Department of Surgery, Division of Trauma, University of California San Diego, San Diego, California, USA.
Wound Repair Regen. 2009 Nov-Dec;17(6):772-9. doi: 10.1111/j.1524-475X.2009.00541.x. Epub 2009 Oct 12.
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.
一项关于复制缺陷型腺病毒编码人血小板衍生生长因子（PDGF）的 1/2 期临床试验结果报告，该腺病毒用牛胶原蛋白（Ad-5PDGF-B；2.6%胶原蛋白；GAM501）凝胶配制，用于治疗非愈合性神经糖尿病足溃疡。该研究的主要目的是评估 GAM501 的安全性、最大耐受剂量和初步生物学活性。15 名患有慢性、不愈合溃疡的患者入组该研究，接受 GAM501 单次给药，剂量分别为三个水平之一，或最多四次，间隔 1 周。所有患者均接受包括清创在内的标准治疗，并要求穿脱载鞋。GAM501 安全且耐受性良好，所有剂量均未出现全身或局部毒性，因此未达到最大耐受剂量。血小板衍生生长因子-B 同源二聚体和胶原蛋白的血清抗体滴度均为阴性，血液中未检测到腺病毒 DNA。在完成研究的 12 名患者中，10 名患者在第 3 个月观察到溃疡闭合，其中 7 名患者单次应用 GAM501。总之，在显示生物学活性的剂量下，GAM501 似乎没有任何毒性。GAM501 有望成为治疗非愈合性糖尿病足溃疡的有效方法。
