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.
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Authors | Gerit Mulder, Arthur J Tallis, V Tracy Marshall, David Mozingo, Laurie Phillips, Glenn F Pierce, Lois A Chandler, Barbara K Sosnowski |
Journal | Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society
(Wound Repair Regen)
2009 Nov-Dec
Vol. 17
Issue 6
Pg. 772-9
ISSN: 1524-475X [Electronic] United States |
PMID | 19821960
(Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Gels
- Proto-Oncogene Proteins c-sis
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Topics |
- Adenoviruses, Human
(genetics, immunology)
- Administration, Topical
- Adult
- Aged
- Bandages, Hydrocolloid
- Debridement
- Diabetic Foot
(drug therapy, surgery)
- Drug Dosage Calculations
- Female
- Gels
- Genetic Therapy
- Humans
- Male
- Middle Aged
- Proto-Oncogene Proteins c-sis
(administration & dosage, adverse effects, genetics)
- Wound Healing
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