Talactoferrin alfa, a recombinant human lactoferrin promotes healing of diabetic neuropathic ulcers

a phase 1/2 clinical study

Thomas E. Lyons, Michael S. Miller, Thomas Serena, Peter Sheehan, Lawrence Lavery, Robert S. Kirsner, David G. Armstrong, Amber Reese, Ernest W. Yankee, Aristidis Veves

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

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 ≥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 ≥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.

Original languageEnglish (US)
Pages (from-to)49-54
Number of pages6
JournalAmerican Journal of Surgery
Volume193
Issue number1
DOIs
StatePublished - Jan 2007

Fingerprint

Lactoferrin
Ulcer
Placebos
Gels
Single-Blind Method
Diabetic Foot
Incidence
Drug-Related Side Effects and Adverse Reactions
Wound Healing
talactoferrin alfa
Clinical Studies
Foot
Arm
Animal Models
Wounds and Injuries
Proteins

Keywords

  • Diabetes
  • Talactoferrin
  • Wound healing

ASJC Scopus subject areas

  • Surgery

Cite this

Talactoferrin alfa, a recombinant human lactoferrin promotes healing of diabetic neuropathic ulcers : a phase 1/2 clinical study. / Lyons, Thomas E.; Miller, Michael S.; Serena, Thomas; Sheehan, Peter; Lavery, Lawrence; Kirsner, Robert S.; Armstrong, David G.; Reese, Amber; Yankee, Ernest W.; Veves, Aristidis.

In: American Journal of Surgery, Vol. 193, No. 1, 01.2007, p. 49-54.

Research output: Contribution to journalArticle

Lyons, TE, Miller, MS, Serena, T, Sheehan, P, Lavery, L, Kirsner, RS, Armstrong, DG, Reese, A, Yankee, EW & Veves, A 2007, 'Talactoferrin alfa, a recombinant human lactoferrin promotes healing of diabetic neuropathic ulcers: a phase 1/2 clinical study', American Journal of Surgery, vol. 193, no. 1, pp. 49-54. https://doi.org/10.1016/j.amjsurg.2006.07.010
Lyons, Thomas E. ; Miller, Michael S. ; Serena, Thomas ; Sheehan, Peter ; Lavery, Lawrence ; Kirsner, Robert S. ; Armstrong, David G. ; Reese, Amber ; Yankee, Ernest W. ; Veves, Aristidis. / Talactoferrin alfa, a recombinant human lactoferrin promotes healing of diabetic neuropathic ulcers : a phase 1/2 clinical study. In: American Journal of Surgery. 2007 ; Vol. 193, No. 1. pp. 49-54.
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abstract = "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 ≥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 ≥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.",
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AU - Serena, Thomas

AU - Sheehan, Peter

AU - Lavery, Lawrence

AU - Kirsner, Robert S.

AU - Armstrong, David G.

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AU - Yankee, Ernest W.

AU - Veves, Aristidis

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AB - 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 ≥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 ≥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.

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