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

Primary Purpose

Healthy Volunteers, Anti-Bacterial Agents, Methicillin-Resistant Staphylococcus Aureus

Status
Completed
Phase
Phase 1
Locations
Korea, Republic of
Study Type
Interventional
Intervention
N-Rephasin® SAL200
INT200-Placebo
Sponsored by
Intron Biotechnology, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Healthy Volunteers focused on measuring Methicillin-Resistant Staphylococcus Aureus, Methicillin-Sensitive Staphylococcus Aureus, N-Rephasin SAL200

Eligibility Criteria

20 Years - 45 Years (Adult)MaleAccepts Healthy Volunteers

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

Sites / Locations

  • Seoul National University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

N-Rephasin® SAL200

INT200-Placebo

Arm 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.

Saline

Outcomes

Primary Outcome Measures

Safety and Tolerability Evaluation
Monitoring of adverse events (AEs) for Safety and Tolerability Evaluation

Secondary Outcome Measures

Full Information

First Posted
February 4, 2018
Last Updated
October 26, 2021
Sponsor
Intron Biotechnology, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03446053
Brief Title
A Study to Evaluate the Safety, PK, PD, Immunogenicity of N-Rephasin® SAL200 in Healthy Male Volunteers
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2021
Overall Recruitment Status
Completed
Study Start Date
February 7, 2018 (Actual)
Primary Completion Date
February 7, 2019 (Actual)
Study Completion Date
February 7, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Intron Biotechnology, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Healthy Volunteers, Anti-Bacterial Agents, Methicillin-Resistant Staphylococcus Aureus, Methicillin-Sensitive Staphylococcus Aureus Infection
Keywords
Methicillin-Resistant Staphylococcus Aureus, Methicillin-Sensitive Staphylococcus Aureus, N-Rephasin SAL200

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
33 (Actual)

8. Arms, Groups, and Interventions

Arm Title
N-Rephasin® SAL200
Arm Type
Experimental
Arm 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.
Arm Title
INT200-Placebo
Arm Type
Placebo Comparator
Arm Description
Saline
Intervention Type
Biological
Intervention Name(s)
N-Rephasin® SAL200
Intervention Description
continuous intravenous infusion over 60 minutes
Intervention Type
Other
Intervention Name(s)
INT200-Placebo
Intervention Description
Formulation buffer except active ingredient for continuous intravenous infusion over 60 minutes
Primary Outcome Measure Information:
Title
Safety and Tolerability Evaluation
Description
Monitoring of adverse events (AEs) for Safety and Tolerability Evaluation
Time Frame
Up to 50D (±2D)
Other Pre-specified Outcome Measures:
Title
Pharmacokinetic Evaluation [Cmax (µg/mL)]
Description
Blood sampling for PK evaluation was performed at the following time points. Summary of PK parameters after single IV administration of N-Rephasin® SAL200.
Time Frame
Single administration: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24 hours post-dose Multiple administration: the above timepoints and 25, 36, 48, 49, 60, 72, 72.25, 72.5, 72.75, 73, 73.5, 74, 75, 76, 77, 78, 80, 82, 84, 96 hours post-dose
Title
Pharmacodynamic Evaluation
Description
Ex vivo antibacterial activity was assessed by bactericidal effects of the serum specimens collected from the trials were compared with calibration samples range of 0.05 to 1.0 μg/mL N-Rephasin®SAL200.
Time Frame
Up to 2hours
Title
Immunogenicity Evaluation
Description
Anti-drug antibody titer was assessed.
Time Frame
Up to 50D (±2D)
Title
Pharmacokinetic Evaluation [AUClast, AUCinf (µg*h/mL)]
Description
Blood sampling for PK evaluation was performed at the following time points. Summary of PK parameters after single IV administration of N-Rephasin® SAL200.
Time Frame
Single administration: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24 hours post-dose Multiple administration: the above timepoints and 25, 36, 48, 49, 60, 72, 72.25, 72.5, 72.75, 73, 73.5, 74, 75, 76, 77, 78, 80, 82, 84, 96 hours post-dose
Title
Pharmacokinetic Evaluation [Tmax, T1/2, MRTinf (h)]
Description
Blood sampling for PK evaluation was performed at the following time points. Summary of PK parameters after single IV administration of N-Rephasin® SAL200
Time Frame
Single administration: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24 hours post-dose Multiple administration: the above timepoints and 25, 36, 48, 49, 60, 72, 72.25, 72.5, 72.75, 73, 73.5, 74, 75, 76, 77, 78, 80, 82, 84, 96 hours post-dose
Title
Pharmacokinetic Evaluation [Vd (L)]
Description
Blood sampling for PK evaluation was performed at the following time points. Summary of PK parameters after single IV administration of N-Rephasin® SAL200.
Time Frame
Single administration: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24 hours post-dose Multiple administration: the above timepoints and 25, 36, 48, 49, 60, 72, 72.25, 72.5, 72.75, 73, 73.5, 74, 75, 76, 77, 78, 80, 82, 84, 96 hours post-dose
Title
Pharmacokinetic Evaluation [CL (L/h)]
Description
Blood sampling for PK evaluation was performed at the following time points. Summary of PK parameters after single IV administration of N-Rephasin® SAL200.
Time Frame
Single administration: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24 hours post-dose Multiple administration: the above timepoints and 25, 36, 48, 49, 60, 72, 72.25, 72.5, 72.75, 73, 73.5, 74, 75, 76, 77, 78, 80, 82, 84, 96 hours post-dose

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
In Jin Jang, M.D., Ph. D.
Organizational Affiliation
Seoul National University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Seoul National University Hospital
City
Seoul
ZIP/Postal Code
110-744
Country
Korea, Republic of

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
There is not a plan to make IPD available.
Citations:
PubMed Identifier
2875256
Citation
Etienne J, Fleurette J, Ninet JF, Favet P, Gruer LD. Staphylococcal endocarditis after dental extraction. Lancet. 1986 Aug 30;2(8505):511-2. doi: 10.1016/s0140-6736(86)90377-6. No abstract available.
Results Reference
background
PubMed Identifier
6939390
Citation
Kundsin RB. Documentation of airborne infection during surgery. Ann N Y Acad Sci. 1980;353:255-61. doi: 10.1111/j.1749-6632.1980.tb18928.x. No abstract available.
Results Reference
background
PubMed Identifier
22491776
Citation
van Hal SJ, Jensen SO, Vaska VL, Espedido BA, Paterson DL, Gosbell IB. Predictors of mortality in Staphylococcus aureus Bacteremia. Clin Microbiol Rev. 2012 Apr;25(2):362-86. doi: 10.1128/CMR.05022-11.
Results Reference
background
PubMed Identifier
35007129
Citation
Wire MB, Jun SY, Jang IJ, Lee SH, Hwang JG, Huang DB. A Phase 1 Study To Evaluate Safety and Pharmacokinetics following Administration of Single and Multiple Doses of the Antistaphylococcal Lysin LSVT-1701 in Healthy Adult Subjects. Antimicrob Agents Chemother. 2022 Mar 15;66(3):e0184221. doi: 10.1128/AAC.01842-21. Epub 2022 Jan 10.
Results Reference
derived
Links:
URL
https://www.kci.go.kr/kciportal/ci/sereArticleSearch/ciSereArtiView.kci?sereArticleSearchBean.artiId=ART001432619
Description
Seung-Ho Han et al., Monitoring of Methicillin-Resistant Staphylococcus aureus in Nasal Swabs Obtained fron Dental Clinic Healthcare Providers and Medical Environments Nurses. Int J Oral Biology. 2010;35:7-12
URL
https://www.semanticscholar.org/paper/Analysis-of-Economic-Outcomes-of-Staphylococcus-Park-Chae/f848ff1bc9cf6e346dbbc24bd4b4bf669dd70b43
Description
Eun Ja Park et al., Analysis of Economic Outcome of Methicillin-Resistant Staphylococcus aureus(MRSA) Bacteremia Using Retrospective Case-Control Study, Kor. J. Clin. Pharm 2007;17:59-64
URL
https://ir.ymlib.yonsei.ac.kr/handle/22282913/147505
Description
Hyuk Min Lee, Dong Eun Yong, Kyungwon Lee., Antimicrobial Resistance of Clinically Important Bacteria Isolated from 12 Hospitals in Korea in 2004 . Korean Journal of Clinical Microbiology 2005;8(1):66-73
URL
https://www.microbiologyresearch.org/content/journal/ijsem/10.1099/00207713-38-2-168
Description
Frency J, Brun Y, Bes M, Meugnier H, Grimont F, Grimon PAD, Newi C, Fleurette J. Staphylococcus lugdunensis sp. and Staphylococcus schleiferi sp. novel two species from human clinical specimens. Int Syst Bacteriol. 1998;38:168-172

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

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