Phase I study of direct administration of a replication deficient adenovirus vector containing the vascular endothelial growth factor cDNA (CI-1023) to patients with claudication. Academic Article Article uri icon

Overview

MeSH

  • Adult
  • Aged
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Extremities
  • Female
  • Follow-Up Studies
  • Humans
  • Immune System
  • Male
  • Middle Aged
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Walking

MeSH Major

  • Adenoviridae
  • DNA, Complementary
  • Endothelial Growth Factors
  • Genetic Vectors
  • Intermittent Claudication
  • Lymphokines
  • Virus Replication

abstract

  • The long-term safety and efficacy of adenoviral delivery of growth factors in patients with peripheral arterial disease (PAD) is unknown. CI-1023 (Ad(GV)VEGF(121.10)) is a replication-deficient adenovirus encoding human vascular endothelial growth factor isoform 121. In this phase I trial, we investigated the safety and efficacy of CI-1023 in subjects with advanced claudication symptoms secondary to infra-inguinal disease. Eighteen subjects >35 years of age with a median ankle brachial index (ABI) at rest of 0.525 (interquartile range 0.4) and angiographic disease involving the infra-inguinal vessels underwent intramuscular injection of CI-1023 (4 x10(8) to 4 x10(10) particle units, n = 15) or placebo (n = 3). Eleven of 15 patients (73%) who received CI-1023 and 1 of 3 subjects (33%) who received placebo, completed 1 year of follow-up. Edema and rash were the most common early adverse event. One infra-inguinal bypass procedure occurred in each of the placebo and CI-1023 groups at days 29 and 104, respectively. One death (day 160) and 1 malignancy (day 274) occurred in the CI-1023 group. Conclusions on efficacy could not be made due to the small number of patients. However, there were encouraging trends in ABI at rest and peak walking time at follow-up.

publication date

  • September 1, 2002

has subject area

  • Adenoviridae
  • Adult
  • Aged
  • DNA, Complementary
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Endothelial Growth Factors
  • Extremities
  • Female
  • Follow-Up Studies
  • Genetic Vectors
  • Humans
  • Immune System
  • Intermittent Claudication
  • Lymphokines
  • Male
  • Middle Aged
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Virus Replication
  • Walking

Research

keywords

  • Clinical Trial
  • Clinical Trial, Phase I
  • Journal Article
  • Multicenter Study

Identity

Language

  • eng

PubMed ID

  • 12208412

Additional Document Info

start page

  • 512

end page

  • 516

volume

  • 90

number

  • 5