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

• Published in: The American journal of cardiology Vol. 90; no. 5; pp. 512 - 516
• Main Authors: Rajagopalan, Sanjay, Trachtenberg, Jeffrey, Mohler, Emile, Olin, Jeffrey, McBride, Scott, Pak, Raphael, Rasmussen, Henrik, Crystal, Ronald
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.09.2002; Elsevier
• Subjects: Adenoviridae - physiology; Adult; Aged; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; DNA, Complementary - administration & dosage; DNA, Complementary - adverse effects; Dose-Response Relationship, Drug; Double-Blind Method; Endothelial Growth Factors - administration & dosage; Endothelial Growth Factors - adverse effects; Endothelial Growth Factors - blood; Extremities - blood supply; Extremities - pathology; Female; Follow-Up Studies; Genetic Vectors - administration & dosage; Genetic Vectors - adverse effects; Genetic Vectors - physiology; Humans; Immune System - drug effects; Immune System - immunology; Intermittent Claudication - drug therapy; Intermittent Claudication - epidemiology; Lymphokines - administration & dosage; Lymphokines - adverse effects; Lymphokines - blood; Male; Medical sciences; Middle Aged; Risk Factors; Time Factors; Treatment Outcome; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors; Virus Replication - physiology; Walking; Human; Claudication; Adenoviridae; Toxicity; Cardiovascular disease; Arterial disease; Vascular disease; Virus; Vascular endothelium growth factor; Treatment; Transfection; Gene; Intermittent; Limb; Phase I trial; Occlusive arterial disease; Gene therapy; Vector
• ISSN: 0002-9149; 1879-1913
• DOI: 10.1016/S0002-9149(02)02524-9

The long-term safety and efficacy of adenoviral delivery of growth factors in patients with peripheral arterial disease (PAD) is unknown. CI-1023 (AdGVVEGF121.10) 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 ×108 to 4 ×1010 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.