ABSTRACT:The results from a Phase 1/2 study of a replication‐defective adenovirus encoding human platelet‐derived growth factor (PDGF)‐B formulated in a bovine collagen (Ad‐5PDGF‐B; 2.6% collagen; GAM501) gel for nonhealing neuropathic diabetic foot ulcers is reported. The primary objectives of the study were to evaluate the safety, maximum‐tolerated dose, and preliminary biological activity of GAM501. Fifteen patients enrolled into the study with chronic, nonhealing ulcers received either a single administration of GAM501 at one of three dose levels, or up to four administrations of GAM501 at 1‐week intervals. All patients received standard of care treatment including debridement and were required to wear an off‐loading shoe. GAM501 was found to be safe and well tolerated with no evidence of systemic or local toxicity at all doses so no maximum‐tolerated dose was reached. Serum antibody titers to platelet‐derived growth factor‐B homodimer and collagen were negative and adenoviral DNA was not detected in the blood. In the 12 patients that completed the study, ulcer closure was observed by Month 3 in 10 patients, seven of whom received a single application of GAM501. In conclusion, GAM501 did not appear to have any toxicity at doses that showed biological activity. GAM501 holds promise as a potentially effective treatment for nonhealing diabetic foot ulcers.
