A Study on the Tolerability and Early Efficacy of hLF1-11 in Patients With Proven Candidaemia

Study Overview
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Brief Summary
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This is a phase-I, double-blind, randomized study with hLF1-11 to study the tolerability and early efficacy of hLF1-11 compared to standard fluconazole therapy in hospitalized patients with invasive Candida infection.

Detailed Description
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RATIONALE FOR THE STUDY Choice of Drug Fluconazole is considered standard care for the treatment of Candida infections, including candidaemia in hospitalized patients. Preclinical data has demonstrated that hLF1-11 possesses potent antimycotic effects against Candida sp and, importantly, to be synergistic with fluconazole, whereby Candida strains that are fluconazole-resistant become sensitive through the addition of hLF1-11 Choice of Patient Population Based on preclinical data hLF1-11 has been shown to possess potent effects on Candida albicans models in vitro and in vivo. Furthermore, candidaemia (bloodstream Candida infection) is one of the most likely settings to elicit a therapeutic response since the product is presented as an intravenous formulation As previously mentioned, fluconazole and hLF1-11 exhibit a synergistic effect in preclinical studies, whereby the effect of fluconazole is enhanced by the addition of hLF1-11.

Official Title
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A Phase-IIa, Double-blind, Randomized Study on the Tolerability and Early Efficacy of hLF1-11 in Hospitalized Patients With Proven Candidaemia. (SLIC: Study of Lactoferrin Peptide in Infections With Candida)

Conditions
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Candidaemia

Intervention / Treatment
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* Drug: hLF1-11
* Drug: hLF1-11
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent must be obtained before admission in the study. Patients in whom Candida species have been confirmed by 2 consecutive blood cultures within 12 hours. Patients who have not received systemic administration of antifungal agents or who have started such administration within 48 hours prior to entry. Patients who have hepatic and renal parameters within 2X ULN (upper level of normality) at screening. Exclusion Criteria: Patients with a history of hypersensitivity to fluconazole or hLF1-11. Patients who have been treated with fluconazole for at least 1 week within the previous 4 weeks. Patients with a history of fluconazole-resistant Candida species within 12 weeks. Neutropenic patients with neutrophil count below 0.5x10^9/L. Patients who are treated with terfenadine, triazolam, cisapride, and ergotamine, which are contraindicated for concomitant use with fluconazole. Patients known to have AIDS or who are HIV-positive. Females who have a positive pregnancy test at baseline or are capable of child-bearing i.e. without appropriate contraception (chemical or mechanical). Patients with suspected candida osteomyelitis, endocarditis, or meningitis. Patients who have received an investigational drug within three months prior to the study. Patients with a concomitant medical condition, in whom, in the opinion of the Investigator, participation may create an unacceptable risk for the patient. Patients considered inappropriate by the PI for enrollment in the study, for any reason.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: hLF1-11<br>hLF1-11 0.5mg | Drug: hLF1-11<br>* The study treatment consists of IV administration of: (A) hLF1-11 (0.5mg IV bolus daily for 14 days) + fluconazole (up to 1g IV four times daily; 14 days): Group #1, n=10; OR (B) Fluconazole (up to 1g IV four times daily; 14 days) + matching placebo for hLF1-11: Group #2, n=10<br>Drug: hLF1-11<br>* 0.5mg hLF1-11 iv per day for 14 consecutive days<br>* Other names: human lactoferrin 1-11;|
| Placebo Comparator: Placebo<br>Placebo formulation is Similar to hLF1-11 iv formulation except for the active component | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Haematology, biochemistry, and microbiological evaluation Adverse event monitoring. |  | 28 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Test of Cure (TOC): Clinical: complete resolution of clinical signs and symptoms or resolution to a point where no further antifungal therapy is judged necessary; and Microbiological: eradication of Candida identified at baseline. |  | 28 Days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hLF1-11, Candida, candidaemia, lactoferrin