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

Healthy Volunteers Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03446053
• Other study ID #: ITB-101_1b
• Status: Completed
• Phase: Phase 1
• Start date: February 7, 2018
• Est. completion date: February 7, 2019

Study information

• Verified date: September 2021
• Source: Intron Biotechnology, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: February 7, 2019
• Est. primary completion date: February 7, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 20 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Anti-Bacterial Agents
• Healthy Volunteers
• Hypersensitivity
• Methicillin-Resistant Staphylococcus Aureus
• Methicillin-Sensitive Staphylococcus Aureus Infection
• Staphylococcal Infections

Intervention

Biological:
• N-Rephasin® SAL200
continuous intravenous infusion over 60 minutes

Other:
• INT200-Placebo
Formulation buffer except active ingredient for continuous intravenous infusion over 60 minutes

Locations

Country	Name	City	State
Korea, Republic of	Seoul National University Hospital	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Intron Biotechnology, Inc.

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (3)

Etienne J, Fleurette J, Ninet JF, Favet P, Gruer LD. Staphylococcal endocarditis after dental extraction. Lancet. 1986 Aug 30;2(8505):511-2. — View Citation

Kundsin RB. Documentation of airborne infection during surgery. Ann N Y Acad Sci. 1980;353:255-61. — View 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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Pharmacokinetic Evaluation [Cmax (µg/mL)]	Blood sampling for PK evaluation was performed at the following time points. Summary of PK parameters after single IV administration of N-Rephasin® SAL200.	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
Other	Pharmacodynamic Evaluation	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.	Up to 2hours
Other	Immunogenicity Evaluation	Anti-drug antibody titer was assessed.	Up to 50D (±2D)
Other	Pharmacokinetic Evaluation [AUClast, AUCinf (µg*h/mL)]	Blood sampling for PK evaluation was performed at the following time points. Summary of PK parameters after single IV administration of N-Rephasin® SAL200.	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
Other	Pharmacokinetic Evaluation [Tmax, T1/2, MRTinf (h)]	Blood sampling for PK evaluation was performed at the following time points. Summary of PK parameters after single IV administration of N-Rephasin® SAL200	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
Other	Pharmacokinetic Evaluation [Vd (L)]	Blood sampling for PK evaluation was performed at the following time points. Summary of PK parameters after single IV administration of N-Rephasin® SAL200.	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
Other	Pharmacokinetic Evaluation [CL (L/h)]	Blood sampling for PK evaluation was performed at the following time points. Summary of PK parameters after single IV administration of N-Rephasin® SAL200.	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
Primary	Safety and Tolerability Evaluation	Monitoring of adverse events (AEs) for Safety and Tolerability Evaluation	Up to 50D (±2D)

External Links

•   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
•   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
•   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
•   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