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

Primary Purpose

Hematopoietic Stem Cell Transplantation, Bacterial Infections and Mycoses

Status

Completed

Phase

Phase 1

Locations

Netherlands

Study Type

Interventional

Intervention

human lactoferrin peptide 1-11

About this trial

This is an interventional prevention trial for Hematopoietic Stem Cell Transplantation focused on measuring immunocompromized, hLF1-11, antimicrobial, peptide, lactoferrin

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

UMC St. Radboud

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm Description

5mg hLF1-11, single dose iv

Outcomes

Primary Outcome Measures

Safety and tolerability by recording the vital signs, clinical chemistry, local tolerability and adverse events during the study

Secondary Outcome Measures

formation of antibodies anti-hLF 1-11 during the study.

Full Information

NCT ID

NCT00509938

First Posted

July 31, 2007

Last Updated

October 16, 2008

Sponsor

AM-Pharma

1. Study Identification

Unique Protocol Identification Number

NCT00509938

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2008

Overall Recruitment Status

Completed

Study Start Date

March 2006 (undefined)

Primary Completion Date

November 2006 (Actual)

Study Completion Date

November 2006 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

AM-Pharma

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hematopoietic Stem Cell Transplantation, Bacterial Infections and Mycoses

Keywords

immunocompromized, hLF1-11, antimicrobial, peptide, lactoferrin

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

8 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Arm Description

5mg hLF1-11, single dose iv

Intervention Type

Drug

Intervention Name(s)

human lactoferrin peptide 1-11

Intervention Description

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.

Primary Outcome Measure Information:

Title

Safety and tolerability by recording the vital signs, clinical chemistry, local tolerability and adverse events during the study

Time Frame

28 Days

Secondary Outcome Measure Information:

Title

formation of antibodies anti-hLF 1-11 during the study.

Time Frame

28 Days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

J.P. Donnelly, PhD

Organizational Affiliation

Radboud University Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

UMC St. Radboud

City

Nijmegen

State/Province

Gelderland

ZIP/Postal Code

6500 HB

Country

Netherlands

12. IPD Sharing Statement

Citations:

PubMed Identifier

19735580

Citation

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.

Results Reference

derived

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

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