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.
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.
Rajagopalan
Sanjay
S
Division of Cardiology, University of Michigan, Ann Arbor, Michigan 48109, USA. srajagop@umich.edu
Trachtenberg
Jeffrey
J
Mohler
Emile
E
Olin
Jeffrey
J
McBride
Scott
S
Pak
Raphael
R
Rasmussen
Henrik
H
Crystal
Ronald
R
D000256:Adenoviridae / Q000502:physiology*; D000328:Adult; D000368:Aged; D018076:DNA, Complementary / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D016228:Endothelial Growth Factors / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D005121:Extremities / Q000098:blood supply / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000009:adverse effects / Q000502:physiology*; D006801:Humans; D007107:Immune System / Q000187:drug effects / Q000276:immunology; D007383:Intermittent Claudication / Q000188:drug therapy* / Q000453:epidemiology; D008222:Lymphokines / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014779:Virus Replication / Q000502:physiology*; D016138:Walking
D018076:DNA, Complementary; D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors