Talactoferrin alfa, a recombinant human lactoferrin promotes healing of diabetic neuropathic ulcers: a phase 1/2 clinical study.
BACKGROUND
Talactoferrin alfa, a recombinant form of human lactoferrin, is a novel immunomodulatory protein with demonstrated ulcer healing properties in animal models.


METHODS
A phase 1/2 clinical study was conducted at 7 clinical sites to determine if talactoferrin can improve wound healing in diabetic patients with foot ulceration. Fifty-five patients with diabetic neuropathic foot ulcers participated in this 2-phase study. In phase 1, groups of 3 patients each received open-label 1%, 2.5%, or 8.5% talactoferrin gel twice daily, in a sequential design, to their ulcer for 30 days. No drug-related adverse events were found at any dose level. Phase 2 was a randomized, placebo-controlled, single-blind study of 2.5% and 8.5% gels, with patients equally divided between the 3 groups. In combination with good wound care, treatment was administered topically twice daily to the ulcers for 12 weeks. The primary endpoint was the incidence of > or = 75% healing (relative to baseline size).


RESULTS
The study, which in phase 2 was powered to detect a difference between the placebo and combined talactoferrin arms with P < .1, met the primary objective. The groups receiving the 2.5% (n = 15) and 8.5% (n = 15) gels had twice the incidence of > or = 75% reduction in ulcer size compared with the placebo group (n = 16): 47%, 53%, and 25%, respectively. On an intent-to-treat basis, the combination of the 2 active groups when compared with the placebo group showed a strong trend toward statistical significance (P = .09). There were no talactoferrin-related adverse events or laboratory abnormalities.


CONCLUSIONS
Topical talactoferrin appears to be safe and well tolerated and improves healing of diabetic neuropathic ulcers.
Lyons
Thomas E
TE
Beth Israel Deaconess Medical Center and Harvard Medical School, Palmer 321 A, West Campus, Boston, MA 02215, USA.
Miller
Michael S
MS
Serena
Thomas
T
Sheehan
Peter
P
Lavery
Lawrence
L
Kirsner
Robert S
RS
Armstrong
David G
DG
Reese
Amber
A
Yankee
Ernest W
EW
Veves
Aristidis
A
D000287:Administration, Topical; D017719:Diabetic Foot / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007781:Lactoferrin / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D016037:Single-Blind Method; D016896:Treatment Outcome; D014945:Wound Healing / Q000187:drug effects
D011994:Recombinant Proteins; C515276:talactoferrin alfa; D007781:Lactoferrin