Treatment of nonhealing diabetic foot ulcers with a platelet-derived growth factor gene-activated matrix (GAM501): results of a phase 1/2 trial.
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.
Mulder
Gerit
G
Department of Surgery, Division of Trauma, University of California San Diego, San Diego, California, USA.
Tallis
Arthur J
AJ
Marshall
V Tracy
VT
Mozingo
David
D
Phillips
Laurie
L
Pierce
Glenn F
GF
Chandler
Lois A
LA
Sosnowski
Barbara K
BK
D000260:Adenoviruses, Human / Q000235:genetics / Q000276:immunology; D000287:Administration, Topical; D000328:Adult; D000368:Aged; D047070:Bandages, Hydrocolloid; D003646:Debridement; D017719:Diabetic Foot / Q000188:drug therapy* / Q000601:surgery; D054796:Drug Dosage Calculations; D005260:Female; D005782:Gels; D015316:Genetic Therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D020574:Proto-Oncogene Proteins c-sis / Q000008:administration & dosage* / Q000009:adverse effects / Q000235:genetics*; D014945:Wound Healing
D005782:Gels; D020574:Proto-Oncogene Proteins c-sis