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

Safety and Efficacy of Human Lactoferrin hLF1-11 for the Treatment of Infectious Complications Among Haematopoietic Stem Cell Transplant Recipients Part A: Clinical Study Protocol SC12: Safety of a Single Dose of 5 mg of hLF1-11 Given to Autologous Haematopoietic Stem Cell Transplant Recipients

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

Study Overview

• Status: Completed
• Conditions: Bacterial Infections and Mycoses; Hematopoietic Stem Cell Transplantation
• Intervention / Treatment: Drug: human lactoferrin peptide 1-11

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.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6500 HB
      • UMC St. Radboud

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 1; 5mg hLF1-11, single dose iv	Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety and tolerability by recording the vital signs, clinical chemistry, local tolerability and adverse events during the study	28 Days

Secondary Outcome Measures

Outcome Measure	Time Frame
formation of antibodies anti-hLF 1-11 during the study.	28 Days

Collaborators and Investigators

• Sponsor: AM-Pharma
• Investigators: Principal Investigator: J.P. Donnelly, PhD, Radboud University Medical Center

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: March 1, 2006
• Primary Completion (ACTUAL): November 1, 2006
• Study Completion (ACTUAL): November 1, 2006

Study Registration Dates

• First Submitted: July 31, 2007
• First Submitted That Met QC Criteria: July 31, 2007
• First Posted (ESTIMATE): August 1, 2007

Study Record Updates

• Last Update Posted (ESTIMATE): October 17, 2008
• Last Update Submitted That Met QC Criteria: October 16, 2008
• Last Verified: October 1, 2008

More Information

Terms related to this study

• Keywords: antimicrobial; lactoferrin; peptide; hLF1-11; immunocompromized
• Additional Relevant MeSH Terms: Infections; Mycoses; Bacterial Infections; Bacterial Infections and Mycoses; Anti-Infective Agents; Lactoferrin
• Other Study ID Numbers: AMP 02-01; SC12; IS 044096