Safety of a Single Dose of 5 mg of hLF1-11 Given to Autologous Haematopoietic Stem Cell Transplant Recipients

NCT ID: NCT00509938

Last Updated: 2008-10-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-03-31
• Study Completion Date: 2006-11-30

Brief Summary

The safety and tolerability of hLF 1-11 has to be established first in HSCT recipients who are at risk of developing, but have not yet developed, infectious complications due to invasive fungal disease. These patients are different from healthy volunteers because they have received myeloablative treatment which not only arrests haematopoiesis resulting in neutropenia but also induces mucosal barrier injury both of which predispose to infections which typically occur during the week after transplant. It is therefore essential to know that hLF 1-11 is when given during neutropenia and mucosal barrier injury before infections ensue

Detailed Description

Background:

Human lactoferrin (hLF) is a glycoprotein containing 692 amino acids and found in the saliva, milk, tears, and other body fluids. Peptide representing the first cationic domain, i.e. a peptide comprising the first eleven residues of hLF (further referred to as hLF1-11) was significantly more effective than the full length hLF or the peptide representing the second cationic domain in killing a variety of bacteria in vivo. The mechanism of action comprises a number of independent factors. The classical way to explain the efficacy is the direct killing effect, which typically is observed in vitro at relatively high concentrations. The results of in vitro and in vivo experiments suggest that the mechanism of action is predominantly through the intermediary of cells and/or components of the host as opposed to a direct interaction with the pathogen.

The objective is to develop hLF1-11 as an effective and safe antibacterial and antifungal for the treatment of fungal and bacterial infections that develop during the neutropenia that results from myeloablative therapy to prepare for a haematopoietic stem cell transplant (HSCT) formerly referred to as bone marrow transplant. Rates of infection and related morbidity are high in this population making it an attractive target for testing clinically the proof-of-principle that hLF1-11 can provided effective treatment. Subsequently, hLF1-11 will be developed further as a systemic antifungal agent.

Conditions

Hematopoietic Stem Cell Transplantation; Bacterial Infections and Mycoses

Keywords

immunocompromized; hLF1-11; antimicrobial; peptide; lactoferrin

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

1

5mg hLF1-11, single dose iv

Group Type: EXPERIMENTAL

human lactoferrin peptide 1-11

Intervention Type: DRUG

Each subject will receive a single intravenous dose of hLF1-11 given in a volume of 20mL given over 20 minutes i.e. 1mL/per minute.

Interventions

human lactoferrin peptide 1-11

Each subject will receive a single intravenous dose of hLF1-11 given in a volume of 20mL given over 20 minutes i.e. 1mL/per minute.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• admitted for an autologous HSCT after myeloablative therapy with high-dose melfalan
• managed with a 4-lumen central venous catheter
• BMI <30
• able and willing to participate
• has provided written informed consent
• there is no medical reason for exclusion
• has adequate renal function (creatinine <110 µmol/L (man); <90 µmol/L (woman))
• has adequate liver function (ASAT <40 U; ALAT <45 U; bilirubin <10µmol/L)
• has no known allergy to lactoferrin
• has no history of hepatitis and is not HIV seropositive
• if a woman, functionally post-menopausal

Exclusion Criteria

• A history of, or presence of, significant respiratory, cardiovascular, neurological, haematological, endocrine, gastrointestinal, hepatic or renal disease or other condition known to interfere with the absorption, distribution, metabolism or excretion of drugs (as judged clinically relevant by the investigator).
• Participation in a study with a new chemical entity or new molecular entity 3 months before or participation in a study with a registered drug less than 5 times of the half life of the registered drug before entering the study.
• A clinically relevant history of intolerance or hypersensitivity to the study drug, or its additives and excipients in the intravenous formulation.
• Evidence of having serum hepatitis or carrying the hepatitis B surface antigen or Hepatitis C antibodies or being HIV positive.
• Subjects, who in the opinion of the investigator should not, for reasons of safety, participate in the study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AM-Pharma

INDUSTRY

Sponsor Role: lead

Responsible Party

AM-Pharma

Principal Investigators

J.P. Donnelly, PhD

Role: PRINCIPAL_INVESTIGATOR

Radboud University Medical Center

Locations

UMC St. Radboud

Nijmegen, Gelderland, Netherlands

Countries

Netherlands

References

Velden WJ, van Iersel TM, Blijlevens NM, Donnelly JP. Safety and tolerability of the antimicrobial peptide human lactoferrin 1-11 (hLF1-11). BMC Med. 2009 Sep 8;7:44. doi: 10.1186/1741-7015-7-44.

Reference Type: DERIVED

PMID: 19735580 (View on PubMed)

Other Identifiers

SC12

Identifier Type: -

Identifier Source: secondary_id

IS 044096

Identifier Type: -

Identifier Source: secondary_id

AMP 02-01

Identifier Type: -

Identifier Source: org_study_id