Therapeutic angiogenesis with intramuscular SeV-hFGF2/dF for the treatment of peripheral arterial disease: a phase I clinical trial

Abstract

Abstract This paper reports a phase I dose-escalation clinical trial for the treatment of peripheral arterial disease (PAD) with BF30, a recombinant Sendai virus vector carrying the human native fibroblast growth factor 2 (hFGF2) gene. Our goal was to evaluate the safety and tolerability of BF30 at varying doses while assessing its preliminary therapeutic effect. Twelve male patients with PAD unsuitable for revascularization procedures that met the enrollment criteria were recruited. Each patient received a BF30 injection on one side of the ischemic lower limb. No deaths occurred prior to the 6-month follow-up. No severe adverse events or Grade 3/4 adverse events related to the BF30 injections were noted. Furthermore, the viral genome level was below the quantization limit after 6 months, and hemagglutination activity was undetectable in seven of the 12 cases. Abnormal changes in hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), and proinflammatory factor serum levels were not observed. None of the cases exhibited a positive anti-drug antibody signal. In addition, a positive therapeutic effect was demonstrated by the reduction in rest pain and Rutherford classification and improvement of the ankle-brachial index. While a higher dose triggered a stronger immune response, it was more effective in improving the Rutherford classification and quality of life.