Phase IIa Clinical Study of N-Rephasin® SAL200

Study Overview
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Brief Summary
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This study is performed to evaluate safety and to explore the efficacy of a single intravenous dose of N-Rephasin® SAL200 (3 mg/kg) in addition to the conventional standard treatment, for persistent Staphylococcus aureus bacteremia in patients, for more than 48 hours even after antibiotic treatment to which Staphylococcus aureus is susceptible.

Detailed Description
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Subjects: Patients with persistent Staphylococcus aureus bacteremia for more than 48 hours from the beginning of antibiotics treatment to which Staphylococcus aureus is susceptible. Study Method: Selection of patients with persistent S.aureus bacteremia for more than 48 hours even after application of the standard treatment for S. aureus bacteremia Randomization according to the trial institutions The control group receives a single intravenous dose of the placebo in addition to the standard treatment for persistent Staphylococcus aureus bacteremia The study group receives a single intravenous dose of the N-Rephasin® SAL200 (3 mg/kg) in addition to the standard treatment for persistent Staphylococcus aureus bacteremia A blood culture is performed 18 hours (±6 hours) after the administration of N-Rephasin® SAL200 Blood cultures continue to be performed every 24 hours (±6 hours) or 48 hours (±6 hours) after the previous blood culture, until two consecutive results of 'no growth (negative conversion)' are obtained Adverse events are monitored at the time of the first blood culture following the administration of N-Rephasin® SAL200 or placebo, and at the subsequent intervals of 24 hours or 48 hours Statistical Analysis: Primary endpoints Safety analysis is conducted in the Safety group. A distribution table of patients who experience at least one adverse event (incidence), and distribution tables of the relationship of the reported adverse events with the investigational product (distribution tables for severity and the relationship with the drug) are presented with respect to the groups (study group, control group), to determine safety of the investigational product. The results of the laboratory tests, anaphylaxis test, inflammatory cytokine test and vital signs at baseline and the last visit are summarized as mean values and standard deviations, to determine the change before and after the treatment within each group. Categorical data are divided into normal and abnormal, and summarized as the frequency and percentage to determine the difference before and after treatment within each group. Secondary endpoints Proportion of patients who are negative for bacterial growth in the first blood culture after administration of the investigational drug. The descriptive statistics for the proportion of patients who are negative for bacterial growth in the first blood culture (the rate of no growth) after the first treatment are presented by treatment group. Whether the rate of no growth is superior in the study group compared to the control group, is evaluated by a descriptive statistical method. Proportion of patients who die due to S. aureus bacteremia by Day14 after the incidence of bacteremia. The descriptive statistics for the proportion of patients who die due to S. aureus bacteremia by Day14 are presented by treatment group and evaluated. Proportion of treatment failure for S. aureus bacteremia by Day 14 (if two consecutive results of 'no growth' are not achieved in the blood cultures which are performed until Day 14. The descriptive statistics for the proportion of treatment failure for S. aureus bacteremia by Day 14 are presented and evaluated.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Multicenter Phase IIa Clinical Study to Evaluate Safety and to Explore Efficacy of N-Rephasin® SAL200, in Patients With Persistent Staphylococcus Aureus Bacteremia

Conditions
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Staphylococcus Aureus Bacteremia, Anti-Bacterial Agents

Intervention / Treatment
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* Biological: N-Rephasin® SAL200
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with MSSA/MRSA bacteremia who are confirmed to have more than a pair of Gram positive bacteria in a blood culture conducted at 48 96 hours after the start of antibiotic treatment to which S. aureus is susceptible. Males or females aged 19 years or older Those who understand the explanatory notes for subjects, and sign the informed consent. Exclusion Criteria: Those who do not receive appropriate antibiotics within 48 hours after the occurrence of bacteremia (the time point of reporting it to the department of laboratory medicine) The Gram positive strain, identified in a blood culture conducted at 48 96 hours after the start of antibiotic treatment to which S. aureus is susceptible, is not the same strain of S. aureus which was cultured when the definite diagnosis of S. aureus bacteremia was made Those who pass 48 hours after confirmation of persistent S. aureus bacteremia through a blood culture conducted at 48 96 hours after the start of antibiotic treatment to which S. aureus is susceptible Those who have symptoms of septic shock at the time of acquisition of the consent form Systolic blood pressure lower than 90 mmHg, or blood pressure lower than usual by more than 40 mmHg, in spite of the application of appropriate fluid therapy Requirement of hypertensor to maintain the systolic blood pressure at 90 mmHg or higher Those who were infected with mixed bacterial species Those who are hypersensitive to N-Rephasin® SAL200, who have a clinically significant hypersensitivity to it, or a past history there of Pregnant or lactating women and women of child-bearing potential (who do not agree to take appropriate contraceptive measures during the trial period) Those who participated in other clinical trial within 30 days prior to enrollment Patients with any conditions that may interfere with study participation or accurate evaluation on investigator's judgment Those who may die within 72 hours due to other serious complications (e.g., cerebral infarction, etc.), as per the investigator's judgment

Ages Eligible for Study
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Minimum Age: 19 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: N-Rephasin® SAL200<br>To assign the study group, administer the conventional standard treatment (CST) (antibiotics) for MRSA/MSSA with N-Rephasin® SAL200 (3mg/kg); N-Rephasin® SAL 200 is given by intravenous only once at Day 1. | Biological: N-Rephasin® SAL200<br>* A single dose of SAL200 (SAL-1, 3mg/kg) intravenous administration of the study drug, in addition to the conventional standard treatment (antibiotics) for MRSA/MSSA<br>|
| Placebo Comparator: Placebo<br>To assign the control group, administer the conventional standard treatment (CST) (antibiotics) for MRSA/MSSA with Formulation buffer (placebo); Placebo (INT200) is given by intravenous only once at Day 1 (same way with Experimental group) | Other: Placebo<br>* A single dose of the formulation buffer (placebo), excluding the main ingredient of the study drug in addition to the conventional standard treatment (antibiotics) for MRSA/MSSA<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety Endpoints - Summary of Treatment-emergent Adverse Events (Safety Set) | The safety analysis was conducted based on the data of all AEs, physical examinations, clinical laboratory tests, and vital signs (blood pressure, pulse rate, body temperature, and respiratory rate) collected from the subjects. All subjects who enrolled in this study (13 subjects in the placebo group and 12 subjects in the N RephasinⓇ SAL200 group) were defined as the Safety Set and included in the analysis. | up to 4 Week ± 5 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy Endpoints 1 | Number of Participants With Negative Result in the First Blood Culture | by day 14 | 
| Efficacy Endpoint 2 | The Proportion (Percentage) of Subjects who Died of Staphylococcus aureus Bacteremia Within 14 Days of Bacteremia Diagnosis | by day 14 | 
| Efficacy Endpoint 3 | Proportion (Percentage) of Treatment Failure Against Staphylococcus aureus Bacteremia by Day 14 | by day 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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N-Rephasin SAL200, Methicillin-Sensitive Staphylococcus aureus, Methicillin Resistant Staphylococcus Aureus