A Study to Evaluate the Safety, PK, PD, Immunogenicity of N-Rephasin® SAL200 in Healthy Male Volunteers

Study Overview
=================
Brief Summary
-----------------
To evaluate the safety, pharmacokinetics, pharmacodynamics and immunogenicity of N-Rephasin® SAL200 following single and multiple ascending doses in healthy male volunteers after continuous intravenous infusion over 60 minutes.

Detailed Description
-----------------
Forty subjects will be randomly assigned to receive either N-Rephasin® SAL200 injection or a placebo administered by a 60-min intravenous infusion. Within each group, 8 subjects (6 active and 2 placebo) will receive a single dose of 6 mg/kg, followed by multiple ascending dose of 3, 6, 9, and 12 mg/kg/day. The clinical trial will be performed in sequence from the lowest level, and the progress of the next dose level will be determined based on the safety results in the previous dose level. Examinations by interview, physical examinations, and screening tests such as clinical laboratory tests and allergenicity will be conducted in volunteers within 4 weeks (-28 -2d) from the previous day ot this clinical trial (-1d) to select subjects who are judged eligible for the study. Eligible subjects will be called in the afternoon (-1d) to examine the allergenicity in the clinical center of Seoul National Unviersity Hospital. Allergen-free subjects will be hospitalized on -1d and assigned with each subject number. All subjects are advised to fast from 10:00 p.m. overnight to the next morning, except drinking water. In the morning (09:00 a.m.) on 1d, subjects in each group will be given N-Rephasin® SAL200 injection or a placebo administered by a 60-min intravenous infusion, After that, the clinical trial will be conducted according to the designated schedule. All subjects receiving at least one dose will undergo a post-study visit test after a certain period of time. Immunogenicity testing will be performed until approximately 50 days after treatment.

Official Title
-----------------
A Randomized, Double-Blind, Placebo-Controlled, Multiple-Dosing, Dose-Escalating Phase 1b Study to Evaluate the Safety, PK, PD and Immunogenicity of N-Rephasin® SAL200 After Continuous IV Infusion in Healthy Volunteers

Conditions
-----------------
Healthy Volunteers, Anti-Bacterial Agents, Methicillin-Resistant Staphylococcus Aureus, Methicillin-Sensitive Staphylococcus Aureus Infection

Intervention / Treatment
-----------------
* Biological: N-Rephasin® SAL200
* Other: INT200-Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy male subjects aged between 20 and 45 years at screening Those whose body weight is between 50kg and 90kg, and BMI is between 18.0 and 27.0 Subjects who have fully understood this clinical trial via detailed explanation, are willing to voluntarily participate in this study, and agree to give written informed consent and to follow all of trial-related rules. Exclusion Criteria: Those who have clinically significant liver, kidney, nervous system, endocrine system, respiratory system, hemato-oncology, cardiovascular system, mental diseases or past history. Those who have been diagnosed or suspected infectious disease within 30 days prior to the first dose of study medication Those who have history of hypersensitivity to drugs containing N-Rephasin® SAL200 or other drugs (aspirin and antibiotics) Those who have taken other drugs containing N-Rephasin® SAL200. Those who are antibody-positive to N-Rephasin® SAL200 Those who have SBP <90mmHg or DBP <50mmHg (otherwise SBP > 150mmHg or DBP > 100mmHg) in vital signs, when measured after a 3-minute rest in sitting position. Those who have medical history of drug abuse or positive to urine drug screening Has taken any prescription drugs or herbal medicines within 14 days prior to first dose of study medication; otherwise, has taken over-the-counter drugs or vitamins within 7 days prior to the first dose of study medication (However, if other conditions are appropriate upon judgment of the investigator, the subject may participate in this study.) Those who has taken other study medications within 3 months prior to the study medication Those who have donated whole blood within 2 months prior to the first dose of study medication or apheresis within 1 month, or received blood transfusion within 1 months prior to the first dose of study medication Those who smoke cigarettes or are found to be nicotine metabolite-positive in urinalysis Those who cannot continuously abstain from drinking alcohol (exceeding 21 units/week, 1 unit = 10g of pure alcohol) or smoking cigarettes during hospitalization Those who are judged ineligible for the clinical study by the investigator due to other reasons, including the results of clinical laboratory tests Those who do not agree to use medically accepted contraceptive measures for 60 days after the first dose of study medication, or those who are unwilling to report the partner's pregnancy until 90 days after the first dose of study medication

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

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

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>Forty subjects will be randomly assigned to receive either N-Rephasin® SAL200 injection or a placebo administered by a 60-min intravenous infusion. Within each group, 8 subjects (6 active and 2 placebo) will receive a single dose of 6 mg/kg, followed by multiple ascending dose of 3, 6, 9, and 12 mg/kg/day. | Biological: N-Rephasin® SAL200<br>* continuous intravenous infusion over 60 minutes<br>|
| Placebo Comparator: INT200-Placebo<br>Saline | Other: INT200-Placebo<br>* Formulation buffer except active ingredient for continuous intravenous infusion over 60 minutes<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability Evaluation | Monitoring of adverse events (AEs) for Safety and Tolerability Evaluation | Up to 50D (±2D) | 

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