Safety and tolerability of the antimicrobial peptide human lactoferrin 1-11 (hLF1-11)

Walter J F M van der Velden, Thijs M P van Iersel, Nicole M A Blijlevens, J Peter Donnelly, Walter J F M van der Velden, Thijs M P van Iersel, Nicole M A Blijlevens, J Peter Donnelly

Abstract

Background: The treatment of patients with haematological malignancies by means of haematopoietic stem cell transplantation (HSCT) is often accompanied by life threatening infections. With emerging antimicrobial resistance there is an increased need for new agents, with a beneficial safety profile. Therefore we evaluated the safety of the promising new antimicrobial peptide human lactoferrrin 1-11 (hLF1-11) in healthy volunteers and patients.

Methods: We undertook a sequential, randomised, double-blind, placebo-controlled study using ascending single (0.005, 0.05, 0.5, 5 mg) and multiple intravenous doses (0.5, 5 mg) in healthy volunteers, and open-label, single intravenous 5 mg doses in autologous HSCT recipients.

Results: Single and multiple doses of hLF1-11 were tolerable up to 5 mg intravenously in healthy volunteers, while 5 mg single dose was tolerable in patients. Elevations in transaminases possibly related to treatment were reversible and not serious.

Conclusion: The new antimicrobial hLF1-11 is well tolerated in healthy volunteers with repeated daily doses up to 5 mg. The side-effect profile is very favourable for an antimicrobial, the only undesirable effect being a possible elevation of transaminases, which may be related to hLF1-11 although the current data do not allow conclusive interpretation of treatment relationship. A lower dose is recommended for the forthcoming multiple dosing studies in HSCT patients.

Trial registration: ClinicalTrials.gov: nct00509938.

Trial registration: ClinicalTrials.gov NCT00509938.

Figures

Figure 1
Figure 1
Serum alanine aminotransferase (ALT) levels in haematopoietic stem cell transplantation (HSCT) patients. The drugs depicted in figure are the drugs used by the patient experiencing elevated transaminases. day 0 = day of haematopoietic stem cell transplantation; HDM = high-dose melphalan.

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