Phase I Study of Direct Administration of a Replication Deficient Adenovirus Vector Containing Vascular Endothelial Growth Factor cDNA (CI-1023) to Patients with Claudication. - Phase I Study of Direct Administration of a Replication Deficient Adenovirus Vector Containing Vascular Endothelial Growth Factor cDNA (CI-1023) to Patients with Claudication.
The goal of this study was to evaluate the safety and efficacy of CI-1023, an adenovirus encoded with endothelial growth factor isoform 121, in advanced claudication associated with infra-inquinal atherosclerotic vascular disease.
Patients Enrolled: 18
This was a double-blind placebo controlled dose escalating study in 18 subjects >40 years of age with disabling claudication. All patients had angiographic disease, patent aortoiliac inflow, and resting ABI <0.90 or exercise ABI <0.75. Efficacy was determined by peak walking time using a standardized variable grade treadmill protocol (Gardner) and change in ABI. The total 20 ml dose of vector was divided into 1 ml aliquots and injected intramuscularly in the area of potential collateralization (thigh or thigh and calf). Because only 1 placebo patient completed the follow-up, efficacy results were not available.
The average age was 63.5years, 78% were male, 33% diabetic, and >50% had undergone previous lower extremity revascularization. 72% had an occlusion of the superficial femoral artery and 5% occlusion of the common femoral artery. 11/15pts receiving CI-1023 and 1 of 3 receiving placebo completed the 1-year follow-up. The median resting ABI at baseline in the CI-1023 group was 0.57 and increased by 0.09 at 360 days. The median peak walk distance was 2.1min at baseline (12 patients), increased at day 30 by 1min (8pts), and continued to increase to 5min at day 360 (4pts). Swelling at the injection site occurred in 1/3rd. 38% of patients who received CI-1023 had a neutralizing antibody titer greater than 1:80 at baseline, and 70% had a doubling of the titer by day 7. There was no dose-response relationship observed.
This small pilot study demonstrated a trend to an increase in resting ABI and peak walk time following intramuscular injection of adenovirus containing a human endothelial growth factor. While encouraging, the study demonstrates the many difficulties inherent in trials designed to assess new therapies for severe claudication. The long-term safety of vascular endothelial growth factor delivered via various vectors and routes remains to be established in large trials.
Rajagopalan S, Trachtenberg J, Mohler E, et al. Phase I Study of Direct Administration of a Replication Deficient Adenovirus Vector Containing Vascular Endothelial Growth Factor cDNA (CI-1023) to Patients with Claudication. Am J Cardiol. 2002;90:512-16.
Keywords: Intermittent Claudication, Walking, Follow-Up Studies, Vascular Endothelial Growth Factor A, Injections, Intramuscular, Endothelial Growth Factors, Antibodies, Neutralizing, Diabetes Mellitus
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