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

Fungal Infection Clinical Trial

Official title:

Safety of a 0.5mg Dose of hLF1-11 Given for 10 Consecutive Days to Autologous Haematopoietic Stem Cell Transplant Recipients

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT00430469
• Other study ID #: AMP 02-02; SC13
• Secondary ID: 2006-004012-52
• Status: Withdrawn
• Phase: Phase 1/Phase 2
• First received: February 1, 2007
• Last updated: June 29, 2015
• Start date: November 2008
• Est. completion date: June 2009

Study information

• Verified date: June 2015
• Source: AM-Pharma
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: June 2009
• Est. primary completion date: March 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Bacterial Infection
• Bacterial Infections
• Communicable Diseases
• Fungal Infection
• Infection
• Mycoses

Intervention

Drug:
• human lactoferrin (hLF1-11)
intravenous 0.5mg in NaCl-solution

Locations

Country	Name	City	State
Netherlands	UMC St. Radboud	Nijmegen	Gelderland

Sponsors (1)

Lead Sponsor	Collaborator
AM-Pharma

Country where clinical trial is conducted

Netherlands, 

References & Publications (2)

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability as measured by adverse events, local tolerability, clinical chemistry, haematology, and vital signs		28 Days	Yes
Secondary	Monitor for possible formation of hLF 1-11 specific antibodies.		28 Days	Yes