Phase I trial on the safety of topical rhVEGF on chronic neuropathic diabetic foot ulcers.
OBJECTIVE
To assess the safety/tolerability and perform a preliminary efficacy evaluation of a multiple-dosing regimen of recombinant human vascular endothelial growth factor (VEGF165 or rhVEGF; telbermin) applied topically to chronic diabetic neuropathic foot ulcers.


METHODS
Subjects with type 1 or 2 diabetes mellitus were randomised to receive either topical applied telbermin (72 microg/cm2) (n=29) or placebo (n=26) treatment to the foot ulcer surface in conjunction with standard ulcer care. Subjects received treatment every 48 hours (maximum three doses per week) for up to six weeks. Weekly 35mm photography, quantitative planimetry and physical examinations documented the ulcer appearance, surface area and stage. Safety endpoints included incidence of clinically significant hypotension, adverse events and ulcer infection. Exploratory efficacy endpoints included percentage reduction in total ulcer surface area, incidence of complete ulcer healing and time to complete ulcer healing.


RESULTS
Incidence of adverse events was comparable in the two treatment groups. None of the adverse events were attributed to study drug, and no hypotension was observed as a result of telbermin treatment. Occurrence of infected study ulcers appeared to be balanced between the treatment groups. Positive trends suggestive of potential signals of biological activity were observed for incidence of complete ulcer healing (41.4% telbermin versus 26.9% placebo at day 43 [P=0.39]) and time to complete ulcer healing (25th percentile of 32.5 days telbermin versus 43.0 days placebo [log-rank P=0.13]).


CONCLUSIONS
The topical application of telbermin 72 microg/cm2 three times a week for up to six weeks appeared to be well tolerated. Further studies are required to characterise the safety/efficacy of telbermin more completely.
Hanft
J R
JR
Doctor's Research Network, South Miami, Florida, USA.
Pollak
R A
RA
Barbul
A
A
van Gils
C
C
Kwon
P S
PS
Gray
S M
SM
Lynch
C J
CJ
Semba
C P
CP
Breen
T J
TJ
D000279:Administration, Cutaneous; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002908:Chronic Disease; D017719:Diabetic Foot / Q000188:drug therapy* / Q000473:pathology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007022:Hypotension / Q000139:chemically induced / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D010781:Photography; D012107:Research Design; D012449:Safety; D017592:Skin Care / Q000379:methods; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D042461:Vascular Endothelial Growth Factor A / Q000009:adverse effects / Q000627:therapeutic use*; D014945:Wound Healing; D014946:Wound Infection / Q000139:chemically induced / Q000453:epidemiology
C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A