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

Study Overview
=================
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

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

Conditions
-----------------
Fungal Infection, Bacterial Infection

Intervention / Treatment
-----------------
* Drug: human lactoferrin (hLF1-11)


Participation Criteria
=================
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: human lactoferrin (hLF1-11)|intravenous 0.5mg in NaCl-solution|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability as measured by adverse events, local tolerability, clinical chemistry, haematology, and vital signs |  | 28 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Monitor for possible formation of hLF 1-11 specific antibodies. |  | 28 Days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Neutropenia, Lactoferrin, hLF, Myeloablative, Treatment, Fungal, Bacterial, Infections, Bone marrow transplant