Safety of hLF1-11 for the Treatment of Infectious Complications Among HSCT Recipients

NCT ID: NCT00430469

Last Updated: 2015-06-30

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1/PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-11-30
• Study Completion Date: 2009-06-30

Brief Summary

The safety and tolerability of hLF 1-11 given in multiple doses 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 or bacterial 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 safe and well tolerated when given during neutropenia and mucosal barrier injury before infections ensue.

Detailed Description

Human lactoferrin (hLF) is a glycoprotein containing 692 amino acids and found in the saliva, milk, tears, and other body fluids. The peptide representing the first cationic domain, i.e. the peptide comprising the first eleven residues of hLF (further referred to as hLF1-11) was significantly more effective than the full length protein or the peptide representing the second cationic domain. As with other antimicrobial peptides, hLF1-11 shows poor antimicrobial activity under physiological conditions in vitro, but it is highly effective in vivo against infections due to a variety of microorganisms, including Gram negative and Gram positive bacteria and fungi. The objective is to develop hLF1-11 for the treatment of fungal and bacterial infections that develop during 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 provide effective treatment. Subsequently, hLF1-11 will be developed further as a systemic antifungal agent

Conditions

Fungal Infection; Bacterial Infection

Study Design

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

Interventions

human lactoferrin (hLF1-11)

intravenous 0.5mg in NaCl-solution

Intervention Type: DRUG

Other Intervention Names

hLF1-11

Eligibility Criteria

Inclusion Criteria

Recipients will be eligible for inclusions if they satisfy the following conditions:

• Has been admitted for an autologous HSCT after myeloablative therapy with high-dose melphalan;
• Is being managed with a 3 or 4-lumen central venous catheter;
• Is at least 18 years old;
• Has a BMI <30 kg/M2;
• Has no medical reason for not participating
• Has adequate renal function (creatinine < 1.5 x ULN)
• Has adequate liver function (ASAT, ALAT < 2.5 x ULN, bilirubin < 1.5 x ULN);
• If a woman, is functionally post-menopausal
• Has not participated in a study of a new chemical molecular entity in the previous 3 months
• Is able and willing to participate;
• Has provided written informed consent.

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

Sponsors

AM-Pharma

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Peter J Donnelly, PhD

Role: PRINCIPAL_INVESTIGATOR

UMC St. Radboud Nijmegen

Locations

UMC St. Radboud

Nijmegen, Gelderland, Netherlands

Countries

Netherlands

References

Dijkshoorn L, Brouwer CP, Bogaards SJ, Nemec A, van den Broek PJ, Nibbering PH. The synthetic N-terminal peptide of human lactoferrin, hLF(1-11), is highly effective against experimental infection caused by multidrug-resistant Acinetobacter baumannii. Antimicrob Agents Chemother. 2004 Dec;48(12):4919-21. doi: 10.1128/AAC.48.12.4919-4921.2004.

Reference Type: BACKGROUND

PMID: 15561882 (View on PubMed)

Nibbering PH, Welling MM, Paulusma-Annema A, Brouwer CP, Lupetti A, Pauwels EK. 99mTc-Labeled UBI 29-41 peptide for monitoring the efficacy of antibacterial agents in mice infected with Staphylococcus aureus. J Nucl Med. 2004 Feb;45(2):321-6.

Reference Type: BACKGROUND

PMID: 14960656 (View on PubMed)

Other Identifiers

2006-004012-52

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

AMP 02-02; SC13

Identifier Type: -

Identifier Source: org_study_id