008222:Lymphokines; D020033:Protein Isoforms; D042461:Vascular Endothelial Growth Factor A