Conditions: MRSA Bacteremia
Keywords: MRSA Staphylococcus aureus bacteremia SAB bloodstream infection BSI Bacteremia
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 40
Healthy volunteers: no

Brief summary:
The objectives of this study is to exploratory whether Vancomycin + Delpazolid is more effective to the standard of treatment (Vancomycin)/ for hospitalized adults with MRSA bacteraemia.

Detailed description:
The mortality from S aureus bacteremia is higher for MRSA than for methicillin-susceptible S aureus (MSSA), typically at 20% to 25%.

The current standard therapy for MRSA bacteremia is Vancomycin. Vancomycin has many shortcomings, including poor tissue penetration and slow killing time. Vancomycin has reduced efficacy against MRSA and tended to increase the MIC level (called MIC creep). Addition of Delpazolid to Vancomycin could improve the known drawbacks of Vancomycin alone.

Arms:
arm 1: Vancomycin: IV infusion per 2020 IDSA guideline

* Intravenous Vancomycin dosed as per 2020 IDSA guideline
* Doses of 15 to 20 mg/kg (based on actual body weight) administered every 8 to 12 hours as an intermittent infusion were recommended for most patients with normal renal function when assuming a MICBMD of 1 mg/L.
* Depending on the investigator's judgment, it was allowed to change to Daptomycin after at least one week of administration of Vancomycin, and also it was allowed to change to oral antibiotics other than oxazolidinones after two weeks of administration of Vancomycin (including Daptomycin).

Delpazolid: 800 mg, BID, PO arm 2: Vancomycin: IV infusion per 2020 IDSA guideline

* Intravenous Vancomycin dosed as per 2020 IDSA guideline
* Doses of 15 to 20 mg/kg (based on actual body weight) administered every 8 to 12 hours as an intermittent infusion were recommended for most patients with normal renal function when assuming a MICBMD of 1 mg/L.
* Depending on the investigator's judgment, it was allowed to change to Daptomycin after at least one week of administration of Vancomycin, and also it was allowed to change to oral antibiotics other than oxazolidinones after two weeks of administration of Vancomycin (including Daptomycin).

Placebo of Delpazolid: BID, PO

Interventions: intervention 1: Delpazolid intervention 2: Vancomycin intervention 3: Placebo of Delpazolid
Intervention descriptions: intervention 1: BID, PO intervention 2: IV infusion per 2020 IDSA guideline intervention 3: BID, PO

Protocol document:
Prot_000.pdf: 
Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 1 of 87 
 
 
 
 
 
Study Protocol 
 
A Multicenter, Double blinded, Randomized, Parallel design, Phase IIa Clinical trial 
to evaluate the Efficacy, Safety and Pharmacokinetics of LCB01-0371 with Vancomycin 
versus Vancomycin standard therapy in patients with Methicillin Resistance 
Staphylococcus aureus (MRSA) Bacteremia 
 
 
 
Investigational Product:  
LCB01-0371 
Protocol No.: 
LCB35-0371-21-2-01 
Protocol Version: 
5.0 
Phase of Development: 
Phase 2a 
Sponsor: 
LegoChem Biosciences, Inc. 
Date of Protocol Preparation: 
2022-12-07 
 
Confidentiality Statement 
All information contained in this protocol is intended for the principal investigator and study personnel, 
institutional review board, and health authorities and may not be disclosed to any third parties without the prior 
written consent of LegoChem Biosciences, Inc., unless you obtain the written consent from the subjects who 
will receive the investigational product in the clinical study. 
 
 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 2 of 87 
 
※ List of Abbreviations and Definition of Terms 
 
ADR 
adverse drug reaction 
ADME 
absorption, distribution, metabolism, excretion 
AE 
adverse event 
ALT 
alanine transaminase 
ANC 
absolute neutrophil count 
aPTT 
activated partial thromboplastin time 
AST 
aspartate transaminase 
AUC 
area under the curve 
AUClast 
area under the concentration-time curve from time 0 to the last measured time point 
AUC0-∞ 
area under the concentration-time curve from time 0 extrapolated to infinity 
BID 
twice daily 
BMD 
broth microdilution 
BMI 
body mass index 
BUN 
blood urea nitrogen 
Ca 
calcium 
CA-MRSA 
community-associated methicillin resistance Staphylococcus aureus 
CFR 
code of federal regulations 
CFU 
colony-forming unit 
CIOMS 
council for international organizations of medical sciences 
Cl 
chloride 
CL 
clearance 
Cmax 
maximum serum concentration 
CPK 
creatine phosphokinase 
CRO 
contract research organization 
CRP 
c-reactive protein 
CS 
clinically significant 
CYP 
cytochrome p450 
DBL 
database lock 
DC 
discontinuation 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EDC 
electronic data capture 
eGFR 
estimated glomerular filtration rate 
EOS 
end of study 
EOT 
end of treatment 
FAS 
full analysis set 
hCG 
human chorionic gonadotropin 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 3 of 87 
 
HCT 
hematocrit 
hERG 
human ether-à-go-go related gene 
HRZE 
ampicin, isoniazid, pyrazinamide, ethambutol 
hVISA 
heterogenous vancomycin intermediate s. aureus 
ICF 
informed consent form 
ICH 
international council for harmonization 
IDMC 
independent data monitoring committees 
IDSA 
infectious diseases society of America 
INR 
international normalized ratio 
IRB 
institutional review board 
ITT 
intention to treat 
IUD 
intrauterine system 
IV 
Intravenous 
IWRS 
interactive web-based response system 
K 
Potassium 
KGCP 
Korea good clinical practice 
LOAEL 
lowest observed adverse effect level 
MCH 
mean corpuscular hemoglobin 
MCHC 
mean cell hemoglobin concentration 
MCV 
mean corpuscular volume 
MedDRA 
medical dictionary for regulatory activities 
MIC 
minimum inhibitory concentration 
MAO 
monoamine oxidase 
MRSA 
methicillin resistance staphylococcus aureus 
MSSA 
methicillin-susceptible staphylococcus aureus 
MTD 
maximum tolerated dose 
Na 
sodium 
NCI-CTCAE 
national cancer institute-common terminology criteria for adverse events 
NCS 
not clinically significant 
NOAEL 
no-observed-adverse-effect level 
P 
phosphorus 
P.O. 
per oral 
PK 
pharmacokinetics 
PPS 
per protocol set 
PT 
prothrombin time 
PT 
preferred term 
RBC 
red blood cell 
rRNA 
ribosomal ribonucleic acid 
SAE 
serious adverse event 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 4 of 87 
 
S.aureus 
Staphylococcus aureus 
S.C. 
subcutaneous 
SAS 
statistical analysis system 
SOC 
system organ class 
SOP 
standard operating procedure 
TDM 
therapeutic drug monitoring 
TEAE 
treatment-emergent adverse events 
Tlag 
absorption delay 
Tmax 
time to maximum concentration 
TB 
tuberculosis 
TOC 
test of cure 
T1/2 
terminal half-life 
Vd 
volume of distribution 
VISA 
vancomycin-intermediate Staphylococcus aureus 
VRSA 
vancomycin-resistant Staphylococcus aureus 
WBC 
white blood cell 
γ-GT 
gamma-glutamyltransferase 
 
 
 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 5 of 87 
 
Table of Contents 
1 
Study Title, Phase of Development, Protocol Identification Number, and Revision 
History ........................................................................................................................................... 8 
1.1 
Title ............................................................................................................................................ 8 
1.2 
Phase of Development ............................................................................................................... 8 
1.3 
Protocol Identification Number and Revision History ............................................................... 8 
2 
Synopsis ......................................................................................................................................... 9 
※ Schedule of Activities ....................................................................................................................... 17 
3 
Introduction ................................................................................................................................ 20 
3.1 
Study Background .................................................................................................................... 20 
3.2 
Study Rationale ........................................................................................................................ 21 
3.3 
Benefit and Risk Assessment ................................................................................................... 21 
3.3.1 
Nonclinical Experience ......................................................................................... 21 
3.3.2 
Clinical Experience ............................................................................................... 25 
3.4 
Justification for Dosage and Administration ............................................................................ 30 
4 
Study Objectives ......................................................................................................................... 31 
4.1 
Primary Objective .................................................................................................................... 31 
4.2 
Secondary Objectives ............................................................................................................... 31 
5 
Study Population ........................................................................................................................ 32 
5.1 
Number of Subjects .................................................................................................................. 32 
5.2 
Selection of Study Population .................................................................................................. 32 
5.2.1 
Inclusion Criteria .................................................................................................. 32 
5.2.2 
Exclusion Criteria ................................................................................................. 32 
5.2.3 
Subject Withdrawal Criteria .................................................................................. 33 
6 
Study Design ............................................................................................................................... 34 
6.1 
Study Period ............................................................................................................................. 34 
6.2 
Study Group and Control Group .............................................................................................. 34 
6.3 
Randomization and Blinding .................................................................................................... 34 
6.3.1. 
Randomization ...................................................................................................... 34 
6.4 
Blinding ................................................................................................................................... 35 
6.4.1. 
Methods for Maintaining Blinding ........................................................................ 35 
6.4.2. 
Unblinding ............................................................................................................ 35 
6.5 
 Study Schema .......................................................................................................................... 36 
7 
Criteria for Study Termination and Early Discontinuation ................................................... 37 
7.1 
Study Termination Criteria ...................................................................................................... 37 
7.2 
Early Discontinuation Criteria ................................................................................................. 37 
8 
Information and Management of Investigational Products and Concomitant 
Medication .................................................................................................................................. 38 
8.1 
Overview of the Investigational Product and Concomitant Medication .................................. 38 
8.1.1 
Study Drug ............................................................................................................ 38 
8.1.2 
Control Drug (Placebo) ......................................................................................... 38 
8.1.3 
Concomitant Medication ....................................................................................... 38 
8.2 
Manufacture, Packaging, and Labeling of the Investigational Product .................................... 38 
8.3 
Storage and Dispensing of the Investigational Product ............................................................ 39 
8.4 
Accountability, Recovery, and Disposal of the Investigational Product .................................. 39 
9 
Study Methodology and Dosing Plan........................................................................................ 40 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 6 of 87 
 
9.1 
Overall Study Methodology ..................................................................................................... 40 
9.2 
Dosage and Administration Method of the Investigational Product ........................................ 40 
9.2.1 
Dosage and Treatment Period ............................................................................... 40 
9.3 
Concomitant Medication/Therapy ........................................................................................... 41 
9.3.1 
Permitted Concomitant Medication and Therapy ................................................. 41 
9.3.2 
Prohibited Concomitant Medication and Therapy ................................................ 42 
9.3.3 
Medications to be Used with Caution ................................................................... 42 
9.4 
Treatment Compliance ............................................................................................................. 42 
10 
Study Procedures and Assessments .......................................................................................... 43 
10.1 
Observation Items .................................................................................................................... 43 
10.1.1 
Informed Consent Form and Allocation of Screening Number and Enrollment 
Number ................................................................................................................. 43 
10.1.2 
Demographic Data ................................................................................................ 43 
10.1.3 
Medical History .................................................................................................... 43 
10.1.4 
Prior/Concomitant Medication/Therapy ............................................................... 43 
10.1.5 
Vital Signs ............................................................................................................. 43 
10.1.6 
Body Measurement ............................................................................................... 43 
10.1.7 
Physical Examination ............................................................................................ 43 
10.1.8 
Laboratory Tests ................................................................................................... 44 
10.1.9 
12-Lead ECG ........................................................................................................ 44 
10.1.10 
Blood Culture ........................................................................................................ 44 
10.1.11 
Minimum Inhibitory Concentration (MIC) ........................................................... 45 
10.1.12 
Efficacy Assessment ............................................................................................. 45 
10.1.13 
PK Assessment ...................................................................................................... 45 
10.1.14 
Randomization and Administration of the Investigational Product ...................... 45 
10.1.15 
Symptoms and Signs of MRSA Bacteremia ......................................................... 45 
10.1.16 
Adverse Events ..................................................................................................... 46 
10.2 
Visit Schedule .......................................................................................................................... 46 
10.2.1 
Screening Visit (Within 5 Days of the Baseline Visit) ......................................... 46 
10.2.2 
Treatment Visit (Day 1 [Baseline Visit], Day 3, Day 5, Day 7, Day 14, Day 21, 
Day 28, Day 35, Day 42) ...................................................................................... 46 
10.2.3 
EOT/DC Visit (+2 Days) ...................................................................................... 47 
10.2.4 
TOC Visit ((EOT +28 Days) ± 4 Days) ................................................................ 48 
10.2.5 
Unscheduled Visit ................................................................................................. 48 
10.3 
Efficacy Assessment ................................................................................................................ 49 
10.3.1 
Efficacy Endpoints and Assessment Methods ...................................................... 49 
10.4 
Safety Assessment.................................................................................................................... 51 
10.4.1 
Safety Endpoints ................................................................................................... 51 
10.4.2 
Safety Assessment Methods .................................................................................. 51 
10.5 
Evaluation Criteria and Reporting of Adverse Events ............................................................. 53 
10.5.1 
Definition of Terms ............................................................................................... 53 
10.5.2 
Criteria for the Evaluation of Adverse Events ...................................................... 54 
10.5.3 
Follow-up of Adverse Events ............................................................................... 59 
10.5.4 
Pregnancy .............................................................................................................. 60 
10.6 
PK Assessment ......................................................................................................................... 60 
10.6.1 
Assessment Methods for PK Parameters and MIC ............................................... 60 
11 
Data Analysis and Statistical Considerations .......................................................................... 61 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 7 of 87 
 
11.1 
Analysis Sets ............................................................................................................................ 61 
11.2 
Statistical Analysis Method...................................................................................................... 61 
11.2.1 
General Principles of Result Analysis ................................................................... 61 
11.2.2 
Demographic Data, Medical History, and Medication History ............................. 61 
11.2.3 
Analysis of Efficacy Endpoints ............................................................................. 62 
11.2.4 
Analysis of Safety Endpoints ................................................................................ 64 
11.2.5 
Assessment of PK Parameters and MIC ............................................................... 65 
11.2.6 
Subgroup Analysis ................................................................................................ 65 
11.2.7 
Safety Data Review Committee ............................................................................ 65 
11.3 
Timing of Statistical Analysis .................................................................................................. 65 
11.4 
Rationale for Sample Size Determination ................................................................................ 66 
12 
Data Management ...................................................................................................................... 67 
12.1 
Records and Access ................................................................................................................. 67 
12.2 
Data Collection ........................................................................................................................ 67 
12.3 
Protection and Retention of Records ........................................................................................ 67 
12.4 
Data Safety Monitoring Plan .................................................................................................... 67 
13 
Ethics Considerations and Administrative Procedures .......................................................... 69 
13.1 
Compliance with Regulations and Ethics (KGCP) .................................................................. 69 
13.2 
Institutional Review Board (IRB) ............................................................................................ 69 
13.3 
Informed Consent Process........................................................................................................ 69 
13.4 
Measures to Protect the Safety of Subjects .............................................................................. 70 
13.4.1 
Measures in the Event of Adverse Events ............................................................. 70 
13.4.2 
Treatment and Care of Subjects after the Study .................................................... 70 
13.4.3 
Compensation Rules ............................................................................................. 71 
13.5 
Publication of Study Results and Confidentiality of Subject Records ..................................... 71 
13.6 
Quality Control and Reliability Assurance .............................................................................. 71 
13.6.1 
Study Site Monitoring ........................................................................................... 71 
13.6.2 
Audit ..................................................................................................................... 71 
13.6.3 
Inspection .............................................................................................................. 71 
14 
Sponsor Information and Name and Title of the Principal Investigator .............................. 73 
14.1 
Sponsor Information ................................................................................................................ 73 
14.2 
Name and Title of the Principal Investigator ........................................................................... 73 
15 
Other Requirements for Safe and Scientific Conduct of the Study ....................................... 74 
15.1 
Protocol Amendment ............................................................................................................... 74 
16 
References ................................................................................................................................... 75 
17 
Appendices .................................................................................................................................. 77 
Appendix 1 Precautions for Use of Vancomycin ................................................................................... 78 
Appendix 2 Precautions for Use of the Study Drug ............................................................................... 81 
Appendix 3 Precautions for Use of Daptomycin .................................................................................... 84 
18 
Attachments ................................................................................................................................ 87 
 
 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 8 of 87 
 
1 
Study Title, Phase of Development, Protocol Identification Number, and Revision H
istory 
1.1 
Title 
A Multicenter, Double blinded, Randomized, Parallel design, Phase IIa Clinical trial to evaluate the Efficacy, 
Safety and Pharmacokinetics of LCB01-0371 with Vancomycin versus Vancomycin standard therapy in patients 
with Methicillin Resistance Staphylococcus aureus (MRSA) Bacteremia 
1.2 
Phase of Development 
Phase 2a study 
1.3 
Protocol Identification Number and Revision History 
 
Protocol identification No.: LCB35-0371-21-2-01 
 
Revision history 
Version 
Date 
Comment 
1.0 
2021-06-11 
• Initial version 
1.1 
2021-12-23 
• Change of the MIC measurement of LCB01-0371 to optional. 
• Addition of details regarding instruction and evaluation of the treatment 
compliance. 
• Change in criteria for assessing causality of adverse events (reclassified 
“unlikely related” to “unrelated”) - applied relevant regulations. 
• Clarification of the criteria for the minimum administration period for the 
investigational product (at least 2 weeks). 
• Correction of typos and inconsistencies. 
1.2 
2022-02-04 
• Changed PK blood sampling time (8h-12h >> 2h-8h). 
• Changed to allow vancomycin MICBMD to be performed in an additional 
analysis institution if required. 
• Correction of typos and clarification of phrases. 
2.0 
2022-04-13 
• Clarification of descriptions for blood cultures [10.1.10] and laboratory 
tests [10.1.8]. 
• Correction of typos. 
3.0 
2022-07-06 
• Changed the MRSA confirmation time before randomization (within 72 
hours >> 96 hours) and the time window for empirical antibiotic use 
[reason: As this study is an exploratory Phase 2a study, the inclusion 
criteria were adjusted to allow for cases where blood culture for MRSA 
confirmation may exceed 72 hours]. 
• Addition of visit window during the treatment period. 
• Integration of Day 0 (baseline) and Day 1 (start of IP administration). 
• Clarification of phrases regarding two consecutive MRSA-negative 
confirmations. 
• Change of the schedule for body weight measurement and laboratory tests. 
• Addition of collection of information on the removal of primary MRSA 
lesion. 
4.0 
2022-11-21 
• Change to the prohibited concomitant medications (allowed a switch to 
oral antibiotics, except for the oxazolidinones, based on investigator 
judgment after at least 14 days of vancomycin administration (including a 
switch to daptomycin)). 
• Addition of subgroup analysis (subjects switched to oral antibiotics after 
administration of vancomycin (including a switch to daptomycin)). 
• Correction of typos in the schedule of activities. 
5.0 
2022-12-07 
• Exclusion criterion 2) 
 Adjustment of the exclusion criterion for 
reinfection “Subjects who have received treatment within the last 3 
months”. 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 9 of 87 
 
2 
Synopsis 
Study Title 
A Multicenter, Double blinded, Randomized, Parallel Design, Phase 2a Clinical trial 
to Evaluate the Efficacy, Safety and Pharmacokinetics of LCB01-0371 with 
Vancomycin versus Vancomycin Standard Therapy in Patients with Methicillin 
Resistance Staphylococcus Aureus (MRSA) Bacteremia 
Phase and Design 
Multicenter, double-blind, randomized, parallel design, Phase 2a study (proof of 
concept) 
Study Site 
See Attachment 3. List of Study Sites and Investigators. 
Sponsor 
LegoChem Biosciences, Inc. 
Study Objectives 
To evaluate the efficacy of the combination therapy of LCB01-0371 and vancomycin 
compared to standard vancomycin therapy in subjects with methicillin-resistant 
Staphylococcus aureus (MRSA) bacteremia and to investigate its safety and 
pharmacokinetic profile. 
 
[Primary Objective] 
To compare the proportion of subjects with overall cure between LCB01-0371 plus 
vancomycin combination therapy and standard vancomycin therapy. 
 
[Secondary Objectives] 
1) Proportion (%) of subjects with overall cure by the end-of-treatment (EOT) visit 
2) Mortality due to MRSA bacteremia during the treatment period with the 
investigational product 
3) Relapse rate of MRSA bacteremia 
4) Proportion of subjects with two consecutive negative MRSA blood culture results 
on Day 3, Day 5, Day 7, Day 14 and at the EOT visit (clearance of MRSA 
bacteremia on Day 3, Day 5, Day 7, Day 14 and at the EOT visit) 
5) Proportion of subjects with persistent MRSA bacteremia based on blood culture 
results on Day 3, Day 5, Day 7, and Day 14 
6) Time to clearance of MRSA bacteremia (in days) 
7) Safety of the combination therapy with vancomycin and LCB01-0371 
8) Pharmacokinetic (PK) profile of the combination therapy with vancomycin and 
LCB01-0371 
Target Population 
Patients with MRSA bacteremia 
Inclusion Criteria 
1) Male or female subjects ≥19 years of age at the time of written consent 
2) Subjects in whom at least one set of blood cultures tested positive for MRSA 
within 72 hours prior to randomization; or subjects in whom at least one set of 
blood cultures tested positive for MRSA within 96 hours prior to randomization 
and who started treatment with vancomycin at least 72 hours prior to 
randomization 
3) Subjects who have clinical symptoms or signs of MRSA bacteremia according to 
the judgment of the investigator 
4) Subjects who have voluntarily decided to participate in this clinical study after 
being fully informed and who have agreed in writing to comply with the study 
requirements 
Exclusion Criteria 
Concurrent diseases and medical history 
1) 
Subjects with polymicrobial bacteremia, including Gram-negative bacteria, or 
infections 
2) 
Subjects who have received treatment within the last 3 months (however, subjects 
may be enrolled if they have reinfection as determined by the investigator, 
regardless of prior treatment within 3 months) 
3) 
Subjects who had received empirical antibiotics for more than 96 hours prior to 
randomization (limited to 72 hours for MRSA-active antibiotics such as 
vancomycin) 
4) 
Subjects with septic shock 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 10 of 11 
 
5) 
Subjects with hypersensitivity to vancomycin or linezolid 
6) 
Subjects infected with bacteria that are resistant to vancomycin or linezolid 
7) 
Subjects with a history of hypersensitivity to peptide antibiotics or 
aminoglycosides 
8) 
Subjects who are currently receiving or have received monoamine oxidase 
(MAO) inhibitors within 14 days prior to the first administration of the 
investigational product 
9) 
Subjects who are currently receiving serotonin reuptake inhibitors, tricyclic 
antidepressants, serotonin 5-HT1 receptor agonists (triptans), meperidine, or 
buspirone 
10) Subjects who are severely immunocompromised (e.g., severe neutropenia 
(absolute neutrophil count (ANC) <0.5×109/L)) 
11) Subjects who, in the opinion of the investigator, are expected to die within 2 days 
from the severe complications of MRSA bacteremia 
Other 
12) Body Mass Index (BMI) ≥35 kg/m2 
13) Subjects who are unable to administer medication orally 
14) Pregnant or lactating subjects or women and men of childbearing potential who 
are unwilling to use appropriate contraceptive methods* during the study period 
and for 14 days after the last administration of the investigational product. 
* Contraceptive methods: Use of at least one barrier method (e.g., implants, injections, 
oral contraceptives, intrauterine devices (IUDs)) in combination with hormonal IUDs, 
absolute abstinence, or vasectomy (subjects must consent to the use of at least two 
contraceptive methods). However, periodic abstinence (e.g., ovulation cycle, 
symptothermal, or post-ovulation methods) and withdrawal are not considered acceptable 
methods of contraception. 
15) Subjects who have received other investigational products within 30 days prior 
to screening 
16) Other subjects who, in the medical judgment of the investigator, are not suitable 
for participation in this study 
Target Number of 
Subjects 
 100 subjects in total (50 subjects per group) 
Treatment group 
Number 
of 
Subjects 
Vancomycin IV + LCB01-0371 P.O. BID 
50 subjects 
Vancomycin IV + Placebo P.O. BID (matching LCB01-0371) 
50 subjects 
 
Study Period 
 Total study period: 24 months from the date of the IRB approval (subject to change 
depending on subject enrollment rates). 
 Duration for each subject: Up to 75 days 
 
Screening period: Up to 5 days 
 
Treatment period: Up to 42 days (at least 14 days) 
 Treatment evaluation period: 28 days 
Investigational 
Product and 
Concomitant 
Medication 
1) 
LCB01-0371 (Delpazolid) 
2) 
Placebo of LCB01-0371: A matching placebo that has the same formulation and 
appearance as LCB01-0371 
3) 
Concomitant medication: Vancomycin  
Dosage, 
Treatment Period, 
and 
Administration 
Method 
1) Treatment Period: Up to 42 days (at least 14 days) 
2) Dosage and Administration Method 
① LCB01-0371 or placebo: 2 tablets per dose, administered orally twice 
daily (morning and evening) 
② Vancomycin: Initial dose of 15-20 mg/kg, administered intravenously 
q8h-q12h (assuming MICBMD = 1 mcg/mL), with subsequent dose 
adjustments to maintain the vancomycin concentration at an 
AUC/MICBMD ratio of 400-600 [see 2020 Infectious Diseases Society of 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 11 of 12 
 
America (IDSA) guidelines]. 
 The investigator can adjust the vancomycin dosage and treatment regimen based on 
the subject’s renal function according to the approved vancomycin labeling and 
therapeutic drug monitoring (TDM) results.  
Study Methodology 
This clinical study is a phase 2a, multicenter, randomized, double-blind, parallel 
design study to evaluate the safety and efficacy of combination therapy with 
vancomycin and LCB01-0371 compared to standard vancomycin therapy in subjects 
with MRSA bacteremia. 
Subjects will voluntarily provide written consent to participate in this study, and 
screening tests and procedures will be performed. Subjects who have started empirical 
antibiotic therapy within 96 hours prior to randomization (limited to 72 hours for 
MRSA-active antibiotics such as vancomycin) and who have at least one positive 
MRSA blood culture and meet the inclusion and exclusion criteria will be enrolled in 
the study. Subjects will then be randomized in a 1:1 ratio to either the study group 
(LCB01-0371 and vancomycin combination) or the control group (standard 
vancomycin therapy [placebo of LCB01-0371 and vancomycin combination]). The 
randomized subjects can receive the investigational product according to their 
assigned group for up to 42 days (at least 14 days). If the investigator determines that 
a switch to an antibiotic other than vancomycin is necessary for the treatment of 
MRSA bacteremia after initiation of therapy, a switch to daptomycin is allowed. After 
at least 14 days of vancomycin therapy (including switching to daptomycin), an oral 
antibiotic (excluding oxazolidinones) can be administered at the discretion of the 
investigator. Subjects who are switched to another antibiotic according to the above 
criteria will continue scheduled visits. 
As the subjects are hospitalized, they will undergo scheduled examinations and 
procedures, including pharmacokinetic assessments, at each time point. Upon 
completion of the administration of the investigational product, subjects will attend 
the EOT and test of cure (TOC) visits for tests and procedures to evaluate efficacy and 
safety. 
 
 
 
 
 
 
 
 
 
 
 
Withdrawal Criteria ① Voluntary withdrawal of consent by the subject. 
② When it is judged by the investigator that it is difficult to conduct further clinical 
trials due to adverse reactions and adverse drug reactions 
③ When the subject’s condition is deteriorating and the investigator determines that 
it is difficult to conduct further clinical trials (shock, cardiopulmonary 
resuscitation, ventilator treatment, etc.) 
④ If the following treatment failure criteria are met during treatment period 
- The investigator determines that a switch to another antibiotic for the 
treatment of MRSA bacteremia is required after at least 7 days of vancomycin 
administration (however, if vancomycin was deemed ineffective during the 
administration period, a switch to daptomycin was allowed at the discretion 
of the investigator. After at least 14 days of vancomycin therapy (including 
switching to daptomycin), an oral antibiotic (excluding oxazolidinones) may 
be administered at the discretion of the investigator. Subjects who are 
switched to another antibiotic according to the above criteria will continue 
Standard therapy 
Vancomycin IV + Placebo PO BID 
Combination therapy 
Vancomycin IV+ LCB01-0371 PO BID 
Screening 
-5d to -1d 
Treatment period: maximum 6wks 
Day 1 
Day 42 EOT 
(Within 2days 
after last IP 
administration) 
TOC 
(EOT+28d) 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 12 of 13 
 
scheduled visits.) 
- New infections other than MRSA or secondary infections resulting from 
MRSA bacteremia requiring treatment are identified after the first 
administration of the investigational product. 
- Confirmed decreased susceptibility to vancomycin. 
⑤ When the pregnancy of the subject is confirmed during administration of the 
clinical investigational drug 
⑥ When investigators decide that the subject should stop participating in the trial 
for other reasons 
Permitted 
Concomitant 
Medications 
and Treatments 
The following medications are allowed during the study period: 
1) Medications other than contraindicated combinations may be administered 
during the study (from the first administration of the investigational product to 
the completion of the TOC visit, as specified in the protocol) at the discretion of 
the investigator, provided the dosage remains stable. 
2) Temporary medications and treatments for symptom control due to MRSA 
bacteremia are allowed, except for antibiotics specifically used to treat MRSA 
bacteremia. 
3) Daptomycin: After at least 7 days of vancomycin administration, subjects can be 
switched to daptomycin if deemed necessary by the investigator for the treatment 
of MRSA bacteremia. Subjects who discontinue vancomycin and are switched to 
daptomycin (6–10 mg/kg, q24h h, IV) will continue scheduled visits. The 
investigator may adjust the dosage and administration of daptomycin according 
to the approved labeling based on the subject’s renal function. 
4) After at least 14 days of treatment with vancomycin (including switching to 
daptomycin), subjects may be switched to oral antibiotics other than 
oxazolidinones at the discretion of the investigator and continue scheduled visits. 
5) Temporary administration of antibiotics for skin and soft tissue infections or 
urinary tract infections is allowed at the discretion of the investigator (however, 
linezolid and tigecycline are prohibited during the study). 
6) Antiviral and antifungal agents used for prophylaxis may be administered 
concomitantly at the discretion of the investigator. 
7) Medications for the temporary treatment of other diseases may be administered 
concomitantly after consultation with the investigator. 
If any concomitant medications (including medications to treat other diseases or 
adverse events [AEs]) are administered, the investigator should record the 
information about the medications (product name, purpose of administration, dose, 
treatment period, etc.) in detail in the electronic case report form (eCRF). 
Prohibited 
Medications 
and Treatments 
The following medications are prohibited throughout the study: 
1) Antibiotics with antibacterial activity against MRSA (e.g., rifampin, 
clindamycin, 
trimethoprim-sulfamethoxazole, 
doxycycline, 
gentamicin, 
linezolid, tigecycline, etc.). However, empirical antibiotics, including 
vancomycin, used to treat Gram-positive bacteria within 72 hours prior to 
administration of the investigational product are allowed. In addition, after at 
least 14 days of treatment with vancomycin (including switching to daptomycin), 
subjects may be switched to oral antibiotics other than oxazolidinones at the 
discretion of the investigator. 
2) MAO inhibitors (drugs that inhibit MAO-A or MAO-B; e.g., phenelzine, 
isocarboxazid, selegiline, moclobemide, etc.) 
3) Selective serotonin reuptake inhibitors, tricyclic antidepressants, serotonin 5-HT1 
receptor agonists (triptans), meperidine, buspirone 
Medications to be 
Used with Caution 
The following medications may be administered concomitantly during the study, but 
must be closely monitored due to possible interactions with vancomycin. 
1) Medications with potential neurotoxicity or nephrotoxicity (e.g., amphotericin B, 
aminoglycosides, bacitracin, polymyxin B, colistin, viomycin, platinum-
containing anticancer drugs (cisplatin, nedaplatin, etc.)) 
2) Anticoagulants 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 13 of 14 
 
Endpoints 
(1) Efficacy Endpoints 
1) Primary endpoint 
 Proportion of subjects with overall cure on Day 14 of treatment (composite 
response rate) 
: “Overall cure” is defined as the disappearance of infection symptoms present 
at study enrollment, no new infections and/or secondary infections caused by 
MRSA (clinical improvement), and two consecutive negative MRSA blood 
cultures (clearance of MRSA bacteremia)a. 
a. 
If the first blood culture result is negative, a subsequent test will be 
performed within 3 days, and clearance of MRSA bacteremia is established 
when two consecutive negative results are confirmed. 
 
2) Secondary endpoints 
① Proportion of subjects with overall cure by the EOT visit (composite response 
rate) 
② Mortality due to MRSA bacteremia during the treatment period with the 
investigational product 
③ Relapse rate of MRSA bacteremia 
: Proportion of subjects with relapse MRSA bacteremia after two consecutive 
negative MRSA test results and prior to the TOC visit 
④ Proportion of subjects with two consecutive negative MRSA blood culture results 
on Day 3, Day 5, Day 7, Day 14 and at the EOT visit (clearance of MRSA 
bacteremia on Day 3, Day 5, Day 7, Day 14 and at the EOT visit) 
⑤ Proportion of subjects with persistent MRSA bacteremia based on blood culture 
results on Day 3, Day 5, Day 7, and Day 14 
⑥ Time to clearance of MRSA bacteremia (in days) 
: If the first negative blood culture result is confirmed, another test will be 
performed within 3 days. Clearance of MRSA bacteremia is confirmed by two 
consecutive negative results. The time to clearance of MRSA bacteremia is 
defined as the period (in days) from the date of the first MRSA-positive blood 
culture before randomization to the date of the first confirmed negative result in 
the blood culture. 
Definition of Clinical Outcome  
Clinical improvement 
Disappearance of the symptoms of infection existing at the 
time of enrollment in the study, without new infections or 
new secondary infections caused by MRSA. 
Clinical failure 
Subjects who experience clinical failure during the 
treatment period will be considered treatment failures for 
the remainder of the study. The following cases are 
classified as clinical failure if any of the following criteria 
are met. 
 Death due to MRSA bacteremia during the treatment 
period with the investigational product 
 A switch to another antibiotic for the treatment of 
MRSA bacteremia is required (however, if the 
treatment with vancomycin fails during the treatment 
period, a switch to daptomycin is allowed at the 
discretion of the investigator. After at least 14 days of 
vancomycin administration (including switching to 
daptomycin), it can be switched to an oral antibiotic 
(excluding oxazolidinones) at the discretion of the 
investigator. Subjects who are switched to another 
antibiotic according to the above criteria will continue 
scheduled visits.) 
 New infections other than MRSA or secondary 
infections resulting from MRSA bacteremia requiring 
treatment are identified. 
 
Definition of Microbiological Outcome  


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 14 of 15 
 
Clearance of MRSA 
bacteremia 
Two consecutive negative MRSA blood cultures. 
Persistent MRSA 
bacteremia 
Persistent MRSA positivity in blood cultures. 
MRSA bacteremia 
relapse 
Relapse of MRSA bacteremia after two consecutive negative 
MRSA test results and before the TOC visit 
 
(2) Safety Endpoints 
① Incidence and severity of treatment-emergent adverse events (TEAEs) and 
adverse drug reactions (ADRs) based on the National Cancer Institute’s Common 
Terminology Criteria for Adverse Events (NCI CTCAE v5.0) 
② Mortality (%) due to exacerbation of MRSA bacteremia at the time of the TOC 
visit (4 weeks after EOT) after starting treatment with the investigational product 
③ Incidence (%) of thrombocytopenia 
④ Abnormal changes in vital signs, electrocardiogram (ECG), laboratory tests, and 
physical examination 
 
(3) Pharmacokinetic (PK) Assessments and Measurement of Minimal Inhibitory 
Concentration (MIC) 
① PK assessments 
 
The time points of blood sampling and the PK parameters are as follows. 
Time 
points of 
blood 
sampling 
Day 1: 30min-1h, 2h-8h 
After reaching steady state (from Day 3 to EOT): 30 min-1 h, 2-8 h 
Endpoints 
Cmax, AUClast, Tmax (hr), T1/2 (hr), clearance (CL), etc. 
 
② Minimal Inhibitory Concentration (MIC) 
The MIC of vancomycin will be measured at the time of screening and at other time 
points as needed at the investigator’s discretion to adjust the vancomycin dose. In 
addition, MICBMD analysis can be performed at a designated laboratory by transferring 
samples when necessary. 
The MIC of LCB01-0371 will be measured at the time of screening and analyzed up 
to Day 14 in subjects whose blood culture results are not negative conversion by Day 
14. In subjects who discontinue treatment before Day 14 or whose blood cultures are 
not negative conversion by the EOT visit, the MIC of LCB01-0371 will be evaluated 
at the EOT visit. However, this evaluation will be performed only when possible and 
analysis of MIC of LCB01-0371 will be conducted at a designated laboratory. 
Statistical Analysis 
Method 
(1) Efficacy Assessment Methods 
1) 
Primary Endpoint 
 
Proportion of subjects with overall cure on Day 14 of treatment (composite 
response rate) 
: The number and percentage of subjects will be presented with the corresponding 
95% confidence intervals by time point and treatment group. Differences in 
proportions between groups will be tested using the chi-square test or Fisher’s 
exact test. 
 
2) 
Secondary Endpoints 
① Proportion of subjects with overall cure by the EOT visit (composite 
response rate) 
② Mortality due to MRSA bacteremia during the treatment period with the 
investigational product 
③ Relapse rate of MRSA bacteremia: Proportion of subjects with relapse 
MRSA bacteremia after two consecutive negative MRSA test results and 
prior to the TOC visit 
④ Proportion of subjects with two consecutive negative MRSA blood culture 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 15 of 16 
 
results on Day 3, Day 5, Day 7, Day 14 and at the EOT visit (clearance of 
MRSA bacteremia on Day 3, Day 5, Day 7, Day 14 and at the EOT visit) 
⑤ Proportion of subjects with persistent MRSA bacteremia based on blood 
culture results on Day 3, Day 5, Day 7, and Day 14 
 
: The analysis methods for the endpoints ① - ⑤ are the same as for the primary 
endpoint. 
 
⑥ Time to clearance of MRSA bacteremia (in days) 
: After testing the proportional hazards assumption for differences between 
groups, the log-rank test will be performed if the assumption is met. If the 
proportional hazards assumption is not met, the generalized Wilcoxon test 
(Gehan test) will be performed using different weights from the weighted log-
rank test family. The proportional hazards assumption will be tested using time-
dependent log(-log S(t)) plots and a residual analysis (Cox-Snell method). 
Survival curves and medians with corresponding two-sided 95% confidence 
intervals for each group will be presented using the Kaplan-Meier method, and 
estimates of hazard ratios with two-sided 95% confidence intervals will be 
provided using a Cox regression model with the treatment group as a covariate. 
 
(2) Safety Assessment Methods 
1) 
Incidence and severity of TEAEs and ADRs 
All adverse events will be coded by using the latest version of the medical 
dictionary for regulatory activities (MedDRA). 
The number of subjects, incidences (%), and number of cases of TEAEs and 
ADRs will be presented by treatment group, as well as the two-sided 95% 
confidence intervals for the incidences. AEs will be categorized and summarized 
as those related to the investigational product and those not related to the 
investigational product (such as concomitant medications and therapies, MRSA 
bacteremia, underlying diseases other than MRSA, none, unknown, or other 
related AEs). 
In addition, the number of subjects, incidences, and number of cases of TEAEs 
and ADRs that occur in each treatment group will be presented by system organ 
class (SOC) and preferred term (PT). 
2) 
Mortality due to exacerbation of MRSA bacteremia at the time of the TOC visit 
(4 weeks after EOT) after starting treatment with the investigational product 
The number and percentage of subjects who die due to exacerbation of MRSA 
bacteremia from the start of treatment with the investigational product to the TOC 
visit will be presented with the corresponding two-sided 95% confidence intervals 
for each treatment group. Differences in proportions between groups will be tested 
using the chi-square test or Fisher’s exact test. 
3) 
Incidence of thrombocytopenia 
The number and percentage of subjects who experience thrombocytopenia after 
administration of the investigational product will be presented with the 
corresponding two-sided 95% confidence intervals for each treatment group. 
Differences in proportions between groups will be tested using the chi-square test 
or Fisher’s exact test. 
4) 
Abnormal changes in vital signs, ECG, and physical examination 
For continuous data such as vital signs, electrocardiogram, and laboratory tests 
(hematology and blood chemistry), descriptive statistics (number of subjects, 
mean, standard deviation, median, minimum, maximum) will be presented for the 
measured value and the change from baseline at each visit. The results of 
laboratory tests and ECGs classified as normal, non-clinically significant (NCS) 
abnormal, or clinically significant (CS) abnormal will be summarized for subjects 
who exhibit CS abnormal results after treatment with the investigational product. 
Subjects who are classified as normal or NCS abnormal before administration of 
the investigational product but change to CS abnormal after administration of the 
investigational product will be listed separately. Subjects with abnormal CS 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 16 of 17 
 
findings on physical examination will also be listed. 
 
(3) Assessment Methods for PK Parameters and MIC 
1) 
PK parameters include Cmax, AUClast, Tmax (hr), T1/2 (hr), CL, etc., which will be 
analyzed by a separate institution and presented descriptively based on the data 
structure. The report on the results of the PK assessment can be presented 
separately from the clinical study report. 
2) 
MIC: Descriptive statistics (mean, standard deviation, median, minimum, and 
maximum) will be provided for MIC measurements. 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 17 of 18 
 
※ Schedule of Activities 
Period 
Screening# 
Treatment Period 
End of 
Treatment 
(EOT)/DC18 
Test of Cure 
(TOC)18 
Visit day 
-5d ~ 
Day 1# 
(Baseline) 
Day 3 
Day 5 
Day 7 
Day 14 
Day 15-42 
- 
EOT 
+ 28 days 
Window period 
- 
- 
- 
- 
±1d 
±2d 
±2d 
+2d 
±4d 
Written informed consent1 
● 
 
 
 
 
 
 
 
 
Review of the inclusion/exclusion 
criteria 
● 
●** 
 
 
 
 
 
 
 
Demographic data2 
● 
 
 
 
 
 
 
 
 
Medical history and current 
medical conditions3 
● 
●* 
 
 
 
 
 
 
 
Prior medications4 
● 
●* 
 
 
 
 
 
 
 
Vital signs5 
● 
●* 
● 
● 
● 
● 
Weekly 
(until discharge) 
● 
● 
Body measurement6 
● 
 
 
 
 
 
 
● 
 
Physical examination7 
● 
●* 
● 
● 
● 
● 
Weekly 
(until discharge) 
● 
● 
Laboratory tests8 
● 
●* 
(●) 
(●) 
● 
● 
Weekly 
(until discharge) 
● 
 
12-lead ECG9 
● 
 
 
 
 
 
 
● 
 
Randomization 
 
●* 
 
Blood cultures10 
● 
(●*) 
● 
●  
● 
● 
(●) 
● 
 
Vancomycin MIC evaluation11 
● 
 
 
 
 
 
 
 
 
LCB01-0371 MIC evaluation 
(optional)11 
● 
 
 
 
 
●  
 
● 
 
Efficacy assessment12 
 
 
● 
● 
● 
● 
 
● 
● 
PK assessment13 
 
● 
One time between Day 3 and EOT 
 
 
Administration of the 
investigational product14 
 
Daily (For at least Day 14 and up to Day 42) 
 
 
Administration of vancomycin14 
 
Daily (up to 42 days) 
 
 
Concomitant 
medication/combination therapy15 
 
● 
● 
● 
● 
● 
● 
● 
● 
Symptoms and signs of MRSA 
bacteremia16 
● 
● 
● 
● 
● 
● 
● 
● 
● 
AEs17 
 
● 
● 
● 
● 
● 
● 
● 
● 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 18 of 19 
 
* Performed prior to administration of the investigational product, (  ) Performed as needed at the discretion of the investigator. 
** The laboratory tests performed at the screening will be used to confirm the subject’s eligibility for participation. 
# The screening visit and Day 1 can be performed on the same day. Administration of vancomycin/investigational product is recommended as soon as possible after randomization. 
 
1 
Informed consent: The informed consent explanation and consent process will be completed prior to the start of any procedures associated with the study. 
2 
Demographic data: The age (year and month of birth) and gender of the subjects will be collected. 
3 
Medical history and current medical conditions: The medical history within 3 months of the screening visit (or within 5 years for malignancies) will be obtained. The collected medical history will also be 
checked for its relevance to MRSA bacteremia. For subjects with suspected endocarditis, echocardiography can be performed at the discretion of the investigator. If subjects have results of previous tests at the 
time of screening, these results will be taken as a medical history. 
4 
Prior medications: Information about medications administered within 30 days prior to the screening visit will be collected. 
5 
Vital signs: Systolic/diastolic blood pressure, pulse, body temperature, and respiratory rate will be measured. Measurements will be taken at the time of screening, Day 1, Day 3, Day 5, and Day 7, and then at 
weekly intervals (Day 14, Day 21, Day 28, Day 35, Day 42), and at the EOT/DC/TOC visit. Additional measurements will be taken as deemed necessary by the investigator. 
6 
Body measurement: Height will be measured only at the time of screening. If a measurement is available before the screening, the most recent result will be collected. Body weight will be measured at screening 
and at the EOT/DC visits. If the data are available to two decimal places, they will be rounded to one decimal place for collection. 
7 
Physical examination: Physical examination will be performed at the time of screening, Day 1, Day 3, Day 5, and Day 7, and then at weekly intervals (Day 14, Day 21, Day 28, Day 35, Day 42), and at the 
EOT/DC/TOC visit. Additional examinations will be performed as deemed necessary by the investigator. 
8 
Laboratory tests: For laboratory tests performed at the screening visit, with the exception of pregnancy tests, results obtained within 1 week (7 days) prior to the screening visit may be used. However, for 
clinically significant abnormal results, the tests should be performed at the screening visit. The laboratory tests will be performed on Day 1 and Day 7 and then weekly (Day 14, Day 21, Day 28, Day 35, Day 
42). Additional tests will be taken as deemed necessary by the investigator. At the EOT visit, the test can be omitted if the results of the previous 3 days are available. For women of childbearing potential, 
serum or urine pregnancy tests will be performed at screening, and participation is allowed if the result is negative. Further pregnancy tests can be performed at the discretion of the investigator. 
 
Laboratory Tests 
Test Items 
Collection Volume 
Hematology 
RBC, hemoglobin, hematocrit, platelet, ANC, WBC, WBC with differential count (neutrophils, lymphocytes, monocytes, eosinophils, basophils) 
Blood: About 15 mL 
per collection 
Urine: About 15 mL per 
collection 
Blood chemistry 
albumin, total protein, alkaline phosphatase, ALT, AST, γ-GT a),b), total bilirubin, blood urea nitrogen (BUN), creatinine, uric acid, glucose, sodium (Na), 
potassium (K), chloride (Cl), calcium (Ca), phosphorus (P), C-reactive protein (CRP), creatine phosphokinase (CPK)a), triglyceride a),b) 
Coagulationc) 
PT (INR), aPTT 
Urinalysis 
pH, occult blood, glucose, albumin (protein), urine microscopy (RBC, WBC), bacteria 
Pregnancy test  
Serum or urine HCG (only for women of childbearing potential) 
         a) These tests are not performed at the screening visit. 
b) The test are performed on Day 1, Day 14, and at the EOT visit. At the EOT visit, the test can be omitted if the results of the previous 3 days are available. 
c) These tests are performed at screening and at the EOT visit. 
9 
12-lead ECG: The ECG will be performed at screening and at the EOT visit to confirm the presence of clinically significant abnormal results. Additional ECGs can be performed as deemed necessary by the 
investigator. The results at the time of screening can be substituted if the results are available within 3 days prior to screening. However, if there are clinically significant abnormal results, the ECG will be 
performed at the screening visit. 
10 
Blood cultures: Two sets of blood cultures will be collected from different sites if possible and performed consecutively (1 set = 2 bottles; 1 anaerobic and 1 aerobic, approximately 20 mL per set). According 
to the inclusion criteria, at least one positive MRSA test result is required before randomization. Blood cultures will be performed at screening, on Day 3, Day 5, and Day 7, and then every 3 days until MRSA 
results are confirmed negative twice consecutively (i.e., if the first negative result is obtained, the second test will be performed within 3 days to confirm the second negative result). The blood cultures will also 
be performed on Day 14 and at the EOT visit. If the MRSA results are confirmed negative twice consecutively before the EOT visit, no blood cultures will be performed at the EOT visit. Additional blood 
cultures may be performed as deemed necessary by the investigator. Blood cultures performed for MRSA confirmation at screening can be based on results obtained during routine medical care prior to obtaining 
consent. However, the test results must be obtained either within 72 hours prior to randomization or within 96 hours prior to randomization if empirical treatment with vancomycin is initiated within 72 hours 
(compliance with inclusion criterion 2). The identification of MRSA can also be confirmed by rapid test results from each study site. 
11 
Vancomycin/LCB01-0371 MIC evaluation: Evaluation of the MIC of vancomycin may be performed after the time of screening at the investigator’s discretion to confirm susceptibility, determine resistance to 
MRSA, and adjust the vancomycin dose. In addition, MICBMD analysis can be performed at a designated laboratory by transferring samples when necessary. 
The MIC of LCB01-0371 will be analyzed on Day 14 in subjects whose blood culture results are not negative conversion by Day 14 after screening. In subjects who discontinue treatment before Day 14 or 
whose blood cultures are not negative conversion by the EOT visit, the MIC of LCB01-0371 will be evaluated at the EOT visit. However, this evaluation will be performed only when possible and at a designated 
laboratory. 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 19 of 20 
 
12 
Efficacy assessment: Efficacy assessment will be conducted on Day 3, Day 5, Day 7, Day 14, at the EOT visit, and at the TOC visit, which includes evaluation of clinical symptoms and signs of MRSA 
bacteremia, review of blood culture results, determination of MRSA bacteremia relapse, and occurrence of death. The blood culture results from each assessment time point will be reviewed at the following 
efficacy assessment. 
13 
PK assessment: For the pharmacokinetic assessments, a single blood sample will be collected at each blood sampling time point on Day 1 and from Day 3 to the EOT visit. 
No. 
Day 
Blood Sampling Time Point 
 
No. 
Day 
Blood Sampling Time Point 
Collection Volume (mL) 
1 
1 
30min-1h  
 
3 
From 
Day 3 to 
EOT 
30min-1h 
8 mL 
2 
2h-8h 
 
4 
2h-8h 
8 mL 
 
14 
Administration of the investigational product/vancomycin: According to the inclusion criteria, at least one positive MRSA result from a blood culture performed prior to randomization is required for enrollment 
in the study. Subsequently, subjects will be randomized to either the standard vancomycin treatment group or the vancomycin plus LCB01-0371 combination treatment group and will receive the investigational 
product from Day 1 to a maximum of 42 days (at least 14 days). If the investigator determines that a switch to an antibiotic other than vancomycin is necessary for the treatment of persistent MRSA bacteremia 
after at least 7 days of vancomycin administration, a switch to daptomycin is allowed. After at least 14 days of vancomycin therapy (including switching to daptomycin), an oral antibiotic (excluding 
oxazolidinones) can be administered at the discretion of the investigator. Subjects who are switched to another antibiotic according to the above criteria will continue scheduled visits. 
The dosage and administration of vancomycin can be adjusted based on the TDM results performed according to institutional guidelines and the judgment of the investigator. 
15 
Concomitant medication/combination therapy: After the baseline visit, information on concomitant medications administered from the time points indicated in the schedule of activities, including drug names 
(generic names), purpose of administration, daily dosage, route of administration, and duration of treatment, will be collected and recorded in the CRF. 
16 
All primary lesions of MRSA infection observed from screening to the end of the study, including whether they are removed, and any bacteremia-related reactions will be collected. Clinical symptoms, 
laboratory test results, vital signs, and other responses will be recorded under a single diagnosis. Symptoms and signs related to the exacerbation of primary lesions from MRSA infection and bacteremia 
following the administration of the investigational product will be collected as AEs related to “MRSA bacteremia”. However, if the exacerbation is not due to the underlying MRSA infection or does not 
correspond to the expected clinical manifestations associated with MRSA bacteremia, it will be collected as an AE or SAE. 
17 
Any clinically significant medical conditions or abnormalities observed from the administration of the investigational product until the end of the study will be collected as AEs. Clinically significant abnormal 
findings will also be collected as AEs, and any AEs confirmed before administration of the investigational product will be collected as new AEs if their severity worsens after administration. 
18 
Subjects who discontinue treatment with the investigational product will undergo the scheduled EOT visit within +2 days of the last administration of the investigational product or the decision to discontinue 
treatment and will be considered withdrawn. However, subjects who discontinue treatment, with the exception of those who voluntarily withdraw consent, will undergo the TOC visit 28 days (±4 days) after 
the EOT visit to complete the study. 
 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 20 of 21 
 
3 
Introduction 
3.1 
Study Background 
Staphylococcus aureus (S. aureus) is a widespread pathogen that causes infections in humans. It primarily 
colonizes the nasopharynx, skin, nasal cavity, and gastrointestinal tract, and is known to cause a variety of 
infections, including skin and soft tissue infections, pneumonia, osteoarthritis, and bacteremia. It is also reported 
as a major cause of healthcare-associated infections. The increasing use of catheters, prostheses, and invasive 
procedures has led to an increase in serious infections caused by S. aureus. Many of these strains are resistant to 
existing antibiotics, making effective antibiotic treatment more challenging.1,2 Since the emergence of methicillin-
resistant S. aureus (MRSA) in 1961, resistance to antibiotics has developed rapidly, leading to an increase in the 
frequency of MRSA infections. MRSA is a major causative pathogen of hospital-acquired infections, and recently, 
community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has emerged as a new problem 
not only in hospitals but also in the community. Although a direct comparison of antibiotic resistance rates is 
difficult due to the lack of standardized testing methods and surveillance systems between countries, the 
methicillin resistance rate of S. aureus in Korea is 67.7%, which is significantly higher than in the UK (13.6%), 
France (20.1%), and Japan (53%).3 
In addition, the continuous increase in vancomycin use in MRSA infections led to the reporting of vancomycin-
intermediate S. aureus (VISA) in 1996, and vancomycin-resistant S. aureus (VRSA) has been reported since 2002, 
making antibiotic resistance in S. aureus a very serious problem.4,5 
MRSA bacteremia is a serious infection of the bloodstream and is associated with a high mortality rate among the 
various infectious diseases.6 The mortality rate for MRSA bacteremia is approximately 20-40%, and it is known 
to be more difficult to treat and more fatal than S. aureus bacteremia.5 Therefore, timely treatment with appropriate 
antibiotics plays a crucial role in improving patient survival. 
According to the Infectious Diseases Society of America (IDSA) guidelines, intravenous injection of vancomycin 
or daptomycin for at least 2 weeks and up to 6 weeks is recommended as first-line therapy for MRSA bacteremia. 
If treatment with vancomycin fails, high-dose daptomycin (10 mg/kg/day) is preferred, although combination 
therapies with gentamicin, rifampin, linezolid, or beta-lactam antibiotics are also recommended.8 
Vancomycin is a glycopeptide antibiotic that has a bactericidal effect by inhibiting bacterial cell wall synthesis 
and is currently the preferred antibiotic for the treatment of MRSA bacteremia. However, vancomycin has a slower 
bactericidal effect than oxacillin, has poor penetration into pulmonary tissue and the central nervous system, and 
is associated with increasing minimum inhibitory concentrations (MICs) for MRSA (a phenomenon known as 
“MIC creep”), which limits its efficacy in the treatment of MRSA bacteremia.8,9 For vancomycin, maintaining an 
area under the curve (AUC)/MIC ratio of at least 400 is critical for optimal therapeutic efficacy. If the MIC of the 
causative organism increases, the AUC must also increase accordingly. Newer MRSA isolates often have MICs 
of 1 or 2 µg/mL, making it difficult to maintain an AUC/MIC ratio of 400 or higher, which has led to an increase 
in vancomycin treatment failure rates. In the treatment of bacteremia associated with severe infections such as 
infective endocarditis, osteomyelitis, and pneumonia, higher doses of vancomycin are required, which increases 
the risk of nephrotoxicity.10 In addition, the increased use of vancomycin has led to an increase in resistant strains 
such as heterogeneous vancomycin-intermediate S. aureus (hVISA), highlighting the need for new antibiotics and 
combination therapies to effectively treat multidrug-resistant S. aureus infections.10-12 
Recently, several new antibiotics that are effective against MRSA, such as daptomycin, linezolid, and ceftaroline, 
have been developed and are now being used in clinical practice. Daptomycin, a cyclic lipopeptide antibiotic, is 
being considered as an alternative to vancomycin. However, its poor penetration into pulmonary tissue makes it 
unsuitable for the treatment of respiratory tract infections, and rhabdomyolysis has been reported as a side effect.6,8 
In addition, despite the non-inferiority of newly developed drugs to vancomycin in the treatment of MRSA 
bacteremia, none of them has shown clear superiority. Due to their high cost and significant side effects, 
vancomycin continues to be used as the first-line choice against MRSA bacteremia.9,11,14 When treatment with 
vancomycin fails, new antibiotics such as daptomycin and linezolid, either alone or in combination, are being 
considered as treatment alternatives. 
Antibiotic combination therapy aims to reduce the development of resistance and improve the antimicrobial effect 
through different mechanisms of action. However, alternatives to vancomycin, such as daptomycin, β-lactam 
antibiotics, and linezolid, have not shown improved antimicrobial activity in combination with vancomycin.10,15,16 
The mechanism of action of vancomycin is bactericidal by inhibiting bacterial cell wall synthesis by attaching to 
the bacterial cell wall and blocking glycopeptide polymerization. LCB01-0371, developed by LegoChem 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 21 of 22 
 
Biosciences, Inc. for the treatment of MRSA bacteremia, is an oral oxazolidinone antibiotic. It binds to domain V 
of bacterial 23S ribosomal ribonucleic acid (rRNA), inhibiting the formation of the initial complex between 30S 
and 50S rRNA, thereby suppressing bacterial protein synthesis and providing antimicrobial activity.17 
Furthermore, due to its different mechanism of action compared to vancomycin, it has no cross-resistance, which 
facilitates combination therapy and could reduce the risk of resistance development to enhance the antibacterial 
effect. 
3.2 
Study Rationale 
Oxazolidinone antibiotics have a novel mechanism of action in which they inhibit bacterial protein biosynthesis 
by binding to the V domain of 23S rRNA in the bacterial 50S ribosome subunit, thereby interfering with the initial 
complex formation of 30S rRNA and 50S rRNA. This different mechanism of action provides the advantage that 
there is no cross-resistance with existing antibiotics.17 Linezolid, a representative oxazolidinone antibiotic, is 
effective against Gram-positive bacteria and shows excellent antimicrobial activity against skin and soft tissue 
infections, pneumonia, and multidrug-resistant Gram-positive bacteria such as MRSA, VRSA, and VRE.1With 
the increased clinical use of linezolid, resistant strains of S. aureus and enterococci have been increasingly 
reported in the United States and Europe. Moreover, long-term use of linezolid is severely limited due to its bone 
marrow toxicity, including inhibition of monoamine oxidase, thrombocytopenia, anemia, and neutropenia.6,18,19 
Therefore, there is a need to develop new oxazolidinone antibiotics that can overcome resistance to linezolid and 
improve its toxicity profile. 
LCB01-0371, developed by LegoChem Biosciences, Inc., is an oral tablet oxazolidinone antibiotic that has fewer 
bone marrow toxicity compared to linezolid and shows superior antimicrobial activity against most Gram-positive 
bacteria and multidrug-resistant Gram-positive bacteria compared to linezolid. In a bacteremia mouse model, 
combination therapy of LCB01-0371 and vancomycin showed a greater reduction in viable blood cell counts than 
vancomycin monotherapy, suggesting potential synergistic antimicrobial effects through the combination of 
vancomycin and LCB01-0371. 
Therefore, this phase 2 clinical study aims to investigate the efficacy, safety, and pharmacokinetic properties of 
LCB01-0371 in combination with vancomycin compared to standard vancomycin therapy in patients with MRSA 
bacteremia. 
3.3 
Benefit and Risk Assessment 
3.3.1 
Nonclinical Experience 
The key nonclinical results are as follows, and detailed information can be found in the investigator’s 
brochure.17 
1) 
Efficacy Study 
① Mouse systemic infection model (Study LCB01-0371-PH-04) 
In the systemic infection model in mice induced by various Gram-positive and Gram-negative bacteria, including 
S. aureus Giorgio and H. influenzae hd2, comparison of antimicrobial activity between LCB01-0371 and linezolid 
showed that LCB01-0371 demonstrated stronger antimicrobial activity with a lower ED50 value than linezolid. 
② 
In vitro MIC test and in vivo efficacy study in a bacteremia infection mouse model using the S. aureus Giorgio 
 
In vitro MIC test: In the S. aureus Giorgio strain, the MIC values for LCB01-0371, linezolid, and vancomycin 
were found to be 1 mg/L, 1 mg/L, and 0.5 mg/L, respectively. LCB01-0371 showed similar antimicrobial 
activity to linezolid and vancomycin. 
 
Confirmation of the effect of LCB01-0371 and vancomycin in the blood of the bacteremia mouse model: To 
establish the bacteremia mouse model, a bacterial suspension of S. aureus Giorgio was administered at a 
concentration of 5 x 106 CFU/mouse. One hour after infection, LCB01-0371 and vancomycin were 
administered subcutaneously (S.C.), while the control group received no treatment. In the control group, the 
number of viable cells increased over time, with all animals dying after 24 hours. In the LCB01-0371 80 
mg/kg group, the number of viable cells decreased similarly to the vancomycin 40 mg/kg group, with the 
number of viable cells in both groups being significantly lower from 12 hours than at 1 hour post-infection. 
These results indicate that LCB01-0371 80 mg/kg demonstrates similar antimicrobial activity to vancomycin 
40 mg/kg against S. aureus Giorgio. 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 22 of 23 
 
 
Confirmation of the effect of LCB01-0371 and linezolid in the blood of the bacteremia mouse model: In the 
mouse systemic infection model induced by a bacterial suspension of S. aureus Giorgio, evaluation of the 
effects of LCB01-0371 and linezolid on the number of viable blood cells showed that the control group had 
increased viable cell counts and death of all animals at 24 hours, while the LCB01-0371 25, 50, and 100 
mg/kg groups showed decreased viable cell counts. From 12 hours onwards, all three groups showed 
significantly lower numbers of viable cells than at 1 hour post-infection with S. aureus Giorgio, with the 
LCB01-0371 50 and 100 mg/kg groups showing similar levels to the linezolid 50 mg/kg group. 
 
Evaluation of the effects of LCB01-0371, vancomycin, and linezolid in the blood and spleen of the 
bacteremia mouse model: The effects of LCB01-0371, vancomycin, and linezolid on the number of viable 
cells in the blood and spleen tissue were investigated in a mouse systemic infection model induced by a 
bacterial suspension of S. aureus Giorgio. The control group showed an increased number of viable S. aureus 
Giorgio cells in the blood and spleen tissue, and all animals died after 24 hours. On the other hand, the 
LCB01-0371 50 and 200 mg/kg, vancomycin 25 mg/kg, and linezolid 50 mg/kg treatment groups showed a 
decreased number of viable cells in the blood up to 24 hours post-infection, which was significantly lower 
than the number 1 hour post-infection. In the spleen, no significant dose dependent differences in the number 
of viable cells were observed between the LCB01-0371 50 and 200 mg/kg groups. 
 
Confirmation of the combination effect of LCB01-0371 and vancomycin in the blood and lung of the 
bacteremia mouse model: In the mouse systemic infection model induced by a bacterial suspension of S. 
aureus Giorgio, the effects of LCB01-0371 administration methods (S.C. or P.O.) and the combination with 
vancomycin on the number of viable cells in the blood and lung tissue were evaluated. The control group 
showed an increased number of viable S. aureus Giorgio cells in the blood and lung tissue and all animals 
died after 24 hours. On the other hand, the LCB01-0371 50 mg/kg S.C. or P.O. group, the vancomycin 25 
mg/kg S.C. group, the group with the combination of LCB01-0371 and vancomycin, and the linezolid 50 
mg/kg group showed a reduced number of viable cells in the blood and lung tissue up to 24 hours post- 
infection, which was significantly lower than the number of cells at 1 hour after infection. There were no 
significant differences in the number of viable S. aureus Giorgio cells in the blood and lung tissue depending 
on the type of drug or the method of administration. However, the LCB01-0371 and vancomycin combination 
group had a lower number of viable cells in the blood after 24 hours than the LCB01-0371 or vancomycin 
monotherapy group. 
2) 
Safety Pharmacology 
To evaluate the cardiovascular safety of LCB01-0371, a human ether-à-go-go related gene (hERG) assay 
was performed with the HEK293 cell line. As a result, LCB01-0371 showed no significant effect on inward 
rectifying potassium current at concentrations of 0.1 - 100 μM (Study 1756-005). 
Single oral administration of LCB01-0371 at doses of 250, 500, and 1000 mg/kg in mice resulted in no deaths, 
clinical signs (changes in physical condition, activity/arousal, autonomic nervous system or changes in 
neurobehavioral assessment of neuromuscular or sensorimotor function), or effects on respiratory rate 
(breaths per minute) or tidal/minute volume (Study 1756-006, 1756-007). 
In beagle dogs, single oral administration of LCB01-0371 at doses of 120, 300, and 750 mg/kg or single 
intravenous administration (IV infusion) at doses of 50, 150, and 300 mg/kg over 1 hour showed no adverse 
events in clinical observations, body temperature, blood pressure, heart rate, and ECG examinations (Study 
1756-008, 1756-017). 
3) 
PK Assessment 
LCB01-0371 was administered orally to mice, rats, and dogs to evaluate its absorption, distribution, metabolism, 
and excretion (ADME). 
① Absorption and bioavailability 
Absorption and bioavailability: Bioavailability was 60-70% in mice and dogs, and 100% in humans. No 
accumulation of LCB01-0371 was observed after 28 days of repeated administration in mice and dogs and after 
21 days of repeated administration in humans. 
 
Oral administration 
When LCB01-0371 was administered orally to male CD-1 mice at a dose of 30 mg/kg, the mean maximum serum 
concentration (Cmax) was 24.45 mg/L, the mean time to maximum plasma concentration (Tmax) was 0.5 hr, the 
mean half-life (T1/2) was 1.11 hr, and the area under the plasma concentration-time curve from zero to infinity 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 23 of 24 
 
(AUC0-∞) was 48.28 mg∙hr/L (Study LCB01-0371-PK-01). 
When LCB01-0371 was administered orally to male Sprague-Dawley rats at a dose of 10 mg/kg (Study LCB01-
0371-PK-02), the mean Cmax was 4.03 mg/L, the mean Tmax was 1.17 hr, the mean T1/2 was 1.13 hr, the mean 
AUC0-∞ was 16.24 mg∙hr/L, and the apparent bioavailability was 68.6% (Study LCB01-0371-PK-02). 
When LCB01-0371 was administered orally to male beagle dogs at a dose of 10 mg/kg, the mean Cmax was 
11321.97 ng/mL, the mean Tmax was 0.67 hr, the mean T1/2 was 3.27 hr, the mean AUC0-∞ was 48.745 mg∙hr/mL, 
and the apparent bioavailability was 58.54%. When LCB01-0371 was administered orally to male beagle dogs at 
a dose of 30 mg/kg, the mean Cmax was 28751.20 ng/mL, the mean Tmax was 0.33 hr, the mean T1/2 was 3.43 hr, 
the mean AUC0-∞ was 151.345 mg∙hr/mL, and the apparent bioavailability was 60.59% (Study LCB-0901). 
In repeated-dose toxicokinetic studies of LCB01-0371 in Sprague-Dawley rats and beagle dogs, no differences in 
PK parameter values were observed between males and females. Exposure to LCB01-0371 increased dose-
proportionally, and no drug accumulation was observed except in rats receiving 400 mg/kg/day. 
② Distribution 
In the plasma protein binding study, LCB01-0371 showed protein binding rates of 69% in mice, rats, and dogs, 
and 37% in humans (Study LCB01-0371-ADME-04). The stability of LCB01-0371 in the plasma of mice, rats, 
dogs, and humans was confirmed for 2 hours (Study LCB01-0371-ADME-05). 
In the mass balance study in Sprague-Dawley rats, LCB01-0371 was distributed from tissues associated with the 
gastrointestinal tract (esophagus, stomach, small intestine, etc.) to tissues not associated with the gastrointestinal 
tract (lungs, heart, skin, etc.) within 2 hours of oral administration and then gradually decreased and was detected 
only in the intestinal contents, adrenal glands, and liver at 48 hours after administration (Study 1756-016). 
③ Metabolism 
The half-life of LCB01-0371 in the liver microsomes of rats, dogs, and humans were more than 60 minutes (Study 
LCB01-0371-ADME-01), and a total of 17 metabolites were identified in rat, dog, and human plasma (Study I17-
001).    
The investigation of the potential of LCB01-0371 to induce and inhibit cytochrome P450 (CYP) isoenzymes 
showed that LCB01-0371 did not inhibit CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, 
CYP2E1, or CYP3A4 isoenzymes (Study B32-160004-03, Study B32-160004-04). In addition, investigation of 
the effects of LCB01-0371 on drug transporters showed that it did not inhibit the transport activity of OCT1, 
OCT2, OAT1, OAT3, OATP1B1, OATP1B3, OATP2B1, or NTCP (Study B32-160004-01, Study B32-160004-
02). 
④ Excretion 
In the mass balance study with male Sprague-Dawley rats, the primary route of excretion was urine, followed by 
fecal excretion. Specifically, at 168 hours after administration, the mean cumulative urinary recovery was 66% 
(97% of which was excreted within 24 hours), and the mean cumulative fecal recovery was 24% (93% of which 
was excreted within 48 hours) (Study 1756-016). 
4) 
Toxicology 
Toxicity was evaluated in Sprague-Dawley rats and beagle dogs after single and repeated oral and intravenous 
administration of various concentrations of LCB01-037. Repeated dose studies included recovery periods of 4, 
26, and 39 weeks, respectively. Single and repeated-dose toxicity studies showed no serious adverse events or 
direct target organ toxicity, and the overall results were comparable to those reported for other oxazolidinone 
antibiotics. 
 
Single dose 
Sprague-Dawley rats (Study No. 1756-009, 020): After single oral administration of LCB01-0371 at doses of 0, 
250, 500, 1,000, 2,000 mg/kg/day and single intravenous administration at doses of 0, 250, 500, 1,000, 1,800 
mg/kg/day, the maximum tolerated dose (MTD) in rats was determined to be 2,000 mg/kg and 1,000 mg/kg/day, 
respectively. 
Beagle dogs (Study No. 1756-010, 021): After single oral and intravenous administration of LCB01-0371 at doses 
of 0, 125, 250, 500, and 1,000 mg/kg, the MTD in beagle dogs was determined to be 1,000 mg/kg/day and 500 
mg/kg/day, respectively. 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 24 of 25 
 
 
Repeat dose 
① 28-Day oral toxicity study in rats (Study No. 1756-011) 
After twice-daily oral administration of LCB01-0371 at doses of 0, 30, 60, 140 mg/kg/day to Sprague-
Dawley rats for 28 days, the no observed adverse effect level (NOAEL) was 60 mg/kg/day, with 
corresponding Cmax and AUC0-24 on Day 28 of 11.2 mg/L and 50.4 mg∙hr/L, respectively. Some rats receiving 
140 mg/kg/day showed clinical and histological abnormalities, which disappeared during the recovery period. 
② 26-Week oral toxicity study in rats (Study No. B15186) 
After twice-daily oral administration of LCB01-0371 at doses of 0, 10, 25, 50, or 100→75 mg/kg/day to 
Sprague-Dawley rats for 26 weeks, the NOAEL in males was 10 mg/kg/day, with corresponding Cmax and 
AUC0-24 on Day 182 of 2.9 mg/L and 10.1 mg∙hr/L, respectively. In females, the NOAEL was 100→75 
mg/kg/day, with corresponding Cmax and AUC0-24 on Day 182 of 14.8 mg/L and 58.0 mg∙hr/L, respectively. 
Some rats receiving 50 or 100→75 mg/kg/day showed hematological and histological abnormalities, and 
these hematological abnormalities and some histological abnormalities recovering during the recovery period. 
③ 28-Day oral toxicity study in beagle dogs (Study No. 1756-012) 
After twice-daily oral administration of LCB01-0371 at doses of 0, 5, 10, or 20 mg/kg/day to beagle dogs 
for 28 days, the NOAEL in males was 20 mg/kg/day, with corresponding Cmax and AUC0-24 on Day 27 of 
11.2 mg/L and 54.9 mg∙hr/L, respectively. In females, the NOAEL was 10 mg/kg/day, with corresponding 
Cmax and AUC0-24 on Day 27 of 6.1 mg/L and 35.4 mg∙hr/L, respectively. 
④ 39-Week oral toxicity study in beagle dogs (Study No. B15189) 
After twice-daily oral administration of LCB01-0371 at doses of 0, 2, 5, 10, or 20→15 mg/kg/day to beagle 
dogs for 39 weeks, the NOAEL was 10 mg/kg/day for both males and females. No deaths occurred in either 
sex, and no test substance-related toxic effects were observed in the ophthalmologic examination, ECG, 
urinalysis, organ weights, and necropsy. 
 
Genotoxicity 
To evaluate the genotoxicity of LCB01-0371, a bacterial reverse mutation assay, mouse lymphoma mutagenesis 
assay using L5178Y/TK+/- cells, rat micronucleus assay, and chromosome aberration assay using human 
peripheral blood lymphocytes were performed. Various in vitro and in vivo genotoxicity tests showed that LCB01-
0371 was negative for mutagenicity and micronucleus formation and had no structural chromosome aberration 
potential. 
 
Reproductive Toxicity 
Studies on fertility, early embryonic development toxicity up to implantation, and embryo-fetal development 
toxicity were conducted in rats. 
① Reproductive toxicity study in rats (Study B15192) 
LCB01-0371 was administered orally to male Sprague Dawley rats from 4 weeks before mating until necropsy 
and to female rats from 2 weeks before mating until implantation at doses of 15, 30, and 60 mg/kg/day to evaluate 
reproductive and developmental toxicity. Male rats receiving 30 and 60 mg/kg/day showed a dose-dependent 
decrease in sperm motility and an increase in abnormal sperm. Histopathological examination revealed retention 
of sperm cells in the testis, oligospermia, and intraluminal cell debris in the epididymis in one male rat at 15 
mg/kg/day and in several male rats at 30 and 60 mg/kg/day. Based on these results, the lowest observed adverse 
effect level (LOAEL) for male rats was determined to be 15 mg/kg/day, and the NOAEL for female rats was 60 
mg/kg/day. 
② Reproductive and developmental toxicity study in rats (Study B15194) 
After oral administration of LCB01-0371 at doses of 15, 30, and 60 mg/kg/day to female Sprague Dawley rats 
from gestation day 7 to 17, fetuses from females receiving 60 mg/kg showed decreased body weights, and rats 
receiving 30 and 60 mg/kg showed decreased placental weights. Fetuses from females receiving 60 mg/kg showed 
visceral variations, including increased cervical thymic remnants and decreased ureteral ridge and dilatation, and 
skeletal variations, including a lack of ossification of the 5th and 6th sternebrae and significantly decreased 
ossification of the sternum, sacrococcygeal vertebrae, forelimbs, and hindlimbs. No abnormalities were noted on 
external examination of the fetus and observation of the placenta. The maternal NOAEL was confirmed as 30 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 25 of 26 
 
mg/kg/day, and the NOAEL for embryonic development was determined to be 15 mg/kg/day based on fetal 
weight, placental weight, visceral and skeletal variations, and number of ossifications. 
③ Embryo-fetal toxicity study in rabbits (Study B15195) 
After oral administration of LCB01-0371 at doses of 0, 1, 3, and 10 mg/kg/day to female New Zealand White 
rabbits during organogenesis (gestation days 6-18), no differences in fetal weight, placental weight, external 
examination of the fetus, or observation of the placenta were observed in all dose groups compared to the control 
group. Visceral and skeletal observations of the delivered fetuses also showed no differences compared to the 
control group. However, maternal animals receiving 10 mg/kg/day showed LCB01-0371-related effects, including 
premature birth, abortion, delivery status, decreased body weight, and decreased food consumption. Based on 
these results, a high and low dose of 3 and 0.3 mg/kg/day, respectively, was established. 
3.3.2 
Clinical Experience 
A total of six Phase 1 studies (5 with oral formulation, 1 with intravenous formulation) were conducted in healthy 
adult male volunteers and one Phase 2a study (with oral formulation) in tuberculosis patients. 
 
Safety Assessment Results 
A total of 239 subjects received the investigational product LCB01-0371 for up to 21 days. Based on previous 
study results of LCB01-0371, the safety data collected from 239 subjects showed a similar safety profile to other 
oxazolidinone antibiotics, and the MTD for repeated administration over 21 days was confirmed to be 2,400 mg 
per day. 
The most frequent adverse events reported in previous clinical studies were headache, nausea, dizziness, decreased 
neutrophil count, diarrhea, abdominal discomfort, increased total bilirubin, rhinorrhea, dyspepsia, vomiting, 
myalgia, decreased appetite, and asthenia, with no significant signs of bone marrow suppression observed. 
 
 PK Assessment Results 
After a single oral administration of LCB01-0371, the PK parameters showed dose proportionality in the dose 
range of 50-3,200 mg. Compared to linezolid (T1/2: 7.94 hr), the T1/2 of LCB01-0371 was 1.41-3.41 hr, and 
therefore, BID dosing of LCB01-0371 was considered appropriate. 
The mean absolute bioavailability of LCB01-0371 was 99.75% at the AUC after oral administration. 
Although the Cmax equivalence was insufficient, this was considered clinically insignificant as the efficacy 
of LCB01-0371, like that of other oxazolidinones, correlates best with the AUC/MIC ratio and not with peak 
exposure (Cmax). 
In repeated-dose studies, the PK parameters of LCB01-0371 were similarly observed after 7 or 21 days of 
administration, suggesting that long-term administration of LCB01-0371 does not significantly affect the ADME 
of the drug. Negligible accumulation of the drug, rapid clearance, and large inter-individual variability were 
observed after 21 days of administration. 
When LCB01-0371 was administered with a high-fat diet, absorption was delayed, the maximum blood 
concentration decreased, and the AUC decreased by 10% compared to administration under fasting conditions. 
However, since the delay in absorption (Tlag) of LCB01-0371 after a high-fat diet was 21 minutes, the food effect 
was considered insignificant. 
A summary of individual results from previous studies can be found in Table 1. Detailed information can be found 
in the investigator’s brochure.17 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 26 of 27 
 
Table 1. Summary of Previous Study Results 
Study No. 
Phase/Objective(s)/Study 
Design 
Dosage and Administration 
Target Population 
Study Results 
LCB01-0371-
11-1-01 
 
Phase 1a 
To evaluate safety, tolerability, 
PK, and PD 
Double-blind, randomized, 
placebo-controlled, single 
ascending dose 
Single dose 
LCB01-0371: 50, 100, 200, 
400, 800, 1,600, 2,400, 3,200 
mg 
Placebo 
Linezolid 600 mg 
Healthy male volunteers 
6 subjects per treatment 
group 
15 subjects 
6 subjects 
1. 
The most commonly reported adverse events included a decrease in neutrophil
count (5 subjects), an increase in total bilirubin (4 subjects), nausea (3 
subjects), headache (2 subjects), and vomiting (2 subjects). 
2. 
Clinically significant abnormal laboratory test results were observed in 12
subjects and reported as adverse events, including a decrease in neutrophil 
count, an increase in total bilirubin, an increase in creatine kinase, and
hypertriglyceridemia. No significant changes were observed in vital signs and 
ECG examinations. 
3. 
The severity of adverse events that occurred up to the dose escalation to 2,400
mg was mostly mild, with moderate adverse events reported only in the 3,200 
mg group. In the 3,200 mg group, gastrointestinal adverse events were 
reported, which were considered attributable to taking sixteen 200 mg tablets. 
Therefore, the MTD in the single-dose study is determined to be 2,400 mg per
day. 
4. 
The blood concentration increased in proportion to the dose increase. The half-
life was 1.41-3.41 hours, which was shorter than that of linezolid (7.94 hours). 
Considering the half-life, BID regimen is considered appropriate. 
LCB01-0371-
12-1-02 
 
Phase 1b 
To evaluate safety, 
tolerability, PK, and PD 
Double-blind, randomized, 
placebo-controlled, multiple 
ascending dose 
Part 1: 7-Day repeat dose 
LCB01-0371: 400, 800, 
1,200, 1,600 mg BID 
Placebo 
 
Part 2: Single dose 
LCB01-0371 800 mg 
Healthy male volunteers 
6 subjects per treatment 
group 
 
8 subjects 
 
 
6 subjects 
1. 
The most commonly reported adverse events were headache (6 subjects),
nausea (5 subjects), dizziness (4 subjects), and abdominal discomfort (3
subjects). 
2. 
Laboratory test results revealed clinically significant abnormal changes 
reported as adverse events in 5 subjects, including a decrease in neutrophil 
count, hypertriglyceridemia, an increase in urine WBC, an increase in creatine 
kinase, and an increase in AST. No significant changes were observed in vital 
signs and ECG examinations. 
3. 
The severity of adverse events was mostly mild, with moderate adverse events
leading to permanent discontinuation of treatment reported only in the 1,600 
mg group. 
4. 
Tolerability was confirmed by dose escalation up to 1,200 mg BID with 
repeated dosing over 7 days, and no safety-related adverse events were
reported. Therefore, the MTD in the 7-day repeated dose study is determined 
to be 1,200 mg BID (2,400 mg per day). 
5. 
The blood concentration increased in proportion to the dose increase. 
LCB01-0371-
14-1-01 
Phase 1b 
Safety, tolerability, popPK 
Double-blind, randomized, 
placebo-controlled, multiple 
ascending dose 
 
21-Day repeat dose 
LCB01-0371 800 mg QD 
LCB01-0371 800 mg BID 
LCB01-0371 1,200 mg BID 
Placebo 
Healthy male volunteers 
13 subjects 
10 subjects 
10 subjects 
6 subjects 
1. 
The most commonly reported adverse events were diarrhea (6 subjects), 
rhinorrhea (4 subjects), dizziness (3 subjects), dyspepsia (3 subjects), headache 
(3 subjects), nausea (3 subjects), abdominal discomfort (2 subjects), asthenia
(2 subjects), and a decrease in neutrophil count (2 subjects). 
2. 
The severity of adverse events was mostly mild, with the exception of the 
decrease in neutrophil count and abnormal changes in hematology and liver


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 27 of 28 
 
Study No. 
Phase/Objective(s)/Study 
Design 
Dosage and Administration 
Target Population 
Study Results 
function tests. 
3. 
In the LCB01-0371 treatment group, 1 subject experienced adverse events 
leading to treatment discontinuation (1 subject with abnormal changes in 
hematology and liver function tests), and 2 subjects experienced adverse events 
leading to treatment interruption (decrease in neutrophil count in 1 subject; 
headache, cold symptoms, and diarrhea in 1 subject). In addition, 2 subjects in 
the LCB01-0371 treatment group permanently discontinued treatment due to 
abnormal laboratory test results (ANC decrease, aPTT increase), although 
these were not reported as adverse events. No clinically significant changes 
were observed in vital signs and ECG examinations. 
4. 
There were no serious adverse events such as bone marrow toxicity (e.g., bone 
marrow suppression), which was reported during the 21-day repeated
administration of linezolid at a dose of 800 mg BID or 1,200 mg BID, and 
other serious adverse events. Therefore, the MTD is determined to be 1,200 
mg BID (2,400 mg per day). 
5. 
The results of the PK analysis after 21 days of repeated administration were
confirmed to be similar to the results of the PK analysis after 7 days of repeated
administration. Therefore, long-term administration is not expected to have a 
significant effect on the ADME of LCB01-0371. 
LCB01-0371-
13-1-03 
Phase 1c 
To evaluate food effect on PK 
and bioequivalence and 
compare 
two 
tablet
formulations (bilayer extended-
release tablet vs. currently
developed tablet formulation) 
Randomized, open-label, single
dose, crossover study 
Single dose 
LCB01-0371-B 800 mg 
LCB01-0371 800 mg 
Healthy male volunteers 
11 subjects 
18 subjects 
1. 
In the LCB01-0371 treatment group, 2 subjects experienced adverse events 
including rhinorrhea, sore throat, cough, pyrexia, non-cardiac chest pain, and
headache, and 1 subject in the LCB01-0371-B treatment group experienced 
dizziness. The severity of all adverse events was reported as mild. 
2. 
No clinically significant changes were observed in laboratory tests, vital signs,
and ECG examinations. 
3. 
When LCB01-0371 800 mg was administered after a high-fat diet, absorption 
was delayed compared to administration under fasting conditions, with a 
decrease in Cmax by approximately 20% and AUC by 10%. After
administration following a high-fat diet, the median Tmax was delayed by 1.25 
hours, and T1/2 was similar. 
4. 
The results of the PK analysis of LCB01-0371-B 800 mg (bilayer extended-
release tablet) were generally comparable to those of LCB01-0371 800 mg. 
5. 
The Tlag after administration after a high-fat diet was 4.2 minutes and 21
minutes for LCB01-0371-B 800mg and LCB01-0371 800mg, respectively, 
with no significant differences between administration in the fasted and fed 
states. 
LCB01-0371-
15-1-01 
Phase 1c 
To compare bioavailability 
Non-randomized, open-label, 
single dose, parallel design 
Single dose 
LCB01-0371-B 400 mg 
LCB01-0371-B 800 mg 
LCB01-0371-B 1,200 mg 
LCB01-0371 400 mg 
Healthy male volunteers 
6 subjects 
0 subjects 
0 subjects 
0 subjects 
1. 
Early termination was decided due to the need to improve the formulation. 
2. 
Hyperbilirubinemia occurred in 1 subject but was determined to have no causal
relationship with the study drug. 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 28 of 29 
 
Study No. 
Phase/Objective(s)/Study 
Design 
Dosage and Administration 
Target Population 
Study Results 
LCB01-0371 800 mg 
LCB01-0371 1,200 mg 
0 subjects 
0 subjects 
LCB01-0371-
16-1-01 
Phase 1 
To compare formulation (IV 
injection vs. oral tablet), 
single-blind, 
To evaluate PK (Cmax), 
safety, and tolerability 
Randomized, placebo-
controlled, single dose, 
Bioavailability study  
Single dose LCB01-0371: 
IV 200 mg* vs placebo 
IV 400 mg* vs 800 mg tablet 
IV 800 mg* vs placebo 
IV 800 mg† vs placebo 
IV 1,200 mg† vs placebo 
* 60 min (± 5 min) constant 
rate infusion 
† 30 min (± 5 min) constant 
rate infusion 
Healthy male volunteers 
6+2 subjects 
4+4 subjects 
6+2 subjects 
6+2 subjects 
4+0 subjects 
1. 
Adverse events related to the injection site occurred most frequently and 
increased in frequency with dose escalation (especially when increasing from 
800 mg to 1,200 mg). 
2. 
The injection site adverse events were paresthesia in 3 subjects, pain at the
injection site and in the periphery in 2 subjects, and phlebitis in 1 subject. 
Adverse events that did not occur at the injection site were nausea in 2 subjects, 
acne in 1 subject, forearm contusion in 1 subject, erythema at the vascular
injection site in 2 subjects, skin rash in 1 subject, left chest pain in 1 subject, 
and sweating in 1 subject. 
3. 
Eight cases of adverse drug reactions were reported (3 cases of injection site
dysesthesia, 2 cases of nausea, 1 case of injection site pain, 1 case of peripheral
pain, 1 case of sweating). 
4. 
Mild adverse events occurred in the 200 mg to 800 mg groups, and 2 cases of
moderate adverse events (Grade 2 nausea in 2 subjects) occurred in the 1,200 
mg group, leading to withdrawal of 2 subjects. 
5. 
Most adverse events recovered during the follow-up period without specific
treatment, and no deaths or serious adverse events occurred. 
6. 
No clinically significant changes in laboratory tests, vital signs, physical 
examination, and ECG examination were observed after administration of the 
investigational product. 
LCB01-0371-
15-2-01 
Phase 2a 
Early bactericidal activity 
(EBA), dose, PK 
Open-label, randomized, 
active-controlled 
14-Day administration 
LCB01-0371 400 mg BID 
LCB01-0371 800 mg QD 
LCB01-0371 800 mg BID 
LCB01-0371 1,200 mg QD 
HRZEa 3 ~ 5 tablets (adjusted 
according to body weight) 
Linezolid 600 mg BID 
TB patients 
16 subjects 
15 subjects 
16 subjects 
16 subjects 
8 subjects 
 
8 subjects 
1. 
The most frequent adverse events were gastrointestinal disorders (nausea, 
diarrhea, vomiting, etc.). 
2. 
The incidence of adverse events in the LCB01-0371 treatment groups was 27%
(4/15 subjects, 12 cases) in the 800 mg QD group, 75% (12/16 subjects, 23
cases) in the 400 mg BID group, 44% (7/16 subjects, 13 cases) in the 800 mg 
BID group, and 63% (10/16 subjects, 22 cases) in the 1,200 mg QD group, 
while the incidence in the control groups was 88% (7/8 subjects, 19 cases) in
the HRZE group and 63% (5/8 subjects, 16 cases) in the linezolid 600 mg BID 
group. 
3. 
The incidence of adverse drug reactions in the LCB01-0371 treatment groups 
was 19% (12/63 subjects, 27 cases), and 50% of subjects in each control group
reported adverse drug reactions. 
4. 
Most adverse events and adverse drug reactions were reported as mild. Only 1 
subject in the HRZE treatment group reported Grade 3 or higher adverse drug 
reactions (increase in alanine aminotransferase, increase in aspartate
aminotransferase). There were no Grade 4 or higher adverse drug reactions. 
5. 
Three serious adverse events occurred: 1 case of tuberculosis (exacerbation of 
underlying disease, resulting in death) in the LCB01-0371 400 mg BID group, 
1 case of pleural effusion in the HRZE group, and hyperkalemia in 1 subject


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 29 of 30 
 
Study No. 
Phase/Objective(s)/Study 
Design 
Dosage and Administration 
Target Population 
Study Results 
in the linezolid 600 mg BID group. 
6. 
Four adverse events leading to permanent discontinuation occurred: 
Tuberculosis (reported term: tuberculosis aggravated) in the LCB01-0371 400
mg BID and 1,200 mg QD groups was assessed as “not related” or “unlikely”
to the investigational product, while the increase in alanine aminotransferase 
and aspartate aminotransferase reported in the HRZE group were assessed as 
adverse drug reactions for which a causal relationship with the investigational 
product cannot be excluded. 
7. 
All clinically significant changes in laboratory test results from baseline were 
considered not related or unlikely related to the investigational product. 
8. 
Although statistically significant changes from baseline were observed in vital 
signs, physical examination, ECG, peripheral nerve scale, and eye examination
results in some subjects, most changes were within the normal range and
recovered to normal. 
a. 
HRZE: isoniazid 75 mg, rifampin 150 mg, pyrazinamide 400 mg, ethambutol 275 mg. 
TB: tuberculosis 
 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 30 of 31 
 
3.4 
Justification for Dosage and Administration 
The results of the Phase 1b study (LCB01-0371-14-1-01), in which healthy adult males received LCB01-0371 at 
a dose of 800 mg and 1,200 mg BID for 21 days, showed a maximum tolerated dose (MTD) of 2,400 mg. Common 
adverse events (AEs) reported following administration of LCB01-0371 included diarrhea, rhinorrhea, dizziness, 
dyspepsia, headache, nausea, abdominal discomfort, asthenia, and neutropenia. Most AEs were mild and not 
clinically significant. 
Based on the results of the previous Phase 1 study in healthy volunteers, a dose of 1,600 mg (800 mg BID), one 
level below the maximum tolerated dose, was chosen as the initial dose for this study. 
 
 
  
 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 31 of 32 
 
4 
Study Objectives 
The purpose of this study is to evaluate the efficacy of the combination therapy of LCB01-0371 and vancomycin 
compared to standard vancomycin therapy in subjects with MRSA bacteremia and to investigate its safety and 
pharmacokinetic profile. 
4.1 
Primary Objective 
To compare the proportion of subjects with overall cure between LCB01-0371 plus vancomycin combination 
therapy and standard vancomycin therapy. 
4.2 
Secondary Objectives 
1) Proportion (%) of subjects with overall cure by the EOT visit 
2) Mortality due to MRSA bacteremia during the treatment period with the investigational product 
3) Relapse rate of MRSA bacteremia 
4) Proportion of subjects with two consecutive negative MRSA blood culture results on Day 3, Day 5, Day 7, 
Day 14 and at the EOT visit (clearance of MRSA bacteremia on Day 3, Day 5, Day 7, Day 14 and at the EOT 
visit) 
5) Proportion of subjects with persistent MRSA bacteremia based on blood culture results on Day 3, Day 5, Day 
7, and Day 14 
6) Time to clearance of MRSA bacteremia (in days) 
7) Safety of the combination therapy with vancomycin and LCB01-0371 
8) PK profile of the combination therapy with vancomycin and LCB01-0371 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 32 of 33 
 
5 
Study Population 
5.1 
Number of Subjects 
Total of 100 subjects (50 subjects per group, two groups) 
5.2 
Selection of Study Population 
5.2.1 
Inclusion Criteria 
1) 
Male or female subjects ≥19 years of age at the time of written consent 
2) 
Subjects in whom at least one set of blood cultures tested positive for MRSA within 72 hours prior to 
randomization; or subjects in whom at least one set of blood cultures tested positive for MRSA within 96 
hours prior to randomization and who started treatment with vancomycin at least 72 hours prior to 
randomization 
3) 
Subjects who have clinical symptoms or signs of MRSA bacteremia according to the judgment of the 
investigator 
4) 
Subjects who have voluntarily decided to participate in this clinical study after being fully informed and who 
have agreed in writing to comply with the study requirements 
5.2.2 
Exclusion Criteria 
Concurrent diseases and medical history 
1) 
Subjects with polymicrobial bacteremia, including Gram-negative bacteria, or infections 
2) 
Subjects who have received treatment within the last 3 months (however, subjects may be enrolled if they 
have reinfection as determined by the investigator, regardless of prior treatment within 3 months) 
3) 
Subjects who had received empirical antibiotics for more than 96 hours prior to randomization (limited to 72 
hours for MRSA-active antibiotics such as vancomycin) 
4) 
Subjects with septic shock 
5) 
Subjects with hypersensitivity to vancomycin or linezolid 
6) 
Subjects infected with bacteria that are resistant to vancomycin or linezolid 
7) 
Subjects with a history of hypersensitivity to peptide antibiotics or aminoglycosides 
8) 
Subjects who are currently receiving or have received monoamine oxidase (MAO) inhibitors within 14 days 
prior to the first administration of the investigational product 
9) 
Subjects who are currently receiving serotonin reuptake inhibitors, tricyclic antidepressants, serotonin 5-HT1 
receptor agonists (triptans), meperidine, or buspirone 
10) Subjects who are severely immunocompromised (e.g., severe neutropenia (absolute neutrophil count (ANC) 
<0.5×109/L)) 
11) Subjects who, in the opinion of the investigator, are expected to die within 2 days from the severe 
complications of MRSA bacteremia 
Other 
12) Body Mass Index (BMI) ≥35 kg/m2 
13) Subjects who are unable to administer medication orally 
14) Pregnant or lactating subjects or women and men of childbearing potential who are unwilling to use 
appropriate contraceptive methods* during the study period and for 14 days after the last administration of 
the investigational product. 
* Contraceptive methods: Use of at least one barrier method (e.g., implants, injections, oral contraceptives, intrauterine 
devices (IUDs)) in combination with hormonal IUDs, absolute abstinence, or vasectomy (subjects must consent to the 
use of at least two contraceptive methods). However, periodic abstinence (e.g., ovulation cycle, symptothermal, or post-
ovulation methods) and withdrawal are not considered acceptable methods of contraception. 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 33 of 34 
 
15) Subjects who have received other investigational products within 30 days prior to screening 
16) Other subjects who, in the medical judgment of the investigator, are not suitable for participation in this study 
5.2.3 
Subject Withdrawal Criteria 
The investigator must record the completion status of all subjects participating in the study and document the 
reason if administration of the investigational product or observation is discontinued. Subjects may discontinue 
investigational product administration or follow-up if any of the following occurs: 
① Voluntary withdrawal of consent by the subject. 
② When it is judged by the investigator that it is difficult to conduct further clinical trials due to adverse 
reactions and adverse drug reactions 
③ When the subject’s condition is deteriorating and the investigator determines that it is difficult to conduct 
further clinical trials (shock, cardiopulmonary resuscitation, ventilator treatment, etc.) 
④ If the following treatment failure criteria are met during treatment period 
- 
The investigator determines that a switch to another antibiotic for the treatment of MRSA bacteremia 
is required after at least 7 days of vancomycin administration (however, if vancomycin was deemed 
ineffective during the treatment period, a switch to daptomycin was allowed at the discretion of the 
investigator. After at least 14 days of vancomycin therapy (including switching to daptomycin), an oral 
antibiotic (excluding oxazolidinones) may be administered at the discretion of the investigator. Subjects 
who are switched to another antibiotic according to the above criteria will continue scheduled visits.) 
- 
New infections other than MRSA or secondary infections resulting from MRSA bacteremia requiring 
treatment are identified after the first administration of the investigational product. 
- 
Confirmed decreased susceptibility to vancomycin. 
⑤ When the pregnancy of the subject is confirmed during administration of the clinical investigational drug 
⑥ When investigators decide that the subject should stop participating in the trial for other reasons 
Subjects who meet the above criteria and discontinue treatment with the investigational product will undergo the 
scheduled EOT visit within +2 days of the last administration of the investigational product or the decision to 
discontinue treatment, and will be considered withdrawn. However, in this case as well, subjects who discontinue 
treatment, with the exception of those who voluntarily withdraw consent, will undergo the TOC visit 28 days (±4 
days) after the EOT visit to complete the study. No further assessments will be conducted after the completion of 
this study. 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 34 of 35 
 
6 
Study Design 
6.1 
Study Period 
The total study period is approximately 24 months from the date of the IRB approval and can change depending 
on subject enrollment rates. 
Duration for each subject: Up to 75 days 
• 
Screening period: Up to 5 days 
• 
Treatment period: Up to 42 days 
• 
Treatment evaluation period: 28 days 
6.2 
Study Group and Control Group 
At the randomization visit (Day 1), the inclusion and exclusion criteria are finally confirmed, and if subjects are 
eligible for this study, they are finally enrolled and randomized in a 1:1 ratio to either the study group or the 
control group, receiving the corresponding investigational product for up to 42 days (at least 14 days). 
Treatment 
Group 
Investigational Product  
Concomitant Administration 
Study group 
LCB01-0371 P.O, BID 
Vancomycin IV 
Control group 
Placebo of LCB01-0371 P.O, BID 
Vancomycin IV 
 
6.3 
Randomization and Blinding 
6.3.1. 
Randomization 
Subjects who have provided written consent to participate in this study will be assigned a screening number in the 
order of written consent. Subsequently, subjects who meet all inclusion/exclusion criteria will be assigned a 
randomization number via the Interactive Web-based Response System (IWRS) in the order in which the 
investigator determines subject enrollment on Day 1. The method of randomization number assignment is 
described in detail in a separate randomization plan document. 
This study will be conducted as a double-blind study. To ensure double-blinding, randomization will be performed 
by an independent statistician using the PLAN procedure (Proc Plan procedure) in SAS® (Ver. 9.4 or higher, SAS 
Institute, Cary, NC, USA) to generate a randomization list and an investigational product packaging list. The 
generated randomization list and investigational product packaging list will be provided to the IWRS developer 
and the person in charge of the investigational product packaging. The verification of the randomization numbers 
and the numbers of the investigational products will be conducted by the IWRS. 
Randomization will be performed in a 1:1 ratio to the study group and the control group only for subjects who 
meet the inclusion criteria, do not fall under the exclusion criteria, and are deemed suitable for this study. A 
stratified block randomization method will be used for randomization, with the study site as a stratification factor. 
The sponsor’s personnel responsible for packaging the investigational products must package the study and 
control groups appropriately and label the numbers of the investigational products in accordance with the 
investigational product packaging list during packaging and labeling of the investigational products. 
The investigator shall obtain randomization numbers in the order of participation for subjects who meet 
inclusion/exclusion criteria through the IWRS, confirm the unique investigational product numbers for each 
subject through the IWRS, and prescribe the investigational products as assigned. 
The investigator, subjects, trial pharmacists, and study personnel must remain blinded until the completion of this 
study. If unblinding is required during the study, it will be performed according to the procedures described in 
Section 6.4.2 of this protocol. 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 35 of 36 
 
6.4 
Blinding 
6.4.1. Methods for Maintaining Blinding 
This study is a randomized, double-blind, multicenter, parallel-design, Phase 2a study and will be conducted as a 
double-blind study to exclude subjective judgment of subjects and investigators. 
After randomization, a placebo with the same dosage form and appearance will be used to blind the subjects and 
the investigator to the type of drug assigned to each subject, and the dispensing packaging will also be kept 
identical to ensure double-blinding. The double-blinding of the investigator and subjects will prevent bias in the 
assessment of therapeutic effect and AEs by the investigator or subjects. Blinding is a crucial factor for the 
integrity of this study. The general principle of blinding to ensure the scientific integrity of the study is to maintain 
the blinding of treatment allocation information (information about assigned treatment groups) for all individuals 
directly involved in the study until database lock and archiving. Accordingly, this general principle of blinding 
will be maintained until the end of the study. Database lock (DBL) and unblinding can be performed after 
completion of the study, followed by the preparation of the clinical study report. 
To ensure double blinding, randomization numbers and investigational product codes will be used during 
randomization so that subjects can only be identified by their randomization numbers. The randomization list and 
the investigational product packaging details for each group will only be disclosed after unblinding. 
6.4.2. Unblinding 
During the study period, unblinding of individual subjects is permitted only in medical emergency situations if 
identification of the investigational product administered is considered crucial to the subject’s medical treatment. 
The investigator must determine whether information about the administered investigational product is important 
to the subject’s treatment decision making before unblinding the subject’s treatment status. 
If unblinding is deemed necessary for reasons such as the occurrence of emergency situations that jeopardize the 
subject’s safety, the investigator must immediately notify the sponsor (LegoChem Biosciences, Inc.) or the 
contract research organization (CRO) monitor delegated by the sponsor. The monitor who receives this 
information is required to contact the sponsor’s personnel immediately. After receiving the relevant information, 
the sponsor’s personnel will consult with the investigator to decide whether unblinding is required and document 
this decision. After consulting with the sponsor, the investigator will access the unblinding screen on the 
randomization web page, enter the required information, obtain the investigational product information for the 
relevant subject, print and sign the unblinding completion notification email, and retain it in the investigator’s file. 
In cases where immediate contact with the sponsor is not possible, the investigator must follow the same procedure 
for unblinding, inform the sponsor of the unblinding as soon as possible, and document the reason for unblinding 
without consulting the sponsor. If the investigator becomes aware of a subject’s randomization code information 
during the study period, the investigator must make every effort to exclude bias in the evaluation of efficacy and 
safety. 
Upon completion of the study, the database will be locked once it has been confirmed to be complete and accurate, 
and the randomization code information will be disclosed upon the sponsor’s approval for unblinding. 
 
 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 36 of 37 
 
6.5 
 Study Schema 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
* The duration of treatment will be determined by the investigator’s judgement based on the patient’s condition and clinical practice guidelines for the treatment of MRSA bacteremia. 
After administration of vancomycin (including switch to daptomycin) for at least 14 days, vancomycin can be changed to oral antibiotics other than oxazolidinones determined by the 
investigator’s judgement. 
Blood cultures taken in patient with suspected 
infection 
MRSA (+) confirmed 
•
Presence of signs and symptoms of 
MRSA bacteremia 
•
<96hr empirical antibiotics received 
(but ≤72hr antibiotics for MRSA) 
Randomize 1:1 (N=100) 
Standard therapy group (N=50) 
Maximum 42 days* 
Vancomycin (IV q8-12h) + Placebo (PO BID) 
Combination therapy group (N=50) 
Maximum 42 days* 
Vancomycin (IV q8-12h) + LCB01-0371  
(PO BID) 
•
Follow-up blood cultures: at Day 3, Day 5, Day 7, then 
within 3 days until negative 2 consecutive cultures & Day 
14, and as clinically indicated 
•
Assessment of MRSA-related signs and symptoms 
EOT within 2 days after last dose of IP 
TOC: 28 days post EOT (±4 days) 
At the investigator’s discretion 
Switch to Daptomycin standard 
therapy 
Daptomycin (IV q24h) + Placebo 
(PO BID)
At the investigator’s discretion, 
Switch to Daptomycin combination 
therapy 
Daptomycin (IV q24h) +LCB01-0371 
(PO BID) 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 37 of 38 
 
7 
Criteria for Study Termination and Early Discontinuation 
7.1 
Study Termination Criteria 
Termination of this study is defined as the end of the study (completion or withdrawal) of the last subject enrolled 
in the study. 
In this study, the “EOS visit” is defined as the TOC visit at which the treatment evaluation is completed, and 
subjects who complete this visit are defined as “completed subjects”. 
The study is considered incomplete in the following cases: 
 If there are subjects in the study site who have not completed the visit schedule specified in the study. 
7.2 
Early Discontinuation Criteria 
If, based on the results observed during the study, the investigator reasonably determines that it is not appropriate 
to continue the study, the investigator may, in consultation with the sponsor, terminate the study in whole or in 
part. In addition, the sponsor may suspend the study in whole or in part for safety or management reasons. Cases 
in which there is new information regarding the investigational product that indicates a negative direction in terms 
of the benefit-risk ratio for the subjects, including but not limited to the following reasons: 
 If there is an evidence that the investigational product is ineffective 
 Occurrence of new and importance adverse drug reactions or if the incidence and severity of the expected 
adverse drug reactions are judged to exceed expectations 
 Other safety reasons 
 If the sponsor determines that the continuation of the study is not justified from a medical and ethical point 
of view 
 If it is determined that the subject enrollment rate at the study site will significantly disrupt the enrollment 
schedule required for this study 
 If the supply of the investigational product is discontinued 
If the sponsor terminates or temporarily suspends the study, the investigator must immediately notify the 
Institutional Review Board and submit a detailed explanation for the early termination or temporary suspension. 
If the study is terminated early or suspended, the investigator must immediately inform the subject of this 
circumstance so that appropriate measures and follow-up can be taken. 
The principal investigator shall organize the eCRF, the status of the study, and the results for the subjects up to 
the time of discontinuation and deliver them to the sponsor, and return the investigational product and all data 
related to the study to the sponsor. 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 38 of 39 
 
8 
Information and Management of Investigational Products and Concomitant Med
ication 
8.1 
Overview of the Investigational Product and Concomitant Medication 
8.1.1 
Study Drug 
1) Code name: LCB01-0371 
2) Formulation and appearance: White or off-white, oblong, film-coated tablet 
3) Active ingredient: LCB01-0371 400 mg per tablet (in 715 mg) 
4) Storage condition: Store in a tight container at room temperature (1-30 ℃). 
8.1.2 
Control Drug (Placebo) 
1) Code name: Placebo of LCB01-0371 
2) Formulation and appearance: White or off-white, oblong, film-coated tablet 
3) Ingredient and content: A matching placebo that has the same formulation and appearance as LCB01-0371 
4) Storage condition: Store in a tight container at room temperature (1-30 ℃). 
8.1.3 
Concomitant Medication 
Vancomycin hydrochloride (including daptomycin, if applicable)* 
* Drugs with the same active ingredient are allowed regardless of brand name. 
Vancomycin (including daptomycin, if applicable) is used as a prescribed drug at the study site, and drugs with 
the same active ingredient are allowed regardless of brand name. Administration information (dosage, duration, 
etc.) of vancomycin and daptomycin will be collected in this study. 
 
Oral antibiotics (excluding oxazolidinones)** 
** Drugs with the same active ingredient are allowed regardless of brand name. 
After at least 14 days of treatment with vancomycin (including switching to daptomycin), subjects may be 
switched to oral antibiotics other than oxazolidinones (e.g., rifampin, fluoroquinolones) as determined by the 
investigator. Information on the administration (dosage, duration, etc.) of the corresponding oral antibiotics will 
be collected in this study. 
 
8.2 
Manufacture, Packaging, and Labeling of the Investigational Product 
The investigational product will be manufactured, packaged, and supplied to the study sites by the sponsor. The 
labeling of the investigational product will comply with Article 8.4 of the Good Manufacturing Practice for 
Investigational Medicinal Products in [Annex 4-2] of the Regulation on Safety of Pharmaceuticals, Etc. (partially 
amended on 08 Mar 2021, Ordinance of the Prime Minister No. 1683) and Article 7.7 of the Good Manufacturing 
Practice for Investigational Medicinal Products in [Annex 11] of the Regulation on Pharmaceutical Manufacturing 
and Quality Control (partially amended on 07 Sep 2020, MFDS Notification No. 2020-82) and will include the 
following information: 
① A statement that it may only be used for clinical trial purposes (e.g., “for 
investigational use only”) 
② Name or identification of the investigational product 
③ Batch or code numbers to identify the contents and packaging process 
④ Name, address, and phone number of the sponsor (IND holder) 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 39 of 40 
 
⑤ Shelf-life (expiry date) 
⑥ Storage conditions 
⑦ Reference code to identify the study (Protocol No.) 
⑧ Subject identification numbers (randomization number), investigational product 
numbers 
 
8.3 
Storage and Dispensing of the Investigational Product 
The investigational products shall be stored in a separate, locked location at the study site to which only authorized 
personnel (trial pharmacist or principal investigator or study personnel managing the investigational products, 
hereinafter referred to as “trial pharmacist, etc.”) shall have access. The trial pharmacist shall ensure an appropriate 
temperature in a suitable storage location to ensure proper storage of the investigational products and maintain a 
storage temperature log. In addition, the trial pharmacist shall comply with the shelf life (expiry date) of the 
investigational products and store and manage the investigational products to ensure that they are not used for 
purposes other than clinical studies. 
8.4 
Accountability, Recovery, and Disposal of the Investigational Product 
The sponsor shall complete the manufacture and packaging of the investigational products and supply them to the 
trial pharmacist at the study site. The clinical trial pharmacist must obtain and retain a receipt for the 
investigational products and must store and manage the investigational products to ensure that they are not used 
for purposes other than clinical studies. During the conduct of the study, the sponsor must check the quantity and 
storage conditions of the investigational products, etc., and take measures to ensure that the study can be conducted 
properly. In addition, if the sponsor suspends or terminates the study, unused investigational products shall be 
recovered and disposed of. 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 40 of 41 
 
9 
Study Methodology and Dosing Plan 
9.1 
Overall Study Methodology 
This study is a Phase 2a, randomized, double-blind, multicenter, parallel design study to evaluate the efficacy, 
safety, and pharmacokinetic properties of LCB01-0371 with vancomycin versus vancomycin standard therapy in 
patients with MRSA bacteremia. 
Subjects will voluntarily provide written consent to participate in this study, and screening tests and procedures 
will be performed. Subjects who have started empirical antibiotic therapy (e.g., vancomycin) within 72 hours prior 
to administration of the investigational product are eligible for enrollment. Those who have at least one positive 
MRSA blood culture and meet the inclusion and exclusion criteria will be enrolled in the study. Subjects will then 
be randomized in a 1:1 ratio to either the study group (LCB01-0371 and vancomycin combination) or the control 
group [standard vancomycin therapy (placebo of LCB01-0371 and vancomycin combination)]. The randomized 
subjects can receive the investigational product according to their assigned group for up to 42 days (at least 14 
days). If the investigator determines that a switch to an antibiotic other than vancomycin is necessary for the 
treatment of MRSA bacteremia after initiation of therapy, a switch to daptomycin is allowed. After at least 14 
days of vancomycin therapy (including switching to daptomycin), an oral antibiotic (excluding oxazolidinones) 
can be administered at the discretion of the investigator. Subjects who are switched to another antibiotic according 
to the above criteria will continue scheduled visits. 
As the subjects are hospitalized, they will undergo scheduled examinations and procedures, including 
pharmacokinetic assessments, at each time point. Upon completion of the administration of the investigational 
product, subjects will attend the EOT and test of cure (TOC) visits for tests and procedures to evaluate efficacy 
and safety. 
 
 
 
 
 
 
 
 
Study Schema 
9.2 
Dosage and Administration Method of the Investigational Product 
9.2.1 
Dosage and Treatment Period 
1) Treatment period: Up to 42 days (at least 14 days) 
* The treatment period will be determined based on the subject’s condition and the investigator’s judgment 
according to the guidelines for the treatment of MRSA bacteremia and may be administered for up to 6 weeks 
(at least 14 days). 
2) Dosage and administration method:  
Treatment 
Group 
Investigational Product 
Concomitant 
Medication* 
 
Morning 
Evening 
Study group 
Single dose of two tablets of 
LCB01-0371 
●● 
●● 
Vancomycin (IV) 
Control 
group 
Single dose of two tablets of 
placebo of LCB01-0371 
○○ 
○○ 
Vancomycin (IV) 
●: LCB01-0371 400 mg  
 
○: Placebo of LCB01-0371 400 mg 
 
Standard therapy 
Vancomycin IV + Placebo PO BID 
Combination therapy 
Vancomycin IV+ LCB01-0371 PO BID 
Screening 
-5d to -1d 
Treatment period: maximum 6wks 
Day 1 
Day 42 EOT 
(Within 2days 
after last IP 
administration) 
TOC 
(EOT+28d) 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 41 of 42 
 
* Switching to daptomycin: After at least 7 days of vancomycin administration, subjects may be switched to 
daptomycin if deemed necessary by the investigator for the treatment of MRSA bacteremia. See “③ 
Daptomycin” for dosage and administration of daptomycin. In addition, subjects may be switched to oral 
antibiotics, except for the oxazolidinones, based on investigator judgment after at least 14 days of vancomycin 
administration (including a switch to daptomycin). Subjects who are switched to another antibiotic according 
to the above criteria will continue scheduled visits. 
① LCB01-0371: 2 tablets per dose, administered orally twice daily (morning and evening) 
② Vancomycin: Initial dose of 15-20 mg/kg, administered intravenously q8h-q12h (assuming MICBMD = 
1 mcg/mL), with subsequent dose adjustments to maintain the vancomycin concentration at an 
AUC/MICBMD ratio of 400-600 (see 2020 Infectious Diseases Society of America (IDSA) guidelines20). 
The investigator can adjust the vancomycin dosage and treatment regimen based on the subject’s renal 
function according to the approved vancomycin labeling and therapeutic drug monitoring (TDM) results. 
*According to the 2020 IDSA guidelines, the recommended dosage and administration of vancomycin 
for patients with normal renal function is 15-20 mg/kg administered intermittently at q8h-q12h intervals. 
According to the 2020 IDSA guidelines, monitoring of the PK/PD parameter AUC/MIC ratio is 
recommended for patients with severe MRSA infections to maintain effective vancomycin blood 
concentrations and minimize nephrotoxicity. Assuming that the MICBMD is 1 mcg/mL, vancomycin is 
considered to achieve optimal effective blood concentrations when maintained at an AUC/MICBMD ratio 
of 400-600. The first follow-up is conducted preferably within the first 24-48 hours after the start of 
treatment. The frequency of monitoring should be determined based on clinical judgment (e.g., weekly 
for hematologically stable patients, more frequently or daily for unstable patients). 
③ Daptomycin: 6-10 mg/kg, q24h, IV injection. The investigator may adjust the dosage and administration 
of daptomycin according to the approved labeling based on the subject’s renal function. 
④ Oral antibiotics (excluding oxazolidinones): After at least 14 days of treatment with vancomycin 
(including switching to daptomycin), subjects may be switched to oral antibiotics other than 
oxazolidinones at the discretion of the investigator. The dosage and administration of each oral antibiotic 
will follow the approved labeling for MRSA treatment. 
9.3 
Concomitant Medication/Therapy 
9.3.1 
Permitted Concomitant Medication and Therapy 
The following medications and treatments are allowed during the study period (from the first administration of 
the investigational product to the completion of the TOC visit, as specified in the protocol). 
1) Medications other than contraindicated combinations may be administered during the study at the discretion 
of the investigator, provided the dosage remains stable. 
2) Temporary medications and treatments for symptom control due to MRSA bacteremia are allowed, except 
for antibiotics specifically used to treat MRSA bacteremia. 
3) Daptomycin: After at least 7 days of vancomycin administration, subjects can be switched to daptomycin if 
deemed necessary by the investigator for the treatment of MRSA bacteremia. Subjects who discontinue 
vancomycin and are switched to daptomycin (6–10 mg/kg, q24h h, IV) will continue scheduled visits. The 
investigator may adjust the dosage and administration of daptomycin according to the approved labeling 
based on the subject’s renal function. 
4) After at least 14 days of treatment with vancomycin (including switching to daptomycin), subjects may be 
switched to oral antibiotics other than oxazolidinones at the discretion of the investigator and continue 
scheduled visits. 
5) Temporary administration of antibiotics for skin and soft tissue infections or urinary tract infections is 
allowed at the discretion of the investigator (however, linezolid and tigecycline are prohibited during the 
study). 
6) Antiviral and antifungal agents used for prophylaxis may be administered concomitantly at the discretion of 
the investigator. 
7) Medications for the temporary treatment of other diseases may be administered concomitantly after 
consultation with the investigator. 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 42 of 43 
 
If any concomitant medications (including medications to treat other diseases or adverse events (AEs)) are 
administered, the investigator should record the information about the medications (product name, purpose of 
administration, dose, treatment period, etc.) in detail in the electronic case report form (eCRF). 
9.3.2 
Prohibited Concomitant Medication and Therapy 
The following medications will be prohibited throughout the study. 
1) 
Antibiotics with antibacterial activity against MRSA (e.g., rifampin, clindamycin, trimethoprim-
sulfamethoxazole, doxycycline, gentamicin, linezolid, tigecycline, etc.). However, empirical antibiotics, 
including vancomycin, used to treat Gram-positive bacteria within 72 hours prior to randomization are 
allowed. In addition, after at least 14 days of treatment with vancomycin (including switching to 
daptomycin), subjects may be switched to oral antibiotics other than oxazolidinones at the discretion of the 
investigator. 
2) 
MAO inhibitors (drugs that inhibit MAO-A or MAO-B; e.g., phenelzine, isocarboxazid, selegiline, 
moclobemide, etc.) 
3) 
Selective serotonin reuptake inhibitors, tricyclic antidepressants, serotonin 5-HT1 receptor agonists 
(triptans), meperidine, buspirone 
If the use of contraindicated medications was necessary or administered for the treatment of a subject during the 
study, the investigator should determine whether the subject’s treatment should be discontinued and document the 
details in the e-CRF. 
9.3.3 
Medications to be Used with Caution 
The following medications may be administered concomitantly during the study, but must be closely monitored 
due to possible interactions with vancomycin. 
1) 
Medications with potential neurotoxicity or nephrotoxicity (e.g., amphotericin B, aminoglycosides, 
bacitracin, polymyxin B, colistin, viomycin, platinum-containing anticancer drugs (cisplatin, nedaplatin, 
etc.)) 
2) 
Anticoagulants 
9.4 
Treatment Compliance 
The investigational product will be administered at the study site and treatment compliance will be assessed 
according to a separate investigational product manual. In addition, information will be collected on the 
administration of vancomycin (and/or daptomycin) as part of standard therapy and on oral antibiotics (with the 
exception of oxazolidinones) administered at the investigator’s discretion. 
The investigator/designee is responsible for instructing the subjects to ensure proper administration of the 
investigational product. 
If a subject forgets to take the investigational product, they will be instructed to take the investigational product 
as follows. 
 
 
If the subject realizes that they have forgotten to take the investigational product before bedtime, they 
should take it immediately. 
 
If the subject realizes the missed dose after waking up the next day, they should skip the previous dose 
and take the scheduled dose for that day. 
 
The treatment compliance is calculated as follows. 
 
Compliance (%) =  Total number of tablets actually taken (administered) 
× 100 
Total number of tablets to be taken (administered) 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 43 of 44 
 
10 
Study Procedures and Assessments 
10.1 
Observation Items 
10.1.1 
Informed Consent Form and Allocation of Screening Number and Enrollment Numb
er 
1) 
Obtaining Informed Consent Form and Assigning Screening Number 
Before starting the study, the investigator shall obtain written informed consent from the subject (or the subject’s 
representative) who wishes to participate in this study, after having fully informed him/her of the purpose and 
content of this study. Written informed consent must be obtained before any study procedures, and the subject 
must review the study information and sign the informed consent form in their own handwriting. The investigator 
must provide the subject with a copy of the signed consent form and the information sheet. 
Screening numbers will be assigned in the order of written informed consent. If a subject who has been assigned 
a screening number fails the screening, that screening number will also be withdrawn and will not be reassigned 
to another subject. 
10.1.2 
Demographic Data 
During the screening visit, demographic data such as age (year/month of birth), gender, etc., will be verified 
through interview, chart review, and questions and recorded in the eCRF. 
10.1.3 
Medical History 
Past medical history including surgical history within 3 months prior to screening and current medical history will 
be examined (diagnosis, date of diagnosis, current status, etc.). In the case of malignancies, however, only data 
from the last 5 years will be collected. The collected medical history will also be checked for its relevance to 
MRSA bacteremia. For subjects with suspected endocarditis, echocardiography can be performed at the discretion 
of the investigator. If subjects have results of previous tests at the time of screening, these results will be taken as 
a medical history. 
10.1.4 
Prior/Concomitant Medication/Therapy 
1) 
Prior medication 
Information about medications administered to the subjects within 30 days of screening will be collected. 
2) 
Concomitant medication/combination therapy 
After the baseline visit, information on concomitant medications administered from the time points indicated in 
the schedule of activities, including drug names (generic names), purpose of administration, daily dosage, route 
of administration, and duration of treatment, will be collected and recorded in the CRF. 
10.1.5 
Vital Signs 
Measurements will be taken at the time of screening tests, Day 1, Day 3, Day 5, and Day 7, and then at weekly 
intervals (Day 14, Day 21, Day 28, Day 35, Day 42), and at the EOT/DC, TOC visit. Additional measurements 
will be taken as deemed necessary by the investigator. If possible, vital signs should be measured before other 
planned examinations. Blood pressure (systolic, diastolic), pulse, temperature, and respiration should be measured 
after at least 5 minutes of rest. 
10.1.6 
Body Measurement 
Height will be measured only at the time of screening. If a measurement is available before the screening, the 
most recent result will be collected. Body weight will be measured at screening and at the EOT/DC visits. If the 
data are available to two decimal places, they will be rounded to one decimal place for collection. 
10.1.7 
Physical Examination 
Physical examination will be conducted at the time of screening tests, Day 1, Day 3, Day 5, and Day 7, and then 
at weekly intervals (Day 14, Day 21, Day 28, Day 35, Day 42), and at the EOT/DC, TOC visit. Additional 
examinations will be performed as deemed necessary by the investigator. During the physical examination, the 
appearance, skin, head/neck, chest/lungs, heart, abdomen, urogenital system, extremities, musculoskeletal system, 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 44 of 45 
 
nervous system, lymph nodes, and other organs will be examined. Significant findings detected during the 
screening test will be recorded in the physical examination section of the eCRF, and significant changes in 
physical findings that meet the definition of adverse events after administration of the investigational product will 
be recorded in the adverse events section of the eCRF. 
10.1.8 
Laboratory Tests 
For screening tests, with the exception of pregnancy tests, the results obtained within 1 week (7 days) prior to 
screening may be used. However, for clinically significant abnormal results, the laboratory tests should be 
performed at the screening visit as well. 
Hematology, blood chemistry, and urinalysis will be performed at screening and on Day 1, Day 7, and every week 
thereafter with the following laboratory tests. Blood coagulation tests will be performed at screening and at the 
EOT visit. Additional tests may be performed as deemed necessary by the investigator. At the EOT visit, the test 
can be omitted if the results of the previous 3 days are available. For women of childbearing potential, serum or 
urine pregnancy tests will be performed at screening, and participation is allowed if the result is negative. Further 
pregnancy tests can be performed at the discretion of the investigator. The laboratory tests include the following 
test items. 
Table 2. Laboratory Test Items 
Laboratory Tests 
Test Items 
Collection Volume 
Hematology 
RBC, hemoglobin, hematocrit, platelet, ANC, WBC, WBC with 
differential 
count 
(neutrophils, 
lymphocytes, 
monocytes, 
eosinophils, basophils) 
Blood: About 15 mL 
per collection 
Urine: About 15 mL 
per collection 
Blood chemistry 
albumin, total protein, alkaline phosphatase, ALT, AST, γ-GT a),b), 
total bilirubin, blood urea nitrogen (BUN), creatinine, uric acid, 
glucose, sodium (Na), potassium (K), chloride (Cl), calcium (Ca), 
phosphorus (P), C-reactive protein (CRP), creatine phosphokinase 
(CPK)a), triglyceride a),b) 
Coagulationc) 
PT (INR), aPTT 
Urinalysis 
pH, occult blood, glucose, albumin (protein), urine microscopy 
(RBC, WBC), bacteria 
Pregnancy test 
Serum or urine HCG (only for women of childbearing potential) 
a) These tests are not performed at the screening visit. 
b) The tests are performed on Day 1, Day 14, and at the EOT visit. At the EOT visit, the test can be omitted if the results of 
the previous 3 days are available. 
 c) These tests are performed at screening and at the EOT visit. 
 
10.1.9 
12-Lead ECG 
The electrocardiogram examination will be performed using a 12-lead ECG at screening and at the EOT visit. 
Additional examinations will be performed as deemed necessary by the investigator. For screening tests, the 
results obtained within 3 days prior to screening may be used. However, for clinically significant abnormal results, 
the tests should be performed at the screening visit as well. 
The results of the ECG evaluation and the determination of normal/abnormal will be recorded in the eCRF. 
Clinically significant abnormal results at screening will be recorded in the medical history section of the eCRF, 
and clinically significant abnormal results after administration of the investigational product will also be recorded 
in the adverse events section of the eCRF. 
 
10.1.10 
Blood Culture 
For blood cultures, two sets of blood cultures will be collected from different sites if possible and performed 
consecutively (1 set = 2 bottles; 1 anaerobic and 1 aerobic, approximately 20 mL per set). According to the 
inclusion criteria, at least one positive MRSA test result is required before randomization. 
Blood cultures performed for MRSA confirmation at screening can be based on results obtained during routine 
medical care prior to obtaining consent. However, the test results must be obtained either within 72 hours prior to 
randomization or within 96 hours prior to randomization if empirical treatment with vancomycin is initiated within 
72 hours (compliance with inclusion criterion 2). The identification of MRSA can also be confirmed by rapid test 
results from each study site. 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 45 of 46 
 
Blood cultures will be performed at screening, on Day 3, Day 5, and Day 7, and then every 3 days until MRSA 
results are confirmed negative twice consecutively (i.e., if the first negative result is obtained, the second test will 
be performed within 3 days to confirm the second negative result). The blood cultures will also be performed on 
Day 14 and at the EOT visit. If the MRSA results are confirmed negative twice consecutively before the EOT 
visit, no blood cultures will be performed at the EOT visit. Additional tests may be performed as deemed necessary 
by the investigator. 
 
10.1.11 
Minimum Inhibitory Concentration (MIC) 
The minimum inhibitory concentration (MIC) is defined as the lowest concentration of the antibiotic that inhibits 
microbial growth in in vitro sensitivity tests and serves as an indicator for measuring the antimicrobial activity of 
the antibiotic. Evaluation of the MIC of vancomycin is performed after the screening at the investigator’s 
discretion to confirm susceptibility, determine resistance to MRSA, and adjust the vancomycin dose. In addition, 
MICBMD analysis can be performed at a designated laboratory by transferring samples when necessary. The 
resistance criteria for vancomycin follow the Clinical and Laboratory Standards Institute (CLSI) M100-S27 (2017) 
guidelines21 (see Table 3). To confirm the resistance of LCB01-0371 to MRSA, the MIC of LCB01-0371 will be 
analyzed on Day 14 in subjects whose blood culture results are not negative conversion by Day 14 after screening. 
In subjects who discontinue treatment before Day 14 or whose blood cultures are not negative conversion by the 
EOT visit, the MIC of LCB01-0371 will be evaluated at the EOT visit. However, this evaluation will be performed 
only when possible and at a designated laboratory. 
 
Table 3 Antibiotic Resistance Criteria for Staphylococcus Aureus (Based on CLSI (M100-S27, 2017) 
Guidelines) 
Classification 
MIC 
Vancomycin 
Susceptible 
Intermediate 
Resistant 
≤2 
4-8 
≥16 
10.1.12 
Efficacy Assessment 
Efficacy assessment will be conducted on Day 3, Day 5, Day 7, Day 14, at the EOT visit, and at the TOC visit, 
which includes evaluation of clinical symptoms and signs of MRSA bacteremia, review of blood culture results, 
determination of MRSA bacteremia relapse, and occurrence of death. 
10.1.13 
PK Assessment 
Blood samples will be collected for PK assessment at the following time points. 
No. 
Day 
Blood 
sampling time 
point 
No. 
Day 
Blood 
sampling time 
point 
Collection 
volume (mL) 
1 
1 
30min-1h 
3 
from Day 3 to 
EOT  
30min-1h 
8 mL 
2 
2h-8h 
4 
2h-8h 
8 mL 
10.1.14 
Randomization and Administration of the Investigational Product 
Subjects in whom at least one set of blood cultures tested positive for MRSA within 72 hours prior to 
randomization or subjects in whom at least one set of blood cultures tested positive for MRSA within 96 hours 
prior to randomization and who started treatment with vancomycin at least 72 hours prior to randomization may 
be enrolled in this study. Subsequently, the subjects will be randomized to the study group or the control group to 
receive the investigational product from Day 1 and up to 42 days (at least 14 days). 
Detailed information can be found in Section 9.2. 
10.1.15 
Symptoms and Signs of MRSA Bacteremia 
Signs and symptoms related to MRSA bacteremia are indicators for assessing clinical improvement and the 
success/failure of treatment. Therefore, the primary lesion of MRSA infection, the status of removal of the primary 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 46 of 47 
 
lesion of MRSA infection, and the infection reactions related to bacteremia from screening to the end of the study 
will be recorded separately as “MRSA infection-related signs and symptoms”. However, complications due to 
bacteremia will be collected as a single diagnosis that includes clinical symptoms, laboratory tests, vital signs, or 
other related reactions (e.g., endocarditis). Symptoms and signs related to the exacerbation of primary lesions 
from MRSA infection and bacteremia following the administration of the investigational product will be collected 
as AEs related to “MRSA bacteremia”. 
 
10.1.16 
Adverse Events 
Any clinically significant medical conditions or abnormalities observed in subjects from the administration of the 
investigational product until the end of the study will be collected as AEs. Any clinically significant abnormal 
findings observed on vital signs, physical examination, laboratory tests, electrocardiogram examination, and other 
safety assessments will be collected as adverse events. Any AEs confirmed before administration of the 
investigational product will be collected as new AEs if their severity worsens after administration. Adverse events 
will be evaluated for their causal relationship with the investigational product LCB01-0371 and for a relationship 
with other than LCB01-0371 (concomitant medications and therapies, MRSA bacteremia, underlying diseases 
other than MRSA, none, unknown, other, etc.). 
The criteria for the evaluation of adverse events and the reporting procedures can be found in Section 10.5. 
10.2 
Visit Schedule 
10.2.1 
Screening Visit (Within 5 Days of the Baseline Visit) 
The screening visit and Day 1 can be performed on the same day. 
The following procedures will be performed to confirm the subject’s eligibility. 
1) Prior to the start of any study procedures, subjects will be informed about the study procedures and written 
informed consent form will be obtained. 
2) Screening numbers will be assigned to the subjects. 
3) Demographic data, past and current medical history, and prior medications will be examined. 
4) Vital signs (systolic/diastolic blood pressure, pulse rate, temperature, and respiratory rate) will be measured. 
5) Body measurement (height and weight): Height will be measured only at the time of screening. If a 
measurement is available before the screening, the most recent result will be collected. 
6) Physical examination will be performed. 
7) Laboratory tests will be performed. (however, pregnancy tests will be performed only for women of 
childbearing potential). 
8) 12-lead ECG will be performed. 
9) Blood cultures will be performed (can be based on the results obtained during routine medical care prior to 
obtaining consent. However, the test results must be obtained either within 72 hours prior to randomization 
or within 96 hours prior to randomization if empirical treatment with vancomycin is initiated within 72 hours 
[compliance with inclusion criterion 2]). 
10) MIC evaluation for vancomycin and LCB01-0371 (optional) will be conducted. 
11) Symptoms and signs related to MRSA bacteremia will be collected. 
 
10.2.2 
Treatment Visit (Day 1 [Baseline Visit], Day 3, Day 5, Day 7, Day 14, Day 21, Day 28, 
Day 35, Day 42) 
The screening visit and Day 1 (baseline visit) can be performed on the same day. Administration of 
vancomycin/investigational product is recommended as soon as possible after randomization. 
 
1) After reconfirmation of the inclusion/exclusion criteria, the subjects will be assigned randomization numbers. 
The results of the laboratory tests at the screening visit will be used to confirm that the subject is suitable for 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 47 of 48 
 
participation. Subjects in whom at least one set of blood cultures tested positive for MRSA within 72 hours 
prior to randomization; or subjects in whom at least one set of blood cultures tested positive for MRSA within 
96 hours prior to randomization and who started treatment with vancomycin at least 72 hours prior to 
randomization can be enrolled in this study. 
2) Past and current medical history, prior medication: On Day 1, past and current medical history as well as prior 
medications administered after screening, which were not collected during the screening, will be checked. 
3) Vital signs (systolic/diastolic blood pressure, pulse rate, temperature, and respiratory rate) will be measured. 
4) Physical examination will be performed. 
5) Laboratory tests: The laboratory tests will be performed on Day 1 and Day 7 and then weekly (Day 14, Day 
21, Day 28, Day 35, Day 42). Additional tests will be performed as deemed necessary by the investigator. 
6) 12-lead ECG: Performed as deemed necessary by the investigator. 
7) Blood cultures: Blood cultures will be performed on Day 3, Day 5, and Day 7, and then every 3 days until 
MRSA results are confirmed negative twice consecutively (i.e., if the first negative result is obtained, the 
second test will be performed within 3 days to confirm the second negative result). The blood cultures will 
also be performed on Day 14 and at the EOT visit. If the MRSA results are confirmed negative twice 
consecutively before the EOT visit, no blood cultures will be performed at the EOT visit. Additional tests 
may be performed as deemed necessary by the investigator. 
8) MIC evaluation: Evaluation of the MIC of vancomycin will be performed at the investigator’s discretion to 
determine resistance to MRSA and adjust the vancomycin dose. In addition, MICBMD analysis can be 
performed at a designated laboratory by transferring samples when necessary. Evaluation of the MIC of 
LCB01-0371 will be performed on Day 14 only in subjects whose blood culture results are not negative 
conversion by Day 14 and at the EOT visit in subjects who discontinue the treatment before Day 14. However, 
this evaluation will be performed only when possible and at a designated laboratory. 
9) Efficacy assessment: Efficacy assessment will be conducted on Day 3, Day 5, Day 7, Day 14, at the EOT visit, 
and at the TOC visit, which includes evaluation of clinical symptoms and signs of MRSA bacteremia, review 
of blood culture results, and occurrence of death. 
10) PK assessment: PK assessments will be performed after administration of the investigational product on Day 
1 and after Day 3 (before the end of treatment). 
11) The investigational product and vancomycin will be administered. If the investigator determines that a switch 
to an antibiotic other than vancomycin is necessary for the treatment of persistent MRSA bacteremia after at 
least 7 days of vancomycin administration, a switch to daptomycin is allowed. After at least 14 days of 
vancomycin therapy (including switching to daptomycin), an oral antibiotic (excluding oxazolidinones) can 
be administered at the discretion of the investigator. Subjects who are switched to another antibiotic according 
to the above criteria will continue scheduled visits. 
12) Concomitant medication/combination therapy will be collected. 
13) Symptoms and signs related to MRSA bacteremia will be collected. 
14) Adverse events will be checked. 
10.2.3 
EOT/DC Visit (+2 Days) 
This visit should be conducted within +2 days of the last administration of the investigational product or the 
decision to withdrawal, and the following procedures will be performed at this visit. 
1) Vital signs (systolic/diastolic blood pressure, pulse rate, temperature, and respiratory rate) and body weight 
will be measured. 
2) Physical examination will be performed. 
3) Laboratory tests and 12-lead ECG will be performed. 
4) Blood cultures: If the MRSA results are confirmed negative twice consecutively before the EOT visit, no 
blood cultures will be performed at the EOT visit. However, additional tests can be performed as deemed 
necessary by the investigator. 
5) Evaluation of the MIC of vancomycin and LCB01-0371 (optional): Evaluation of the MIC of vancomycin 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 48 of 49 
 
will be performed as deemed necessary by the investigator. In addition, MICBMD analysis can be performed 
at a designated laboratory by transferring samples when necessary. Evaluation of the MIC of LCB01-0371 
will be performed only in subjects who discontinue the treatment before Day 14 and those whose blood culture 
results are not negative conversion by EOT. This evaluation will be performed only when possible and at a 
designated laboratory. 
6) Efficacy assessment: Clinical signs and symptoms of MRSA bacteremia will be evaluated and blood culture 
results will be confirmed. 
7) Concomitant medication/combination therapy will be collected. 
8) Symptoms and signs related to MRSA bacteremia will be collected. 
9) Adverse events will be checked. 
10.2.4 
TOC Visit ((EOT +28 Days) ± 4 Days) 
This visit will be conducted 28 days (±4 days) after the EOT visit or DC visit to assess continued clinical response 
and for the safety follow-up, and the procedures for this visit are as follows. 
1) Vital signs (systolic/diastolic blood pressure, pulse rate, temperature, and respiratory rate) and body weight 
will be measured. 
2) Physical examination will be performed. 
3) Laboratory tests and 12-lead ECG: Performed as deemed necessary by the investigator. 
4) Blood cultures: Performed as deemed necessary by the investigator. 
5) Efficacy assessment: Clinical signs and symptoms of MRSA bacteremia will be evaluated and recurrence of 
MRSA bacteremia will be determined. 
6) Concomitant medication/combination therapy will be collected. 
7) Symptoms and signs related to MRSA bacteremia will be collected. 
8) Adverse events will be checked. 
10.2.5 
Unscheduled Visit 
If a subject visits the study site on an unscheduled date as medical treatment is required due to test results or 
adverse events during the study, these circumstances must be recorded in the relevant forms. The planned site 
visit schedule must not be changed due to unscheduled visits. 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 49 of 50 
 
 
10.3 
Efficacy Assessment 
10.3.1 
Efficacy Endpoints and Assessment Methods 
1) 
Primary Endpoint 
Proportion of subjects with overall cure on Day 14 of treatment (composite response rate): Overall cure is 
defined as the disappearance of infection symptoms present at study enrollment, no new infections and/or 
secondary infections caused by MRSA (clinical improvement), and two consecutive negative MRSA blood 
cultures (clearance of MRSA bacteremia)a. 
a. 
If the first blood culture result is negative, a subsequent test will be performed within 3 days, and 
clearance of MRSA bacteremia is established when two consecutive negative results are confirmed. 
The proportion of subjects with overall cure (composite response rate) is calculated as follows. 
Composite response rate (%) = (number of subjects with overall cure within 14 days / number of subjects in 
the efficacy analysis set) * 100 
2) 
Secondary Endpoints 
① Proportion of subjects with overall cure by the EOT visit (composite response rate) 
Composite response rate (%) = (number of subjects with overall cure by the EOT visit / number of 
subjects in the efficacy analysis set) * 100 
② Mortality due to MRSA bacteremia during the treatment period with the investigational product 
Mortality due to MRSA bacteremia during the treatment period = (number of subjects who died of 
MRSA bacteremia during the treatment period after starting the administration of the investigational 
product / number of subjects in the efficacy analysis set) * 100 
③ Relapse rate of MRSA bacteremia 
: Proportion of subjects with relapse MRSA bacteremia after two consecutive negative MRSA test 
results and prior to the TOC visit 
Relapse rate of MRSA bacteremia = (number of subjects with a relapse of MRSA bacteremia after 
clearance of bacteremia up to the TOC visit / number of subjects with clearance of bacteremia) * 100 
④ Proportion of subjects with two consecutive negative MRSA blood culture results on Day 3, Day 5, Day 
7, Day 14 and at the EOT visit (clearance of MRSA bacteremia on Day 3, Day 5, Day 7, Day 14 and at 
the EOT visit) 
Clearance rate = (number of subjects with clearance of bacteremia on Day 3, Day 5, Day 7, Day 14 and 
at the EOT visit* / number of subjects in the efficacy analysis set on Day 3, Day 5, Day 7, Day 14 and 
at the EOT visit) * 100 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 50 of 51 
 
 
* If two consecutive negative MRSA blood culture results are obtained prior to the EOT visit, these 
results can be considered as the blood culture results for the EOT visit. 
⑤ Proportion of subjects with persistent MRSA bacteremia based on blood culture results on Day 3, Day 
5, Day 7, and Day 14 
Proportion of subjects with positive MRSA blood cultures at each time point (Day 3, Day 5, Day 7, Day 
14) after the first positive MRSA result (index blood culture) confirmed before randomization 
• 
Proportion of subjects with persistently positive MRSA blood cultures up to Day 3 = (number of 
subjects with the first positive MRSA result before randomization and positive MRSA results on 
Day 3 / number of subjects in the efficacy analysis set on Day 3) * 100 
• 
Proportion of subjects with persistently positive MRSA blood cultures up to Day 5 = (number of 
subjects with the first positive MRSA result before randomization and positive MRSA results on 
Day 3 and Day 5/ number of subjects in the efficacy analysis set on Day 5) * 100 
• 
Proportion of subjects with persistently positive MRSA blood cultures up to Day 7 = (number of 
subjects with the first positive MRSA result before randomization and positive MRSA results on 
Day 3, Day 5, and Day 7 / number of subjects in the efficacy analysis set on Day 7) * 100 
• 
Proportion of subjects with persistently positive MRSA blood cultures up to Day 14 = (number of 
subjects with the first positive MRSA result before randomization and positive MRSA results on 
Day 3, Day 5, Day 7, and Day 14 / number of subjects in the efficacy analysis set on Day 14) * 
100 
⑥ Time to clearance of MRSA bacteremia (in days): 
If the first negative blood culture result is confirmed, another test will be performed within 3 days. 
Clearance of MRSA bacteremia is confirmed by two consecutive negative results. The time to clearance 
of MRSA bacteremia is defined as the period (in days) from the date of the first MRSA-positive blood 
culture before randomization to the date of the first confirmed negative result in the blood culture. 
Definition of Clinical Outcome  
Clinical improvement 
Disappearance of the symptoms of infection existing at the time of enrollment in the 
study, without new infections or new secondary infections caused by MRSA. 
Clinical failure 
Subjects who experience clinical failure during the treatment period will be considered 
treatment failures for the remainder of the study. The following cases are classified as 
clinical failure if any of the following criteria are met. 
 Death due to MRSA bacteremia during the treatment period with the 
investigational product 
 A switch to another antibiotic for the treatment of MRSA bacteremia is required 
(however, if the treatment with vancomycin fails during the treatment period, a 
switch to daptomycin is allowed at the discretion of the investigator. After at least 
14 days of vancomycin administration (including switching to daptomycin), it can 
be switched to an oral antibiotic (excluding oxazolidinones) at the discretion of 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 51 of 52 
 
 
the investigator. Subjects who are switched to another antibiotic according to the 
above criteria will continue scheduled visits.) 
 New infections other than MRSA or secondary infections resulting from MRSA 
bacteremia requiring treatment are identified. 
Definition of Microbiological Outcome  
Clearance of MRSA 
bacteremia 
Two consecutive negative MRSA blood cultures. 
Persistent MRSA 
bacteremia 
Persistent MRSA positivity in blood cultures. 
MRSA bacteremia 
relapse 
Relapse of MRSA bacteremia after two consecutive negative MRSA test results and 
before the TOC visit 
10.4 
Safety Assessment 
Safety assessment will be conducted through monitoring of subjective and objective adverse events, vital signs, 
physical examination, laboratory tests (hematology/blood chemistry/coagulation/urinalysis), and ECGs. 
10.4.1 
Safety Endpoints 
1) 
Incidence and severity of treatment-emergent adverse events (TEAEs) and adverse drug reactions (ADRs) 
based on the National Cancer Institute’s Common Terminology Criteria for Adverse Events (NCI CTCAE 
v5.0) 
2) 
Mortality due to exacerbation of MRSA bacteremia at the time of the TOC visit (4 weeks (28 days) after 
EOT) after starting treatment with the investigational product 
3) 
Incidence of thrombocytopenia 
4) 
Abnormal changes in vital signs, electrocardiogram (ECG), laboratory tests, and physical examination 
10.4.2 
Safety Assessment Methods 
1) 
Adverse Events 
AE refers to any symptoms, signs, or abnormal laboratory test results that occur or worsen after administration of 
the investigational product. The type, date of onset and end, severity, treatment and outcome, causal relationship 
with the investigational product, and causal relationship with factors other than the investigational product will be 
recorded in the AE section of the e-CRF. AEs will be categorized and summarized as those related to the 
investigational product and those not related to the investigational product (such as concomitant medications and 
therapies, MRSA bacteremia, underlying diseases other than MRSA, none, unknown, or other related AEs). All 
AEs will be coded and classified by system organ class (SOC) and preferred term (PT) using the latest version of 
the Medical Dictionary for Regulatory Activities (MedDRA). For detailed information on adverse event 
evaluation criteria, evaluation methods, and follow-up, see Section 10.5. 
2) 
Mortality due to exacerbation of MRSA bacteremia at the time of the TOC visit (4 weeks after EOT) 
after starting treatment with the investigational product 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 52 of 53 
 
 
Mortality due to exacerbation of MRSA bacteremia at the time of the TOC visit = (number of subjects who 
died after administration of the investigational product up to the TOC visit / number of subjects in the safety 
set) * 100 
3) 
Incidence of thrombocytopenia 
Proportion (%) of subjects with thrombocytopenia after administration of the investigational product 
4) 
Vital signs 
Vital signs are measured at each visit whenever possible before other scheduled tests are performed. After resting 
for at least 5 minutes, the subjects’ systolic and diastolic blood pressure, pulse, body temperature, and respiratory 
rate will be measured in a sitting position. 
Abnormal findings in vital signs that meet the definition of an abnormality should be reported as AEs. However, 
not all abnormal vital sign results are considered AEs. Vital sign results are reported as AEs if they meet any of 
the following criteria: 
• 
Accompanied by clinical symptoms, 
• 
Leading to a change in the administration of the investigational product (e.g., temporary interruption or 
permanent discontinuation), 
• 
Leading to medical interventions or changes in concomitant therapy. 
If considered clinically significant, the investigator is responsible for reviewing all vital signs and determining 
whether individual abnormal results should be classified as AEs based on medical and scientific judgment. 
If clinically significant abnormal vital signs indicate a disease or sign of a syndrome (e.g., high blood pressure), 
only the diagnosis (e.g., hypertension) should be recorded in the AE section of the e-CRF. 
5) 
Laboratory Tests 
The results of the laboratory tests are classified as normal or abnormal (not clinically significant (NCS) and 
clinically significant (CS)). If the laboratory test results are determined to be clinically significant after 
administration of the investigational product compared to before administration, it will be reported as an AE, and 
the findings on the abnormal values will be recorded. 
Not all laboratory abnormalities are considered AEs. Laboratory abnormalities are reported as AEs if they meet 
any of the following criteria: 
• 
Accompanied by clinical symptoms, 
• 
Leading to a change in the administration of the investigational product (e.g., temporary interruption or 
permanent discontinuation), 
• 
Leading to medical interventions (e.g., potassium supplementation for hypokalemia) or changes in 
concomitant therapy, 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 53 of 54 
 
 
• 
If deemed clinically significant by the investigator. 
The investigator is responsible for reviewing all laboratory test results and determining whether individual 
laboratory abnormalities should be classified as AEs based on medical and scientific judgment. 
If clinically significant laboratory abnormalities indicate a disease or sign of a syndrome (e.g., bilirubin value 
increased with cholestasis), only the diagnosis (e.g., cholestasis) should be recorded in the AE section of the e-
CRF. 
If clinically significant laboratory abnormalities are not indicative of a disease or syndrome, both the abnormality 
and a descriptor indicating whether the result is above or below the normal range should be recorded in the AE 
section of the e-CRF (e.g., “potassium increased” instead of “potassium abnormal”). 
If laboratory abnormalities can be classified according to standard definitions using the appropriate clinical terms, 
these clinical terms should be recorded as AEs. For example, an increase in serum potassium level to 7.0 mEq/L 
should be recorded as “hyperkalemia”. 
6) 
Physical Examination and ECG 
Any significant changes observed on physical examination or ECG results following administration of the 
investigational product that meet the definition of an AE should be reported as AEs. 
10.5 
Evaluation Criteria and Reporting of Adverse Events 
10.5.1 
Definition of Terms 
1) 
Adverse Event (AE) 
An adverse event (AE) refers to any unfavorable and unintended sign (including abnormal laboratory test results), 
symptom, or disease that occurs in subjects who have received an investigational product, which does not 
necessarily have a causal relationship with the investigational product. 
Adverse events that occur after treatment are referred to as treatment-emergent adverse events (TEAEs), i.e. 
adverse events that were not present before administration of the investigational product but occurred after 
administration, or adverse events that were present at baseline but worsened in severity after administration of the 
investigational product. 
2) 
Adverse Drug Reaction (ADR) 
An adverse drug reaction (ADR) refers to A harmful and unintended reaction that occurs at any dose of an 
investigational product and for which the causal relationship with the investigational product cannot be excluded. 
3) 
Serious AE/ADR 
A serious adverse event/adverse drug reaction (SAE/SADR) refers to any of the following cases among the AEs 
or ADRs that occur at any dose of the investigational product. 
① Results in death or is life-threatening1 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 54 of 55 
 
 
② Requires hospitalization or prolonged hospitalization2 
③ Results in persistent or significant disability/incapacity 
④ Results in a congenital anomaly/birth defect 
⑤ In addition to cases above, cases where other important medical events occur, such as development of drug 
dependence or drug abuse, or hematological disease, etc.3 
1Death is included as an efficacy endpoint, and deaths due to exacerbation of complications (e.g., sepsis) caused 
by MRSA bacteremia will not be collected as serious adverse events. However, unexpected sudden deaths not due 
to causes other than complications (e.g., sepsis) resulting from MRSA bacteremia or deaths of unknown cause 
must be reported as serious adverse events. 
2The following cases do not constitute “cases requiring hospitalization or prolonged existing hospitalization” and 
are not reported as serious adverse events: 
 
Hospitalization or prolongation of hospitalization for procedures (e.g., surgery, examination) that 
were planned prior to the study. 
 
Hospitalization or prolongation of hospitalization for follow-up of previously cured or improved 
conditions. 
 
Hospitalization or prolonged hospitalization for examination or education. 
 
Hospitalization or prolonged hospitalization for non-medical reasons (e.g., temporary absence of 
family members). 
 
Hospitalization or prolonged hospitalization in hospice facilities, nursing care facilities, or 
rehabilitation facilities. 
 
Hospitalization or prolonged hospitalization planned before signing the informed consent form 
3Other medically important situations (e.g., acute allergic reactions) are considered serious adverse events in the 
medical judgment of the investigator, even if they are not immediately life-threatening or result in death or 
hospitalization, as they jeopardize the subject or require intervention to prevent the occurrence of such symptoms. 
Since this study is conducted in hospitalized patients with MRSA bacteremia, hospitalization and prolonged 
hospitalization due to MRSA bacteremia are not considered serious adverse events. However, prolonged 
hospitalization due to worsening of existing symptoms or occurrence of new symptoms after administration of the 
investigational product should be reported as a serious adverse event. 
10.5.2 
Criteria for the Evaluation of Adverse Events 
10.5.2.1. Severity 
The severity of adverse events is assessed according to NCI-CTCAE22 ver 5.0. If an evaluation according to NCI-
CTCAE is not possible, the following criteria will be used:  


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 55 of 56 
 
 
Severity 
Grade 
Description 
Mild 
1 
Symptoms are barely noticeable to the subject and do not interfere with 
daily activities. The use of medication to alleviate the symptoms is 
generally not necessary. 
Moderate 
2 
Symptoms are severe enough to cause discomfort to the subject; the 
subject can continue the study but may require symptomatic treatment. 
Severe 
3 
Symptoms cause significant discomfort and may be severe enough to 
prevent the subject from continuing the study. The severity of 
symptoms may result in discontinuation of the investigational product; 
treatment of symptoms may be required, and/or hospitalization may be 
necessary. 
Life-threatening 
(Life-threatening) 
4 
Symptoms caused by the adverse event may pose an immediate threat 
to the subject’s life. This does not include more severe events but may 
result in death. 
Death 
5 
Subject has died due to the adverse event. 
 
10.5.2.2. Causal Relationship with the Investigational Product 
The relationship between the administration of the investigational product and the occurrence of adverse events 
is determined by the investigator. 
Causal Relationship 
Rationale 
Related 
1) 
Definitely 
 
• 
If there is evidence that the investigational 
product has been administered and the temporal 
sequence between the administration of the 
investigational product and the occurrence of 
the adverse event is reasonable. 
• 
If the adverse event is most plausibly explained 
by the administration of the investigational 
product and not by any other reason. 
• 
If the adverse event disappears as a result of the 
interruption of administration. 
• 
If the result is positive following rechallenge 
(performed if practically feasible). 
• 
If the adverse event exhibits a pattern consistent 
with information already known about the 
investigational product or drugs in the same 
class. 
2) 
Probably, Likely 
 
• 
If there is evidence that the investigational 
product has been administered and the temporal 
sequence between the administration of the 
investigational product and the occurrence of the 
adverse event is reasonable. 
• 
If the adverse event is most plausibly explained 
by the administration of the investigational 
product and not by any other reason. 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 56 of 57 
 
 
Causal Relationship 
Rationale 
• 
If the adverse event disappears as a result of the 
interruption of administration. 
3) 
Possible 
 
• 
If there is evidence that the investigational 
product has been administered and the temporal 
sequence between the administration of the 
investigational product and the occurrence of the 
adverse event is reasonable. 
• 
If the adverse event is determined to be 
attributable to the administration of the 
investigational product at the same extent as 
other possible causes. 
• 
If the adverse event disappears as a result of the 
interruption of administration (if performed). 
4) 
Unassessable 
 
• 
If there is insufficient evidence to determine 
causality. 
• 
Cases in which the causal relationship cannot be 
judged because information is insufficient or 
contradictory and cannot be supplemented or 
verified. 
Not related 
1) 
Unlikely 
 
• 
If there is evidence that the investigational 
product has been administered. 
• 
If there is another, more plausible cause for the 
adverse event. 
• 
If the result is negative or equivocal as a result of 
the interruption of administration (if performed). 
• 
If the result is negative or equivocal following 
rechallenge (if performed). 
2) 
Not related 
• 
If 
the 
investigational 
product 
was 
not 
administered to the subject. 
• 
If the adverse event is not reasonably related in 
time to the administration of the investigational 
product. 
• 
If there is another obvious cause for the adverse 
event. 
 
10.5.2.3. Causal Relationship with Other Than the Investigational Product 
Causal relationship with other than the investigational product is classified as follows. 
① Concomitant medication/combination therapy 
② MRSA bacteremia 
③ Underlying disease other than MRSA bacteremia 
④ None 
⑤ Unknown 
⑥ Other 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 57 of 58 
 
 
10.5.2.4. Treatment and Outcome 
During the study period, the investigator must make every effort to ensure the safety of the subjects. In the event 
of a serious adverse drug reaction, the investigator must take immediate and appropriate action to minimize the 
adverse drug reaction and may suspend the study in consultation with the sponsor. All adverse events that occurred 
during the study period, even if not related to the investigational product, must be recorded in detail in the eCRF, 
including symptoms and signs, start/end date, duration, severity, treatment and outcome, causal relationship to the 
investigational product, seriousness, etc. In addition, adverse events shall be monitored for as long as possible 
until the condition or baseline prior to administration of the investigational product is restored, or until the 
investigator can determine that the adverse events have normalized, or until further observation is deemed 
unnecessary. 
The criteria for the actions taken for the investigational product, the outcome of the adverse event, and the 
treatment of the adverse event are classified as follows. 
1) 
Actions for the Investigational Product 
① Drug withdrawn 
② Dose reduced 
③ Dose increased 
④ Dose not changed 
⑤ Unknown 
⑥ Not applicable 
2) 
Outcome of Adverse Event 
① Recovered/resolved 
② Recovering/resolving 
③ Not recovered/not resolved/ongoing 
④ Recovered/resolved with sequelae 
⑤ Fatal 
⑥ Unknown 
3) 
Actions for Adverse Event 
① Drug treatment 
② Non-drug treatment 
③ Drug and non-drug treatment 
④ No treatment performed 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 58 of 59 
 
 
10.5.2.1 
Reporting of Adverse Events 
The investigator will inform subjects (or their representatives) of any adverse events that may occur during the 
study period and instruct them to report any symptoms that occur during the study period. For adverse events that 
occur during the study period, the investigator shall record in the eCRF the type, start and end date, severity, 
treatment and outcome, and causal relationship to the investigational product. In addition, the adverse event should 
be followed up until its termination (disappearance of the adverse event, lost to follow-up, etc). 
10.5.2.2 
Expedited Reporting 
The investigator must report all serious adverse events that occur during the study period to the sponsor (or the 
sponsor’s designee) by e-mail or fax immediately or within one business day of becoming aware of them, 
regardless of their relationship to the investigational product. The investigator must also report to the IRB of each 
study site’s within the specified reporting period. 
If possible, all information on the serious adverse event form should be included in the initial report. The 
completed form should be sent to the sponsor and entered on the adverse event page of the eCRF. 
Upon receipt of the initial report, the sponsor (or the sponsor’s designee) and the IRB must review the information 
and request additional information from study personnel as appropriate. After reviewing the adverse event 
information, the causal relationship to the investigational product will be investigated. 
If necessary, a follow-up report with any new information about the serious adverse event should be completed 
on the serious adverse event form and sent to the sponsor. 
The sponsor must report serious and unexpected adverse drug reactions to the investigator, the Minister of Food 
and Drug Safety, and, if required, to the IRB within the following time limits. 
 
Death or life-threatening events: Within 7 days from the date the sponsor receives the report or becomes 
aware of the event. However, if not all information has been reported according to the adverse drug 
reaction report in the Annex Form No. 77, such as name of the adverse drug reaction, final observation 
result, summary of the adverse drug reaction, etc., an additional report with detailed information on the 
adverse drug reaction must be submitted within 15 days from the date on which the sponsor first received 
the report or became aware of the adverse drug reaction. 
 
For all other serious and unexpected adverse drug reactions, within 15 days from the date the sponsor 
receives the report or becomes aware of the case. 
Contact information for reporting serious adverse events can be found in Attachment 6. 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 59 of 60 
 
 
10.5.2.3 
Duties of the Study Personnel in the Event of Serious Adverse Drug Reaction 
During this study, the principal investigator and study personnel must make every effort to ensure the safety of 
the subjects and take immediate and appropriate measures to minimize adverse events. If a “serious adverse drug 
reaction” occurs during the study, each study personnel shall have the following duties. 
1) 
Duties of the principal investigator 
If a serious adverse drug reaction occurs during the study, the principal investigator must report it to the sponsor 
within 24 hours of becoming aware of it, or no later than the next working day, and to the IRB within the specified 
deadline so that a decision can be made as to whether the study should be continued or discontinued. In addition, 
the principal investigator must inform the subjects and take appropriate measures to minimize the adverse reaction. 
2) 
Duties of the study personnel 
If a serious adverse drug reaction occurs during the study, the study personnel must report it immediately to the 
principal investigator and the sponsor. 
3) 
Duties of the Institutional Review Board 
If a serious adverse drug reaction occurs during the study, the IRB must review the severity and causality of the 
adverse reaction and take the necessary measures, such as instructing the principal investigator to suspend all or 
part of the study. 
4) 
Duties of the sponsor 
If the sponsor receives a report of a serious and unexpected adverse drug reaction from the principal investigator 
or study personnel, the sponsor must include a summary of the adverse drug reaction, such as the adverse drug 
reaction report (Council for International Organizations of Medical Sciences form, CIOMS-I), submit it to the 
Minister of Food and Drug Safety, and immediately notify the institution of the case in accordance with the 
corresponding IRB regulations. 
Serious adverse events will be followed and reported, including those that occur during the study period. The 
investigator will follow subjects until all serious adverse events have resolved or have been confirmed to persist 
in a semi-permanent state. 
10.5.3 
Follow-up of Adverse Events 
Collected adverse events will be monitored until completion of the scheduled administration and all visit 
procedures. However, if new adverse events occur or if persistent adverse events are not resolved at the final visit, 
follow-up will continue until possible resolution has occurred or until the investigator determines that further 
follow-up is futile. The subject will be considered to have completed the study at the end of follow-up. 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 60 of 61 
 
 
10.5.4 
Pregnancy 
Women of childbearing potential may only participate in this study if a pregnancy test confirms a negative result. 
Subjects must use adequate contraception during the study period and for 14 days after the end of the 
administration of the investigational product. Contraceptive methods allowed in this study are as follows. 
* Contraceptive methods: Use of at least one barrier method (e.g., implants, injections, oral contraceptives, 
intrauterine devices (IUDs)) in combination with hormonal IUDs, absolute abstinence, or vasectomy 
(subjects must consent to the use of at least two contraceptive methods). 
If pregnancy is confirmed during the study, this is not considered a serious adverse event or adverse drug reaction. 
However, the subject must be withdrawn from the study, and the progress of the pregnant woman and fetus should 
be followed and reported. 
The investigator must complete and submit an initial pregnancy report to the sponsor (or the sponsor’s designee) 
within 24 hours or by the next business day after becoming aware of the pregnancy. The investigator must track 
and document the progress and outcome of all pregnancies to the maximum extent possible, even if the subject 
withdraws consent or discontinues the study. In addition, the investigator must complete and submit a pregnancy 
follow-up report to the sponsor (or the sponsor’s designee) within 24 hours or by the next business day of 
becoming aware of the pregnancy outcome. In addition, if consent is obtained, the newborn will be followed up 
until 28 days after birth. 
10.6 
PK Assessment 
10.6.1 
Assessment Methods for PK Parameters and MIC 
1) 
PK parameters include Cmax, AUClast, Tmax (hr), T1/2 (hr), and CL and will be analyzed with samples collected 
at the time points specified in Section 10.1.13. PK analysis will be performed at a designated analysis 
institution according to a separate PK analysis plan. 
2) 
Evaluation of the MIC of vancomycin will be performed at screening and when deemed necessary by the 
investigator. The analysis will be performed at the study site. In addition, MICBMD analysis can be performed 
at a designated laboratory by transferring samples when necessary. Evaluation of the MIC of LCB01-0371 
will be performed at the time points specified in Section 10.1.11 when feasible, and the analysis will be 
performed separately at a designated analysis institution. 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 61 of 62 
 
 
11 
Data Analysis and Statistical Considerations 
11.1 
Analysis Sets 
1) 
Safety Set (SS) 
The SS will include all subjects who have received at least one dose of the study drug. For the safety analyses, 
subjects will be analyzed based on the treatment group to which they are actually administered. 
2) 
Efficacy Analysis Set 
The efficacy assessment will use the full analysis set (FAS) as the main analysis set, while the per protocol set 
(PPS) will be additionally analyzed as a subset. 
FAS (Full analysis set) 
The FAS will include subjects who have received at least one dose of the investigational product after 
randomization and for whom at least one efficacy assessment result is available. In addition, subjects who violate 
the inclusion/exclusion criteria will be excluded from the FAS analysis. 
PPS (Per Protocol Set) 
The PPS consists of subjects from the FAS who completed the study without any major protocol deviations. 
Major protocol deviations include violation of the inclusion/exclusion criteria and administration of prohibited 
medications during the study period, treatment compliance < 80%, etc. Subjects with other major protocol 
deviations will be determined by case review (or blind data review). 
11.2 
Statistical Analysis Method 
11.2.1 
General Principles of Result Analysis 
The efficacy evaluation analysis will be performed based on the “Full Analysis Set (FAS)” and the “Per Protocol 
Set (PPS)”, and the safety data will be analyzed using the Safety Set. 
All statistical analyses will be performed using SAS® version 9.4 (or higher) and will be based on a two-sided test 
with a significance level of 5% when a significance test is required. If missing values occur at any time point, they 
will be treated as missing without imputation. 
11.2.2 
Demographic Data, Medical History, and Medication History 
For subject demographic information (age, gender, etc.) and baseline characteristics in the safety set, continuous 
variables will be presented with descriptive statistics (number of subjects, mean, standard deviation, median, 
minimum, maximum), and categorical variables will be presented with frequencies and percentages. 
All collected medical history information will be standardized into SOC and PT using the latest version of 
MedDRA and frequencies, percentages, and number of cases by SOC and PT will be presented for the safety set. 
All collected information on medication history will be standardized using the latest version of the Anatomical 
Therapeutic Chemical code (ATC code), and the number of subjects and the incidence and number of cases of 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 62 of 63 
 
 
medication use will be presented based on the Anatomical Main Group (Level 1) and Therapeutic Subgroup (Level 
2). 
11.2.3 
Analysis of Efficacy Endpoints 
The efficacy evaluation analysis will be performed based on the “Full Analysis Set (FAS)” and the “Per Protocol 
Set (PPS)”, and the FAS will be the primary analysis set. The time points for the assessment of the efficacy 
variables will be based on the time of blood collection for the blood cultures. 
11.2.3.1. Primary Efficacy Endpoint 
Proportion (%) of subjects with overall cure on Day 14 of treatment (composite response rate): Overall cure is 
defined as the disappearance of infection symptoms present at study enrollment, no new infections and/or 
secondary infections caused by MRSA (clinical improvement), and two consecutive negative MRSA blood 
cultures (clearance of MRSA bacteremia)a. 
a. 
If the first blood culture result is negative, a subsequent test will be performed within 3 days, and clearance 
of MRSA bacteremia is established when two consecutive negative results are confirmed. 
The number and percentage of subjects with overall cure within Day 14 of treatment will be presented with the 
corresponding two-sided 95% confidence intervals by time point and treatment group. Differences in proportions 
between groups will be tested using the chi-square test or Fisher’s exact test. 
11.2.3.2. Secondary Efficacy Endpoints 
1) 
Proportion (%) of subjects with overall cure by the EOT visit (composite response rate) 
The number and percentage of subjects with overall cure by the EOT visit will be presented with the 
corresponding two-sided 95% confidence intervals by time point and treatment group. Differences in 
proportions between groups will be tested using the chi-square test or Fisher’s exact test. 
2) 
Mortality (%) due to MRSA bacteremia during the treatment period with the investigational product 
The number and percentage of subjects who died during the treatment period with the investigational product 
will be presented with the corresponding two-sided 95% confidence intervals for each treatment group. 
Differences in proportions between groups will be tested using the chi-square test or Fisher’s exact test. 
3) 
Relapse rate of MRSA bacteremia: Proportion (%) of subjects with relapse MRSA bacteremia after two 
consecutive negative MRSA test results and prior to the TOC visit 
The number and percentage of subjects with relapse MRSA bacteremia after two consecutive negative MRSA 
test results and up to the TOC visit will be presented with the corresponding two-sided 95% confidence 
intervals for each treatment group. Differences in proportions between groups will be tested using the chi-
square test or Fisher’s exact test. 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 63 of 64 
 
 
4) 
Proportion of subjects with two consecutive negative MRSA blood culture results on Day 3, Day 5, Day 7, 
Day 14 and at the EOT visit (clearance of MRSA bacteremia on Day 3, Day 5, Day 7, Day 14 and at the EOT 
visit) 
The number and percentage of subjects with clearance of MRSA bacteremia on Day 3, Day 5, Day 7, Day 
14 and at the EOT visit will be presented with the corresponding two-sided 95% confidence intervals by time 
point and treatment group. Differences in proportions between groups will be tested using the chi-square test 
or Fisher’s exact test. 
5) 
Proportion (%) of subjects with persistent MRSA bacteremia based on blood culture results on Day 3, Day 
5, Day 7, and Day 14. 
The number and percentage of subjects with persistent MRSA-positive results in blood culture tests from the 
time of first MRSA positivity before randomization to each subsequent time point (Day 3, Day 5, Day 7, Day 
14) will be presented with the corresponding two-sided 95% confidence intervals by time point and treatment 
group. Differences in proportions between groups will be tested using the chi-square test or Fisher’s exact 
test. 
6) 
Time to clearance of MRSA bacteremia (in days) 
If the first negative blood culture result is confirmed, another test will be performed within 3 days. Clearance 
of MRSA bacteremia is confirmed by two consecutive negative results. The time to clearance of MRSA 
bacteremia is defined as the period (in days) from the date of the first MRSA-positive blood culture before 
randomization to the date of the first confirmed negative result in the blood culture. 
<Handling of the data for survival variables> 
① Time to clearance of MRSA bacteremia 
Status = 1 (event), if clearance of MRSA bacteremia 
0 (censored), if no clearance of MRSA bacteremia 
② Duration (days) = [(date of assessment of event/censored) – (date of first documented positive of 
MRSA before randomization) + 1] 
The clearance of MRSA bacteremia is defined as an event, and the evaluation date is the date on which the 
first clearance of MRSA bacteremia is confirmed. In addition, subjects in whom MRSA bacteremia does not 
resolve and who are withdrawn from the study or lost to follow-up will be censored, and the evaluation date 
will be the date of withdrawal or the end of the study. 
After testing the proportional hazards assumption for differences between groups, the log-rank test will be 
performed if the assumption is met. If the proportional hazards assumption is not met, the generalized 
Wilcoxon test (Gehan test) will be performed using different weights from the weighted log-rank test family. 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 64 of 65 
 
 
The proportional hazards assumption will be tested using time-dependent log(-log S(t)) plots and a residual 
analysis (Cox-Snell method). Survival curves and medians with corresponding two-sided 95% confidence 
intervals for each group will be presented using the Kaplan-Meier method, and estimates of hazard ratios 
with two-sided 95% confidence intervals will be provided using a Cox regression model with the treatment 
group as a covariate. 
11.2.4 
Analysis of Safety Endpoints 
The efficacy analyses will be summarized and presented for the safety set. 
1) 
Adverse events 
The summary and analysis of adverse events will be performed for treatment-emergent adverse events (TEAEs). 
TEAEs are adverse events that were not present before administration of the investigational product but occurred 
after administration or adverse events that were present at baseline but worsened in severity after administration 
of the investigational product. The occurrence of treatment-emergent adverse events (TEAEs), adverse drug 
reactions (ADRs), serious adverse events (SAEs), and serious adverse drug reactions (SADRs) will be presented 
with the number and percentage (%) of subjects, number of occurrences, and the two-sided 95% confidence 
intervals for the percentages. In addition, AEs will be categorized and summarized as those related to the 
investigational product and those not related to the investigational product (such as concomitant medications and 
therapies, MRSA bacteremia, underlying diseases other than MRSA, none, unknown, or other related AEs). All 
TEAEs will be coded by SOC and PT based on the latest version of MedDRA, and their severity will be graded 
according to NCI-CTCAE v5.0. In addition, the number of subjects, incidence, number of cases will be presented 
for each code. 
2) 
Mortality due to exacerbation of MRSA bacteremia at the time of the TOC visit (4 weeks after EOT) 
after starting treatment with the investigational product 
The number and percentage of subjects who die due to exacerbation of MRSA bacteremia from the start of 
treatment with the investigational product to the TOC visit will be presented with the corresponding two-sided 
95% confidence intervals for each treatment group. Differences in proportions between groups will be tested 
using the chi-square test or Fisher’s exact test. 
3) 
Incidence of thrombocytopenia 
The number and percentage of subjects who experience thrombocytopenia after administration of the 
investigational product will be presented with the corresponding two-sided 95% confidence intervals for each 
treatment group. Differences in proportions between groups will be tested using the chi-square test or Fisher’s 
exact test. 
4) 
Abnormal changes in vital signs, electrocardiogram (ECG), laboratory tests, and physical examination 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 65 of 66 
 
 
For continuous data such as vital signs, electrocardiogram, and laboratory tests (hematology and blood chemistry), 
descriptive statistics (number of subjects, mean, standard deviation, median, minimum, maximum) will be 
presented for the measured value and the change from baseline at each visit. The results of laboratory tests and 
ECGs classified as normal, non-clinically significant (NCS) abnormal, or clinically significant (CS) abnormal will 
be summarized for subjects who exhibit CS abnormal results after treatment with the investigational product. 
Subjects who are classified as normal or NCS abnormal before administration of the investigational product but 
change to CS abnormal after administration of the investigational product will be listed separately. Subjects with 
abnormal CS findings on physical examination will also be listed. 
11.2.5 
Assessment of PK Parameters and MIC 
1) 
PK assessment will be analyzed by a separate institution and summarized descriptively based on the data 
structure. The report on the results of the PK assessment can be presented separately from the clinical study 
report. 
2) 
For MIC assessment, descriptive statistics (mean, standard deviation, median, minimum, and maximum) will 
be provided for MIC measurements. 
11.2.6 
Subgroup Analysis 
Subgroup analyses will be performed only for the following cases, and the detailed information will be described 
in the statistical analysis plan. 
 
Subjects who are switched to daptomycin treatment 
 
Subjects who are switched to oral antibiotics after treatment with vancomycin (including switching to 
daptomycin) 
 
Subjects who have received antiviral or antifungal medication during the study period 
11.2.7 
Safety Data Review Committee 
The Safety Data Review Committee (SDRC), composed of members independent of the sponsor and investigator, 
will review blinded safety data by treatment group to assess causality with the investigational product and other 
factors, and the adverse event analysis will be conducted based on the causality assessment results by the SDRC. 
During the study, the SDRC will be convened as needed to review the safety data on a case-by-case basis, assess 
the causality of adverse events, and evaluate the benefits and risks of the treatment. The SDRC meetings will be 
held regularly, but the frequency will be appropriately adjusted according to the recruitment rate of subjects, 
collected data, etc. Other activities and responsibilities of the Safety Monitoring Committee are specified in the 
Charter of the Safety Data Review Committee (SDRC Charter). 
11.3 
Timing of Statistical Analysis 
The final analysis of this study will be performed after the observation of all enrolled subjects is completed. 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 66 of 67 
 
 
11.4 
Rationale for Sample Size Determination 
The purpose of this study is to evaluate the efficacy and safety of LCB01-0371 in combination with vancomycin 
compared to standard vancomycin therapy. Therefore, the number of subjects required for statistical hypothesis 
testing to ensure sufficient statistical power is not calculated. The target number of subjects is 100 (50 in the study 
group, 50 in the control group) who have received the investigational product. 
 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 67 of 68 
 
 
12 
Data Management 
12.1 
Records and Access 
Source documents are defined as the results of the data collection activities and observations in the study. The 
source documents include medical records, electronic data, recorded measurements from instruments, etc., and 
may also include other records. All source documents available in this study will be recorded and retained by the 
investigator at the study institution, and only authorized personnel may access and review the source documents. 
12.2 
Data Collection 
The Electronic Data Capture (EDC) system used in this study is in compliance with 21 Code of Federal 
Regulations (CFR) Part 11. The EDC system can only be accessed if authorized, and all traces of eCRF entered, 
modified, saved, or deleted through the EDC system will be recorded. The investigator shall guarantee that the 
data entered into the eCRF by electronic signature is accurate, complete, legible, and timely. 
The eCRF generated through the EDC system will be delivered to each study site in an electronic storage medium 
upon completion of the study and retained according to the same standards as other trial master files. 
12.3 
Protection and Retention of Records 
According to the relevant regulations for record retention in clinical studies, the principal investigator must retain 
various data (including electronic documents) related to the conduct of the study, such as the protocol and records 
of the manufacture and management of investigational products, etc., under appropriate retention conditions for 
at least 3 years from the date of completion of the study (or from the date of product approval). However, the 
retention period may be extended if deemed necessary by the sponsor. 
These documents will be examined in case of an inspection by the sponsor or related regulatory authorities, and 
the investigator may not destroy any documents related to the study without written authorization from the 
sponsor. The investigator should take precautions to prevent inadvertent or premature destruction of these 
documents. 
12.4 
Data Safety Monitoring Plan 
The principal investigator must protect the subject’s information by managing the documents related to this study 
so that they cannot be disclosed. To ensure the completeness of the study data, the principal investigator will 
periodically check to see if the storage location of the source documents has changed and if unauthorized persons 
have accessed them. In addition, the principal investigator must verify that the study is proceeding according to 
the objectives of the protocol (adequacy of subject recruitment, safety and efficacy assessments in accordance 
with the protocol, proper reporting/recording of adverse events, etc.), protect subject safety, and ensure 
completeness of data by preparing case report forms based on the source documents. 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 68 of 69 
 
 
In addition, the monitor must report the safety data confirmed by this monitoring process to the investigator, who 
is in a position to make a medical judgment, and the investigator makes the final decision on recommendations 
resulting from this data safety monitoring: 
 
Recommendations to continue or discontinue the study 
 
Recommendations on subject recruitment/selection/retention and management, improving adherence to 
the protocol, and data management and quality control procedures to ensure the integrity of the study 
 
Evaluation of information on risks that exceed the benefits of the investigational product or on adverse 
events, suboptimal effects for recommendation of methods to reduce risks such as adverse events 
 
Review data completeness etc., by obtaining monitoring results related to protocol deviations and study 
withdrawals as they occur 
 
 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 69 of 70 
 
 
13 
Ethics Considerations and Administrative Procedures 
13.1 
Compliance with Regulations and Ethics (KGCP) 
This study will be conducted ethically and scientifically in accordance with the Korean Good Clinical Practice 
(KGCP) and all relevant regulations. In addition, based on the Helsinki Declaration, the study will respect human 
dignity and rights and will not cause any disadvantage to the subjects. 
13.2 
Institutional Review Board (IRB) 
Prior to the start of the study, the investigator must obtain written approval from the IRB for the study protocol, 
informed consent form, subject recruitment materials and procedures, and subject information sheets. 
The IRB of each study site shall review the ethical, scientific, and medical validity of the study and communicates 
its decisions in writing to the principal investigator and the sponsor prior to the start of the study. 
The principal investigator will report to the IRB on the progress of the study and any SAEs, life-threatening issues, 
or deaths and must inform the IRB at the end of the study. 
13.3 
Informed Consent Process 
In conducting this study, the investigator must obtain written informed consent from the subject (or the subject’s 
representative) after adequately informing the subject of the content and procedures of the study, the effects of the 
investigational product, and the possible adverse events. The written informed consent must be obtained prior to 
all other study procedures. The investigator must provide the subject (or the subject’s representative) with a copy 
of the signed informed consent form and a copy of the subject information sheet, and the original must be retained 
in the investigator’s file. 
See Attachment 4. Subject Information Sheet and Informed Consent Form. 
The principal investigator or study personnel must never coerce participation or exert undue influence, and the 
informed consent form and study-related information (including both verbal and written information) must not 
contain any content that restricts or could restrict the rights of the subject or the subject’s representative, or any 
content that relieves or could relieve the investigator, study site, sponsor, or sponsor’s representative from 
responsibility. 
In addition, simple terms that can be understood by the subject, the subject’s representative, or witnesses must be 
used. 
Prior to obtaining informed consent from the subject, the principal investigator or his/her designee shall give the 
subject or his/her representative sufficient time and opportunity to ask questions about the details of the study and 
to decide whether the subject wishes to participate in the study, and will honestly answer any questions the subject 
or his/her representative may have about the study. 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 70 of 71 
 
 
If the subject or the subject’s representative is unable to read the informed consent form, the subject information 
sheet or other documented information, a witness must be present throughout the informed consent process. In 
this case, the principal investigator or his/her designee must read and explain the consent form, subject information 
sheet, and other documented information to the subject or his/her representative, and the subject or his/her 
representative must verbally consent to participate in the study and, if possible, personally sign and date the 
consent form. The witness must personally sign and date the consent form. Before signing the consent form, the 
witness must confirm the following: 
 
Whether the consent form, subject information sheet, and other documented information were 
accurately explained to the subject or the subject’s representative 
 
Whether the subject or the subject’s representative understood the information 
 
Whether the consent process was conducted according to the free will of the subject or the subject’s 
representative 
By signing the informed consent form, the subjects agree to participate in the study and to the collection and use 
of their personal information in connection with the study. The personal information collected in connection with 
the study will include personal identification data (name, contact information, etc.), demographic data, medical 
records (medical history, treatment history, etc.), and test results performed in connection with the study. All data 
collected will be handled in accordance with the laws, rules, and regulations on the protection of personal data. 
13.4 
Measures to Protect the Safety of Subjects 
The IRB shall evaluate/approve this protocol in accordance with Good Clinical Practice (GCP) and will 
periodically review the protocol compliance of the study. The study personnel and participating investigator will 
thoroughly analyze and familiarize themselves with the protocol. The principal investigator will take preparatory 
measures, such as sufficient preparation for unexpected adverse events, necessary reporting, adequate training of 
the investigator, and conduct of the study according to GCP standards. 
13.4.1 Measures in the Event of Adverse Events 
If adverse events occur due to this study despite the investigator conducting the study in strict compliance with 
all relevant laws and regulations and following the protocol and various related literature, recommendations, and 
suggestions of the sponsor, the investigator must immediately initiate the necessary examinations and treatment. 
In addition, if necessary, observation should be performed until the adverse event resolves or the subject is lost to 
follow-up. 
13.4.2 Treatment and Care of Subjects after the Study 
Subjects who are withdrawn from the study can receive other appropriate treatment. Subjects who have completed 
the study will receive the most appropriate treatment as determined by the investigator. 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 71 of 72 
 
 
13.4.3 Compensation Rules 
In the event of harm caused by the investigational product, the sponsor will compensate the subject in accordance 
with the compensation rules for injured subjects. 
See Attachment 2. Subject Compensation Rule. 
13.5 
Publication of Study Results and Confidentiality of Subject Records 
All records that can identify the subject must be kept confidential. All documents related to the study, such as case 
report forms, will be recorded and classified using the subject identification code and not the subject’s name. The 
identity of the subjects will be kept confidential, even if the results of the study are published. 
The sponsor or monitors and inspectors, as well as the Ministry of Food and Drug Safety and the IRB, may access 
the subjects’ medical records to verify the information collected. However, subject information must be kept 
strictly confidential even during such reviews. 
The sponsor will fully analyze the data received from all study sites and inform the investigator of the results of 
the study by preparing a clinical study report. 
13.6 
Quality Control and Reliability Assurance 
13.6.1 
Study Site Monitoring 
Monitoring of the study will be conducted to protect the rights and welfare of the subjects and to ensure that the 
data reported in the study are accurate, complete, and verifiable against the source documents and that the study 
is conducted in compliance with the approved protocol, the KGCP, and relevant regulations. The study will be 
monitored through regular visits and contacts with the study site by the sponsor (the sponsor’s designee) or a 
monitor. These visit schedules should be appropriately discussed and distributed between the investigator and the 
monitor. Basically, the monitor must review the source documents, management records of the investigational 
product, document retention status, etc., and examine the overall progress of the study. In addition, any issues 
found must be discussed with the investigator, and the investigator must cooperate in this process. 
13.6.2 
Audit 
The sponsor may conduct audits during or after the study to ensure the reliability of the study. The audit will 
include checking whether this study is conducted in compliance with the relevant regulations such as the protocol, 
standard operating procedures, KGCP, etc., and review of all source data, drug history, medical history, etc. The 
sponsor (the sponsor’s designee) may request access to the source documents and other trial master files for the 
audit of the study site, and the investigator must allow it and cooperate in this process. 
13.6.3 
Inspection 
The Ministry of Food and Drug Safety may conduct inspections during or after the study. If inspections are 
scheduled, the investigator must inform the sponsor immediately. The Ministry of Food and Drug Safety may 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 72 of 73 
 
 
request access to source documents and other trial master files for the inspection of the study site, and the 
investigator must allow it and cooperate with this process. 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 73 of 74 
 
 
14 
Sponsor Information and Name and Title of the Principal Investigator 
14.1 
Sponsor Information 
Sponsor: LegoChem Biosciences, Inc. 
CEO: Yong Joo Kim 
Address: 8-26, Munpyeongseo-ro, Daedeok-gu, Daejeon, Republic of Korea 
14.2 
Name and Title of the Principal Investigator 
 
See Attachment 3. List of Study Sites and Investigators for the names and positions of the principal investigator 
of each study site. 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 74 of 75 
 
 
15 
Other Requirements for Safe and Scientific Conduct of the Study 
15.1 
Protocol Amendment 
If the approval of the study is to be obtained or if the approved study has been modified, IRB approval must be 
obtained for the amended study protocol and, if required, approval must also be obtained from the Minister of 
Food and Drug Safety. 
 
 
 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 75 of 76 
 
 
16 
References 
1. 
Choo, EJ, Antimicrobial therapy for methicillin-resistant Staphylococcus aureus, J Korean Med Assoc. 2018 
Mar; 61(3): 207-213 
2. 
Lee YJ, et al. Risk factors associated with complicated methicillin-resistant Staphylococcus aureus 
bacteremia in neonates. Korean J Pediatr. 2010; 53(2):173-177 
3. 
Press release of the 86th National Policy Coordination Meeting [National Antibiotic Resistance Management 
Plan (2016-2020)] 
4. 
Joon Young Song, Woo Ju Kim, Antibiotic Treatment of Multidrug-Resistant Gram-Positive Bacteria 
Infections, The Korean Journal of Internal Medicine 2006;71(2) 
5. 
Holubar M. et al. Bacteremia due to Methicillin-Resistant Staphylococcus aureus New Therapeutic 
Approaches. Infect Dis Clin North Am. 2016 Jun; 30(20): 491-507 
6. 
Ortwine JK. et al. Morbidity, mortality, and management of methicillin-resistant S. aureus bacteremia in the 
USA: update on antibacterial choices and understanding. Hosp Pract. 2018 Apr; 46(2): 64-7 
7. 
Yoon YK, et al. Fatal Peripheral Septic Thrombophlebitis Complicated with Infective Endocarditis due to 
Methicillin-resistant Staphylococcus aureus: A Case Report with Autopsy Findings. Infect Chemother. 2010 
Aug; 42(4): 249-252 
8. 
Liu C. et al. Clinical Practice Guidelines by the InfectiousDiseases Society of America for the Treatment of 
Methicillin-Resistant Staphylococcus aureus Infections in Adults and Children. Clin Infect Dis. 2011 Feb; 
52(3): e18-55 
9. 
Paiva JA. et al. Treatment of severe MRSA infections: current practice and further development. Intensive 
Care Med. 2017 Feb; 43(2): 233-236 
10. Nguyen HM. et al. Limitations of antibiotic options for invasive infections caused by methicillin-resistant 
Staphylococcus aureus: is combination therapy the answer? J Antimicrob Chemother. 2010 Jan; 65(1): 24-
36 
11. Tong SYC. Et al. CAMERA2 – combination antibiotic therapy for methicillin-resistant Staphylococcus 
aureus infection: study protocol for a randomised controlled trial. Trials. 2016 Mar 31; 17: 170 
12. Howden B. et al. The evolution of vancomycin intermediate Staphylococcus aureus (VISA) and 
heterogenous-VISA. Infect Genet Evol. 2015 Jan; 21: 575-582 
13. Foweler VG. et al. Daptomycin versus Standard Therapy for Bacteremia and Endocarditis Caused by 
Staphylococcus aureus. N Engl J Med. 2006 Aug; 255(7): 6530665 
14. Vardakas, et al. Meta-analysis of rando-mized controlled trials of vancomycin for the treatment of patients 
with gram-positive infectins: Focus on the Study Design. Mayo Clin Proc. 2012 Apr; 87(4): 349-363 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 76 of 77 
 
 
15. Deresinski S. Vancomycin in Combination with Other Antibiotics for the Treatment of Serious Methicillin-
Resistant Staphylococcus aureus Infections. Clin Infect Dis. 2009 Oct; 49(7): 1072-1079 
16. Tong SY. et al. Effect of Vancomycin or Daptomycin With vs Without an Antistaphylococcal β-Lactam on 
Mortality, Bacteremia, Relapse, or Treatment Failure in Patients With MRSA Bacteremia. JAMA. 2020 Feb; 
323(6): 527-537 
17. LCB01-0371 (Delpazolid) Investigator’s Brochure v9.0 (02JUL2020) 
18. Hyeon Hui Lee, Soo No Lee, Jin Hwan Kwak. Resistance Mechanism of Enterococcus faecalis to LCB01-
0371, a New Oxazolidinone. Journal of the Korean Academy of community Pharmacy. 2014; 58(1) 7-11 
19. Pillai SK. et al. Linezolid Resistance in Staphylococcus aureus: Characterization and Stability of Resistant 
Phenotype. J Infect Dis. 2002 Dec; 186(11): 1603-1607 
20. Rybak MJ. et al. Therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus 
aureus infections: A revised consensus guideline and review by the American Society of Health-System 
Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the 
Society of Infectious Diseases Pharmacists. Am J Health-Syst Pharm. 2020 Jun; 77: 835-864 
21. Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing: 
27th informational supplement, M100-S27. Wayne (PA): Clinical and Laboratory Standards Institute, 2017 
22. NCI CTCAE version 5.0. 
https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_
5x7.pdf 
 
 
 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 77 of 78 
 
 
17 
Appendices 
 
 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 78 of 79 
 
 
Appendix 1 Precautions for Use of Vancomycin 
1. Do not administer to the following patients: 
1) 
Patients with a history of shock to vancomycin 
2) 
Patients with a history of hypersensitivity to vancomycin, peptide antibiotics, or aminoglycosides 
2. Vancomycin should be administered carefully to the following patients: 
1) 
In principle, vancomycin should not be administered to patients with hearing loss or hearing loss caused 
by peptide antibiotics and aminoglycoside antibiotics. However, if administration is unavoidable, it 
should be done with caution. 
2) 
Patients with renal impairment such as acute urinary retention (administer with caution while monitoring 
blood concentrations as excretion is delayed and accumulation occurs). 
3) 
Patients with hepatic impairment (vancomycin may cause or exacerbate hepatic impairment). 
4) 
Elderly 
5) 
Premature infants, neonates 
6) 
Patients with vestibular and cochlear damage 
3. Adverse events 
1) 
Psychiatric and nervous system: Shock and anaphylactoid reactions may occur in rare cases. Therefore, 
observe carefully and discontinue administration and take appropriate action if adverse reactions occur. 
2) 
Digestive system: Rarely, red stools, diarrhea, nausea, vomiting, and abdominal pain may occur. 
3) 
Blood system: Occasionally, decreased red blood cells, decreased white blood cells, decreased platelets, 
and increased eosinophils may occur. Reversible neutropenia has been reported, which recovered 
immediately after discontinuation of the drug. In addition, reversible agranulocytosis (granulocyte count 
≤ 500/mm3) has been reported in rare cases, although causality has not been established. 
4) 
Central nervous system: Disorders of the 8th cranial nerve such as dizziness, tinnitus, and reduced 
hearing may occur rarely. Therefore, monitor the patient carefully including conducting hearing tests. If 
these symptoms occur, it is generally recommended to discontinue the administration, but caution is 
advised if administration must continue. Hearing loss has been reported in patients with renal impairment, 
a history of hearing loss, or concomitant administration of other ototoxic drugs in conjunction with 
vancomycin. 
5) 
Liver: Elevated bilirubin, AST, ALT, and ALP, and rarely elevated LDH, γ-GTP, and LAP may occur. 
Therefore, conduct regular tests, observe carefully and discontinue the administration or take appropriate 
action if adverse reactions occur. 
6) 
Kidney: Renal failure, including elevated BUN and creatinine may occur. Therefore, perform regular 
tests and observe the patient carefully. If adverse reactions occur, it is generally recommended to 
discontinue the administration, but caution is advised if administration must continue. In addition, 
interstitial nephritis has been reported rarely in patients receiving concomitant aminoglycoside 
antibiotics and in patients with a history of renal impairment. Azotemia was resolved upon 
discontinuation of vancomycin treatment. 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 79 of 80 
 
 
7) 
Skin: Exfoliative dermatitis, bullous dermatitis, Stevens-Johnson syndrome, and toxic epidermal 
necrolysis may occur. 
8) 
Hypersensitivity: Rash, erythema, facial flushing, hypotension, wheezing, dyspnea, urticaria, and 
pruritus may occur; if these symptoms occur, take appropriate action. In addition, a rapid infusion can 
also cause red man syndrome (erythematous flushing of the skin on the neck, shoulders, and upper body) 
or pain and muscle spasm of the chest and back. These reactions usually resolve within 20 minutes but 
may persist for several hours. In animal studies, hypotension and bradycardia occurred in animals 
receiving a rapid, high-dose intravenous infusion. Such reactions are infrequent if vancomycin is given 
by a slow infusion over 60 minutes. In studies of healthy volunteers, infusion-related reactions did not 
occur when vancomycin was administered at a rate of 10 mg/min or less. 
9) 
Other: Occasionally fever, vascular access pain, and phlebitis may occur, and rarely nausea, chills, and 
vasculitis may occur. In addition, pseudomembranous colitis caused by Clostridium difficile has been 
rarely reported in patients receiving vancomycin intravenously. 
10) Based on the analysis and evaluation of adverse reaction reports in Korea, the following adverse 
reactions are added. 
 
Skin: Maculopapular rash, purpura (purpuric rash), vesicular rash 
 
Hepatobiliary system: Jaundice 
 
Injection site: Rash 
11) Based on the analysis of the data from the post-marketing adverse reaction reports (December 1989-
December 2018), the following new adverse reactions were identified. 
 
Genitourinary system - Renal tubular necrosis (acute tubular necrosis) 
4. Drug interactions 
1) 
Concomitant administration of vancomycin and anesthetic agents has been associated with increased 
anaphylactoid reactions, including erythema, histamine-like flushing, hypotension, wheezing, dyspnea, 
urticaria, or pruritus. These reactions can be lessened by infusing vancomycin over at least 60 minutes 
before anesthetic induction. 
2) 
Caution should be exercised in patients receiving vancomycin and concurrent and/or sequential systemic 
or topical use of other potentially, neurotoxic and/or nephrotoxic drugs, such as amphotericin B, 
aminoglycosides, bacitracin, polymyxin B, colistin, viomycin, or platinum-containing anticancer drugs 
(cisplatin, nedaplatin, etc.) as it can enhance the adverse reactions. 
3) 
International Normalized Ratio (INR) changes: Increased anticoagulant activity has been reported in 
patients receiving antibiotics, including vancomycin, concomitantly with anticoagulants. Infectious 
diseases (and associated with inflammatory processes), the patient's age and general condition are risk 
factors. Although the interaction between vancomycin and warfarin has not been established through 
clinical studies, the INR monitoring should be conducted and the dosage of the oral anticoagulant 
adjusted accordingly if necessary. This is more severe with certain types of antibiotics, particularly 
fluoroquinolones, macrolides, cyclines, cotrimoxazole, and some cephalosporins. 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 80 of 81 
 
 
5. Management of overdose 
1) 
Symptoms: Renal disorders such as acute renal failure and 8th cranial nerve disorders such as hearing 
loss may occur. 
2) 
Treatment: Supportive care is advised, with maintenance of glomerular filtration. Vancomycin is poorly 
removed by dialysis. Hemofiltration and hemoperfusion with polysulfone resin have been reported to 
result in increased vancomycin clearance. The mean lethal intravenous dose is 319 mg/kg in rats and 400 
mg/kg in mice. 
6. Precautions for storage and handling 
1) 
Vancomycin is irritating to tissue and must be given by a secure IV route of administration. Pain, 
tenderness, necrosis, etc., may occur with intramuscular (IM) injection of vancomycin or with 
inadvertent extravasation. 
2) 
IV injection of high concentrations may cause thrombophlebitis. The frequency and severity of which 
can be minimized by administering the drug slowly as a dilute solution (2.5-5 g/L) and by rotation of 
venous access sites. 
3) 
Rapid bolus administration (e.g., over several minutes) may be associated with exaggerated hypotension, 
including shock and rarely cardiac arrest. Therefore, vancomycin should be administered over a period 
of not less than 60 minutes to avoid infusion-related reactions. Stopping the infusion usually results in 
prompt cessation of these reactions. 
4) 
The safety and efficacy of administering vancomycin by the intrathecal (intralumbar or intraventricular) 
route have not been assessed. 
5) 
Vancomycin solution has a low pH and may cause chemical or physical instability when it is mixed with 
other compounds. Vancomycin should not be mixed with alkaline solutions. 
6) 
Mixtures of solutions of vancomycin and beta-lactam antibacterial drugs have been shown to be 
physically incompatible. The likelihood of precipitation increases with higher concentrations of 
vancomycin. It is recommended to adequately flush the intravenous lines between the administration of 
these antibacterial drugs. It is also recommended to dilute solutions of vancomycin to 5 mg/mL or less. 
7) 
Although intravitreal injection is not an approved route of administration for vancomycin, precipitation 
has been reported after intravitreal injection of vancomycin and ceftazidime for endophthalmitis using 
different syringes and needles. The precipitates dissolved gradually, with complete clearing of the 
vitreous cavity over two months and with improvement of visual acuity. 
8) 
The drug product should be visually inspected for particulate matter and discoloration prior to 
administration via injection. 
 
 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 81 of 82 
 
 
Appendix 2 Precautions for Use of the Study Drug 
The following adverse drug reactions were reported in six Phase 1 clinical studies of LCB01-0371 in healthy adult 
male volunteers and in one Phase 2a clinical study of LCB01-0371 in tuberculosis patients. 
Comprehensive Adverse Event and Potential Risk List (17 Jun 2022) 
Adverse Event 
Severity 
Ear and labyrinth disorders 
Ear swelling 
Mild 
Eye disorders 
Hordeolum left 
Mild 
Ocular hyperaemia 
Mild 
Visual impairment 
Mild 
Gastrointestinal disorders 
Abdominal discomfort 
Mild 
Abdominal distension 
Mild 
Abdominal pain 
Mild 
Constipation 
Mild 
Diarrhoea 
Severe 
Dyspepsia 
Moderate 
Gastric discomfort 
Mild 
Nausea 
Moderate 
Pangastritis 
Severe 
Vomiting 
Moderate 
General disorders and administration site conditions 
Asthenia 
Mild 
Feeling cold 
Mild 
Fever 
Mild 
Infusion site pain, Right arm 
Mild 
Infusion site paraesthesia, right lower arm 
Mild 
Infusion site phlebitis left arm 
Mild 
Left sided chest pain 
Mild 
Malaise 
Mild 
Vessel puncture site erythema, right 
Mild 
Injury, poisoning and procedural complications 
Laceration, right eyebrow 
Mild 
Laceration, 2nd right finger 
Mild 
Forearm bruise, left 
Mild 
Infections and infestations 
Periumbilical abscess 
Moderate 
Tuberculosis 
Death 
Investigations 
Hematology test abnormal 
Mild 
Liver function test abnormal 
Moderate 
ALT increased 
Mild 
AST increased 
Mild 
Bilirubin total increased 
Mild 
Blood bilirubin increased 
Mild 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 82 of 83 
 
 
Blood creatine phosphokinase increased 
Severe 
Creatine kinase increased 
Mild 
Neutrophil count decreased 
Severe 
Platelet count decreased 
Mild 
White blood cell count decreased 
Moderate 
White blood cells urine positive 
Mild 
Metabolism and nutrition disorders 
Decreased appetite 
Mild 
Gout 
Moderate 
Hypertriglyceridemia 
Mild 
Hyperuricemia 
Mild 
Hypoglycemia 
Mild 
Malnutrition 
Mild 
Musculoskeletal and connective tissue disorders 
Arthralgia 
Moderate 
Acne, forehead 
Mild 
Back pain 
Mild 
Musculoskeletal pain 
Mild 
Swelling of the right knee 
Mild 
Myalgia 
Mild 
Pain in extremity 
Mild 
Nervous system disorders 
Dizziness 
Moderate 
Headache 
Moderate 
Migraine 
Mild 
Tingling sense, left leg 
Mild 
Paraesthesia 
Mild 
Psychiatric disorders 
Sleep disorder 
Mild 
Insomnia 
Mild 
Renal and urinary disorders 
Urinary hesitation 
Moderate 
Respiratory, thoracic and mediastinal disorders 
Cough 
Mild 
Dyspnea 
Moderate 
Hemoptysis 
Mild 
Nasal stuffiness 
Mild 
Sore throat 
Mild 
Non-cardiac chest pain 
Mild 
Oropharyngeal pain 
Mild 
Pneumothorax 
Mild 
Rhinorrhea 
Mild 
Somnolence 
Mild 
Tracheal stenosis 
Moderate 
Skin and subcutaneous tissue disorders 
Acne 
Mild 
Eczema 
Mild 
Pruritus 
Mild 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 83 of 84 
 
 
Rash 
Mild 
Rash maculo-papular 
Mild 
Skin eruption, neck and trunk 
Mild 
Sweating 
Moderate 
Urticaria 
Mild 
Vascular disorders 
Distributive shock 
Moderate 
 
 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 84 of 85 
 
 
Appendix 3 Precautions for Use of Daptomycin 
1. Do not administer to the following patients: 
1) 
Patients history with hypersensitivity to daptomycin or any of its other components. 
2. Daptomycin should be administered carefully to the following patients: 
1) 
Patients with persisting or relapsing S. aureus bacteremia/endocarditis. 
2) 
Patients with moderate to severe renal impairment. 
3) 
Patients with symptoms or signs of peripheral neuropathy. 
4) 
Patients receiving warfarin. 
3. Adverse events 
1) 
Blood/lymphatic system: Eosinophilia, lymphadenopathy, thrombocythemia, thrombocytopenia 
2) 
Cardiovascular system: Atrial flutter, cardiac arrest 
3) 
Ear and labyrinth system: Tinnitus 
4) 
Ophthalmic system: Blurred vision 
5) 
Gastrointestinal system: Upper abdominal discomfort, gingival pain, oral hypesthesia 
6) 
Infections and infestations: Candida infection, vaginal candidiasis, fungemia, oral candidiasis, urinary 
tract fungal infection 
7) 
Investigations: Phosphorus increased, ALP increased, INR increased, abnormal liver function test, ALT 
increased, AST increased, prolonged prothrombin time 
8) 
Metabolism and nutritional system: Decreased appetite 
9) 
Musculoskeletal system: Myalgia 
10) Nervous system: Dyskinesia, paresthesia 
11) Psychiatric system: Hallucination 
12) Renal/urinary system: Proteinuria, renal failure 
13) Skin and subcutaneous tissue system: Miliaria, generalized pruritus, vesicular rash 
4. Drug interactions 
1) 
Tobramycin: In a study in which 6 healthy adult males received a single dose of daptomycin 2 mg/kg 
IV, tobramycin 1 mg/kg IV, and both in combination, the mean Cmax and AUC0-∞ of daptomycin were 
12.7% and 8.7% higher, respectively, when daptomycin was co-administered with tobramycin. Similarly, 
the mean Cmax and AUC0-∞ of tobramycin were 10.7% and 6.6% lower, respectively, when tobramycin 
was co-administered with daptomycin. However, these differences were not statistically significant. The 
interaction between daptomycin and tobramycin with a clinical dose (4 mg/kg) of daptomycin is 
unknown. Caution should be exercised when daptomycin is administered concomitantly with 
tobramycin. 
2) 
Warfarin: In 16 healthy adult subjects, administration of daptomycin 6 mg/kg every 24 hours by IV 
infusion over 30 minutes for 5 days, with co-administration of a single oral dose of warfarin (25 mg), 
had no significant effect on the pharmacokinetics of either drug and did not significantly alter the 
international normalized ratio (INR). 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 85 of 86 
 
 
3) 
Simvastatin: In subjects on a stable daily dose of simvastatin 40 mg, administration of daptomycin 4 
mg/kg IV for at least 30 minutes every 24 hours for 14 days (n=10) had no effect on plasma 
concentrations of simvastatin and was not associated with a higher incidence of adverse events, 
including skeletal myopathy, than in subjects receiving placebo once daily (n=10). 
4) 
Probenecid: Concomitant administration of probenecid (500 mg 4 times daily) and a single dose of 
daptomycin 4 mg/kg IV did not significantly alter the Cmax or AUC0-∞ of daptomycin. No dose 
adjustment is required for the concomitant administration of probenecid and daptomycin. 
5. Management of overdose 
Supportive care is required for the maintenance of glomerular filtration in case of overdose with daptomycin. 
Approximately 15% of daptomycin is cleared slowly from the body by hemodialysis over 4 hours, and 
approximately 11% of daptomycin is cleared by peritoneal dialysis over 48 hours. Use of high-flux dialysis 
membrane hemodialysis for 4 hours may increase the percentage of dose removal compared to the low-flux 
membrane. 
6. Precautions for storage and handling 
1) This drug is supplied as a sterile lyophilized powder in a single-use vial containing 500 mg or 350 mg of 
daptomycin. Before use, daptomycin should be reconstituted with 0.9% sodium chloride injection to a 
concentration of 50 mg/mL. 
① To minimize foaming, avoid vigorous agitation or shaking of the vial during or after reconstitution. 
② Remove the polypropylene flip-off cap from the glass vial to expose the central portion of the rubber 
stopper. 
③ Wipe the top of the rubber stopper with an alcohol swab or other antiseptic solution and allow to dry. 
After cleaning, do not touch the rubber stopper or allow it to touch any other surface. 
④ Slowly transfer 10 mL (7 mL for 350 mg) of 0.9% sodium chloride injection through the center of the 
rubber stopper into the daptomycin for injection vial, pointing the transfer needle toward the wall of the 
vial. It is recommended that a sterile transfer needle that is 21 gauge or smaller in diameter, or a 
needleless device is used, pointing the transfer needle toward the wall of the vial. 
⑤ Ensure that all of the daptomycin for injection powder is wetted by gently rotating the vial. 
A. Allow the wetted product to stand undisturbed for 10 minutes. 
B. Gently rotate or swirl the vial contents, as needed, to obtain a completely reconstituted solution. 
2) The drug product should be inspected visually for particulate matter prior to administration. 
3) The reconstituted daptomycin should be further diluted with 0.9% sodium chloride injection and 
administered IV for more than 30 minutes. 
4) No preservative or bacteriostatic agent is included in this product. Aseptic technique must be used in the 
preparation of final IV solution. 
5) Stability studies have shown that the reconstituted solution is physically and chemically stable for 12 
hours at 25℃ and up to 48 hours at 2-8℃. The diluted solution is stable in the infusion bag for 12 hours 
at 25℃ and up to 24 hours at 2-8℃. 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 86 of 87 
 
 
6) Since only limited data are available on the compatibility of daptomycin with other IV substances, 
additives and other medications should not be added to daptomycin single-use vials or infusion bags, or 
infused simultaneously through the same IV line. If the same IV line is used for sequential infusion of 
different drugs, the line should be flushed with a compatible intravenous solution before and after 
infusion with daptomycin. 
7) Compatible infusion solutions: 0.9% Sodium chloride injection and lactated Ringer’s injection. 
8) Daptomycin is not compatible with dextrose-containing diluents. 
9) Daptomycin should not be used in conjunction with ReadyMED® elastomeric infusion pumps. 
 


Protocol No.: LCB35-0371-21-2-01 
Version/Date: 5.0/2022-12-07 
 
 
Confidential 
Page 87 of 87 
 
18 
Attachments 
Attachment 1. Protocol Agreement 
Attachment 2. Subject Compensation Rule 
Attachment 3. List of Study Sites and Investigators 
Attachment 4. Subject Information Sheet and Informed Consent Form 
Attachment 5. Information Sheet and Informed Consent Form for Use of Pregnancy Information 
Attachment 6. Contact Information for Serious Adverse Event Reporting 

SAP_001.pdf: 
 
Statistical Analysis Plan 
 
 
Statistical Analysis Plan 
Protocol No. LCB35-0371-21-2-01 
CONFIDENTIAL 
1/30 page 
SD 0400 A v5.0/Effective Date: 15-Jan-2024 
(Ref. SOP 0400) 
 
 
STATISTICAL ANALYSIS PLAN 
Study Title 
A Multicenter, Double blinded, Randomized, Parallel design, Phase IIa Clinical trial  
to evaluate the Efficacy, Safety and Pharmacokinetics of LCB01-0371 with Vancomycin 
versus Vancomycin standard therapy in patients with Methicillin Resistance Staphylococcus 
aureus (MRSA) Bacteremia  
 
Protocol No./Version/Date 
LCB35-0371-21-2-01/5.0/07-Dec-2022 
Sponsor 
LigaChem Biosciences, Inc. 
Version No./Date 
1.1/04-Jul-2024 
 
 
Prepared by  
C&R Research 
 


 
Statistical Analysis Plan 
 
 
Statistical Analysis Plan 
Protocol No. LCB35-0371-21-2-01 
CONFIDENTIAL 
2/30 page 
SD 0400 A v5.0/Effective Date: 15-Jan-2024 
(Ref. SOP 0400) 
 
 
Signature Page 
 
C&R Research 
 
Prepared by: 
 
 
 
 
Ji Eun Park/BSPL 
 
See eTMF Signature page. 
Name/ Role 
 
Signature/Date (DD-MMM-YYYY) 
 
 
 
 
 
Reviewed by: 
 
 
 
 
Ye Eun Kwon/BSR 
 
See eTMF Signature page. 
Name/ Role 
 
Signature/Date (DD-MMM-YYYY) 
 
 
 
 
 
 
 
 
 
 
 


 
Statistical Analysis Plan 
 
 
Statistical Analysis Plan 
Protocol No. LCB35-0371-21-2-01 
CONFIDENTIAL 
3/30 page 
SD 0400 A v5.0/Effective Date: 15-Jan-2024 
(Ref. SOP 0400) 
 
 
Sponsor 
 
Approved by Sponsor: 
 
 
 
 
Seonghye Cheon/Project Manager 
 
See eTMF Signature page. 
Name/ Role 
 
Signature/Date (DD-MMM-YYYY) 
 
 
 
 
 
Yoon Hee Lee/Team Manager 
 
See eTMF Signature page. 
Name/ Role 
 
Signature/Date (DD-MMM-YYYY) 
 
 
 
 
 
 
 


 
Statistical Analysis Plan 
 
 
Statistical Analysis Plan 
Protocol No. LCB35-0371-21-2-01 
CONFIDENTIAL 
4/30 page 
SD 0400 A v5.0/Effective Date: 15-Jan-2024 
(Ref. SOP 0400) 
 
 
Version Information (Document revision history) 
Version 
Date 
Prepared by 
Revisions 
1.0 
19-Jun-2024 
Ji Eun Park 
First Version 
1.1 
04-Jul-2024 
Ji Eun Park 
- [7.1 Handling of Missing Data] Addition 
of handling of missing data for subjects 
who have taken prohibited medications 
after the EOT. 
- 
[9.2.3 
Relapse 
Rate 
of 
MRSA 
Bacteremia] Addition 
of 
verification 
methods for Day 3, Day 5, and 
Unscheduled time points. 
 


 
Statistical Analysis Plan 
 
 
Statistical Analysis Plan 
Protocol No. LCB35-0371-21-2-01 
CONFIDENTIAL 
5/30 page 
SD 0400 A v5.0/Effective Date: 15-Jan-2024 
(Ref. SOP 0400) 
 
 
Abbreviation 
Term 
Definition 
ADR 
Adverse Drug Reaction 
AE 
Adverse Event 
ATC code 
Anatomical Therapeutic Chemical code 
ARS 
All Randomized Set 
BMD 
Broth Microdilution 
BMI 
Body Mass Index 
CS 
Clinically Significant 
DC 
Discontinuation 
EOS 
End of Study 
EOT 
End of Treatment 
FAS 
Full Analysis Set 
ICH 
International Council for Harmonization 
ITT 
Intention To Treat 
MedDRA 
Medical Dictionary for Regulatory Activities 
MIC 
Minimum Inhibitory Concentration 
MRSA 
Methicillin Resistance Staphylococcus Aureus 
NCS 
Not Clinically Significant 
OC 
Observed Case 
PK 
Pharmacokinetics 
PPS 
Per Protocol Set 
PT 
Preferred Term 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SAS 
Statistical Analysis System 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
SS 
Safety Set 
TEAE 
Treatment-Emergent Adverse Events 
TOC 
Test of Cure 
 
 
 
 
 


 
Statistical Analysis Plan 
 
 
Statistical Analysis Plan 
Protocol No. LCB35-0371-21-2-01 
CONFIDENTIAL 
6/30 page 
SD 0400 A v5.0/Effective Date: 15-Jan-2024 
(Ref. SOP 0400) 
 
 
Table of Contents 
Signature Page .................................................................................................................................................. 2 
Version Information (Document revision history) ........................................................................................... 4 
Abbreviation ..................................................................................................................................................... 5 
Table of Contents .............................................................................................................................................. 6 
List of Tables ..................................................................................................................................................... 9 
List of Appendices ............................................................................................................................................ 9 
1. 
Introduction .............................................................................................................................................. 10 
2. 
Study Objectives ...................................................................................................................................... 10 
2.1 
Primary Objective ....................................................................................................................... 10 
2.2 
Secondary Objectives ................................................................................................................. 10 
3. 
Study Endpoints ....................................................................................................................................... 11 
3.1 
Efficacy Endpoints ..................................................................................................................... 11 
3.1.1 Primary Efficacy Endpoint ................................................................................................... 11 
3.1.2 Secondary Efficacy Endpoints ............................................................................................. 11 
3.2 
Safety Endpoints ......................................................................................................................... 11 
3.3 
PK Parameters ............................................................................................................................ 11 
3.4 
Other Parameters ........................................................................................................................ 12 
4. 
Study Design ............................................................................................................................................ 12 
4.1 
Summary..................................................................................................................................... 12 
4.2 
Rationale for Sample Size Determination .................................................................................. 12 
4.3 
Randomization Method .............................................................................................................. 12 
5. 
Analysis Sets ............................................................................................................................................ 12 
5.1 
Errors in the Administration of Investigational Products ............................................................ 13 
6. 
Statistical Methods ................................................................................................................................... 14 
6.1 
Analysis Program ....................................................................................................................... 14 
6.2 
General Statistical Considerations .............................................................................................. 14 
6.3 
Multicenter Study ....................................................................................................................... 14 
6.4 
Subgroup Analysis ...................................................................................................................... 14 
6.5 
Multiple Comparison or Multiplicity of the Test ........................................................................ 15 
7. 
Data Processing Methods ......................................................................................................................... 15 
7.1 
Handling of Missing Data ........................................................................................................... 15 
7.1.1 Censoring Rules ................................................................................................................... 15 
7.2 
Handling of Missing Data for Date Variables ............................................................................. 16 
7.3 
Derived or Transformed Variables .............................................................................................. 17 
7.4 
Definition of Analysis Visits ....................................................................................................... 18 


 
Statistical Analysis Plan 
 
 
Statistical Analysis Plan 
Protocol No. LCB35-0371-21-2-01 
CONFIDENTIAL 
7/30 page 
SD 0400 A v5.0/Effective Date: 15-Jan-2024 
(Ref. SOP 0400) 
 
 
7.5 
Handling of Data Errors After DB Lock ..................................................................................... 19 
8. 
Subject Information .................................................................................................................................. 19 
8.1 
Subject Disposition ..................................................................................................................... 19 
8.2 
Protocol Deviation ...................................................................................................................... 19 
8.3 
Analysis Set ................................................................................................................................ 19 
8.4 
Evaluation of Demographic Data and Baseline Characteristics ................................................. 19 
8.4.1 Demographic Data and Baseline Characteristics .................................................................. 19 
8.4.2 Medical History/Current Medical Conditions ...................................................................... 20 
8.4.3 Prior/Concomitant Medication ............................................................................................. 20 
8.4.4 Concomitant Therapy ........................................................................................................... 21 
8.5 
Treatment Compliance ................................................................................................................ 21 
9. 
Efficacy Analysis ..................................................................................................................................... 21 
9.1 
Analysis of the Primary Efficacy Endpoint ................................................................................ 21 
9.1.1 Proportion (%) of Subjects with Overall Cure on Day 14 of Treatment .............................. 21 
9.2 
Analysis of the Secondary Efficacy Endpoints ........................................................................... 22 
9.2.1 Proportion (%) of Subjects with Overall Cure by the EOT Visit ......................................... 22 
9.2.2 Mortality (%) due to MRSA Bacteremia During the Treatment Period with the Investigational 
Product ................................................................................................................................. 22 
9.2.3 Relapse Rate of MRSA Bacteremia ..................................................................................... 22 
9.2.4 Proportion of Subjects with Two Consecutive Negative MRSA Blood Culture Results on Day 3, 
Day 5, Day 7, Day 14 and at the EOT Visit ......................................................................... 23 
9.2.5 Proportion of Subjects with Persistent MRSA Bacteremia Based on Blood Culture Results on 
Day 3, Day 5, Day 7, and Day 14 ......................................................................................... 23 
9.2.6 Time to Clearance of MRSA Bacteremia (in Days) ............................................................. 24 
10. Safety Analysis ......................................................................................................................................... 25 
10.1 
Extent of Exposure ..................................................................................................................... 25 
10.2 
Adverse Events ........................................................................................................................... 25 
10.2.1 Summary of Adverse Events ................................................................................................ 26 
10.2.2 Analysis of Adverse Events .................................................................................................. 26 
10.3 
Mortality due to Exacerbation of MRSA Bacteremia at the Time of the TOC Visit (4 Weeks after 
EOT) After Starting Treatment with the Investigational Product ............................................................. 26 
10.4 
Incidence of Thrombocytopenia ................................................................................................. 27 
10.5 
Laboratory Tests ......................................................................................................................... 27 
10.6 
Vital Signs .................................................................................................................................. 28 
10.7 
12-lead ECG ............................................................................................................................... 28 
10.8 
Physical Examination ................................................................................................................. 28 


 
Statistical Analysis Plan 
 
 
Statistical Analysis Plan 
Protocol No. LCB35-0371-21-2-01 
CONFIDENTIAL 
8/30 page 
SD 0400 A v5.0/Effective Date: 15-Jan-2024 
(Ref. SOP 0400) 
 
 
10.9 
Pregnancy Test ............................................................................................................................ 28 
11. PK Analysis .............................................................................................................................................. 28 
11.1 
PK Parameters ............................................................................................................................ 28 
11.2 
Other Parameters - MIC Evaluation ........................................................................................... 28 
11.2.1 Evaluation of the MIC of Vancomycin ................................................................................. 28 
11.2.2 Evaluation of the MIC of LCB01-0371 ................................................................................ 29 
12. Interim Analysis ....................................................................................................................................... 29 
13. Changes to the Planned Analysis Methods ............................................................................................... 29 
14. SAS Program Code .................................................................................................................................. 30 
15. References ................................................................................................................................................ 30 
 
 
 


 
Statistical Analysis Plan 
 
 
Statistical Analysis Plan 
Protocol No. LCB35-0371-21-2-01 
CONFIDENTIAL 
9/30 page 
SD 0400 A v5.0/Effective Date: 15-Jan-2024 
(Ref. SOP 0400) 
 
 
List of Tables 
Table 1 Censoring Rules ....................................................................................................................................... 15 
Table 2 Handling of Missing Data for Date Variables........................................................................................... 16 
Table 3 Definition of Derived or Transformed Variables ...................................................................................... 17 
Table 4 Definition of Analysis Visits .................................................................................................................... 18 
Table 5 SAS program code ................................................................................................................................... 30 
 
 
List of Appendices 
[Appendix 1] List of TFL (Table, figure and listing) shells 
 
 


 
Statistical Analysis Plan 
 
 
Statistical Analysis Plan 
Protocol No. LCB35-0371-21-2-01 
CONFIDENTIAL 
10/30 page 
SD 0400 A v5.0/Effective Date: 15-Jan-2024 
(Ref. SOP 0400) 
 
 
1. 
Introduction 
The purpose of this Statistical Analysis Plan (SAP) is to provide detailed descriptions of the statistical analysis 
methods, data processing methods, and definitions of analysis sets for the final analysis of the study <LCB35-
0371-21-2-01, Version 5.0, A multicenter, double blinded, randomized, parallel design, phase IIa clinical trial to 
evaluate the efficacy, safety and pharmacokinetics of LCB01-0371 with vancomycin versus vancomycin standard 
therapy in patients with methicillin resistance staphylococcus aureus (MRSA) bacteremia, 07 Dec 2022> based on 
ICH E9. The format and table of contents of the tables, figures, and listings in which the analysis results are 
recorded will be developed in a separate document. 
If the analyses are performed using methods other than those described in this document, the modified methods 
and the reasons for the modifications will be detailed in the Clinical Study Report (CSR). 
 
2. 
Study Objectives 
2.1 
Primary Objective 
To compare the proportion of subjects with overall cure between LCB01-0371 plus vancomycin combination 
therapy and standard vancomycin therapy. 
 
2.2 
Secondary Objectives 
To evaluate the following efficacy parameters of LCB01-0371 plus vancomycin combination therapy in subjects 
with MRSA bacteremia: 
 
1) Proportion (%) of subjects with overall cure by the end-of-treatment (EOT) visit 
2) Mortality due to MRSA bacteremia during the treatment period with the investigational product  
3) Relapse rate of MRSA bacteremia 
4) Proportion of subjects with two consecutive negative MRSA blood culture results on Day 3, Day 5, Day 7, 
Day 14 and at the EOT visit (clearance of MRSA bacteremia at Day 3, Day 5, Day 7, Day 14, EOT) 
5) Proportion of subjects with persistent MRSA bacteremia based on blood culture results on Day 3, Day 5, Day 
7, and Day 14 
6) Time to clearance of MRSA bacteremia (in days) 
7) Safety of the combination therapy with vancomycin and LCB01-0371 
8) Pharmacokinetic (PK) profile of the combination therapy with vancomycin and LCB01-0371 
 


 
Statistical Analysis Plan 
 
 
Statistical Analysis Plan 
Protocol No. LCB35-0371-21-2-01 
CONFIDENTIAL 
11/30 page 
SD 0400 A v5.0/Effective Date: 15-Jan-2024 
(Ref. SOP 0400) 
 
 
3. 
Study Endpoints  
3.1 
Efficacy Endpoints 
3.1.1 
Primary Efficacy Endpoint 
Proportion of subjects with overall cure on Day 14 of treatment (composite response rate) 
 
3.1.2 
Secondary Efficacy Endpoints 
1) 
Proportion of subjects with overall cure by the EOT visit (composite response rate) 
2) 
Mortality due to MRSA bacteremia during the treatment period with the investigational product  
3) 
Relapse rate of MRSA bacteremia  
4) 
Proportion of subjects with two consecutive negative MRSA blood culture results on Day 3, Day 5, Day 7, 
Day 14 and at the EOT visit 
5) 
Proportion of subjects with persistent MRSA bacteremia based on blood culture results on Day 3, Day 5, Day 
7, and Day 14 
6) 
Time to clearance of MRSA bacteremia (in days) 
 
3.2 
Safety Endpoints 
1) 
Incidence and severity of treatment-emergent adverse events (TEAEs) and adverse drug reactions (ADRs) 
based on the National Cancer Institute’s Common Terminology Criteria for Adverse Events (NCI CTCAE 
v5.0) 
2) 
Mortality due to exacerbation of MRSA bacteremia at the time of the TOC visit (4 weeks (28 days) after EOT) 
after starting treatment with the investigational product 
3) 
Incidence (%) of thrombocytopenia 
4) 
Vital signs 
5) 
Electrocardiogram (ECG) 
6) 
Laboratory tests 
7) 
Abnormal changes in physical examination 
 
3.3 
PK Parameters 
1) 
Cmax  
2) 
AUClast  
3) 
Tmax (hr)  
4) 
T1/2 (hr)  
5) 
CL 


 
Statistical Analysis Plan 
 
 
Statistical Analysis Plan 
Protocol No. LCB35-0371-21-2-01 
CONFIDENTIAL 
12/30 page 
SD 0400 A v5.0/Effective Date: 15-Jan-2024 
(Ref. SOP 0400) 
 
 
 
3.4 
Other Parameters 
1) 
MICBMD 
 
4. 
Study Design 
4.1 
Summary 
This clinical study is a phase 2a, multicenter, randomized, double-blind, parallel design study to evaluate the safety 
and efficacy of combination therapy with vancomycin and LCB01-0371 compared to standard vancomycin therapy 
in subjects with MRSA bacteremia. 
 
Figure 1 Study Schema 
 
4.2 
Rationale for Sample Size Determination 
The purpose of this study is to evaluate the efficacy and safety of LCB01-0371 in combination with vancomycin 
compared to standard vancomycin therapy. Therefore, the number of subjects required for statistical hypothesis 
testing to ensure sufficient statistical power is not calculated. The target number of subjects is 100 (50 in the study 
group, 50 in the control group) who have received the investigational product. 
 
4.3 
Randomization Method 
The randomization codes for this study were generated using SAS® (Version 9.4, SAS Institute Inc., Cary, NC, 
USA) by a statistician unrelated to this study, employing the block randomization method for each study site to 
ensure a 1:1 allocation ratio between treatment groups at each study site. Subsequently, subjects who meet the 
inclusion/exclusion criteria are assigned to each treatment group in order of enrollment using the randomization 
codes via Interactive Web Response System (IWRS). 
 
5. 
Analysis Sets 
 
Enrolled Set  
The Enrolled Set consists of subjects who have signed the informed consent form.  


 
Statistical Analysis Plan 
 
 
Statistical Analysis Plan 
Protocol No. LCB35-0371-21-2-01 
CONFIDENTIAL 
13/30 page 
SD 0400 A v5.0/Effective Date: 15-Jan-2024 
(Ref. SOP 0400) 
 
 
 
 
All Randomized Set (ARS) 
The All Randomized Set (ARS) consists of subjects who were randomized into the study. 
 
 
Safety Set 
The safety set consists of all subjects who have received at least one dose of the investigational product. 
For the safety analyses, subjects will be analyzed based on the treatment group to which they are actually 
administered. 
 
 
Full Analysis Set (FAS) 
The FAS will include subjects who have received at least one dose of the investigational product after 
randomization and for whom at least one efficacy assessment result is available. In addition, subjects 
who violate the inclusion/exclusion criteria will be excluded from the FAS analysis. The FAS is analyzed 
based on the treatment group to which the subjects were randomized. 
 
 
Per-Protocol Set (PPS) 
Among the FAS, the Per-Protocol Set (PPS) includes subjects who completed the study without major 
protocol deviations. The final PPS will be determined by blind data review. Protocol deviations (PD) 
that may lead to exclusion from the analysis sets are as follows and are defined in a separate document 
(SD 0406 A. Definition of Analysis Population). 
 
 
Violation of the inclusion/exclusion criteria 
 
Administration of prohibited medication 
 
Treatment compliance < 80% 
 
Randomization errors 
 
Errors in the administration of investigational products 
 
Other major protocol deviation* 
* Protocol deviations that are not included in the PPS as indicated in the PD Specification. 
 
5.1 
Errors in the Administration of Investigational Products 
If a subject did not receive the investigational product according to the randomized treatment group, the analysis 
will be performed as follows: 
 
 
If a subject did not receive the investigational product according to the randomized treatment group for 
part of the study period, the safety assessment analysis will be performed based on the treatment group 
corresponding to the drug administered for more than 50% of the total treatment period. If no treatment 
group accounts for more than 50% of the total treatment period, the analysis will be conducted according 
to the randomized treatment group. The analysis of the efficacy assessment will be performed according 
to the randomized treatment group. 
 


 
Statistical Analysis Plan 
 
 
Statistical Analysis Plan 
Protocol No. LCB35-0371-21-2-01 
CONFIDENTIAL 
14/30 page 
SD 0400 A v5.0/Effective Date: 15-Jan-2024 
(Ref. SOP 0400) 
 
 
 
If a subject did not receive the investigational product during the entire study period according to the 
randomized treatment group, the safety assessment analysis will be performed according to the actual 
treatment group, and the efficacy assessment analysis will be performed according to the randomized 
treatment group as per the Intention To Treat (ITT) principle. 
 
6. 
Statistical Methods 
6.1 
Analysis Program 
Statistical analyses will be performed using the SAS® Enterprise Guide (version 8.2 or higher) interface with 9.4 
64bit (SAS Institute Inc., Cary, NC, USA.) or higher versions. 
 
6.2 
General Statistical Considerations 
Continuous variables are presented with the number of subjects, mean, standard deviation, median, minimum, and 
maximum, while categorical variables are presented with frequency and percentage. In principle, all tests will be 
performed with a two-sided test at a significance level of 5%, unless otherwise specified. 
 
Means and medians are presented with one significant figure more than the raw data, and standard deviations are 
presented with two significant figures more than the raw data. The minimum, maximum, MIC 50, and MIC 90 are 
presented with the same number of significant digits as the raw data. The percentages are given to two decimal 
places. However, if the number of significant digits exceeds four, they are rounded to four digits (rounded at the 
fifth decimal place). For derived variables (e.g., BMI), values up to two decimal places are treated as raw data for 
analysis. 
The p-values are presented to four decimal places (rounded at the fifth decimal place). p-values less than 0.0001 
are reported as <0.0001, and p-values greater than 0.9999 are reported as >0.9999. 
 
All data used in the statistical analysis are presented in listings, and if there are missing data imputation, both the 
original data without imputation and the imputed data are presented. 
 
6.3 
Multicenter Study 
This study does not conduct analyses by study site. 
 
6.4 
Subgroup Analysis 
According to [9. Efficacy Analysis], the following subgroup analyses will be performed for the primary and 
secondary efficacy endpoints (overall cure and time to clearance of MRSA bacteremia), which will be restricted 
to the FAS. 
 
 
Subjects who are switched to daptomycin treatment 


 
Statistical Analysis Plan 
 
 
Statistical Analysis Plan 
Protocol No. LCB35-0371-21-2-01 
CONFIDENTIAL 
15/30 page 
SD 0400 A v5.0/Effective Date: 15-Jan-2024 
(Ref. SOP 0400) 
 
 
 
Subjects who are switched to oral antibiotics after treatment with vancomycin (including switching to 
daptomycin) 
 
Administration of oral antibiotics (for MRSA) 14 days after administration of the investigational product 
 
Vancomycin high MIC (<1.5 vs >=1.5) 
 
Removal of the primary lesion 
 
Complication status (complicated vs. uncomplicated) 
 
Subjects who have received antiviral or antifungal medication during the study period 
 
6.5 
Multiple Comparison or Multiplicity of the Test 
No multiple comparisons or multiplicity of tests will be performed in this study. 
 
7. 
Data Processing Methods 
7.1 
Handling of Missing Data 
All efficacy and safety endpoints will be analyzed using the observed case (OC) method without imputing missing 
data. 
 
If a subject’s visit date for an efficacy endpoint analysis is outside the planned visit window, the measurement for 
that visit will be treated as missing. In addition, for subjects who have received a contraindicated medication after 
the EOT visit that could affect efficacy, the measurement for the TOC visit will be treated as missing in the PPS 
analysis. 
 
For laboratory tests, etc., the final visit measurement will be defined as the last measurement regardless of the 
planned visit window. 
 
7.1.1 
Censoring Rules 
To evaluate the clearance of MRSA bacteremia, the reference date for the time of occurrence of the event will 
follow [Table 1]. 
 
Table 1 Censoring Rules 
Scenario 
Date of MRSA Clearance or Censoring 
Outcome 
If two consecutive negative results 
are confirmed, with the second test 
performed within three days of the 
first negative result 
Date of the blood culture with the first negative result 
Event 
occurred 
(event) 
If two consecutive negative results 
are not confirmed 
Date of completion/withdrawal 
Censored 
Withdrawal and follow-up loss 
Date of completion/withdrawal 
Censored 
 


 
Statistical Analysis Plan 
 
 
Statistical Analysis Plan 
Protocol No. LCB35-0371-21-2-01 
CONFIDENTIAL 
16/30 page 
SD 0400 A v5.0/Effective Date: 15-Jan-2024 
(Ref. SOP 0400) 
 
 
 
7.2 
Handling of Missing Data for Date Variables 
Any missing data for date variables will be imputed as follows. 
 
Table 2 Handling of Missing Data for Date Variables 
Missing Date 
Missing 
Value 
Imputation 
Example 
1. Start date of 
prior/concomitant 
medication 
 
2. Start date of 
concomitant 
therapy 
Year-
Month-
Day 
[Year]-01-01 of the date of informed consent 
Date of informed consent: 2021-
12-05 
Date collected: UK-UK-UK 
Imputed date: 2021-01-01 
Month-
Day 
01-01 
Date collected: 2021-UK-UK 
Imputed date: 2021-01-01 
Day 
01 
Date collected: 2021-12-UK 
Imputed date: 2021-12-01 
1. End date of 
prior/concomitant 
medication 
 
2. End date of 
concomitant 
therapy 
Year-
Month-
Day 
Date of last visit 
Date of last visit: 2021-12-25 
Date collected: UK-UK-UK 
Imputed date: 2021-12-25 
Month-
Day 
12-31 
Date collected: 2021-UK-UK 
Imputed date: 2021-12-31 
Day 
Last [day] of month 
Date collected: 2021-12-UK 
Imputed date: 2021-12-31 
Onset date of 
adverse event 
Year-
Month-
Day 
Start date of the investigational product 
Start date of administration: 2021-
12-05 
Date collected: UK-UK-UK 
Imputed date: 2021-12-05 
Month-
Day 
1. If [year] is the same as the start date of the 
investigational product: Use the [month-day] of the start 
date of the investigational product. 
 
 
2. If [year] is different from the start date of the 
investigational product: 01-01 
1. Start date of administration: 
2021-12-05 
Date collected: 2021-UK-UK 
Imputed date: 2021-12-05 
 
2. Start date of administration: 
2021-12-05 
Date collected: 2022-UK-UK 
Imputed date: 2022-01-01 
Day 
1. If [year-month] is the same as the start date of the 
investigational product: Use the [day] of the start date of 
the investigational product. 
 
 
2. If [year-month] is different from the start date of the 
investigational product: Use 1. 
1. Start date of administration: 
2021-12-05 
Date collected: 2021-12-UK 
Imputed date: 2021-12-05 
 
2. Start date of administration: 
2021-12-05 
Date collected: 2022-05-UK 
Imputed date: 2022-05-01 
AE end date 
Year-
Month-
Day 
 Date of last visit 
End date of administration: 2021-
12-30 
Date collected: UK-UK-UK 
Imputed date: 2021-12-30 
Month-
Day 
1. If [Year] is the same as the date of last visit: Use the 
[month-day] of the date of last visit. 
 
2. If [Year] is different from the date of last visit: 12-31 
1. End date of administration: 
2021-12-30 
Date collected: 2021-UK-UK 
Imputed date: 2021-12-30 
 
2. End date of administration: 
2021-12-30 
Date collected: 2022-UK-UK 
Imputed date: 2022-12-31 
Day 
1. If [year-month] is the same as the date of last visit: Use 
the [day] of the date of last visit. 
1. End date of administration: 
2021-12-30 


 
Statistical Analysis Plan 
 
 
Statistical Analysis Plan 
Protocol No. LCB35-0371-21-2-01 
CONFIDENTIAL 
17/30 page 
SD 0400 A v5.0/Effective Date: 15-Jan-2024 
(Ref. SOP 0400) 
 
 
Missing Date 
Missing 
Value 
Imputation 
Example 
 
 
 
2. If [year-month] is different from the date of last visit: 
Last [day] of month 
Date collected: 2021-12-UK 
Imputed date: 2021-12-30 
 
2. End date of administration: 
2021-12-30 
Date collected: 2021-05-UK 
Imputed date: 2021-05-31 
 
7.3 
Derived or Transformed Variables 
Baseline values will be defined as the last measured values among those measured before or on the day of the first 
administration of the investigational product.  
 
Table 3 Definition of Derived or Transformed Variables 
Variable 
Method 
Change 
Post-baseline measurement – Baseline measurement 
BMI (kg/m2) 
Weight (kg)
Height (m)2 
Rounded to two decimal places (rounding at the third decimal place). 
Age group 
Age < 65 years, Age ≥ 65 years 
Duration of adverse events 
(days) 
Adverse event end date – Adverse event onset date + 1 
If the adverse event end date is ongoing, it is replaced by the ‘date of last visit’ 
and indicated with ≥ (e.g., ≥ 15). 
Time point of onset of adverse 
event (days) 
Adverse event start date – Start date of the investigational product + 1 
Switch to daptomycin treatment Defined as cases where ‘vancomycin’ was administered first and then 
‘daptomycin,’ based on the ‘Drug Name (Generic Name)’ on the CRF [Antibiotic 
Administration] page. 
Switch to oral antibiotics after 
treatment with vancomycin 
(including switching to 
daptomycin) 
Defined as cases where ‘vancomycin’ and ‘daptomycin’ were administered first 
and then ‘oral antibiotic,’ based on the ‘Drug Name (Generic Name)’ on the CRF 
[Antibiotic Administration] page. 
Administration of oral 
antibiotics (for MRSA) 14 days 
after administration of the 
investigational product 
Defined as cases in which the ‘Drug Name (Generic Name)’ on the CRF 
[Antibiotic Administration] page is an ‘oral antibiotic,’ ‘Purpose of 
Administration’ is ‘Concomitant Medication for Investigational Product,’ and the 
start date is 14 days after the first administration of the investigational product. 
Vancomycin high MIC 
Categorized as < 1.5 µg/mL or ≥ 1.5 µg/mL based on the minimum inhibitory 
concentration (MIC) at the time of screening. 
However, if the Local Lab value is higher than the Central Lab value, the Local 
Lab value will be used. 
Feasibility of primary lesion 
removal  
Defined as cases where the CRF [Primary Lesion] page indicates ‘Yes’ to the 
question ‘Is the primary lesion removable?.’ 
Removal of the primary lesion Defined as cases where the CRF [Primary Lesion] page indicates ‘Yes’ to both 
‘Is the primary lesion removable?’ and ‘Was the primary lesion removed?’ 


 
Statistical Analysis Plan 
 
 
Statistical Analysis Plan 
Protocol No. LCB35-0371-21-2-01 
CONFIDENTIAL 
18/30 page 
SD 0400 A v5.0/Effective Date: 15-Jan-2024 
(Ref. SOP 0400) 
 
 
Variable 
Method 
Presence of complication 
1) 
Defined as cases where the CRF [Past and Current Medical History] page 
records ‘Yes’ for ‘Related to MRSA Bacteremia’ and at least one of the 
following conditions is present: 
 Septic arthritis 
 Deep tissue abscess 
 Vertebral osteomyelitis 
 Epidural abscess 
 Septic thrombophlebitis 
 Psoas abscess 
 Meningitis 
 Mycotic aneurysm 
 empyema 
 pericarditis 
 pneumonia  
2) 
or cases where CRF [Primary Lesion] page indicates ‘infective 
endocarditis’ as the primary lesion.  
Antiviral or antifungal treatment 
during the study period 
Defined as cases where there is a history of antiviral or antifungal treatment. 
 
7.4 
Definition of Analysis Visits 
Subjects who discontinued the investigational product and were withdrawn from the study must conduct an end-
of-treatment (EOT) visit. If the date of the EOT visit is within the planned visit period and no results are available 
for that visit, the results of the EOT visit will be considered the results of the scheduled visit and included in the 
analysis. If results are available for the corresponding visit, the results closer to the visit planned in the protocol 
will be considered results for that visit and included in the analysis. If the absolute values of the differences in visit 
dates based on the scheduled visit are identical (e.g., -3 days, +3 days), the previously measured results (-3 days) 
will be considered results for that visit and included in the analysis. In addition, the results of unscheduled visits 
will be analyzed in the same way.  
All visit results, including unscheduled visits, will be shown in listings, regardless of whether they are within the 
allowed range of analysis visits. 
 
Analysis visits are defined as follows. However, if there are variables with different visit dates and measurement 
dates (or test dates), the analysis will be based on the measurement date (or test date). 
 
Table 4 Definition of Analysis Visits 
Analysis Visit 
Visit Day Interval 
(days) 
Visit Window (days) 
Allowed Range for Analysis Visit 
(days) 
Screening (Visit 1) 
-5 
 
 
Baseline (Visit 2) 
1 
 
 
Visit 3 
3 
 
3 ≤ Visit 3-Baseline+1 ≤ 3 
Visit 4 
5 
 
5 ≤ Visit 4-Baseline+1 ≤ 5 
Visit 5 
7 
± 1 
6 ≤ Visit 5-Baseline+1 ≤ 8 
Visit 6 
14 
± 2 
12 ≤ Visit 6-Baseline+1 ≤ 16 
End of Treatment 
- 
+ 2 
EOT/DC ≤ Date of the last dose of the 


 
Statistical Analysis Plan 
 
 
Statistical Analysis Plan 
Protocol No. LCB35-0371-21-2-01 
CONFIDENTIAL 
19/30 page 
SD 0400 A v5.0/Effective Date: 15-Jan-2024 
(Ref. SOP 0400) 
 
 
Analysis Visit 
Visit Day Interval 
(days) 
Visit Window (days) 
Allowed Range for Analysis Visit 
(days) 
(EOT)/DC 
investigational product + 2 
Test of Cure (TOC) 
28 
± 4 
24 ≤ TOC-EOT+1 ≤ 32 
 
7.5 
Handling of Data Errors After DB Lock 
If an error list is created after database (DB) lock, the related content will not be reflected in the analysis but will 
be noted in the annotations. 
 
8. 
Subject Information 
8.1 
Subject Disposition 
The frequency of the screening, screening failures, and reasons for the failure will be indicated. For subjects who 
were randomized, study completion status, reasons for withdrawal, and detailed reasons for treatment failure will 
be reported as frequencies and percentages for each treatment group and the total number. In addition, the 
frequencies of enrolled subjects per study site and subjects who were randomized, as well as the completion status 
of the study, will be reported as frequencies and percentages for each treatment group and the total number per 
study site. The analyses will be performed on the Enrolled Set or ARS, and the study participation status of subjects 
in the Enrolled Set will be presented in the listing. 
 
8.2 
Protocol Deviation 
For each major protocol deviation, frequencies, percentages, and the number of occurrences for each treatment 
group and the total number will be presented. The analyses will be performed for the ARS, and protocol deviations 
for the ARS will be presented in the listing categorized as major/minor.  
 
8.3 
Analysis Set 
For SS, FAS, and PPS, frequencies and percentages will be presented for each treatment group and the total number. 
Reasons for exclusion from each analysis set will be presented as frequencies and percentages for each treatment 
group and the total number. The analyses will be performed for the ARS, and the analysis sets of the study for the 
ARS will be presented in the listing. 
 
8.4 
Evaluation of Demographic Data and Baseline Characteristics 
8.4.1 
Demographic Data and Baseline Characteristics 
For the following evaluation items, continuous variables will be presented as number of subjects, mean, standard 
deviation, median, minimum, and maximum for each treatment group and the total number. Categorical variables 
will be presented as frequencies and percentages for each treatment group and the total number. The analyses will 
be performed on the SS, and demographic and baseline data will be presented in listings for the ARS. 
 
 
Age (years), age group (less than 65 years, 65 years or older), gender, fertility status 


 
Statistical Analysis Plan 
 
 
Statistical Analysis Plan 
Protocol No. LCB35-0371-21-2-01 
CONFIDENTIAL 
20/30 page 
SD 0400 A v5.0/Effective Date: 15-Jan-2024 
(Ref. SOP 0400) 
 
 
 
Height (cm), weight (kg), BMI (kg/m2) 
 
Classification of primary lesion, feasibility of primary lesion removal, removal of primary focus 
 
Vancomycin MIC(<1.5 ug/mL, >=1.5 ug/mL) 
 
8.4.2 
Medical History/Current Medical Conditions 
Past medical history is defined as cases where [Presence at Visit] is [No], and current medical conditions are 
defined as cases where [Presence at Visit] is [Yes]. 
For subjects with past medical history and current medical conditions, frequencies, percentages, and number of 
occurrences will be presented for each treatment group and total number of cases. They will be coded according 
to the System Organ Class (SOC) and Preferred Term (PT) of Medical Dictionary for Regulatory Activities 
(MedDRA) Latest Major Version and show frequencies, percentages, and number of occurrences by treatment 
group. For the frequency count, a subject will be counted as 1 person in each classification (subjects with a past 
medical history/current medical condition, SOC, PT), even if they have several past medical history/current 
medical conditions. 
 
The MedDRA version will be noted in the tables and listings. The analyses will be performed on the SS, and the 
medical history/concomitant disease information for the ARS will be presented in the listing. 
 
8.4.3 
Prior/Concomitant Medication 
Prior medication is defined as a medication started prior to the administration of the investigational product, and 
concomitant medication is defined as a medication started after the administration of the investigational product. 
 
Classification of prior medications 
 
 Administration start date < Start date of the investigational product  
 
Classification of concomitant medications 
 
 Administration start date ≥ Start date of the investigational product 
 
In addition, missing values in the date variables will be processed according to [7.2 Handling of Missing Data for 
Date Variables] to classify the prior/concomitant medication. 
 
For subjects with prior medications and concomitant medications, frequencies, percentages, and the number of 
occurrences for each treatment group and the total number will be presented. They will be coded according to level 
1 (anatomical main group) and preferred name of the World Health Organization Drug Dictionary (WHO-DD) 
Latest version to show frequencies, percentages, and the number of occurrences for each treatment group and the 
total number. For the frequency count, a subject will be counted as 1 person in each classification (subjects with 


 
Statistical Analysis Plan 
 
 
Statistical Analysis Plan 
Protocol No. LCB35-0371-21-2-01 
CONFIDENTIAL 
21/30 page 
SD 0400 A v5.0/Effective Date: 15-Jan-2024 
(Ref. SOP 0400) 
 
 
prior/concomitant medication, level 1, preferred name), even if they have several prior/concomitant medications.  
 
The WHO ATC index version will be noted in the tables and listings. The analyses will be performed on the SS, 
and the prior/concomitant medication information for the ARS will be presented in the listing. 
 
8.4.4 
Concomitant Therapy 
Concomitant therapy is defined as non-drug treatment other than the investigational product from the time of 
administration of the investigational product until the end of the study. 
 
For subjects with concomitant therapy, frequencies, percentages, and number of occurrences will be presented for 
each treatment group and total number of cases. They will be coded according to the System Organ Class (SOC) 
and Preferred Term (PT) of Medical Dictionary for Regulatory Activities (MedDRA) Latest Major Version and 
show frequencies, percentages, and number of occurrences. For the frequency count, a subject will be counted as 
1 person in each classification (subjects with concomitant therapy, SOC, PT), even if they have several concomitant 
therapies.  
 
The MedDRA version will be noted in the tables and listings. The analyses will be performed on the SS, and the 
concomitant therapy information for the ARS will be presented in the listing. 
 
8.5 
Treatment Compliance 
For treatment compliance, the number of subjects, mean, standard deviation, median, minimum, and maximum 
for each treatment group and the total number will be presented. In addition, treatment compliance will be 
classified as less than 80% and 80% or more, and frequencies and percentages will be presented. The analyses will 
be performed on the FAS and the PPS, and the treatment compliance information for the SS will be presented in 
the listing. 
 
Overall treatment compliance 
(%) = 
Total number of tablets actually taken (administered) 
X 100 
Total number of tablets to be taken (administered) 
 
9. 
Efficacy Analysis 
The efficacy assessment will be primarily analyzed using the FAS, with additional analyses performed using the 
PPS. In addition, the listing will provide information on the primary efficacy endpoint and the secondary efficacy 
endpoints for the FAS. 
 
9.1 
Analysis of the Primary Efficacy Endpoint 
9.1.1 
Proportion (%) of Subjects with Overall Cure on Day 14 of Treatment 
The number and percentage of subjects with overall cure on Day 14 of treatment will be presented with the 


 
Statistical Analysis Plan 
 
 
Statistical Analysis Plan 
Protocol No. LCB35-0371-21-2-01 
CONFIDENTIAL 
22/30 page 
SD 0400 A v5.0/Effective Date: 15-Jan-2024 
(Ref. SOP 0400) 
 
 
corresponding 95% confidence intervals by treatment group. Differences in proportions between groups will be 
tested using the chi-square test or Fisher’s exact test. 
 
Overall cure is defined as the disappearance of infection symptoms present at study enrollment, no new infections 
and/or secondary infections caused by MRSA (clinical improvement), and two consecutive negative MRSA blood 
cultures (clearance of MRSA bacteremia)*. 
*If the first blood culture result is negative, a subsequent test will be performed within 3 days, and clearance of MRSA 
bacteremia will be established when two consecutive negative results are confirmed. 
 
Composite Response Rate (%) = The number of subjects with overall cure on Day 14
The number of subjects per group
× 100 
 
9.2 
Analysis of the Secondary Efficacy Endpoints 
9.2.1 
Proportion (%) of Subjects with Overall Cure by the EOT Visit 
The number and percentage of subjects with overall cure at 7 days before the EOT visit and at the time of the EOT 
visit will be presented with the corresponding 95% confidence intervals by time point and treatment group. 
Differences in proportions between groups will be tested using the chi-square test or Fisher’s exact test. 
 
Composite Response Rate(%) = The number of subjects with overall cure at each time point
The number of subjects per group
× 100 
 
9.2.2 
Mortality (%) due to MRSA Bacteremia During the Treatment Period with the Investigational 
Product 
It is defined as the proportion of subjects who died from MRSA bacteremia during the treatment period after the 
start of the investigational product. The number and percentage of subjects who died during the treatment period 
after the start of the investigational product will be reported along with the 95% confidence interval for each 
treatment group. Differences in proportions between groups will be tested using the chi-square test or Fisher’s 
exact test. 
 
Mortality due to MRSA bacteremia =
The number of subjectswho died due to exacerbation of
MRSA bacteremia during the treatment period
The number of subjects per group
× 100 
 
9.2.3 
Relapse Rate of MRSA Bacteremia 
The relapse rate of MRSA bacteremia is defined as the proportion of subjects with relapse of MRSA bacteremia 


 
Statistical Analysis Plan 
 
 
Statistical Analysis Plan 
Protocol No. LCB35-0371-21-2-01 
CONFIDENTIAL 
23/30 page 
SD 0400 A v5.0/Effective Date: 15-Jan-2024 
(Ref. SOP 0400) 
 
 
after two consecutive negative MRSA test results and within the TOC visit. The relapse of MRSA bacteremia 
refers to microbiological relapse, i.e., a positive MRSA in blood culture after two consecutive negative MRSA 
confirmations. The number and percentage of subjects with relapse of MRSA bacteremia will be presented with 
the corresponding 95% confidence intervals for each treatment group. Differences in proportions between groups 
will be tested using the chi-square test or Fisher’s exact test. However, to confirm the denominator, the results 
collected on the [Blood Culture] page will be used for analysis at Day 3, Day 5, and unscheduled time points. 
 
Relapse Rate of MRSA Bacteremia =
The number of subjects with relapse MRSA bacteremia 
after two consecutive negative MRSA test results
and prior to the TOC visit
The number of subjects
with two consecutive negative MRSA test results per group
× 100 
 
9.2.4 
Proportion of Subjects with Two Consecutive Negative MRSA Blood Culture Results on Day 3, 
Day 5, Day 7, Day 14 and at the EOT Visit 
It is defined as the proportion of subjects who had two consecutive negative MRSA confirmations at each time 
point on Day 3, Day 5, Day 7, Day 14, and EOT*. The number and percentage of subjects with two consecutive 
negative MRSA confirmations will be presented along with the 95% confidence interval for each time point and 
treatment group. Differences in proportions between groups will be tested using the chi-square test or Fisher’s 
exact test. However, for the analysis of Day 3 and Day 5, the results recorded on the [Blood Culture] page will be 
used. 
* If two consecutive negative MRSA blood culture results are obtained prior to the EOT visit, these results can be considered 
as the blood culture results for the EOT visit. 
 
Clearance Rate =
The number of subjects
with two consecutive negative MRSA test results at each time point
The number of subjects at each time point
× 100 
 
9.2.5 
Proportion of Subjects with Persistent MRSA Bacteremia Based on Blood Culture Results on Day 
3, Day 5, Day 7, and Day 14 
It is defined as the proportion of subjects with positive MRSA blood cultures at each time point (Day 3, Day 5, 
Day 7, Day 14) after the first positive MRSA result (index blood culture) confirmed before randomization. The 
number and percentage of subjects with persistent MRSA bacteremia will be reported along with the 95% 
confidence interval for each time point and treatment group. Differences in proportions between groups will be 
tested using the chi-square test or Fisher’s exact test. However, for the analysis of Day 3 and Day 5, the results 
recorded on the [Blood Culture] page will be used. 


 
Statistical Analysis Plan 
 
 
Statistical Analysis Plan 
Protocol No. LCB35-0371-21-2-01 
CONFIDENTIAL 
24/30 page 
SD 0400 A v5.0/Effective Date: 15-Jan-2024 
(Ref. SOP 0400) 
 
 
 
Proportion of subjects with persistent MRSA bacteremia
=
The number of subjects with persistent
MRSA bacteremia at each time point
The number of subjects at each time point × 100 
 
9.2.6 
Time to Clearance of MRSA Bacteremia (in Days) 
If the first negative blood culture result is confirmed, another test will be performed within 3 days. Clearance of 
MRSA bacteremia is confirmed by two consecutive negative results. The time to clearance of MRSA bacteremia 
is defined as the period (in days) from the date of the first MRSA-positive blood culture before randomization to 
the date of the first confirmed negative result in the blood culture. 
 
Censoring is defined as cases where two consecutive negative results are not confirmed, and the censoring date 
follows the method in [7.1.1 Censoring Rules]. 
 
 
Duration (days) = (date of clearance of MRSA bacteremia or censoring) – (date of first positive MRSA 
confirmation before randomization) + 1 
 
After testing the proportional hazards assumption for differences between groups, the log-rank test will be 
performed if the assumption is met. If the proportional hazards assumption is not met, the generalized Wilcoxon 
test (Gehan test) will be performed using different weights from the weighted log-rank test family. The proportional 
hazards assumption will be tested using time-dependent log(-log S(t)) plots and a residual analysis (Cox-Snell 
method). If the cumulative hazard function of the Cox-Snell residuals is estimated and the dispersion of the 
residuals appears as a straight line with a slope of 1, it can be assumed that the assumption is fulfilled. Survival 
curves and medians with corresponding two-sided 95% confidence intervals for each group will be presented using 
the Kaplan-Meier method, and estimates of hazard ratios with two-sided 95% confidence intervals will be provided 
using a Cox regression model with the treatment group as a covariate. 
 
In addition, the time to clearance of MRSA bacteremia will be presented using the status of complication and the 
presence/absence of primary lesion as covariates. 
The log-rank test will be performed if the proportional hazards assumption is met. If the proportional hazards 
assumption is not met, the generalized Wilcoxon test (Gehan test) will be performed. Survival curves and medians 
with corresponding two-sided 95% confidence intervals for each group will be presented using the Kaplan-Meier 
method, and estimates of hazard ratios with two-sided 95% confidence intervals will be provided using a Cox 
regression model. 
 


 
Statistical Analysis Plan 
 
 
Statistical Analysis Plan 
Protocol No. LCB35-0371-21-2-01 
CONFIDENTIAL 
25/30 page 
SD 0400 A v5.0/Effective Date: 15-Jan-2024 
(Ref. SOP 0400) 
 
 
10. Safety Analysis 
The safety analyses will be performed for the SS. 
 
10.1 Extent of Exposure 
The number of subjects, mean, standard deviation, median, minimum and maximum for each treatment group will 
be reported for the total treatment period (days) and the total administered dose (mg) of the investigational product 
(LCB01-0371). In addition, exposure information for the SS will be presented in the listing. 
 
Each endpoint is defined as follows. 
 
Total treatment period (days): Date of the last administration – date of the first administration + 1 
 
Total administered dose (mg): Number of the tablets of the investigational product administered X 400 
mg 
 
10.2 Adverse Events 
A treatment-emergent adverse event (TEAE) is defined as an adverse event that either occurs after the 
administration of the investigational product or represents an exacerbation of a pre-existing condition after the 
administration of the investigational product. TEAEs will be classified by date of occurrence as follows: 
 
 
TEAE: 
Start date of the investigational product ≤ Date of occurrence of the adverse event  
 
An adverse drug reaction (ADR) refers to a harmful and unintended reaction that occurs at any dose of an 
investigational product and for which the causal relationship with the investigational product cannot be excluded. 
An ADR is defined as an AE for which causal relationship to the investigational product is assessed as one of the 
following by the investigator. 
 
 
Definitely 
 
Probable/Likely 
 
Possible 
 
Unassessable 
 
A serious adverse event (SAE) refers to any of the following AEs that occur at any dose of the investigational 
product. 
 
 
Results in death or is life-threatening 
 
Requires hospitalization or prolonged hospitalization 


 
Statistical Analysis Plan 
 
 
Statistical Analysis Plan 
Protocol No. LCB35-0371-21-2-01 
CONFIDENTIAL 
26/30 page 
SD 0400 A v5.0/Effective Date: 15-Jan-2024 
(Ref. SOP 0400) 
 
 
 
Results in persistent or significant disability/incapacity 
 
Results in a congenital anomaly/birth defect 
 
In addition to cases above, cases where other important medical events occur, such as development of 
drug dependence or drug abuse, or hematological disease, etc. 
 
10.2.1 
Summary of Adverse Events 
The following AEs will be reported with the number of subjects with occurrence, incidences, number of cases by 
treatment group, and the 95% confidence intervals for incidence. Differences in proportions between groups will 
be tested using the chi-square test or Fisher’s exact test. Adverse event information for the SS will also be presented 
in listings. 
 
 
Treatment-emergent adverse events (TEAEs) 
 
Adverse drug reactions (ADRs) 
 
Serious adverse events (SAEs) 
 
Serious adverse drug reactions (SADRs) 
 
AEs leading to treatment discontinuation 
 
10.2.2 
Analysis of Adverse Events 
The following AEs will be coded according to the latest version of MedDRA SOC and PT, and the number of 
subjects, incidences, and number of cases by treatment group will be reported. The MedDRA version will be noted 
in the tables and listings. 
 
 
Treatment-emergent adverse events (TEAEs) 
 
Adverse drug reactions (ADRs) 
 
Serious adverse events (SAEs) 
 
Serious adverse drug reactions (SADRs) 
 
AEs leading to treatment discontinuation 
 
TEAEs by severity 
 
ADRs by severity 
 
AE information for the SS will also be presented in listings, and SAEs will be presented in separate listings. 
 
10.3 Mortality due to Exacerbation of MRSA Bacteremia at the Time of the TOC Visit (4 Weeks after EOT) 
After Starting Treatment with the Investigational Product 
The number and percentage of subjects who die due to exacerbation of MRSA bacteremia from the start of 
treatment with the investigational product to the TOC visit will be presented with the corresponding two-sided 95% 


 
Statistical Analysis Plan 
 
 
Statistical Analysis Plan 
Protocol No. LCB35-0371-21-2-01 
CONFIDENTIAL 
27/30 page 
SD 0400 A v5.0/Effective Date: 15-Jan-2024 
(Ref. SOP 0400) 
 
 
confidence intervals for each treatment group. Differences in proportions between groups will be tested using the 
chi-square test or Fisher’s exact test. 
 
Mortality due to exacerbation of MRSA bacteremia at the time of the TOC visit 
=
The number of subjects who died
after administration of the investigational product up to the TOC visit
The number of subjects per group
× 100 
 
10.4 Incidence of Thrombocytopenia 
The number and percentage of subjects who experience thrombocytopenia after administration of the 
investigational product will be presented with the corresponding two-sided 95% confidence intervals for each 
treatment group. Differences in proportions between groups will be tested using the chi-square test or Fisher’s 
exact test. 
 
Incidence of thrombocytopenia =
The number of subjects who experience thrombocytopenia
after administration of the investigational product
The number of subjects per group
× 100 
 
10.5 Laboratory Tests 
If the units of laboratory tests differ by study site, they will be standardized to the most commonly used unit for 
each item. Results with inequality signs will be analyzed as their numeric value. 
e.g., < 1.002 will be analyzed as 1.002. 
 
For continuous variables, the mean, standard deviation, median, minimum, and maximum for each treatment group 
will be provided for each measurement at different time points, measurements at the final visit, and changes from 
baseline. 
 
Test results will be classified as normal/abnormal (NCS: not clinically significant; CS: clinically significant) and 
presented in shift tables with frequencies and percentages of change from baseline at each time point and at the 
final visit. The results will be further classified as low (< lower limit), normal (within the reference range), and 
high (> upper limit) and presented in shift tables with frequencies and percentages of change from baseline at each 
time point and at the final visit. 
 
For categorical variables, test results will be classified as normal/abnormal (NCS, CS) and presented in shift tables 
with frequencies and percentages of change from baseline at each time point and at the final visit. 
 


 
Statistical Analysis Plan 
 
 
Statistical Analysis Plan 
Protocol No. LCB35-0371-21-2-01 
CONFIDENTIAL 
28/30 page 
SD 0400 A v5.0/Effective Date: 15-Jan-2024 
(Ref. SOP 0400) 
 
 
Laboratory test data for the SS will also be presented in listings, with all abnormal CS results after baseline 
provided in separate listings for each time point. 
 
10.6 Vital Signs 
For the following vital signs, the mean, standard deviation, median, minimum, and maximum for each treatment 
group will be provided for each measurement at different time points, measurements at the final visit, and changes 
from baseline. Vital sign information for the SS will also be presented in listings. 
 
 
Vital signs: Systolic blood pressure (mmHg), diastolic blood pressure (mmHg), pulse (bpm), temperature 
(℃), respiratory rate (breaths per minute) 
 
10.7 12-lead ECG 
The test results will be classified as normal/abnormal (NCS, CS) and presented in shift tables with frequencies and 
percentages of change from baseline at the final visit. 12-Lead ECG information for the SS will also be presented 
in listings. 
 
10.8 Physical Examination 
For the SS, clinically significant abnormal findings in physical examination will be presented in the listing. 
 
10.9 Pregnancy Test 
For the SS, information on the pregnancy tests performed at each time point will be presented in the listing. 
 
11. PK Analysis 
11.1 PK Parameters 
PK analysis will be performed at a designated analysis institution according to a separate PK analysis plan. 
 
11.2 Other Parameters - MIC Evaluation  
11.2.1 
Evaluation of the MIC of Vancomycin  
The following MICs at baseline will be reported with mean, standard deviation, median, minimum, maximum, 
MIC50*, and MIC90** for each treatment group.  The analysis will be performed using the SS, and the vancomycin 
MIC evaluation data for the ARS will be presented in a listing. 
*This refers to the value corresponding to the n × 0.5th position in the ordered list of MIC values. If n × 0.5 is not an integer, 
it is rounded up to the first decimal place. 
**This refers to the value corresponding to the n × 0.9th position in the ordered list of MIC values. If n × 0.9 is not an integer, 
it is rounded up to the first decimal place. 
 


 
Statistical Analysis Plan 
 
 
Statistical Analysis Plan 
Protocol No. LCB35-0371-21-2-01 
CONFIDENTIAL 
29/30 page 
SD 0400 A v5.0/Effective Date: 15-Jan-2024 
(Ref. SOP 0400) 
 
 
 
Vancomycin MIC evaluation: Minimum inhibitory concentration (mcg/mL)  
 
Evaluation of the MIC of vancomycin will be performed at screening and when deemed necessary by the 
investigator. The analysis will be performed at the study site. In addition, MICBMD analysis can be performed at a 
designated laboratory by transferring samples when necessary. 
 
11.2.2 
Evaluation of the MIC of LCB01-0371  
The following MICs will be presented for each treatment group at baseline and at the final visit. The changes from 
baseline at each time point and at the final visit will also be reported, including the number of subjects in each 
treatment group, mean, standard deviation, median, minimum, maximum, MIC50*, and MIC90**.  
In addition, the measurements will be classified according to whether they increase 3-fold or more from baseline, 
and the corresponding frequency and percentage for each treatment group at each time point and at the final visit 
will be reported. The analysis will be performed using the SS, and the LCB01-0371 MIC evaluation data for the 
ARS will be presented in a listing. 
*This refers to the value corresponding to the n × 0.5th position in the ordered list of MIC values. If n × 0.5 is not an integer, 
it is rounded up to the first decimal place. 
**This refers to the value corresponding to the n × 0.9th position in the ordered list of MIC values. If n × 0.9 is not an integer, 
it is rounded up to the first decimal place. 
 
 
Evaluation of the MIC of LCB01-0371: Minimum inhibitory concentration (mcg/mL) 
 
Evaluation of the MIC of LCB01-0371 will be performed at the time points specified when feasible, and the 
analysis will be performed separately at a designated analysis institution. 
 
12. Interim Analysis 
Not applicable. 
 
13. Changes to the Planned Analysis Methods 
Subgroups not defined in Section 11.2.6 Subgroup Analysis of the protocol were added (administration of oral 
antibiotics (for MRSA) after 14 days of the investigational product administration, vancomycin high MIC, removal 
of primary lesion, presence of complications).  
Although no covariate adjustment was planned in the protocol, it was additionally changed to present the results 
adjusted for covariates (presence of complications and removal of primary lesion) for the secondary efficacy 
endpoint ‘time to clearance of MRSA bacteremia.’  
 


 
Statistical Analysis Plan 
 
 
Statistical Analysis Plan 
Protocol No. LCB35-0371-21-2-01 
CONFIDENTIAL 
30/30 page 
SD 0400 A v5.0/Effective Date: 15-Jan-2024 
(Ref. SOP 0400) 
 
 
14. SAS Program Code 
The SAS program codes used for the statistical analysis in this study are as follows. 
 
Table 5 SAS Program Code 
Analysis Method 
SAS program code 
Descriptive statistics (mean, standard 
deviation, media, minimum, maximum) 
PROC MEANS DATA= dataset N MEAN STD MEDIAN MIN 
MAX; 
VAR variable; 
RUN; 
Descriptive statistics (frequency, 
percentage) 
PROC FREQ DATA= dataset; 
TABLE variable; 
RUN; 
Chi-square test 
Fisher’s exact test 
 
PROC FREQ DATA=dataset; 
TABLE variable*treatment/CHISQ EXACT FISHER; 
RUN; 
Proportional Hazard Model 
PROC PHREG DATA = dataset; 
CLASS treatment; 
MODEL time*event(0) = treatment (covariate) / risklimits; 
RUN; 
Log-rank test 
PROC LIFETEST DATA=dataset PLOTS=(survival logsurv) 
graphics METHOD=KM ALPHAQT=0.05;  
TIME time*event(0); 
STRATA treatment/test=logrank (or wilcoxon);  
RUN; 
15. References 
Not applicable.