Clinical trial NCT03653208
Conditions: Healthy
Sponsor: ImmuneMed, Inc.
Start date: 2018-11-20; Completion date: 2020-02-29
Enrollment: 56 participants; Allocation: RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
To investigate the safety/tolerability and pharmacokinetic characteristics after single intravenous (IV) administration of hzVSF-v13 (humanized Virus Suppressing Factor-variant 13) in healthy male volunteers

Detailed description:
Dose blocked-randomized, double-blind, placebo controlled, single dose, dose-escalation study to investigate the safety/tolerability and pharmacokinetic characteristics of hzVSF-v13 after IV administration in healthy male volunteers

Arms: arm 1: Group 1 received a single 10mg dose of hzVSF-v13 on Day 1. arm 2: Group 2 received a single 20mg dose of hzVSF-v13 on Day 1. arm 3: Group 3 received a single 50mg dose of hzVSF-v13 on Day 1. arm 4: Group 4 received a single 100mg dose of hzVSF-v13 on Day 1. arm 5: Group 5 received a single 200mg dose of hzVSF-v13 on Day 1. arm 6: Group 6 received a single 400mg dose of hzVSF-v13 on Day 1. arm 7: Group 7 received a single 800mg dose of hzVSF-v13 on Day 1. arm 8: Group 8 received a single 1200mg dose of hzVSF-v13 on Day 1. arm 9: Placebo group received a single placebo on Day 1.
Interventions: intervention 1: hzVSF-v13 intervention 2: Placebo
Intervention descriptions: intervention 1: Dosage form: 10mg / 20mg / 50mg / 100mg / 200mg / 400mg / 800mg / 1200mg of hzVSF-v13 (40 mg/mL in a 5 mL vial) Frequency: Dose at Day 1 (single administration) intervention 2: Dosage form: 0.9% NaCl Solution Frequency: Dose at Day 1 (single administration)

Protocol documents:
Prot_000.pdf: 
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Clinical Study Protocol 
 
 
 
 
A phase 1, dose blocked-randomized, double-blind, placebo controlled, single dosing, dose-escalation study to 
investigate the safety, tolerability, pharmacokinetic characteristics of hzVSF-v13 after intravenous(IV) 
administration in healthy male subjects 
 
Investigational Product:  
hzVSF-v13 
 
 
Study No.: IM_hzVSF_v13-0001 
 
Version: 3.5 
 
Date of completion: 10/02/2019 
Date of amendment: N/A 
 
Confidential Document 
The information contained in this document is provided to you, who is the investigator or advisor, for a review by 
you, your study staff, and the applicable Institutional Review Board/independent Safety Monitoring Committee. 
Your acceptance of this document is regarded as an agreement that you will not disclose the information contained 
in this document to others without a written permission of ImmuneMed Inc. 


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SIGNATURE PAGE 
 
 
A phase 1, dose blocked-randomized, double-blind, placebo controlled, single dosing, dose-escalation study to 
investigate the safety, tolerability, pharmacokinetic characteristics of hzVSF-v13 after intravenous(IV) 
administration in healthy male subjects 
 
Study No.: IM_hzVSF_v13-0001 
 
Document Creator 
Mu Seong Ban 
 
 
 
 
 
Signature 
 
Name         In Jin Jang 
 
Date 
Principal Investigator 
 
 
 
Signature 
 
Name       Yoon Won Kim, CEO 
 
Date  
Sponsor       ImmuneMed Inc.  
 


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SYNOPSIS 
Title 
A phase 1, dose blocked-randomized, double-blind, placebo controlled, single dosing, dose-
escalation study to investigate the safety, tolerability, pharmacokinetic characteristics of 
hzVSF-v13 after intravenous(IV) administration in healthy male subjects 
Objective 
 
To evaluate the safety and tolerability after intravenous administration of a single dose 
of the study drug hzVSF-v13 in healthy male subjects. 
 
To evaluate the pharmacokinetic characteristics after intravenous administration of a 
single dose of the study drug hzVSF-v13 in healthy male subjects. 
Principal 
Investigator 
Professor In Jin Jang, M.D., Ph.D. 
Study Site 
Seoul National University College of Medicine/Department of Clinical Pharmacology and 
Therapeutics, Seoul National University Hospital 
Sponsor 
ImmuneMed Inc. 
Analytical 
Testing 
Institution 
APACE Co., Ltd. (pharmacokinetics) 
Hallym University College of Medicine Laboratory (immunogenicity) 
Expected 
Target Disease 
Influenza, hepatitis B and C 
Investigational 
Product 
• 
hzVSF-v13  
• 
Placebo 
Clinical Study 
Phase 
Phase 1 
Number of 
Subjects 
 
Number of Subjects 
56 subjects in total  
 
hzVSF-v13 IV 10 mg, 20 mg – 4 subjects in each dose group  
(3 subjects for the study drug, 1 subject for the placebo) 
 
hzVSF-v13 IV 50 mg, 100 mg, 200 mg, 400 mg, 800 mg, 1,200 mg – 8 subjects in each dose 
group  
(6 subjects for the study drug, 2 subject for the placebo) 


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 
Single-dose study (intravenous administration) 
Dose Group 
Number of Subjects 
Group 1 (10 mg IV) 
hzVSF-v13: 3 subjects 
Placebo: 1 subject 
Group 2 (20 mg IV) 
hzVSF-v13: 3 subjects 
Placebo: 1 subject 
Group 3 (50 mg IV) 
hzVSF-v13: 6 subjects 
Placebo: 2 subjects 
Group 4 (100 mg IV) 
hzVSF-v13: 6 subjects 
Placebo: 2 subjects 
Group 5 (200 mg IV) 
hzVSF-v13: 6 subjects 
Placebo: 2 subjects 
Group 6 (400 mg IV) 
hzVSF-v13: 6 subjects 
Placebo: 2 subjects 
Group 7 (800 mg IV) 
hzVSF-v13: 6 subjects 
Placebo: 2 subjects 
Group 8 (1200 mg IV) 
hzVSF-v13: 6 subjects 
Placebo: 2 subjects 
 
• 
Rationale for Calculation of the Number of Subjects 
The purpose of the study is exploratory which is not to verify statistical hypotheses, and in 
the case of Phase 1 clinical studies being conducted using new drugs for which safety is not 
established, it is ethically desirable to conduct the study in the minimum number of subjects 
while satisfying the study objectives. In addition, dose groups had a certain ratio of subjects 
who will receive the placebo to enable double-blind for an objective safety and tolerability 
review. In this study, for the low dose groups (Groups 1 and 2), the sentinel dose groups, the 
target number of subjects per dose group has been set to 4 subjects per dose group, and the 
target number of subjects for other dose groups has been set to 8 subjects per dose group.  
Inclusion/Excl
usion Criteria 
• 
Inclusion Criteria 
1) 
Healthy males aged 19 to 45 years inclusive at the time of the screening visit 
2) 
Individuals with a BMI of not less than 18.0 kg/m2 to not more than 27.0 kg/m2 and 


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weighed not less than 55 kg and less than 90 kg at the time of the screening visit  
3) 
Individuals confirmed clinically healthy based on medical history, physical 
examination, vital sign, electrocardiography (ECG), and appropriate clinical 
laboratory tests (provided that individuals outside the normal range may participate 
subject to investigator discretion) 
4) 
Individuals who have agreed to use a medically acceptable method of dual 
contraception and not to donate sperm from the first day until 30 days after the last 
day of investigational product administration 
5) 
Individuals who have voluntarily decided to participate in this clinical study and have 
given a written consent to comply with the requirements of the clinical study 
 
• 
Exclusion Criteria 
1) 
Individuals with a clinically significant hepatic, renal, digestive, respiratory, 
musculoskeletal, endocrine, neuropsychological, hemato-oncologic, cardiovascular, 
or other disease or history 
2) 
Individuals with a clinically significant history of hypersensitivity reactions to the 
components of hzVSF-v13, drugs containing components of the same class, or other 
drugs (aspirin, non-steroidal anti-inflammatory drugs, antibiotics, etc.) 
3) 
Individuals with a positive result in the immunogenicity test for hzVSF-v13 
conducted during the screening test 
4) 
Individuals who have a history of drug abuse, or who have positive in the test for 
abuse-likely drugs in the urine drug screening test 
5) 
Individuals with abnormal results for any of the following vital signs at the time of 
the screening visit: 
A. Systolic blood pressure: < 90 mmHg or > 140 mmHg 
B. 
Diastolic blood pressure: < 50 mmHg or > 90 mmHg 
C. 
Heart rate: < 50 bpm or > 90 bpm 
6) 
Individuals with abnormal results for any of the following ECG items at the time of 
the screening visit: 
A. PR > 210 msec 
B. 
QRS complex: > 120 msec 
C. 
QTc > 450 msec  


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7) 
Individuals who have participated in another clinical study or bioequivalence study 
and received an investigational product within 3 months prior to the first day of 
administration (provided that 6 months from 06/12/2019) 
8) 
Individuals who have donated whole blood within 2 months prior to the first day of 
administration, or donated blood components or received blood within 1 month prior 
to the first day of administration 
9) 
Individuals who have taken drug-metabolizing enzyme inducers or inhibitors, such 
as barbitals, within 1 month prior to the screening 
10) Individuals who have consumed grapefruit/caffeine-containing foods within 3 days 
of the first administration, and individuals who are unable to avoid consuming 
grapefruit-containing foods from 3 days prior to admission until the date of discharge 
11) Individuals who have taken prescription drugs or oriental medications within 2 weeks 
prior to the first day of administration, or who have taken over-the-counter (OTC) 
drugs within 1 week prior to the first day of administration (provided that individuals 
who meet other requirements may participate in the clinical study subject to 
investigator discretion) 
12) Individuals who consume high amounts of caffeine or alcohol and individuals who 
are heavy smokers (caffeine > 5 units/day, alcohol > 21 units/week (1 unit = 10 mL 
of pure alcohol), smoking > 10 cigarettes/day) 
13) Individuals who are unable to eat meals provided by the study site 
14) Individuals who have participated in this study 
15) Individuals who have a positive result for serology (hepatitis B, human 
immunodeficiency virus [HIV], and hepatitis C tests) 
16) Individuals with veins that are not suitable for intravenous catheter insertion or 
multiple venipunctures 
17) Individuals who do not agree to use a medically acceptable method of dual 
contraception from the first day until 30 days after the last day of investigational 
product administration 
18) Other individuals deemed unsuitable as a subject by an investigator 
 
• 
Withdrawal Criteria 
1) In the case that a subject requests discontinuation of the investigational product 


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administration during the clinical study, or withdraws his consent to participation in 
the study 
2) In the case that a subject has received a drug that is expected to affect the evaluation 
of the safety or pharmacokinetics of the study drug during the clinical study 
3) In the case that serious adverse events/adverse drug reactions have occurred 
4) In the case that a subject is unable to perform blood sampling for the testing for 
pharmacokinetics/safety 
5) In the case that significant protocol violation cases have been newly identified during 
the clinical study 
6) In the case that the sponsor or the Ministry of Food and Drug Safety requests 
discontinuation 
7) In the case that the principal investigator/investigator determines that the study has to 
be discontinued due to other reasons 
Analytical 
Procedure  
This is a Phase 1, dose blocked-randomized, double-blind, placebo controlled, single dosing, 
dose-escalation study to investigate the safety, tolerability, pharmacokinetic characteristics 
of hzVSF-v13 after intravenous administration in healthy male subjects.  
 
Each dose group will have hzVSF-v13 and the placebo randomized at a 3:1 ratio to conduct 
the clinical study. The study will be proceeded sequentially from the lowest dose, and 
whether to proceed with the next dose will be determined based on the tolerability and safety 
results of the previous dose.  
Each subject in Group 1 and Group 2 will be administered, and if no significant dose-limiting 
toxicity (DLT) occurs within 72 hours, the next subject will be administered.  
In the case of all dose groups except for Group 1 and Group 2 (Group 3–Group 8), 3 out of 
8 subjects in each dose group (2 subjects for the study drug and 1 subject for the placebo) 
will receive the investigational product (hzVSF-v13 or placebo) at least 72 hours earlier than 
the remaining subjects in the same dose group. If no significant dose-limiting toxicity occurs 
within 72 hours, the remaining subjects in the relevant dose group will receive the 
investigational product (hzVSF-v13 or placebo) depending on the randomization.  
 
In the case that at least 3 subjects experience a Grade 3 adverse event or at least 1 subject in 
certain dose groups experience a Grade 4 adverse event based on the Common Terminology 


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Criteria for Adverse Events (CTCAE) published by the United States National Cancer 
Institute (NCI), the principal investigator shall consult the Safety Monitoring Committee 
(SMC) and discuss discontinuation of the relevant dose group and dose escalation with the 
sponsor. (For Group 1 and Group 2, discontinuation of the dose group and dose escalation 
shall be considered based on the following criterion: occurrence of Grade 3 adverse event in 
at least 2 subjects or Grade 4 adverse event in at least 1 subject.) 
 
The screening tests shall only be performed in volunteers within 4 weeks prior to the first 
day (1 d) of investigational product administration (−28 d to −2 d) in order to select the 
subjects considered to be eligible for this clinical study. 
 
 Single-Dose Study (Intravenous Administration) 
- 10 mg, 20 mg, 50 mg, 100 mg, 200 mg, 400 mg, 800 mg, 1,200 mg IV  
 
The selected subjects will be admitted to the Seoul National University Hospital Clinical 
Trials Center 2 days (-2d) prior to administration of the investigational product. The skin 
test will be performed a day (-1d) prior to administration of the investigational product. Only 
the subjects who did not have clinically significant findings in the skin test will have 
intravenous (IV) administration of the investigational product (hzVSF-v13 or placebo) at 9 
a.m. on the day (1d) of investigational product administration . The subjects will be required 
to perform the clinical study procedures in accordance with the predefined schedule and will 
be discharged 7 days (8d) after the administration. Thereafter, the subjects will visit the 
Seoul National University Hospital Clinical Trial Center as outpatients from 9 d to 92 d in 
order to perform the clinical study procedures according to the predefined schedule. After 
completing all scheduled tests up to 15 d for each dose group, an independent SMC, 
established separately from this study, will evaluate the safety-related data. With reference 
to the evaluation result of the SMC, the principal investigator and the sponsor will decide 


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by mutual consent whether to continue the clinical study and to proceed with the next step.  
Evaluation 
Items 
 Safety and Tolerability Assessments 
- Monitoring of adverse events, such as subject and objective symptom 
- Physical examination 
- Vital signs 
- Electrocardiography (12-lead ECG) 
- Clinical laboratory tests 
- Immunogenicity test 
 
 
Pharmacokinetic Assessment 
Blood samples will be collected to assess the pharmacokinetics of hzVSF-v13 until 2,184 
hours after administration of the investigational product. 
 
- Blood collection time: 1 d 0 h (pre-dose), 0.5, 1, 2, 4, 6, 8, 10, 12, 24 (2 d 0 h), 36 (2 d 12 
h), 48 (3 d 0 h), 60 (3 d 12 h), 72 (4 d 0 h), 96 (5 d 0 h), 120 (6 d 0 h), 144 (7 d 0 h), 168 (8 
d 0 h), 336 (15 d 0 h), 504 (22 d 0 h), 672 (29 d 0 h), 840 (36 d 0 h), 1,176 (50 d 0 h), 1,512 
(64 d 0 h), 1,848 (78 d 0 h) and 2,184 h (92 d 0 h; post-dose). 
 
- Endpoints: Cmax, AUClast, AUCinf, Tmax, t1/2, CL (or CL/F), and Vd (or Vd/F) 
 
 
Immunogenicity Test 
Immunogenicity will be evaluated by confirming the production of antibodies against 
hzVSF-v13. 
 
- Blood collection time: Screening, 168 (8 d 0 h), 336 (15 d 0 h), 672 (29 d 0 h), 1,344 (57 
d 0 h) and 2,184 h (92 d 0 h; post-dose). 
Data Analysis 
• 
Demographic Data Analysis 
Descriptive statistics (mean, standard deviation, etc.) will be obtained for all subjects and 
each dose group for basic demographic information of subjects, such as age, height, and 
weight. 
 
 


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• 
Pharmacokinetic Analysis 
Pharmacokinetic variables will be obtained through a noncompartmental method using an 
appropriate and verified pharmacokinetics software (e.g., Phoenix WinNonlin®  [Version 6.3 
or higher; Pharsight, CA, USA]), and descriptive statistics (mean, standard deviation, 
median, maximum, minimum, etc.) will be obtained for each dose group.  
 
• 
Safety Analysis 
Adverse events will be tabulated for each dose group based on severity and causal 
relationship to the investigational product, and the frequency and percentage of subjects who 
experienced adverse events will be compared and evaluated. The results of vital sign, 
electrocardiography, clinical laboratory tests, and immunogenicity test will be reviewed 
comprehensively, and statistical analysis will be done as needed for the items that are 
considered clinically significant.  


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SUMMARY OF CLINICAL STUDY SCHEDULE  
Schedule 
Screening 
Hospitalization period 
Outpatient 
period 
Day (d) 
Item 
-28 ~ -2 
-2 
-1 
1 
2 ~ 7 
8 
9 ~ 92 
Obtaining a written consent 
● 
  
  
  
  
  
  
Checking demographic information/medical 
history 
● 
  
  
  
  
  
  
Serology1 
● 
  
  
  
  
  
  
Urine drug test2 
● 
  
  
  
  
  
  
Checking the inclusion/exclusion criteria 
● 
  
  
  
  
  
  
Assigning the randomization/subject numbers3 
 
  
●  
  
  
  
  
Admission4 
  
● 
  
  
  
  
  
Discharge5 
  
  
  
  
  
● 
  
Skin test6 
  
  
● 
  
  
  
  
Administration of the investigational product7 
  
  
  
● 
  
  
  
Physical examination8 
● 
  
  
● 
  
● 
● 
Vital signs9 
● 
  
  
● 
● 
● 
● 
Electrocardiography (12-lead ECG)10 
● 
  
  
● 
  
● 
● 
Clinical laboratory tests11 
● 
  
  
● 
● 
● 
● 
Blood collection for pharmacokinetics12 
  
  
  
● 
● 
● 
● 
Immunogenicity test13 
● 
  
  
  
  
●  
● 
Monitoring of adverse events 
  
● 
● 
● 
● 
● 
● 
Checking on the concomitant medications 
● 
● 
● 
● 
● 
● 
● 
Tolerability/safety assessments14 
  
  
  
  
  
  
● 
 
1 Serology: Hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) tests shall be performed 
only at the screening. 
2 Urine drug test: It shall be performed only at the screening (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, opiates). 
3 Assigning the randomization/subject numbers: The randomization and subject numbers shall be assigned after the skin test at −1 d. 
4 Admission: Subjects shall be admitted in the afternoon at −2 d. 
5 Discharge: Subjects shall be discharged after completing all scheduled tasks in the morning at 8 d. 
6 Skin test: The skin test shall be performed at −1 d. 
7 Administration of the investigational product: hzVSF-v13 (or the placebo) shall be administered intravenously at 9 a.m. at 1 d.  
8 Physical examination: It shall be performed at the screening, 1 d 0 h (pre-dose), 168 (8 d 0 h), 336 (15 d 0 h), 504 (22 d 0 h), 672 (29 d 0 h), 
840 (36 d 0 h), 1,176 (50 d 0 h), 1,512 (64 d 0 h), 1,848 (78 d 0 h) and 2,184 h (92 d 0 h; post-dose). 
9 Vital signs: It shall be performed at the screening, 1 d 0 h (pre-dose), 0.5, 1, 2, 4, 6, 8, 10, 12, 24 (2 d 0 h), 36 (2 d 12 h), 48 (3 d 0 h), 60 (3 
d 12 h), 72 (4 d 0 h), 96 (5 d 0 h), 120 (6 d 0 h), 144 (7 d 0 h), 168 (8 d 0 h), 336 (15 d 0 h), 504 (22 d 0 h), 672 (29 d 0 h), 840 (36 d 0 h), 
1,176 (50 d 0 h), 1,512 (64 d 0 h), 1,848 (78 d 0 h) and 2,184 h (92 d 0 h; post-dose) (systolic blood pressure, diastolic blood pressure, pulse 
rate, and temperature). 
10 Electrocardiography (12-lead ECG): It shall be performed at the screening, 1 d 0 h (pre-dose), 168 (8 d 0 h), 336 (15 d 0 h), 504 (22 d 0 h), 
672 (29 d 0 h), 840 (36 d 0 h), 1,176 (50 d 0 h), 1,512 (64 d 0 h), 1,848 (78 d 0 h) and 2,184 h (92 d 0 h; post-dose). 
11 Clinical laboratory tests: It shall be performed at the screening, 1 d 0 h (pre-dose), 24 (2 d 0 h), 72 (4 d 0 h), 168 (8 d 0 h), 336 (15 d 0 h), 
504 (22 d 0 h), 672 (29 d 0 h), 840 (36 d 0 h), 1,176 (50 d 0 h), 1,512 (64 d 0 h), 1,848 (78 d 0 h) and 2,184 h (92 d 0 h; post-dose) (hematology, 
blood chemistry, and urinalysis). 
12 Blood collection for pharmacokinetics: It shall be performed at 1 d 0 h (pre-dose), 0.5, 1, 2, 4, 6, 8, 10, 12, 24 (2 d 0 h), 36 (2 d 12 h), 48 (3 
d 0 h), 60 (3 d 12 h), 72 (4 d 0 h), 96 (5 d 0 h), 120 (6 d 0 h), 144 (7 d 0 h), 168 (8 d 0 h), 336 (15 d 0 h), 504 (22 d 0 h), 672 (29 d 0 h), 840 
(36 d 0 h), 1,176 (50 d 0 h), 1,512 (64 d 0 h), 1,848 (78 d 0 h) and 2,184 h (92 d 0 h; post-dose). 
13 Immunogenicity test: It shall be performed at the screening, 168 (8 d 0 h), 336 (15 d 0 h), 672 (29 d 0 h), 1,344 (57 d 0 h) and 2,184 h (92 
d 0 h; post-dose). 
14 Tolerability/safety assessments: The tolerance and safety of the relevant dose group shall be evaluated after completing all scheduled tests 
up to 15 d in order to determine whether to proceed to the next dose group. 
 


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Table of Contents (Contents) 
Synopsis ............................................................................................................................................................ 3 
Summary of Clinical Study Schedule ........................................................................................................... 11 
Abbreviations and Definition of Terms ........................................................................................................ 15 
1. Title and Phase of the Clinical Study ....................................................................................................... 17 
2. Study Site and Analysis Institution ........................................................................................................... 17 
2.1. Study Site ................................................................................................................................................. 17 
2.2. Analysis Institution ................................................................................................................................. 17 
3. Name and Title of the Principal Investigator, investigators, and Co-investigators .............................. 17 
3.1. Principal Investigator ............................................................................................................................. 17 
3.2. Co-investigators ...................................................................................................................................... 17 
3.3. investigators ............................................................................................................................................. 18 
3.4. Clinical Trial Pharmacists ...................................................................................................................... 18 
4. Name and Address of the Sponsor ............................................................................................................ 18 
5. Background of the Clinical Study ............................................................................................................. 18 
5.1. Details of the Development ..................................................................................................................... 18 
5.2. Efficacy Pharmacology Test ................................................................................................................... 18 
5.3. Mechanism of Action .............................................................................................................................. 19 
5.4. Safety Pharmacology Test ...................................................................................................................... 19 
5.5. Pharmacokinetic Test.............................................................................................................................. 20 
5.6. Toxicity Test ............................................................................................................................................. 21 
6. Objectives of the Clinical Study ................................................................................................................ 23 
6.1. Primary Objective ................................................................................................................................... 23 
6.2. Secondary Objective ............................................................................................................................... 23 
7. Investigational Product ............................................................................................................................. 23 
7.1. 
Study Drug .................................................................................................................................... 23 
7.2. 
Placebo .......................................................................................................................................... 23 
7.3. 
Expected Adverse Events (Side Effects) and Precautions for Use ............................................ 23 
7.3.1. Expected Side Effects from Non-clinical Laboratory Studies Results ............................................. 23 
7.4. 
Packaging and Labeling ............................................................................................................... 24 
7.5. 
Storage ........................................................................................................................................... 24 
8. Target Diseases ........................................................................................................................................... 24 
9.1. Number of Subjects ................................................................................................................................. 24 
9.2. Rationale for Calculation of the Number of Subjects .......................................................................... 25 
9.3. Subject Inclusion/Exclusion Criteria..................................................................................................... 25 
9.3.1. 
Inclusion Criteria ...................................................... 25 
9.3.2. 
Exclusion Criteria ...................................................... 26 
9.4. Subject Number ...................................................................................................................................... 27 
9.5. Subject Precautions/Restrictions ........................................................................................................... 27 


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9.6. Drop-out and Subject Substitution ........................................................................................................ 28 
9.7. Study Completion ................................................................................................................................... 29 
9.8. Backup Subjects (Subject Candidates) ................................................................................................. 29 
10. Analyti Method ......................................................................................................................................... 29 
10.1. Study Design .......................................................................................................................................... 29 
Rationale for Administration Doses ............................................................................................................. 29 
Rationale for Blood Collection Times ........................................................................................................... 30 
Definition of Dose-Limiting Toxicity (DLT) ................................................................................................. 30 
Dose Escalation/Discontinuation Criteria .................................................................................................... 30 
Overall Schedule ............................................................................................................................................ 31 
10.2. Randomization, Maintaining Double-Blind and Unblinding ............................................................ 32 
Randomization ............................................................................................................................................... 32 
Double-Blind .................................................................................................................................................. 33 
Maintaining Double-Blind............................................................................................................................. 33 
Unblinding ...................................................................................................................................................... 33 
10.3. Method of Investigational Product Administration ........................................................................... 34 
10.3.1. 
Other Combination Therapies ............................................ 34 
10.4. Skin Test Method .................................................................................................................................. 35 
10.5. Details of the Clinical Study Schedule ................................................................................................. 36 
10.5.1. 
Screening Tests ........................................................ 36 
10.5.2. 
Single-Dose Study (Group 1 to Group 8) ................................... 36 
10.5.3. 
Early Termination Visit ................................................. 38 
10.5.4. 
Discontinuation of the Clinical Study ...................................... 38 
10.6. Adverse Events ...................................................................................................................................... 39 
10.6.1. 
Recording and Reporting Adverse Events .................................. 39 
10.6.1.2. 
Adverse Drug Reaction (ADR) ........................................... 39 
10.6.1.3. 
Unexpected Adverse Drug Reaction (ADR) ................................. 40 
10.6.2. 
Evaluation of the Severity of Adverse Events ................................ 40 
10.6.3. 
Evaluation of the Causal Relationship of Adverse Events to the Study Drug ...... 40 
10.6.4. 
Reporting Serious Adverse Event/Adverse Drug Reaction (AE/ADR) ........... 41 
10.6.5. 
Follow-Up on Adverse Events ............................................ 42 
10.7. Blood Collection and Analysis for Pharmacokinetic Evaluation ...................................................... 42 
10.7.1. 
Specimens and Analytes ................................................. 42 
10.7.2. 
Blood Collection Method and Pre-processing and Storage Methods of Separated 
Serum 
 ..................................................................... 42 
10.7.3. 
Analytical Method ...................................................... 43 
  10.8 Blood collection and analysis for exploratory evaluation…………………………………………….43 
       10.8.1    Sample and analysis of Substance ………………………………………………………..43 
       10.8.2    Blood collection method and pre-processing of separated serum,storage method……43 
       10.8.3    Analytical method …………………………………………………………………………43 
10.9. Endpoints and Analytical Method ....................................................................................................... 43 
10.9.1 
Safety Endpoints ....................................................... 43 
10.9.2 
Pharmacokinetic Endpoints .............................................. 45 
10.9.3 
Statistical Analysis Method .............................................. 45 


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10.9.4 
Subject Group to Be Analyzed ............................................ 45 
10.9.5 
Demographic Information ............................................... 46 
10.9.6 
Pharmacokinetic Assessment ............................................. 46 
10.9.7 
Safety Assessment ...................................................... 46 
10.10. Storage and Destruction of Samples .................................................................................................. 46 
11. Research Ethics ........................................................................................................................................ 46 
11.1. Taken Action for Protection of Subjects’ Safety ................................................................................. 46 
11.2. Examinations and Treatment Criteria for Subjects after the Clinical Study ................................... 47 
11.3. Other Items Required to Conduct the Clinical Study Safely and Scientifically .............................. 48 
11.3.1 
Study Site ............................................................. 48 
11.3.2 
Monitoring of the Clinical Study .......................................... 48 
11.3.3 
Management of the Investigational Products ................................ 48 
11.3.4 
Amendment to the Protocol .............................................. 49 
11.3.5 
Inspection and Audit.................................................... 49 
11.4. Data Processing and Data Quality Assurance ..................................................................................... 49 
11.4.1 
Source Data ........................................................... 49 
11.4.2 
Recording in Case Report Forms and Verifying Source Documents ............. 49 
11.4.3 
Data Entry Process ..................................................... 50 
11.4.4 
Storage of Research Documents .......................................... 50 
11.4.5 
Data Quality Assurance ................................................. 50 
11.4.6 
Data Security .......................................................... 51 
11.5. Confidentiality and Publication of Study Results ............................................................................... 51 
12. Reference .................................................................................................................................................. 51 
13. Attachments .............................................................................................................................................. 51 
 


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ABBREVIATIONS AND DEFINITION OF TERMS 
 
Dose Group 
Groups based on doses of the study drug 
Investigational 
product 
The study drug and placebo used in this clinical study 
ADR 
Adverse drug reaction 
AE 
Adverse event 
ALT 
Alanine transaminase 
anti-HCV Ab 
Anti-hepatitis C virus antibody 
anti-HIV Ab 
Anti-human immunodeficiency virus antibody 
AST 
Aspartate transaminase 
 
 
AUClast 
Area under the plasma drug concentration-time curve over the time interval from 
0 to the last quantifiable plasma concentration 
Area under the blood concentration–time curve to the time of the last blood 
collection that can be measured, calculated using the trapezoidal rule. The interval 
of an increase in blood concentration is calculated using the linear trapezoidal 
method, and the interval of a decrease in blood concentration is calculated using 
the log–linear trapezoidal summation. 
 
AUCinf 
Area under the plasma drug concentration-time curve over the time interval from 
0 extrapolated to infinity 
Area under the blood concentration–time curve extrapolated to infinity after 
administration of a single dose. AUCinf = AUClast + Clast / z 
AUC,7d 
Area under the blood concentration–time curve between dosing intervals after 
repeat-doses at 7 d 
t1/2 
Terminal half-life 
BP 
Blood pressure 
BUN 
Blood urea nitrogen 
Cav,7d 
Average plasma concentration during a dosing interval at 7 day 
Clast 
Last concentration of drug in plasma 
Concentration in blood at the last blood collection time measurable 
Cmax 
Maximum concentration of drug in plasma 
Maximum concentration in plasma/serum/blood 


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CL 
Clearance of drug (mL/day/Kg) 
CL/F 
Apparent clearance 
CPE 
Cytopathic effect 
CPK 
Creatine phosphokinase 
CRF 
Case report form 
DBP 
Diastolic blood pressure 
ECG 
Electrocardiogram 
EMC 
Encephalomyocardititis 
EMC-D 
D-variant of EMC virus 
ECG 
Electrocardiogram 
γ-GT 
Gamma-glutamyl transpeptidase 
HBsAg 
Hepatitis B virus surface antigen 
hzVSF-v13 
Humanized immunoglobulin of virus suppressing factor variant 13 
HR 
Heart rate 
IRB 
Institutional Review Board 
LDH 
Lactate dehydrogenase 
LLOQ 
Lower limit of quantification 
PR 
Pulse rate 
RBC 
Red blood cell 
SBP 
Systolic blood pressure 
SOP 
Standard operating procedure 
Tmax 
Time of maximum concentration 
Time to reach the maximum blood concentration after drug administration 
Vd 
Volume of distribution  
WBC 
White blood cell 


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1. TITLE AND PHASE OF THE CLINICAL STUDY 
A phase 1, dose blocked-randomized, double-blind, placebo controlled, single dosing, dose-escalation study to 
investigate the safety, tolerability, pharmacokinetic characteristics of hzVSF-v13 after intravenous(IV) 
administration in healthy male subjects 
 
A phase 1, dose blocked-randomized, double-blind, placebo controlled, single dosing, dose-escalation study 
to investigate the safety, tolerability, pharmacokinetic characteristics of hzVSF-v13 after intravenous(IV) 
administration in healthy male subjects 
 
2. STUDY SITE AND ANALYSIS INSTITUTION 
2.1. STUDY SITE 
Seoul 
National 
University 
Hospital 
Clinical Trials Center  
101, Daehak-ro, Jongno-gu, Seoul, 03080, 
Korea 
2.2. ANALYSIS INSTITUTION 
Pharmacokinetic Analysis 
APACE Co., Ltd. 
#502, 101, Daehak-ro, Jongno-gu, Seoul, Korea  
Convergence 
Research 
Building, 
Seoul 
National University College of Medicine, 
Yeongeon-dong 
 
Immunogenicity Analysis 
Hallym University College of Medicine Laboratory 
#3603, Hallym University College of Medicine, 1, Hallymdaehak-gil, 
Chuncheon-si, Gangwon-do, Korea 
 
3. NAME AND TITLE OF THE PRINCIPAL INVESTIGATOR, INVESTIGATORS, 
AND CO-INVESTIGATORS 
3.1. PRINCIPAL INVESTIGATOR 
Seoul National University College of Medicine/Department of Clinical 
Pharmacology and Therapeutics, Seoul National University Hospital  
Professor In Jin Jang, MD, PhD 
 
3.2. CO-INVESTIGATORS 
Seoul National University College of Medicine/Department of Clinical 
Pharmacology and Therapeutics, Seoul National University Hospital 
Professor Kyung Sang Yu, MD, PhD 
Seoul National University College of Medicine/Department of Clinical Pharmacology and Therapeutics, 
Seoul National University Hospital 
Associate Professor Joo Youn Cho, PhD 
Seoul National University Hospital Clinical Trials Center/Department of Clinical Pharmacology and 


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Therapeutics, Seoul National University Hospital 
Clinical Assistant Professor Seung Hwan Lee, MD, PhD 
 
3.3. INVESTIGATORS 
<See Attachment 3. Name and Title of investigators and Clinical Trial Pharmacists> 
 
3.4. CLINICAL TRIAL PHARMACISTS 
<See Attachment 3. Name and Title of investigators and Clinical Trial Pharmacists> 
 
4. NAME AND ADDRESS OF THE SPONSOR 
Sponsor: ImmuneMed Inc. 
Address: #2-2, Bio-3, Chuncheon Bioindustry Foundation, Special Research Center, 32, Soyanggang-ro, 
Chuncheon-si, Gangwon-do, Korea 
 
5. BACKGROUND OF THE CLINICAL STUDY 
5.1. DETAILS OF THE DEVELOPMENT 
Cells isolated from the spleen of mice infected with EMC virus were fused with cancer cells to obtain 
hybridoma cells, and then screened for substances with antiviral activity from these cells and selected. The 
substances secreted by these cells were named “VSF (virus suppressing factor)” derived from mice, and it 
was confirmed that VSF has antiviral activity against various viruses. Mouse-derived VSF has been 
humanized (hzVSF) with human immunoglobulin IgG4. The in silico method of Lonza was used to receive 
recommendation for thirteen variants of hzVSF-expected to have low immunogenicity. Among these, 
hzVSF-v13 has excellent antiviral activity and is unlikely to act as an immunogen in clinical because it does 
not cause T cell activity according to an in vitro peripheral blood mononuclear cells (PBMC) assay; therefore, 
it has been selected as a candidate substance. In addition, it is intended to be developed as a treatment of 
influenza virus by identifying the antiviral and anti-inflammatory activity in mice, ferrets and beagle dogs 
infected with influenza virus.  
Also, it is intended to be developed as a treatment for hepatitis B and C because it has an excellent function 
to suppress proliferation of hepatitis B virus and hepatitis C virus. 
 
5.2. EFFICACY PHARMACOLOGY TEST 
Mice, ferrets, and beagle dogs were used for non-clinical efficacy evaluation. In the case of mice, 3 to 5 each 
of male and female mice were used for evaluation, and the doses were administered from 0.1 mg/kg to 2 
mg/kg (1,000 U/kg to 20,000 U/kg). In the case of ferrets, 2 female ferrets per group were administered 
intravenously at 0.134 to 8.571 mg/kg 2 times, at 2 days and at 4 days after virus infection. In the case of 
beagle dogs, female dogs were administered a single dose of 0.5 mg/kg intravenously at 2 days after virus 
infection. In all laboratory animals administered, it was confirmed that influenza virus replication was 
suppressed and infiltration of immune cells into the lungs after influenza virus was suppressed by 
administration of hzVSF-v13. In the serum of mice, it was confirmed that the administration of hzVSF-v13 
suppressed the production of inflammatory cytokines and inflammatory mediators.  
In the cell experiment on hepatitis B virus and hepatitis C virus, it was confirmed that the synthesis of genes 
and proteins of not only cccDNA of hepatitis B virus but also viral proteins and 1a, 1b and 2a genotypes of 
hepatitis C virus was inhibited. In addition, in the cell experiment on mouse hepatitis virus which has similar 
pathology to human hepatitis, suppression of virus proliferation as well as suppression of growth, 


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suppression of inflammation, relief of symptoms and promotion of treatment were confirmed. 
 
5.3. MECHANISM OF ACTION 
hzVSF-v13 acts as a ligand for the mutated vimentin (VSF receptor, VR) that appears on the cell surface 
specifically in cells infected with virus, and it induces antiviral and anti-inflammatory mechanisms of action 
in cells. The binding site of the mutated vimentin to which hzVSF-v13 binds was confirmed, and it was 
confirmed that the antiviral action of hzVSF-v13 was absent in cells that do not express vimentin. In addition, 
in the case of cells expressed by introducing vimentin genes into the cells, antiviral ability against hzVSF-
v13 process after virus infection was restored, whereas in the case of cells expressed by introducing mutated 
vimentin genes that do not bind to hzVSF-v13, cytotoxicity due to virus infection could not be suppressed 
even after hzVSF-v13 processing. Also, as a result of investigating the location in cells by binding 
fluorescence to hzVSF-v13 after virus infection, it was confirmed that hzVSF-v13 bound to mutated 
vimentin in the cell membrane on the cell surface and decomposed in lysosomes through endocytosis. It is 
considered that hzVSF-v13 processing in cells infected with EMC virus induces AKT protein 
phosphorylation which results in suppression of replication of the virus, whereas it inhibits NF-kB 
phosphorylation which results in suppression of inflammation. 
 
5.4. SAFETY PHARMACOLOGY TEST 
Evaluation of the effect on the cardiovascular system of anesthetic and unrestrained dogs by intravenous 
administration of hzVSF-v13: In this test, 4 male anesthetic and unrestrained beagle dogs with a remote 
transmitter inserted were administered the test substance hzVSF-v13 intravenously, and blood pressure and 
heart rate measurement and electrocardiography were performed to evaluate the effect on the cardiovascular 
system.  
Dulbecco’s phosphate buffered saline (DPBS) was an excipient administered as a reference substance for 
the first administration, and 6.25, 25 and 100 mg/kg doses of the test substance was administered for the 
second, third and fourth administration. The same animal received intravenous administration of a single 
dose of each dose at an interval of 1 week. 
Cardiovascular parameters (blood pressure, heart rate and electrocardiogram) were assessed at 0 hours 
before initiation of the administration (pre-dose), and 0.083, 0.25, 0.5, 1, 2, 4, 6 and 24 hours after initiation 
of the administration.  
Blood pressure (systolic, diastolic and mean blood pressure) and heart rate did not show any change by 
administration of 6.25 and 25 mg/kg doses of the test substance. In 1 case after administration of a 100 
mg/kg dose of the test substance, blood pressure decreased and heart rate increased between 0.083 hours 
and 1 hour after initiation of the administration. 
For electrocardiogram parameters (PR, QRS, QT and QTc intervals), the QRS, QT and QTc intervals were 
not influenced by administration of 6.25, 25 and 100 mg/kg doses of the test substance, but in 1 case after 
administration of a 100 mg/kg dose of the test substance, the PR interval showed a shortened trend compared 
to the reference substance administration at 0.25 hours to 2 hours after initiation of the administration. 
Temperature did not show any change by administration of 6.25, 25 and 100 mg/kg doses of the test 
substance. 
As a result of observation of general symptoms, vomiting was observed in 1 case after administration of a 


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100 mg/kg dose of the test substance. 
From the above results, the test substance hzVSF-v13 was found to have no cardiovascular effect at 6.25 
and 25 mg/kg doses when a single dose was administered intravenously to beagle dogs under this test 
condition. Decreased blood pressure, increased heart rate, and shortened PR interval were observed due to 
the effect of test substance administration in 1 case after administration of a 100 mg/kg dose, but they 
recovered within 24 hours after initiation of the administration. 
 
5.5. PHARMACOKINETIC TEST 
The concentration of hzVSF-v13 in the plasma was measured after intravenous administration of a single 
dose to mice in order to calculate toxicokinetic parameters. In the case of the systemic exposure level of 
hzVSF-v13, AUC was 78.8 g•day/mL to 6,839.9 g•day/mL, Cmax was 5.2 g/mL to 563.0 g/mL, and t1/2 
was 8.9 to 10.1 days in male mice. In female mice, AUC was 113.0 g•day/mL to 8,686.9 g•day/mL, Cmax 
was 5.5 g/mL to 607.2 g/mL, and t1/2 was 10.2 to 13.4 days.  
After intramuscular administration of a single dose of hzVSF to mice, they had a 6-week observation period. 
The administration concentrations were 0.2 mg/kg, 0.8 mg/kg and 3.2 mg/kg, blood samples were collected 
at 1, 2, 4, 7, 14, 21, 28 and 42 days during the observation period to measure the concentration of hzVSF in 
the plasma in order to calculate toxicokinetic parameters. In the case of the systemic exposure level of 
hzVSF-v13, AUC was 35.7 kg•day/mL to 906.7 kg•day/mL, Cmax was 3.5 mg/mL to 60.7 mg/mL, and t1/2 
was 6.4 to 8.0 days in male mice. In female mice, AUC was 32.4 kg•day/mL to 859.5 kg•day/mL, Cmax was 
3.6 mg/mL to 61.6 mg/mL, and t1/2 was 4.6 to 6.5 days. An increase in the blood concentration was observed 
in higher administration doses, and a decrease in the blood concentration was observed for the 6-week 
observation period thereafter. The systemic exposure level (Cmax) increased at a ratio similar to the increase 
in administration dose, and it was determined that there was not much difference between the gender. In 
addition, cases of death and abnormal general symptoms were not observed. 
As a result of measuring the concentration of hzVSF-v13 in the plasma after intravenous administration to 
rats for 2 week at 3 doses per week, 6 doses in total, and calculating toxicokinetic parameters, Tmax was 14 
to 14.02 days. For the systemic exposure level of hzVSF, the AUCall and Cmax were 4,095 ng•hr/mL to 59,151 
ng•hr/mL and 307 ng/mL to 5,190 ng/mL in female animals. The AUCall and Cmax were 3,679 ng•hr/mL to 
72,727 ng•hr/mL and 238 ng/mL to 6,153 ng/mL in female animals. In rats, the blood collection days in the 
2-week administration period (administered 6 doses in total; administration days: Days 1, 3, 6, 9, 11 and 14) 
were Days 1, 6, 11, and 14, and an increase in the blood concentration was observed as the number of doses 
administered increased at all doses. The highest concentration was observed after the administration (0.5 hr) 
at the final administration day (Day 14) (excluding male low-dose group), and a decrease in the blood 
concentration was observed during the following 6-week observation period. The systemic exposure level 
(AUCall, Cmax) increased at a ratio similar to the increase in administration dose, and it is determined that 
there was no difference between the gender. 
As a result of measuring the concentration of hzVSF-v13 in the plasma after intravenous administration to 
beagle dogs for 2 week at 3 doses per week, 6 doses in total, and calculating toxicokinetic parameters, Tmax 
was 11.0 to 16.0 days. For the systemic exposure level of hzVSF-v13, the AUCall and Cmax were 2,842.1 
g•hr/mL to 62,769.4 g•hr/mL and 276.0 g/mL to 4,090.0 g/mL in male animals. The AUCall and Cmax 
were 2,727.7 g•hr/mL to 57,247.4 g•hr/mL and 229.0 g/mL to 4,180.0 g/mL in female animals. In 
beagle dogs, the systemic exposure level (AUCall, Cmax) of the test substance hzVSF increased at a ratio 
similar to the increase in administration dose, and it increased according to the increase in the number of 
doses administered at all doses. The highest blood concentration (Tmax) was observed at Day 11 (5th 
administration) in male animals in the 6.25 and 100 mg/kg treatment groups and female animals in the 6.25 


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and 25 mg/kg treatment groups, and at Day 14 (6th administration) and at 0.5 hr after the administration in 
male animals in the 25 mg/kg treatment group and female animals in the 100 mg/kg treatment group. Based 
on the results of analyses performed subsequently at every week up to weeks 3 to 8 (blood collection days: 
Days 22, 29, 36, 43, 50 and 57), blood concentration gradually decreased, and the test substance was detected 
up to week 8 in 1/2 male cases and up to week 7 in 1/2 female cases in the 100 mg/kg treatment group. In 
addition, differences between females and males were not observed. In addition, the half-life (t1/2) after 
administering 6 doses for 2 weeks was 16.5 to 22.6 days at all doses in male and female animals. 
 
5.6. TOXICITY TEST 
- Single-dose toxicity test 
• Single-intravenous-dose toxicity test of hzVSF-v13 using rats: This test was performed to evaluate the 
toxicity after intravenous administration of a single dose of the test substance hzVSF-v13 to 6-week-old 
male and female Sprague-Dawley rats, and to estimate the approximate lethal dose. The study was composed 
of 2 groups—a group treated with the test substance at a dose of 100 mg/kg and a control group (DPBS)—
and a single dose was administered intravenously to 5 male and female animals respectively. For 14 days 
after the administration, general symptoms were observed and body weight was measured. Once the 
observation period was over, the animals were euthanized, and necropsy was performed. Cases of death 
were not observed in male and female animals in the 100 mg/kg treatment group. In addition, the effects of 
administration of the test substance on general symptoms, weight measurements, and necropsies were not 
recognized. Based on the results of intravenous administration of a single dose of hzVSF-v13 to rats under 
the conditions of this test, the approximate lethal dose has been determined to exceed 100 mg/kg in both 
male and female animals. 
• Single-intramuscular-dose toxicity test of hzVSF-v13 using rats: This test was performed to evaluate the 
toxicity after intramuscular administration of a single dose of the test substance hzVSF-v13 to 6-week-old 
male and female Sprague-Dawley rats, and to estimate the approximate lethal dose. The study was composed 
of a group treated with the test substance at a dose of 80 mg/kg and a control group (DPBS), and a single 
dose was administered intramuscularly to 5 male and female animals respectively. For 14 days after the 
administration, general symptoms were observed and body weight was measured. Once the observation 
period was over, the animals were euthanized, and necropsy was performed. Cases of death and abnormal 
general symptoms were not observed in male and female animals in the 80 mg/kg treatment group. The 
effects of administration of the test substance on weight measurements and necropsies were not recognized. 
Based on the results of intramuscular administration of a single dose of hzVSF-v13 to rats under the 
conditions of this test, the approximate lethal dose has been determined to exceed 80 mg/kg in both male 
and female animals. 
- Repeat-dose toxicity test 
• The results of 4-week repeat-dose and 4-week recovery tests in rats were as follows. This test was 
performed to evaluate the toxic responses and safety observed in necropsies performed 2 weeks after 
the final administration of the repeated intravenous administration of hzVSF-v13 to male and female 
Sprague-Dawley (Crl: CD [SD]) rats 3 times weekly for 2 weeks—6 times in total—and to set a 4-
week recovery group and evaluate the reversibility of toxic changes. The test substance was 
administered intravenously at 3 doses—6.25, 25 and 100 mg/kg—to 10, 10 and 15 each of male and 
female animals in each group 6 times in total for 2 weeks. A control group (DPBS) was set as well, 
and intravenous administration was given to 15 animals 6 times in total for 2 weeks. A 4-week recovery 
period was scheduled from 2 weeks after the final administration in order to evaluate the reversibility 
of toxicity in 5 each of male and female animals in the control group and 100 mg/kg treatment group. 


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In addition, a toxicokinetic test group was set, and 3 each of male and female animals in each group 
were analyzed at each time point of blood collection. General symptom observation, body weight 
measurement, feed intake measurement, functional test (only applicable to the main test group), 
ophthalmologic examination, and urinalysis were performed during the observation period, and 
hematology, blood biochemistry, organ weight measurement, visual inspection at necropsy, and 
histopathological examination were performed after the end of the observation period. The systemic 
exposure level of the drug was confirmed as well through a toxicokinetic test. No effect of 
administration of the test substance on the general symptoms, weight, feed intake, ophthalmologic 
examination, urinalysis, hematology, blood biochemistry, organ weight, and necropsy was observed 
in male and female animals in the 6.25, 25 and 100 mg/kg treatment groups. As a result of the 
histopathological examination, no effect of administration of the test substance was observed in male 
and female animals in the 100 mg/kg treatment group. In addition, it was determined that there was 
local tolerance because evidence of myofiber damage was not observed at the administration site of 
male and female animals in the 6.25, 25 and 100 mg/kg treatment groups. During the 2-week 
administration period, an increase in the blood concentration was observed as the number of doses 
administered increased at all doses. The highest concentration was observed after the administration 
(0.5 hr) at the final administration day (Day 14) (excluding male low-dose group), and a decrease in 
the blood concentration was observed during the following 6-week observation period. The systemic 
exposure level (AUCall, Cmax) increased at a ratio similar to the increase in administration dose, and it 
is determined that there was no difference between the gender. As described above, based on the results 
of repeated intravenous administration of the test substance hzVSF-v13 to rats 3 times weekly for 2 
weeks—6 times in total—under the conditions of this test, the no-observed-adverse-effect level 
(NOAEL) has been determined to be not less than 100 mg/kg in both male and female animals. 
• 
The results of 4-week repeat-dose and 4-week recovery tests in beagle dogs were as follows. This test 
was performed to evaluate the toxic responses and safety observed in necropsies performed 2 weeks after 
the final administration of the repeated intravenous administration of the test substance hzVSF-v13 at 
doses of 0 (control group), 6.25, 25 and 100 mg/kg 3 times weekly for 2 weeks using 3 each of male and 
female beagle dogs per group. Furthermore, starting from 2 weeks after the final administration, a 4-
week recovery group composed of 2 each of male and female animals was set in the control group and 
the high-dose group to check the reversibility of the toxic changes. Also, a toxicokinetic test was 
performed to evaluate the systemic exposure level of the drug. Animal deaths did not occur in male and 
female animals in all test groups during the test period. However, symptoms deemed to be 
hypersensitivity reactions, such as hypoactivity, vomiting, paleness, or hyperemia, were observed after 
the 4th to 6th administrations in male and female animals in the 100 mg/kg treatment groups, and after 
the 6th administration in the 25 mg/kg treatment group. In the histopathological examination, the size of 
germinal centers of the spleen increased in male and female animals in all test substance treatment groups, 
and this is considered to be due to the immune response of the test substance. No toxicological effect of 
administration of the test substance on the weight, feed intake, eye examination, electrocardiography, 
urinalysis, hematology, blood biochemistry, organ weight, necropsy and local tolerance test was observed. 
In the toxicokinetic test, the systemic exposure level (AUCall, Cmax) of the test substance hzVSF-v13 
increased in proportion to the increase in administration dose, and it increased according to the increase 
in the number of doses administered. The highest blood concentration (Tmax) was observed at Day 11 (5th 
administration) in several treatment groups, and after the administration (at 0.5 hr) at Day 14 (6th 
administration) in several treatment group. Thereafter, the blood concentration gradually decreased from 
Week 3, and no difference was observed between male and female animals. In addition, as a result of 
measuring anti-drug antibodies (ADAs) against hzVSF-v13, it was confirmed that ADAs were produced 
in most of the animals starting from about 11 days after initiating administration of the test substance. 
Due to the results described above, it has been determined that the no-observed-adverse-effect level 
(NOAEL) for male and female beagle dogs under these test conditions is 6.25 mg/kg. 


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6. OBJECTIVES OF THE CLINICAL STUDY 
6.1. PRIMARY OBJECTIVE 
To evaluate the safety and tolerability after intravenous administration of a single dose of the study drug 
hzVSF-v13 in healthy male subjects. 
6.2. SECONDARY OBJECTIVE 
To evaluate the pharmacokinetic characteristics after intravenous administration of a single dose of the 
study drug hzVSF-v13 in healthy male subjects. 
 
7. INVESTIGATIONAL PRODUCT 
7.1. STUDY DRUG  
Generic 
Name 
(Code 
Name) 
Active 
Ingredie
nt 
Amount 
Other Additives 
Storage 
Method 
Remar
ks 
hzVSF-v13 
hzVSF 
40 mg/ml  
x 5 ml 
L-histidine 
Histidine hydrochloride 
polysorbates 20 
Sucrose  
Water for injection 
2 to 8°C,  
Sealed 
container 
 
 
7.2. PLACEBO 
Normal saline 
 
7.3. EXPECTED ADVERSE EVENTS (SIDE EFFECTS) AND PRECAUTIONS FOR USE 
7.3.1. EXPECTED SIDE EFFECTS FROM NON-CLINICAL LABORATORY STUDIES RESULTS 
Since hzVSF-v13 has never been administered to human subjects, there are no known adverse events. Also, 
since there are no similar drugs of the same class targeting vimentin or mutant vimentin, it is not possible to 
predict adverse events based on the adverse event reports of similar drugs. During the observation period in the 
4-week repeat-intravenous-dose toxicity test in beagle dogs, no animal deaths occurred in male and female 
animals in all test groups, and no symptoms were observed until the 3rd administration. However, after the 4th 
and 5th administration (9 and 11 days after initiating the administration), symptoms such as hypoactivity, 
vomiting, paleness, or hyperemia were observed in 2 to 3 out of 5 male animals and 4 out of 5 female animals 
in the 100 mg/kg treatment group. At the 6th administration (14 days after initiating the administration), 
symptoms such as hypoactivity, vomiting, paleness, or hyperemia were observed in all female and male animals 
in the 25 mg/kg treatment group, and 4 out of 5 male animals and 3 out of 5 female animals in the 100 mg/kg 
treatment group. Besides, 1 to 2 cases of soft stool were observed in the control group and 1 each of female 
animals the 6.25 and 25 mg/kg treatment groups, and no symptoms were observed in the recovery group.  
During the observation period in the 4-week repeat-intravenous-dose toxicity test using rats, cases of death and 
abnormal general symptoms were not observed in male and female animals in the 6.25, 25 and 100 mg/kg 
treatment groups during the administration period. Loss of teeth was observed in 1 female animal in the control 


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group, but it was an incidental change observed in the control group. During the recovery period, cases of death 
and abnormal general symptoms were not observed in male and female animals in the control group and the 
100 mg/kg treatment group. 
 
7.4. PACKAGING AND LABELING 
The packaging container of the investigational product shall be labeled in Korean containing the following 
information: 
• 
“For Clinical Trial Use Only” indication 
• 
Name or drug identification mark of the investigational product 
• 
Batch number or code number 
• 
Name, address and telephone number of the sponsor (IND holder in the case that a clinical study 
plan has been approved) 
• 
Shelf life 
• 
Storage condition 
• 
Reference code that identifies the clinical study 
• 
Subject identification number, clinical drug number, and visit number (These can be documented 
and omitted if documentation is unnecessary.) 
 
7.5. STORAGE 
A clinical trial pharmacist who manages the investigational products (hereinafter, “clinical trial pharmacist”) 
is responsible for the receipt, storage, dispensation, management and return of the investigational products 
used in the clinical study. The clinical trial pharmacist should confirm the receipt of the investigational 
products and the number of products in writing, sign and manage them properly. The clinical trial pharmacist 
should ensure that the investigational products are administered to the subjects only in accordance with the 
protocol, and the records of the management of all investigational products provided to each subject should 
be accurate. Unused investigational products will be stored at 2 to 8°C until the sponsor makes a decision 
on destruction or recall. Upon the end of study, all unused drugs and a copy of the investigational product 
management record have to be sent to the clinical research associate in charge of this study. 
 
8. TARGET DISEASES 
Influenza, hepatitis B and C  
9. Subjects 
9.1. NUMBER OF SUBJECTS 
The targeted number of subjects is 56 subjects in total, and 4 or 8 subjects will be assigned per dose group. 
 
hzVSF-v13 IV 10 mg, 20 mg – 4 subjects in each dose group  
(3 subjects for the study drug, 1 subject for the placebo) 
 
hzVSF-v13 IV 50 mg, 100 mg, 200 mg, 400 mg, 800 mg, 1,200 mg – 8 subjects in each dose group  


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(6 subjects for the study drug, 2 subject for the placebo) 
 
 
Single-dose study (intravenous administration) 
Dose Group 
Number of Subjects 
Group 1 (10 mg IV) 
hzVSF-v13: 3 subjects 
Placebo: 1 subject 
Group 2 (20 mg IV) 
hzVSF-v13: 3 subjects 
Placebo: 1 subject 
Group 3 (50 mg IV) 
hzVSF-v13: 6 subjects 
Placebo: 2 subjects 
Group 4 (100 mg IV) 
hzVSF-v13: 6 subjects 
Placebo: 2 subjects 
Group 5 (200 mg IV) 
hzVSF-v13: 6 subjects 
Placebo: 2 subjects 
Group 6 (400 mg IV) 
hzVSF-v13: 6 subjects 
Placebo: 2 subjects 
Group 7 (800 mg IV) 
hzVSF-v13: 6 subjects 
Placebo: 2 subjects 
Group 8 (1200 mg IV) 
hzVSF-v13: 6 subjects 
Placebo: 2 subjects 
 
9.2. RATIONALE FOR CALCULATION OF THE NUMBER OF SUBJECTS 
The purpose of the study is exploratory which is not to verify statistical hypotheses, and in the case of Phase 
1 clinical studies being conducted using new drugs for which safety is not established, it is ethically desirable 
to conduct the study in the minimum number of subjects while satisfying the study objectives. In addition, 
dose groups had a certain ratio of subjects who will receive the placebo to enable double-blind for an objective 
safety and tolerability review. In this study, for the low dose groups (Groups 1 and 2), the sentinel dose groups, 
the target number of subjects per dose group has been set to 4 subjects per dose group, and the target number 
of subjects for other dose groups has been set to 8 subjects per dose group.  
9.3. SUBJECT INCLUSION/EXCLUSION CRITERIA 
9.3.1. Inclusion Criteria 
1) 
Healthy males aged 19 to 45 years inclusive at the time of the screening visit 
2) 
Individuals with a BMI of not less than 18.0 kg/m2 to not more than 27.0 kg/m2 and weighed not less 
than 55 kg and less than 90 kg at the time of the screening visit  
3) 
Individuals confirmed clinically healthy based on medical history, physical examination, vital sign, 
electrocardiography (ECG), and appropriate clinical laboratory tests (provided that individuals outside 
the normal range may participate subject to investigator discretion) 
4) 
Individuals who have agreed to use a medically acceptable method of dual contraception and not to 


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donate sperm from the first day until 30 days after the last day of investigational product administration 
5) 
Individuals who have voluntarily decided to participate in this clinical study and have given a written 
consent to comply with the requirements of the clinical study 
9.3.2. Exclusion Criteria 
1) 
Individuals with a clinically significant hepatic, renal, digestive, respiratory, musculoskeletal, endocrine, 
neuropsychological, hemato-oncologic, cardiovascular, or other disease or history 
2) 
Individuals with a clinically significant history of hypersensitivity reactions to the components of 
hzVSF-v13, drugs containing components of the same class, or other drugs (aspirin, non-steroidal anti-
inflammatory drugs, antibiotics, etc.) 
3) 
Individuals with a positive result in the immunogenicity test for hzVSF-v13 conducted during the 
screening test 
4) 
Individuals who have a history of drug abuse, or who have positive in the test for abuse-likely drugs in 
the urine drug screening test 
5) 
Individuals with abnormal results for any of the following vital signs at the time of the screening visit: 
A. Systolic blood pressure: < 90 mmHg or > 140 mmHg 
B. 
Diastolic blood pressure: < 50 mmHg or > 90 mmHg 
C. 
Heart rate: < 50 bpm or > 90 bpm 
6) 
Individuals with abnormal results for any of the following ECG items at the time of the screening visit: 
A. PR > 210 msec 
B. 
QRS complex: > 120 msec 
C. 
QTc > 450 msec  
7) 
Individuals who have participated in another clinical study or bioequivalence study and received an 
investigational product within 3 months prior to the first day of administration (provided that 6 months 
from 06/12/2019)  
8) 
Individuals who have donated whole blood within 2 months prior to the first day of administration, or 
donated blood components or received blood within 1 month prior to the first day of administration 
9) 
Individuals who have taken drug-metabolizing enzyme inducers or inhibitors, such as barbitals, within 
1 month prior to the screening 
10) Individuals who have consumed grapefruit/caffeine-containing foods within 3 days of the first 
administration, and individuals who are unable to avoid consuming grapefruit-containing foods from 3 
days prior to admission until the date of discharge 
11) Individuals who have taken prescription drugs or oriental medications within 2 weeks prior to the first 
day of administration, or who have taken over-the-counter (OTC) drugs within 1 week prior to the first 
day of administration (provided that individuals who meet other requirements may participate in the 
clinical study subject to investigator discretion) 
12) Individuals who consume high amounts of caffeine or alcohol and individuals who are heavy smokers 
(caffeine > 5 units/day, alcohol > 21 units/week (1 unit = 10 mL of pure alcohol), smoking > 10 
cigarettes/day) 
13) Individuals who are unable to eat meals provided by the study site 
14) Individuals who have participated in this study 
15) Individuals who have a positive result for serology (hepatitis B, human immunodeficiency virus [HIV], 
and hepatitis C tests) 
16) Individuals with veins that are not suitable for intravenous catheter insertion or multiple venipunctures 
17) Individuals who do not agree to use a medically acceptable method of dual contraception from the first 
day until 30 days after the last day of investigational product administration 
18) Other individuals deemed unsuitable as a subject by an investigator 
 
 


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9.4. SUBJECT NUMBER 
4-figure screening numbers starting from S001 will be assigned to the volunteers who provided a written 
consent to participate in the clinical study in the order of the informed consent form signed (e.g., S001, 
S002, etc. will be assigned in the order of the informed consent form signed). 
Subject ID will be assigned in the order of passing the screening tests finally. If the subjects pass the 
screening tests on the same day, subject numbers will be assigned in the order of the informed consent 
form signed. The subject ID is composed of five figures starting from R1001—the first figure indicates 
whether a subject has been substituted (1: not a substituted subject; 2: a substituted subject), the second 
figure indicates the dose group, and the last two digits indicate the order of the subjects participating in 
this study.  
The subject ID assigned to each subject will be used as subject identification codes that identify the subjects 
until the end of the clinical study. 
 
Single-dose study (intravenous administration) 
 
Dose Group 
Subject Number 
Group 1 (10 mg IV) 
R1101 ~ 
Group 2 (20 mg IV) 
R1201 ~ 
Group 3 (50 mg IV) 
R1301 ~ 
Group 4 (100 mg IV) 
R1401 ~ 
Group 5 (200 mg IV) 
R1501 ~ 
Group 6 (400 mg IV) 
R1601 ~ 
Group 7 (800 mg IV) 
R1701 ~ 
Group 8 (1200 mg IV) 
R1801 ~ 
 
 
9.5. SUBJECT PRECAUTIONS/RESTRICTIONS 
In principle, no food intake should be allowed except for the foods and drinking water provided during the 
hospitalization period; however, snacks will be allowed to be provided as long as they do not have any 
impact on the clinical study. Ingestion of caffeinated or grapefruit-containing beverages or foods, cigarette 


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smoking and alcohol consumption will be prohibited from 3 days before the admission until the day of 
discharge. Also, strenuous exercises exceeding activities of daily living will be prohibited and use of 
contraception has to be maintained throughout the clinical study period. In addition, the subjects will be 
required to fast, except for drinking water, after 10 p.m. on the day before the scheduled date of clinical 
laboratory tests, and any external factors that could have an effect on the clinical laboratory tests (drinking, 
smoking, strenuous exercise, etc.) will be restricted if possible prior to the tests even after the discharge. In 
addition, fluid intake is also prohibited from an hour before the administration to 2 hours after the 
administration, and food intake is prohibited for 4 hours after the administration.  
9.6. DROP-OUT AND SUBJECT SUBSTITUTION 
“Enrollment” refers to the randomization (assignment of subject ID) of subjects participating in the study (i.e., 
those who signed the informed consent form) due to their eligibility based on the inclusion/exclusion criteria. 
Incompletion of a study by an enrolled subject is called “drop-out.” The drop-out of a subject may be decided 
at any time during the study period. A subject who applies to one of the situations shown below is processed 
as a dropout, and the date of drop-out, date of the last administration and reason for drop-out have to be recorded 
in a CRF at the moment of drop-out. 
1) In the case that a subject requests discontinuation of the investigational product administration during 
the clinical study, or withdraws his consent to participation in the study 
2) In the case that a subject has received a drug that is expected to affect the evaluation of the safety or 
pharmacokinetics of the study drug during the clinical study 
3) In the case that serious adverse events/adverse drug reactions have occurred 
4) In the case that a subject is unable to perform blood sampling for the testing for pharmacokinetics/safety 
5) In the case that significant protocol violation cases are newly identified during the clinical study 
6) In the case that the sponsor or the Ministry of Food and Drug Safety requests discontinuation 
7) In the case that the principal investigator/investigator determines that the study has to be discontinued 
due to other reasons 
 
This study allows enrollment of a small number of backup subjects in advance considering the drop-out rate 
prior to the initial administration, and a dropped out subject may be substituted with a backup subject in case 
of dropping out prior to the initial administration. In the event of more than 2 subjects in the same dose 
group drop out after administration of the investigational product, substitution of the subjects shall be 
decided after a discussion among the principal investigator, sponsor, pharmacokinetic and statistical analysts. 
The first figure of the substituted subject’s subject number will be 2, and the last 3 figures will be the same 
number as the dropped out subject’s subject number (e.g., if Subject R1104 drops out and is replaced, the 
subject number to be assigned will be R2104). The substituted subject will be assigned to the same dose 
group as the dropped out subject. The test results of the relevant subject may be reviewed in the finally 
evaluable items up until the time of discontinuation/drop-out. 
 


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9.7. STUDY COMPLETION 
“Completion” in this clinical study refers to the case that the subject meets the inclusion/exclusion criteria 
specified in the protocol and has completed the entire study process and all visits. 
 
9.8. BACKUP SUBJECTS (SUBJECT CANDIDATES) 
This study can recruit backup subjects (subject candidates) for smooth progress. Those who participate as 
backup subjects and have not received the study drug will be sent home after other subjects complete the 
initial administration, and backup subjects may participate in the next treatment group. 
 
10. ANALYTICAL METHOD 
10.1. STUDY DESIGN 
This is a Phase 1, dose blocked-randomized, double-blind, placebo controlled, single dosing, dose-escalation 
study to investigate the safety, tolerability, pharmacokinetic characteristics of hzVSF-v13 after intravenous 
administration in healthy male subjects. Subjects will be randomized to the test group and the control group 
at a 3:1 ratio in each dose groups; however, in the case of all dose groups except for Group 1 and Group 2 
(Group 3–Group 8), the first 3 out of 8 subjects in each dose group will be randomized to be 2 subjects for 
the study drug and 1 subject for the placebo. Collection of adverse events, physical examinations, vital sign, 
electrocardiography (12-lead ECG), clinical laboratory tests, immunogenicity test, etc. will be performed to 
evaluate the safety and tolerability, and blood collection will be carried out to evaluate the pharmacokinetic 
characteristics. 
RATIONALE FOR ADMINISTRATION DOSES 
 
Human Equivalent Doses and MRSD 
Species 
NOAEL 
HED by FDA guidance 
Safety factor (1/10) 
Human (60kg) dose 
Rat 
100 mg/kg 
100 mg/kg 
10 mg/kg 
600 mg 
Dog 
6.25 mg/kg 
6.25 mg/kg 
0.625 mg/kg 
37.5 mg 
In the homogeneous population of health volunteers with similar demographic characteristics, the effect of 
differences in individual weights on pharmacokinetic characteristics is considered to be insignificant. In 
addition, if the drug is administered at doses depending on body weights or body surface areas, there may be 
difficulties to conduct the study compared to administration at a fixed dose, and there may be difficulties 
compared to administration at a fixed dose even in evaluation of the safety and tolerability. Therefore, the 
administration dose of the investigational product will be a fixed dose. 
The results of beagle dogs, which are the most sensitive species of those applied, have confirmed that the 
maximum no-observed-adverse-effect level (NOAEL) is 6.25 mg/kg. Large molecules (not less than 100,000 
daltons), such as antibodies, are scaled by body weight, not by body surface area [HED (mg/kg) = NOAEL 
(mg/kg)]. In this case, the human equivalent dose (HED) converted into weight of the maximum no-observed-
adverse-effect level (NOAEL) is 6.25 mg/kg, and the maximum recommended starting dose (MRSD), given 
a safety factor of 10, is 37.5 mg, assuming that healthy adult males weigh 60 kg. 
Furthermore, pharmacological effects that suppress viral replication and inflammatory reaction have been 


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confirmed at 2 mg/kg upon intravenous administration to influenza mouse models. The human equivalent dose 
(HED) of this dose converted into weight that has been scaled by body weight [HED (mg/kg) = NOAEL 
(mg/kg)] is 2 mg/kg, and given a safety factor of 10, it is 12 mg respectively, assuming that healthy adult males 
weigh 60 kg. 
Therefore, the initial administration dose has been determined to be 10 mg taking into account that the weight-
corrected pharmacologically active dose is the smaller dose between the MRSD and the weight-corrected 
pharmacologically active dose. 
 
RATIONALE FOR BLOOD COLLECTION TIMES 
The pharmacokinetic parameters reported in animal studies on intravenous administration of hzVSF-v13 are 
as shown below. 
LC51-0255 
BW (kg) 
CL (mL/day/kg) 
Vd7d (mL/kg) 
Mouse 
0.03 
2.80 – 4.90 
54.03 – 62.80 
Rats 
0.3 
1.21 – 1.70 
42.30 – 56.79 
Dogs 
10.0 
1.58 – 2.19 
46.87 – 51.99 
Considering that the half-life of the study drug in the human body estimated using the allometry method based 
on these is estimated to be approximately 23 to 34 days, the half-life of the study drug is estimated to be 
approximately 30 days. Therefore, the last blood collection time point has been set as 2,184 hours (92 d 0 h). 
Based on these, the pharmacokinetic blood collection time points in the single-dose study have been set as 
follows: 0 h (pre-dose), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 336 (15 d 0 h), 504 (22 
d 0 h), 672 (29 d 0 h), 840 (36 d 0 h), 1,176 (50 d 0 h), 1,512 (64 d 0 h), 1,848 (78 d 0 h) and 2,184 h (92 d 0 
h; post-dose) (26 points).  
Excluding the volunteers who were positive in the immunogenicity test for hzVSF-v13 during the screening 
tests, the blood collection time points in the single-dose study have been set as the time of screening tests, 168 
(8 d 0 h), 336 (15 d 0 h), 672 (29 d 0 h), 1,344 (57 d 0 h), 2,184 h (92 d 0 h; post-dose) (6 points) in order to 
confirm the production of antibodies against hzVSF-v13. 
 
DEFINITION OF DOSE-LIMITING TOXICITY (DLT) 
Dose limiting toxicity (DLT) is hematologic or non-hematologic toxicity related to the investigational product, 
and it is defined as adverse events of at least Grade 3 based on the National Cancer Institute (NCI) - Common 
Terminology Criteria for Adverse Events (CTCAE) version 4.03. 
 
DOSE ESCALATION/DISCONTINUATION CRITERIA 
Each dose group will have hzVSF-v13 and the placebo randomized at a 3:1 ratio to conduct the clinical study. 
The study will be proceeded sequentially from the lowest dose, and whether to proceed with the next dose will 


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be determined based on the tolerability and safety results of the previous dose.  
Each subject in Group 1 and Group 2 will be administered, and if no significant dose-limiting toxicity (DLT) 
occurs within 72 hours, then the next subject will be administered.  
In the case of all dose groups except for Group 1 and Group 2 (Group 3–Group 8), 3 out of 8 subjects in each 
dose group (2 subjects for the study drug and 1 subject for the placebo) will receive the investigational product 
(hzVSF-v13 or placebo) at least 72 hours earlier than the remaining subjects in the same dose group. If no 
significant dose-limiting toxicity occurs within 72 hours, the remaining subjects in the relevant dose group 
will receive the investigational product (hzVSF-v13 or placebo) depending on the randomization.  
In the case that at least 3 subjects experience a Grade 3 adverse event or at least 1 subject in certain dose 
groups experience a Grade 4 adverse event based on the CTCAE published by the United States NCI, the 
principal investigator shall consult the independent SMC, established separately from this study, and discuss 
discontinuation of the relevant dose group and dose escalation with the sponsor. (For Group 1 and Group 2, 
discontinuation of the dose group and dose escalation shall be considered based on the following criterion: 
occurrence of Grade 3 adverse event in at least 2 subjects or Grade 4 adverse event in at least 1 subject.) 
Empirically, acute stage adverse events, such as acute hypersensitivity reactions requiring therapeutic 
interventions, are considered assessable by observing for 2 weeks after administration of the investigational 
product. Accordingly, after all subjects complete all scheduled tests up to 15 d for each dose group, the SMC 
will evaluate the safety-related data. With reference to the evaluation result of the SMC, the principal 
investigator and the sponsor will decide by mutual consent whether to continue the clinical study and to 
proceed with the next step. 
 
OVERALL SCHEDULE 
The screening tests shall only be performed in volunteers within 4 weeks prior to the first day (1 d) of 
investigational product administration (−28 d to −2 d) in order to select the subjects considered to be eligible 
for this clinical study. The selected subjects will be randomly assigned to either the test group or the control 
group (−1 d) and will be admitted to the Seoul National University Hospital Clinical Trials Center 2 days (-
2d) prior to administration of the investigational product. 
 
 
 
 
 
 
 
 
 
 
 
 


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 
Single-Dose Study (Intravenous Administration) 
- 10 mg, 20 mg, 50 mg, 100 mg, 200 mg, 400 mg, 800 mg, 1,200 mg IV 
 
 
The selected subjects will be admitted to the Seoul National University Hospital Clinical Trials Center 2 days 
(-2d) prior to administration of the investigational product. The skin test will be performed a day (-1 d) prior 
to administration of the investigational product. Only the subjects who did not have clinically significant 
findings in the skin test will have intravenous (IV) administration of the investigational product (hzVSF-v13 
or placebo) at 9 a.m. on the day (1d) of investigational product administration. The subjects will be required 
to perform the clinical study procedures in accordance with the predefined schedule and will be discharged 7 
days (8d) after the administration. Thereafter, the subjects will visit the Seoul National University Hospital 
Clinical Trial Center as outpatients from 9 d to 92 d in order to perform the clinical study procedures according 
to the predefined schedule. After completing all scheduled tests up to 15 d for each dose group, an independent 
SMC, established separately from this study, will evaluate the safety-related data. With reference to the 
evaluation result of the SMC, the principal investigator and the sponsor will decide by mutual consent whether 
to continue the clinical study and to proceed with the next step. 
 
10.2. RANDOMIZATION, MAINTAINING DOUBLE-BLIND AND UNBLINDING 
RANDOMIZATION 
For randomization in this clinical study, an independent person in charge of randomization will randomize 
using SAS®  ver. 9.3 (or a later version) and provide a randomization table for a code manager. The person 
in charge of randomization will deliver randomization codes, which will be prepared before the study, to the 
code manager, and the investigator will assign subject numbers in the order of subjects’ enrollment in the 
study. Each subject will be assigned the investigational product (study drug or placebo) according to the 
relevant subject number, and the clinical trial pharmacist will dispense the investigational product (study 
drug or placebo) assigned for each subject number. Randomization codes will be kept separately by the 
administrator. Using random numbers that are only open to the code manager as seed numbers, subjects 
could be assigned to the study group and the control group at a 3:1 ratio in each dose group. However, in the 
case of all dose groups except for Group 1 and Group 2 (Group 3–Group 8), the first 3 out of 8 subjects in 
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DOUBLE-BLIND 
As it has been designed to investigate the safety, tolerability and pharmacokinetic characteristics after 
intravenous administration of a single dose of hzVSF-v13, it will be conducted using a double-blind method 
for each dose group.  
MAINTAINING DOUBLE-BLIND 
1. Confirmation that the investigational product cannot be distinguished 
The clinical trial pharmacist will dispense the study drug or placebo in a normal saline bag prepared to maintain 
double blinding, thereby maintaining double blinding for the principal investigator and the subjects. The label 
indicated in the protocol is a label for the study drug and placebo that are only provided to the pharmacy, and 
neither the principal investigator nor the subject will be aware of the type of drug being administered prior to 
the end of the study. The investigational products will be monitored by a separate clinical research associate 
who is not involved in this clinical study, and the relevant clinical research associate and the clinical trial 
pharmacist will be exempted from blinding. 
2. Preparation and maintenance of the randomization code and blinding envelop 
The code manager will generate randomization codes according to the randomization method, and the clinical 
trial pharmacist will dispense the investigational product (study drug or placebo) assigned for each subject 
number accordingly. The randomization codes shall be kept safe until unblinding occurs. 
The investigational product assigned to each subject will be decided based on the relevant randomization 
number, and the randomization codes shall not be disclosed unless the randomization codes are unblinded upon 
termination of the clinical study for each stage. However, to be prepared for unblinding due to occurrence of 
an emergency situation, such as a serious adverse event, the code manager will make a blinding envelop with 
randomization numbers and deliver it to the investigator for storage. In addition, the blinding envelop should 
be stored properly by the sponsor and the principal investigator until the end of the clinical study and can only 
be opened by a prescribed procedure. 
3. Storage of the investigational product 
The blinding status should be maintained before unblinding. For this, the remaining investigational products 
have to be stored and sealed properly. 
UNBLINDING  
1. Unblinding process at the end of each study or the clinical study  
After the end of each study or the the clinical study and all case report forms and data (excluding blood 
concentration measurement results) are locked, the final unblinding (randomization code for each stage) should 
be done. 
After the data are locked, the investigator makes a request for unblinding (e-mail, fax, etc.) to the code manager. 
The code manager records all information related to unblinding (unblinding date, time, and name of investigator 


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requesting unblinding) and send unblinded randomization codes for each stage to the investigator (e-mail, fax, 
etc.). 
2. Unblinding process at an emergency situation 
The unblinding process for unblinding due to occurrence of an emergency situation, such as a serious adverse 
event, is as follows: 
1) The subject’s safety results will be evaluated based on the United States NCI “CTCAE version 4.03.” For 
reference, in the case of being determined as a clinically significant finding, the investigator should evaluate 
the causal relationship to the investigational product while blinded. 
2) Before unblinding individually, the investigator will send the relevant information to the sponsor. 
3) It should be confirmed whether at least half of the members required to be present when unblinding have 
participated (participants when unblinding: principal investigator, investigators, and sponsor’s 
representative). 
4) All attendees will share and reconfirm the reason for unblinding. 
5) Randomization codes will be unblinded and disclosed by opening the blinding envelop, etc. 
6) After all participants confirm the disclosed randomization codes, they will sign for confirmation on a 
randomization code disclosure confirmation form. 
7) In the case that adverse events occur in the hzVSF-v13 treatment group, the investigator and the sponsor 
must discuss whether to continue the clinical study. In the case that adverse events occur in the placebo 
group, the clinical study shall continue without having a discussion. 
8) in the case that immediate disclosure of randomization codes is required to ensure the rights and interests 
as well as safety of the subject, the subject’s code may be disclosed under the responsibility of the person in 
charge of disclosure. At this time, the person in charge of disclosure shall immediately inform the sponsor 
of the randomization information of the subject and the disclosure. 
 
10.3. METHOD OF INVESTIGATIONAL PRODUCT ADMINISTRATION 
 Single-Dose Study (Intravenous Administration) 
The relevant dose of hzVSF-v13 (10–1,200 mg) will be dissolved in 100 mL of 0.9% normal saline solution 
and administered intravenously for approximately 30 minutes at 9 a.m. of 1 d.  
 
10.3.1. Other Combination Therapies 
In principle, no other drugs should be administered during the clinical study, except for the investigational 
products stated in the protocol. However, drugs may be administered depending on the decision of the 
principal investigator, if they are necessary to treat adverse events, etc. If a drug taken arbitrarily by a subject 


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without the decision of the principal investigator is expected to possibly have an effect on the safety and 
pharmacokinetic evaluation in this clinical study, the subject will drop out (see 9.6 Drop-out and Subject 
Substitution). The drug name (product name), administration route, daily dose, dosing period, reason for 
administration, etc. of all drugs (prescription drugs and over-the-counter drugs) administered concomitantly 
during the clinical study period have to be recorded in a CRF. 
 
10.4. SKIN TEST METHOD 
 
To be performed by an expert who is easily able to perform the procedure and interpret the result. 
 
Perform in the environment where can handle dangerous situations such as anaphylaxis. 
 
Site to be performed: Perform on the inside the forearm 
 
Wipe the area to be performed with an alcohol swab and dry it, and then drop hzVSF-v13, 
positive control solution (histamine, 1 mg/mL), and negative control solution (normal saline) on 
the skin at a distance of at least 2 to 3 cm. 
 
Lift the skin slightly with a lancet or needle to allow the test solutions to reach the epidermis. 
 
Concentration of procedure: Perform the test at a concentration diluted to approximately 1/10 of 
the scheduled dose of hzVSF-v13, and then increase to a concentration of 1/1. 
 
If the result is negative at 15 to 20 minutes after performing at a concentration of 1/10, proceed to 
a 1/1 concentration. 
 
Positive response: In the case that a wheal of at least 3 mm or swelling of at least the same size as 
the positive control solution accompanies redness 
 
 
 


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10.5. DETAILS OF THE CLINICAL STUDY SCHEDULE 
10.4 
 
10.5.1.  Screening Tests 
The screening tests to review the eligibility of the subjects who voluntarily provided a written consent to 
participate in the clinical study will be performed within 4 weeks from the initial administration (−28 d to 
−1 d), and any subjects who have clinically significant abnormalities in the following tests shall be excluded: 
 
Demographic information and history taking 
 
Vital signs 
 
Physical examination 
 
Clinical laboratory tests (hematology, blood chemistry, and urinalysis) 
 
12-lead ECG (electrocardiography) 
 
Immunogenicity Test 
 
Checking on the concomitant medications 
 
Urine drug screening 
Amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, opiates  
 
Serology 
HBsAg, anti-HCV Ab, anti-HIV (Ag, Ab) tests 
 
 
10.5.2. Single-Dose Study (Group 1 to Group 8) 
 
 Admission (−2 d to 8 d) 
All subjects will be admitted to the Clinical Trials Center 2 days prior to the administration (−2 d). During 
this time, all subjects will perform the following procedures: 
 
Skin test 
-1d  
 
Randomization/subject numbers assigned (to be done after the skin test at −1 d) 
 
Administration of the investigational product 
The subjects will be administered the investigational product (hzVSF-v13 or the placebo) on an empty 
stomach at 9 a.m. at 1 d. The subjects shall fast, except for drinking water, from 10 p.m. at −1 d. Water 
intake shall be prohibited from an hour before the administration to 2 hours after the administration.  
 
Vital signs 
1d 0h(pre-dose), 0.5, 1, 2, 4, 6, 8, 10, 12, 24(2d 0h), 36(2d 12h), 48(3d 0h), 60(3d 12h), 72(4d 0h), 
96(5d 0h), 120(6d 0h), 144(7d 0h), 168h(8d 0h)(post-dose)(systolic blood pressure, diastolic blood 
pressure, pulse rate, and temperature)  
 
Physical examination 
1d 0h(pre-dose), 168h(8d 0h)(post-dose) 
 
Clinical laboratory tests (hematology, blood chemistry, and urinalysis) 
1d 0h(pre-dose), 24(2d 0h), 72(4d 0h), 168h(8d 0h)(post-dose) 
 
12-lead ECG (electrocardiography) 
1d 0h(pre-dose), 168h(8d 0h)(post-dose) 
 
Blood collection for pharmacokinetics 
1d 0h(pre-dose), 0.5, 1, 2, 4, 6, 8, 10, 12, 24(2d 0h), 36(2d 12h), 48(3d 0h), 60(3d 


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12h), 72(4d 0h), 96(5d 0h), 120(6d 0h), 144(7d 0h), 168h(8d 0h) (post-dose) 
 
Immunogenicity Test 
1d 168h(8d 0h)(post-dose) 
 
Monitoring of adverse events 
 
Checking on the concomitant medications 
The subjects who completed the clinical study procedures according to the predefined schedule will be 
allowed to be discharged in the morning at 8 d. 
 
 Outpatient (9 d to 92 d) 
All subjects will visit the Seoul National University Hospital Clinical Trial Center as outpatients after 
discharge in order to perform the clinical study procedures according to the predefined schedule. During this 
time, all subjects will perform the following procedures: 
 
Vital signs 
1d 336(15d 0h), 504(22d 0h), 672(29d 0h), 840(36d 0h), 1176(50d 0h), 1512(64d 0h), 1848(78d 0h), 
2184h(92d 0h)(post-dose)(systolic blood pressure, diastolic blood pressure, pulse rate, and 
temperature)  
 
Physical examination 
1d 336(15d 0h), 504(22d oh), 672(29d 0h), 840(36d 0h), 1176(50d 0h), 1512(64d 0h), 1848(78d 0h), 
2184h(92d 0h)(post-dose) 
 
Clinical laboratory tests (hematology, blood chemistry, and urinalysis) 
1d 336(15d 0h), 504(22d oh), 672(29d 0h), 840(36d 0h), 1176(50d 0h), 1512(64d 0h), 1848(78d 0h), 
2184h(92d 0h)(post-dose) 
 
12-lead ECG (electrocardiography) 
1d 336(15d 0h), 504(22d oh), 672(29d 0h), 840(36d 0h), 1176(50d 0h), 1512(64d 0h), 1848(78d 0h), 
2184h(92d 0h)(post-dose) 
 
Blood collection for pharmacokinetics 
1d 336(15d 0h), 504(22d oh), 672(29d 0h), 840(36d 0h), 1176(50d 0h), 1512(64d 
0h), 1848(78d 0h), 2184h(92d 0h)(post-dose) 
 
Immunogenicity Test 
1d 336(15d 0h), 672(29d 0h), 1344(57d 0h), 2184h(92d 0h)(post-dose) 
 
Monitoring of adverse events 
 
Checking on the concomitant medications 
 
Tolerability/safety assessments 
The tolerance and safety of the relevant dose group shall be evaluated after completing all scheduled 
tests up to 15 d in order to determine whether to proceed to the next dose group. 
 
If the investigator decides that additional visits are necessary for the safety of the subjects, the subjects may 
need to visit the Seoul National University Hospital Clinical Trials Center additionally. 
 


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10.5.3. Early Termination Visit 
If a subject drops out prior to the administration, no separate safety assessments will be performed. If a 
subject drops out during the hospitalization, the scheduled dose will be discontinued, and the subject will be 
discharged after completing the vital sign, electrocardiography, clinical laboratory tests, physical 
examination, and monitoring of adverse events and checking on concomitant medications by the next 
morning if possible. In case of dropping out, the dropped out subject will be requested to visit the Clinical 
Trials Center within 4 weeks (28 days) from the date of drop-out if possible in order to perform the following 
observation and tests:  
 
Physical examination 
 
Vital signs 
 
Electrocardiography (12-lead ECG) 
 
Clinical laboratory tests 
 
Monitoring of adverse events 
 
Checking on the concomitant medications 
If a subject drops out prior to the administration, no separate safety assessments will be performed. If the 
investigator decides that additional visits are necessary for the safety of the subjects, the subjects may need 
to visit the Seoul National University Hospital Clinical Trials Center additionally. 
 
10.5.4. Discontinuation of the Clinical Study 
In the case that the principal investigator determines that continuation of the clinical study is not a wise 
decision based on the results observed during the process of the clinical study, the principal investigator may 
discontinue a part of the study or the whole study after having a discussion with the sponsor. 
 
If the principal investigator determines that a subject cannot continue the clinical study due to 
a serious reason that has occurred during the clinical study and emergency measures are 
required, the principal investigator may discontinue a part of the clinical study or the whole 
clinical study even without a discussion with the sponsor. 
 
The sponsor may discontinue a part of the clinical study or the whole clinical study for a 
reason of safety or management. 
 
In case of early termination or temporary suspension of the clinical study, the principal 
investigator has to notify the subjects, take action and follow up adequately. 
 
CRFs, clinical study progress reports and clinical study results up to the moment of 
discontinuation have to be summarized and delivered to the sponsor, and all data related to the 
study (complete or incomplete CRFs, CRFs without entries, investigational products, etc.) 
have to be returned to the sponsor. 
 
In the event of discontinuation of the clinical study, it has to be reported to the Institutional 
Review Board (IRB) and the Ministry of Food and Drug Safety. 
 


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10.6. ADVERSE EVENTS 
10.6 
 
10.6.1. Recording and Reporting Adverse Events 
10.6.1.1. Adverse Event (AE) 
An adverse event is any undesirable and unintended sign (e.g., an abnormal laboratory test result), symptom, 
or disease that occurred in a subject who was administered an investigational product, and it does not 
necessarily have to have a causal relationship to the drug used in the clinical study. 
The principal investigator and investigator delegated by the principal investigator shall record all adverse 
events that occur during the clinical study. Adverse events have to be recorded using terms in the MedDRA®  
as much as possible, but if this is not possible, they should be recorded using the terms for the signs and 
symptoms observed by the principal investigator or investigator or reported by the subject. 
Symptoms and signs that appeared in the subject prior to the screening should be recorded in the 
“Medical/Surgical History” section in the subject’s CRF. All adverse events that appeared after 
administration of the investigational product should be recorded the adverse event section in the CRF, 
regardless of their relevance to the drug. The subject’s pre-existing signs and symptoms of which their 
intensity, nature, or frequency has changed or the pre-existing diseases of which their names have changed 
after administration of the investigational product shall be considered and recorded as adverse events. 
Adverse events shall be evaluated by the principal investigator and investigator delegated by the principal 
investigator. Adverse events that are recorded for the first time shall be recorded in the “Adverse Event” 
section of the CRF. Symptoms and signs of adverse events, actions taken in connection with the study drug, 
date and time of onset (if available), outcomes, course (i.e., continuous or intermittent), severity, seriousness, 
actions taken, and causal relationship to the study drug should be documented in the CRF. Details of dose 
changes and treatment information should be recorded in the appropriate pages of the CRF. 
Adverse events previously recorded in the CRF and indicated as “ongoing” in the Outcome section should 
be reviewed in subsequent visits, if necessary. In the case that adverse events are resolved, records in the 
CRF should be completed. If the frequency and severity of adverse events increase during the study period, 
new records should be started in the adverse event section. 
Besides the voluntary report from the subjects, ask the subjects in a manner not inducing to have a desired 
answer, such as “do you feel different since the last visit or administration?”, as a consistent method to 
identify adverse events. 
 
10.6.1.2. Adverse Drug Reaction (ADR) 
It refers to any harmful and unintended reaction that occurred at a certain dose of the investigational product 
where a causal relationship to the investigational product is ruled out. 
The causal relationship shall be evaluated with reference to the available information on the drug (e.g., 
investigator’s brochure or a package insert of the drug). 
 
 


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10.6.1.3. Unexpected Adverse Drug Reaction  
It refers to a reaction that shows a difference in the characteristics or degree of harm of the adverse drug 
reaction in view of the available information on the drug (e.g., investigator’s brochure or a package insert 
of the drug). 
 
10.6.2. Evaluation of the Severity of Adverse Events 
The severity of adverse events shall be classified based on the following criteria in consideration of the 
maximal intensity. 
 
Mild: In the case that the subject can easily tolerate with the minimal discomfort without 
disturbing the normal daily life (or function) of the subject 
 
Moderate: In the case that it causes significant discomfort disturbing the normal daily life 
(or function) of the subject 
 
Severe: In the case that it makes the normal daily life (or function) of the subject impossible 
10.6.1 
 
10.6.3. Evaluation of the Causal Relationship of Adverse Events to the Study Drug 
The causal relationship of adverse events to the investigational product shall be evaluated as 6 levels shown 
below, and the principal investigator or investigator delegated by the principal investigator shall describe 
his/her opinion. 
 
Definite relationship: In the case that an adverse event has a reasonable temporal relationship 
from the point of administration of the drug, and symptoms subside when the administration 
is discontinued and appear again when the administration is given 
 
Probable relationship: In the case that an adverse event has a reasonable temporal relationship 
from the point of administration of the drug, symptoms subside when the administration is 
discontinued, and symptoms cannot be explained reasonably based on known characteristics 
of the subject’s clinical condition 
 
Possible relationship: In the case that an adverse event has a reasonable temporal relationship 
from the point of administration of the drug, but it may have possibly occurred due to the 
subject’s clinical condition or study procedure/conditions 
 
Unlikely related: In the case that there is no reasonable relationship in terms of the temporal 
relationship between the adverse event and the drug 
 
Not related: In the case that an adverse event is clearly due to the subject’s clinical condition 
or study procedure/conditions 
 
Unassessable: In the case that a judgment cannot be made because the information is insufficient 
or contradictory, and the information cannot be supplemented or verified 
 
The causal relationship between the drug and the adverse event shall be evaluated considering the following: 
 
Temporal relationship: Is there a temporal probability between the drug administration and 
the adverse event occurrence? 


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 
De-challenge: Did the adverse event disappear or improve when the drug administration was 
discontinued? 
 
Re-challenge: Did the adverse event recur or worsen when the drug administration was 
resumed? 
 
Other alternate causes: Are there other possible causes of the adverse event (e.g., past disease, 
present medical disease, concomitant medications, or other risk factors)? 
 
Pharmacological relationship: Is there a pharmacological relevance when referring to the 
mechanism of action of the drug, drug information documents (e.g., IB, product manual) and 
safety information of drugs in the same class? 
 
10.6.4. Reporting Serious Adverse Event/Adverse Drug Reaction (AE/ADR) 
It refers to an adverse event or an adverse drug reaction that occurred at a certain dose of the investigational 
product that one of the following applies: 
 
In the case that results in death or is life-threatening 
A life-threatening case refers to an emergency situation which might cause death if medical 
treatment is not given (e.g., hepatic necrosis requiring liver transplantation, anaphylactic 
shock requiring emergency resuscitation).  
 
In the case that requires hospitalization or prolongation of hospitalization 
Receiving medical care in an emergency room, not in an inpatient room, is also considered 
hospitalization at the investigator’s discretion (e.g., acute allergic reactions). 
Hospitalization for the following are not considered as serious adverse events: 
 
Routine treatment or monitoring that is not related to a worsening of the condition, 
such as examination for hospitalization or diagnosis during pharmacokinetic 
sampling or training for administration of the study drug 
 
Hospitalization for scheduled treatment and surgery for a pre-existing condition that 
is not related to the indications of an ongoing clinical study and has not been 
deteriorated 
 
In the case that results in permanent or serious disability and dysfunction 
 
In the case that results in congenital anomaly or birth defect 
If the subject’s partner becomes pregnant during the clinical study, it should be reported 
immediately to the clinical research associate (or staff member) of ImmuneMed Inc., but it is 
not a serious adverse event, and the miscarriage, birth of deformed baby or developmental 
disorder should be reported as serious adverse events. 
 In the case that is made by other medically important decisions 
 
If a serious adverse event occurs between the administration of the investigational product and the last visit, 
the principal investigator or investigator shall report it to the PV (or staff member) of ImmuneMed Inc. 
within 24 hours regardless of the relationship of the adverse event to the study drug. 


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Pharmacovigilance  
Staff member: Yoon Won Kim 
Address: #2-2, Bio-3, Chuncheon Bioindustry Foundation, 32, Soyanggang-ro, Chuncheon-si, Gangwon-do, 
Korea 
Telephone: +82-33-241-1664, +82-10-2480-1664 
Fax: +82-33-258-6553 
E-mail address: ywkim@immunemed.co.kr 
 
The report shall be submitted to the relevant site in accordance with the criteria of the Institutional Review 
Board of the relevant site where the serious adverse event occurred. If it is considered a serious adverse 
event is related to the administration of the study drug, it should be reported to the clinical research associate 
(or staff member) of ImmuneMed Inc. at any time even after the end of the study. 
 
10.6.5. Follow-Up on Adverse Events 
The principal investigator or investigator followed up on the subjects who experienced adverse events until 
the symptom subsided, the abnormal clinical laboratory tests returns to the reference range, or the observed 
changes could be explained to satisfaction. 
 
10.7. 
BLOOD 
COLLECTION 
AND 
ANALYSIS 
FOR 
PHARMACOKINETIC 
EVALUATION 
10.7 
 
10.7.1. Specimens and Analytes 
Depending on the dose group, the concentration of the following substance in the serum shall be analyzed: 
 
Concentration of hzVSF-v13 
 
10.7.2. Blood Collection Method and Pre-processing and Storage Methods of Separated Serum 
 
Single-dose study 
 
Blood collection will be performed at 1 d 0 h (pre-dose), 0.5, 1, 2, 4, 6, 8, 10, 12, 24 (2 d 0 h), 36 
(2 d 12 h), 48 (3 d 0 h), 60 (3 d 12 h), 72 (4 d 0 h), 96 (5 d 0 h), 120 (6 d 0 h), 144 (7 d 0 h), 168 
(8 d 0 h), 336 (15 d 0 h), 504 (22 d 0 h), 672 (29 d 0 h), 840 (36 d 0 h), 1,176 (50 d 0 h), 1,512 (64 
d 0 h), 1,848 (78 d 0 h) and 2,184 h (92 d 0 h; post-dose). At each time point, 5 mL of blood will 
be collected. 
 
Rationale for blood collection time points  
Blood will be collected for a duration of 2,184 h (approximately 13 weeks after the administration), 
which is 3 times the expected half-life (approximately 30 days) based on preclinical study results.  
 
Blood will be collected via venipuncture or a saline-locked angiocatheter inserted into the brachial 
vein. In the case of collecting blood using a saline-locked angiocatheter, approximately 1 mL of 
blood will be drawn and discarded, and approximately 5 mL of blood will be collected. Then, 1 
mL of saline will be injected into the catheter to prevent coagulation of the blood. 


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 
The collected blood will be immediately placed in a serum separate tube (SST) and stored at room 
temperature. After leaving it for at least 30 minutes, it will be centrifuged at 4°C for 10 minutes at 
3,000 rpm in order to separate the serum. 
 
Approximately 0.7 mL of the serum separated by centrifugation will be placed in tubes to have 3 
samples and prepared for storage in a freezer. 
 
The prepared samples will be transferred to a freezer at not more than −70°C within 1 hour and 
stored until they are analyzed. 
 
One of the three frozen samples (back-up sample) will be stored at the Seoul National University 
Hospital Clinical Trials Center, and the other two will be sent to the analyzing institution through 
a specialized shipping company. 
 
10.7.3. Analytical Method 
See Drug Concentration Analysis Method. 
 
10.8 BLOOD COLLECTION AND ANALYSIS FOR EXPORATORY EVALUATION 
 
10.8.1 Samples and Substances for Analysis 
When stability and pharmacokinetics for investigational product is decided respectively, at the maximal 10mL 
of blood collection can be performed for the subjects who already agreed upon the written consent form for the 
research of the epidemiology of the genetic variance. Also, exploraryly evaluate the change in the proportion 
of immune cells in the lymphocytes to the baselines in peripheral blood.   
Blood collection timepoint: 5mL of blood is collected on screening day and day 92 after administrated, 
respectively.  
 
10.8.2 Blood collection method and pre-treatment and storage methods for separated serum 
5mL of blood is collected for whole blood, which is performed through saline-locked angiocatheter which is 
equipped in either venipuncture or brachial veins. When blood is collected using a saline-locked angiocatheter, 
take 1mL of blood first to be discarded then 5mL of blood is collected and 1 mL of saline is injected into 
catheter in order to prevent the blood coagulation .  
5mL of collected blood should be contained in a container (EDTA TUBE) immediately and stored in freezing 
condition (below -70℃). 
 
10.8.3 Analytical method 
In case of large deviations of individual study drug effects, they can be explored through analysis, including 
genetype, if necessary. In this case, they are prepared in a separate result report.  
 
10.9. ENDPOINTS AND ANALYTICAL METHOD 
10.9.1 
Safety Endpoints 
1) Adverse events, such as subject and objective symptom 


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The investigator should record all adverse events that occurred during the clinical study. Also, adverse 
events have to be recorded using terms in the MedDRA®  as much as possible, but if this is not possible, 
they should be recorded using the terms for the signs and symptoms observed by the investigator or 
reported by the subject. Signs and symptoms of adverse events, duration (start/end date), severity (mild, 
moderate, severe), causal relationship to the study drug, measures taken against adverse events, serious 
adverse event (yes/no), etc. shall be recorded in the CRF. 
2) Vital sign, physical examinations, electrocardiography (12-lead ECG), clinical laboratory tests, 
immunogenicity test 
The purpose of this clinical study is to evaluate the safety and pharmacokinetic characteristics, and this 
clinical study has only a small number of subjects assigned to each dose group, and the baseline values 
vary by subject. For this reason, strict statistical analysis of all subjects will not be performed. 
The results of vital sign , physical examination, electrocardiography (12-lead ECG), clinical laboratory 
tests, and immunogenicity test will be reviewed comprehensively. Then, abnormalities of clinical 
laboratory test results will be evaluated for each subject, the clinical significance of the results will be 
recorded, and the relevance to the study drug will be reviewed. 
 
 
Vital signs: Blood pressure (systolic blood pressure and diastolic blood pressure), pulse rate 
and temperature shall be measured while maintaining a sitting position for at least 3 minutes 
without any sudden posture change. 
 
Physical examination: The investigator shall perform a physical examination at the 
scheduled examination time. During the screening tests, all signs and symptoms of physical 
examination shall be recorded in the case report form (CRF), and newly observed 
abnormalities or any changes to previously observed abnormalities (deterioration or 
improvement) in subsequent tests shall be recorded in the case report form (CRF). 
 
Electrocardiography (12-lead ECG): Besides the basic items, ventricular rate, PR interval, 
QRS, QT, QTc, etc. shall also be recorded in the case report form. 
 
Clinical laboratory tests: 
Hematology 
WBC with differential count (neutrophil [seg.], lymphocyte, 
monocyte, eosinophil, basophil), RBC, hemoglobin, hematocrit, 
platelet 
Blood chemistry 
Calcium, phosphorus, glucose, BUN, uric acid, cholesterol, total 
protein, albumin, total bilirubin, alkaline phosphatase, AST, ALT, γ-
GT, CPK, LDH, creatinine, sodium, potassium, chloride, triglyceride, 
amylase, lipase 
Urinalysis 
Color, specific gravity, pH, WBC(s), nitrite, albumin, glucose, ketone, 
urobilinogen, bilirubin, occult blood with microscopy 
 
Immunogenicity test: Immunogenicity will be evaluated by confirming the production of 
antibodies against hzVSF-v13. 
 
Urine drug test: Amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, 
opiates (to be performed only at the screening) 


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 
Serology: Hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV), and human 
immunodeficiency virus (HIV) (to be performed only at the screening) 
 
10.9.2 
Pharmacokinetic Endpoints 
The actual blood collection time by subject will be used during the analysis of pharmacokinetic 
characteristics. If the measured concentration is lower than the lower limit of quantification (LLOQ), the 
actual blood collection has not been performed (not applicable), or the blood sample is missed (missing 
data), “<LLOQ,” “N/A” or “MD” will be entered in the blood drug concentration data. A blood 
concentration–time pattern of the study drug will be shown as a graph in a linear or log/linear shape for each 
subject, and the mean blood concentration–time curve by dose group will be shown in the same way. The 
obtained data will be used to calculate the following pharmacokinetic parameters through a 
noncompartmental method by using Phoenix®  (Pharsight, CA, USA): 
1) Single-dose study:  
Cmax, AUClast, AUCinf, Tmax, t1/2, CL (or CL/F), and Vd (or Vd/F) of hzVSG v13 
 
Cmax 
Maximum blood concentration after administration of a single dose 
AUCinf 
Area under the blood concentration–time curve extrapolated to infinity after 
administration of a single dose. AUCinf = AUClast + Clast / z 
Tmax 
Time to reach the maximum blood concentration after administration of a single dose 
t1/2 
Elimination half-life 
CL  
Clearance after administration of a single dose. CL = Dose / AUClast 
Vd  
Volume of distribution after administration of a single dose. Vd = CL / λz 
 
 
10.9.3 
Statistical Analysis Method 
The results of the safety and pharmacokinetic/pharmacodynamic assessments will be statistically analyzed 
as shown below at a significance level of 0.05 using software such as SAS®  or SPSS® . 
 
10.9.4 
Subject Group to Be Analyzed 
All subjects who were randomized, who received the drug administration, and who has evaluable 
pharmacokinetic results will be classified and analyzed. Demographic data will be analyzed for all subjects 
who have been randomized (intention-to-treat), and the safety assessment will be performed for subjects 
who have received the investigational product (hzVSF-v13 or placebo) at least once. The pharmacokinetic 
assessment will be performed for subjects who completed the clinical study as planned without any serious 


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protocol violation that may have an impact on the pharmacokinetic results (per protocol). However, 
information of drop-out subjects may be referenced for the pharmacokinetic assessment. 
 
10.9.5 
Demographic Information 
Descriptive statistics (mean, standard deviation, etc.) will be obtained for all subjects and each dose group 
for basic demographic information of subjects, such as age, height, and weight. 
 
10.9.6 
Pharmacokinetic Assessment 
Pharmacokinetic parameters will be obtained through a noncompartmental method using an appropriate and 
verified pharmacokinetics software (e.g., Phoenix WinNonlin®  [Version 6.3 or higher; Pharsight, CA, 
USA]), and descriptive statistics (mean, standard deviation, median, maximum, minimum, etc.) will be 
obtained for each dose group.  
 
 
10.9.7 
Safety Assessment 
With regard to the occurrence of adverse events, number of cases occurred, number of subjects who 
experienced adverse events, severity, seriousness and causal relationship to the study drug will be analyzed 
by treatment group using descriptive statistics and compared by applying the non-parametric method as 
needed.  
The investigator will perform statistical analysis as needed for the items that are considered clinically 
significant.  
 
10.10. STORAGE AND DESTRUCTION OF SAMPLES 
Blood and urine samples collected for various clinical laboratory tests shall be stored and destroyed of at the place 
designated by Seoul National University Hospital Department of Laboratory Medicine. Besides, samples collected 
for pharmacokinetic analysis, immunogenicity analysis, etc. shall be stored and destroyed of in accordance with 
the management standards of APACE Co., Ltd. or Hallym University College of Medicine Laboratory. 
 
11. RESEARCH ETHICS 
11.1. TAKEN ACTION FOR PROTECTION OF SUBJECTS’ SAFETY 
The principal investigator or investigator shall take full responsibility for all medical decisions related to the 
clinical study.  
If adverse events occur from after administration of the investigational product or after the final administration 
until the last visit, the principal investigator shall take action for appropriate medical treatment against any adverse 
events that occurred in subjects in the clinical study, including clinically significant laboratory test results. In the 
case that medical treatment is required for subjects’ intercurrent diseases that have been notified to the principal 
investigator, the subjects have to be informed of such information. 
The subjects have to be instructed to visit the hospital immediately in case of adverse events in order to recieve 


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the necessary tests which will be performed by the investigator, to receive treatment, and to be followed up until 
symptoms subside. In the case that serious adverse events occur during the clinical study, the obligations of the 
principal investigator, investigator, Institutional Review Board (IRB) and sponsor are as shown below.  
 
Obligations of the principal investigator 
The principal investigator has to immediately inform the sponsor of all serious adverse events, except for the ones 
specified in the protocol that an immediate report is not required, and submit a document including detailed 
information as an additional report. Afterward, a report has to be submitted to the Institutional Review Board 
(IRB) in accordance with the standards of the Institutional Review Board (IRB) of the site. 
 
Obligations of the investigator 
The investigator has to fully understand the expected adverse events and precautions for use that are stated in the 
protocol in advance, and report to the principal investigator in case of serious adverse events while conducting 
the clinical study. 
 
Obligations of the Institutional Review Board (IRB) 
The Institutional Review Board (IRB) has to notify the principal investigator of the required action through an 
expedited review if the serious adverse events reported by the investigator are serious adverse drug reactions. 
 
Obligations of the sponsor 
If the principal investigator or investigator reports serious adverse events, the sponsor has to attach a copy of the 
adverse event report submitted by the principal investigator or investigator to an adverse event report and submit 
the document to the Ministry of Food and Drug Safety immediately (if they are deemed to be suspected unexpected 
serious adverse reactions). In the case that the clinical study is conducted at multiple study sites, the relevant study 
sites have to be notified immediately. 
 
11.2. EXAMINATIONS AND TREATMENT CRITERIA FOR SUBJECTS AFTER THE 
CLINICAL STUDY 
The follow-up shall only be performed on the subjects who experienced adverse events after the end of the clinical 
study. In this case, all adverse events and changes in concomitant medications shall be recorded, and clinical 
laboratory tests shall be conducted if necessary. The subjects who experienced adverse events should be followed 
up until the symptom subsided, the abnormal clinical laboratory tests returns to the reference range, or the 
observed changes could be explained to satisfaction. In addition, the progress of adverse events should be reported 
to the staff member of ImmuneMed Inc.  
 
 
 


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11.3. OTHER ITEMS REQUIRED TO CONDUCT THE CLINICAL STUDY SAFELY AND 
SCIENTIFICALLY 
This clinical study has been designed in consideration of the rights and welfare of subjects based on the 
Declaration of Helsinki. The principal investigator or the investigator shall explain the objective of this 
study and all possible results, and the subjects who voluntarily sign the informed consent form to 
participate in the clinical study will be selected as the subjects.  
All investigators and participating study staff members have to fully analyze and understand the clinical 
study, and the principal investigator shall take action in advance, including countermeasures against 
unexpected adverse events, etc. and required reports as well as sufficient training for study staff members 
participating in the study. The clinical study shall be conducted in accordance with the ICH-GCP 
guidelines. 
The conduct of this clinical study and storage of the clinical study-related records, etc. shall be based on the 
“Korean Good Clinical Practice for Drugs” announced by the Ministry of Food and Drug Safety, and this 
clinical study shall be monitored by a clinical research associate designated by the sponsor, ImmuneMed 
Inc.  
 
11.3.1 
Study Site 
Equipment and professional personnel required for the clinical study should be prepared and the perfection 
in the preparation for the appropriate performance of this clinical study should be aimed. 
 
11.3.2 
Monitoring of the Clinical Site 
The sponsor shall designate a clinical research associate who will be in charge of this study and will visit 
the study site at appropriate intervals, including the time point at which the first subject in each dose group 
completes the schedule up to 15 d and the time point at which the last subject in each dose group completed 
the schedule up to 15 d. During the monitoring visit, the clinical research associate will confirm the 
compliance with the protocol, current study progress reported by the principal investigator and investigator, 
consistency of data between hospital records and CRFs, adverse events, control of the investigational 
product, etc. For this, the principal investigator and investigator has to provide proper time and space for the 
monitoring visit made by the clinical research associate and give access to CRFs and hospital records. 
 
11.3.3 
Management of the Investigational Products 
The clinical trial pharmacist shall sign the document verifying that the investigational products required for 
the study have been received, shall handle and store them as described in the “Code Name of the 
Investigational Product (or Generic Name of the Active Ingredient), Ingredients and Their Amounts, 
Formulation, etc.” section, and shall administer the investigational product only to the subjects who 
participate in the study. 
At the end of the study, the quantity of drugs used and returned has to be identical to the drug accountability 


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log; if there is any difference, the reason for such difference has to be explained. In order to guarantee the 
return of all unused investigational products, including all opened and unopened drug bottles and packages, 
the clinical trial pharmacist shall record and sign the final inventory/accountability logs. 
 
11.3.4 
Amendment to the Protocol 
Any information in this protocol shall not be amended/revised unless there is mutual agreement after having 
a detailed discussion with the sponsor. 
The amended/revised information in the protocol shall be applied to all subjects after obtaining an approval 
from the Institutional Review Board (IRB) as well as from the Ministry of Food and Drug Safety if the 
approval of Ministry of Food and Drug is required. 
 
11.3.5 
Inspection and Audit 
For audits and inspections, the principal investigator and investigator shall comply with the requirements of 
the sponsor and the Ministry of Food and Drug Safety. 
 
11.4. DATA PROCESSING AND DATA QUALITY ASSURANCE 
The data management in this clinical study will be performed in accordance with the standard operating 
procedures of the Seoul National University Hospital Medical Research Collaborating Center and Clinical 
Trials Center as well as Department of Clinical Pharmacology and Therapeutics, Seoul National University 
College of Medicine. Other items not stated in the protocol will be performed in accordance with the ICH-GCP 
and KGCP regulations. 
 
11.4.1 
Source Data 
Source data refers to any document, data and recordings, including medical records, electrocardiograms, 
clinical laboratory test results and drug accountability logs. The data collected during the study should be 
recorded in the appropriate source data. The data recorded in the screening/registration logs should include 
the subject identification number, screening date, reason for drop-out (in the case of drop-out), etc. All 
screened volunteers should be recorded in these logs. 
The access to source data will be given in the event of the study monitoring, audit, review by the IRB, and 
inspection by regulatory authorities. 
 
11.4.2 
Recording in Case Report Forms and Verifying Source Documents  
In this study, eCRFs developed using Medidata will be used. eCRFs will be recorded whenever data that 
need to be recorded are generated. If the data are not recorded until the finalization of the case, a proper 
reason for missing should be recorded. Data collection for all eCRFs will be done remotely based on source 
documents. The clinical research associate of the sponsor will periodically review and electronically sign 
eCRFs. The principal investigator will review the completeness and accuracy of eCRFs and electronically 


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sign them.  
Data validation will be performed using a computer program (SAS) in order to verify whether there are 
logical errors, missing values, outliers, etc. for eCRFs of which the review sign is completed by the clinical 
research associate. Queries will be issued to the study site after making decisions on all errors found 
whether they are queries, and the site will correct eCRFs after checking the original data. 
Even after computerization of all data, source documents and eCRFs will be retained to allow the 
verification of data by the relevant government agencies, IRB, etc. when requested. In addition, the 
investigator will provide normal ranges or reference values to other appropriate documents, such as eCRFs, 
prior to the initiation of the clinical study in order to use them for verification and validation of 
computerized records. 
 
11.4.3 
Data Entry Process 
In this study, eCRFs will be used. All information recorded in eCRFs is based on the source document of 
the subjects and eCRFs of all subjects who have signed the informed consent form shall be completed. Data 
in eCRFs are entered through a database system developed using Medidata, and the data entry process is 
performed according to the SOP of the study site. Since complete pharmacokinetic data are generated after 
completion of eCRF entry, pharmacokinetic data will be excluded from the database system entry items. 
The principal investigator will review the completeness and accuracy of eCRFs and electronically sign 
them. 
 
11.4.4 
Storage of Research Documents 
In accordance with the KGCP, essential documents required to be retained should be retained for 3 years 
from the date of investigational product approval. The retention period may be extended if the Minister of 
Food and Drug Safety orders or if the sponsor considers it is necessary.  
In relation to this study, the original data are regarded as data on the Medidata server, and these data shall 
be kept at the Department of Clinical Pharmacology and Therapeutics, Seoul National University Hospital. 
If the sponsor wants to have access to the data, they may visit Seoul National University Hospital and to 
have access. In this case, Department of Clinical Pharmacology and Therapeutics shall grant authorization 
to have access. Even if Department of Clinical Pharmacology and Therapeutics no longer continues the 
Medidata program, authorization to have access to the data related to this study will remain on the Medidata 
server. In addition, electronic case report forms and audit trails will be converted into PDF files, which will 
then be sent to the sponsor via e-mail in order to archive. 
 
11.4.5 
Data Quality Assurance 
The initiation meeting with participation of the investigators and the sponsor will be held prior to the 


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beginning of the clinical study. At this meeting, the protocol and the study conduct method, case report 
form completion method, sample collection method and pre-treatment method will be discussed in detail. 
The clinical research associate will monitor in accordance with the monitoring plan. 
The study coordinator and clinical research associate will double check all data recorded in case report 
forms. If any abnormality is found, it will be compared to source documents. Data of case report forms 
should be entered into the database system using the single-entry method. 
The list of queries for unresolved queries should be resolved with the investigators through the clinical 
research associate. The database shall be modified based on the signed query resolution.  
Once data entry is confirmed, the database system shall be locked. 
 
11.4.6 
Data Security 
All documents, such as source documents and eCRF obtained through the study, have to be retained 
securely, and the investigators shall not disclose such information without the sponsor’s consent.  
Since anonymity of the subjects has to be guaranteed, all documents shall use subject numbers and initials 
instead of names of the subjects. Any documents that may identify the subjects shall be retained securely by 
the investigator. 
 
11.5. CONFIDENTIALITY AND PUBLICATION OF STUDY RESULTS 
All information obtained during the clinical study is proprietary intellectual assets of the sponsor; therefore, the 
investigators and other persons related to the clinical study have to strictly maintain the confidentiality of such 
information. 
 
12. REFERENCE 
 
13. ATTACHMENTS 
Attachment 1. Subject Information Sheet/Informed Consent Form for Participation 
Attachment 2. Subject Recruitment Advertisement 
Attachment 3. Name and Title of investigators and Clinical Trial Pharmacists  
Attachment 4. Clinical Study Compensation Policy 
Attachment 5. Subject Information Sheet for Collection of Human-Derived Materials 
Attachment 6. Informed Consent Form for Research on Human-Derived Materials 
Attachment 7. Informed Consent Form for Release of Information on Pregnancy  
 

SAP_001.pdf: 
Protocol No. IM_hzVSF_v13-0001 
Statistical Analysis Plan Ver. 1.0 (29Nov2019) 
CONFIDENTIAL 
1 
 
 
 
Statistical Analysis Plan 
 
 
 
Study Title 
A phase 1, dose blocked-randomized, double-blind, placebo 
controlled, single dosing, dose-escalation study to investigate the 
safety, tolerability, pharmacokinetic characteristics of hzVSF-v13 
after intravenous(IV) administration in healthy male subjects 
 
 
 
 
 
 
Protocol No. 
IM_hzVSF_v13-0001 
Principal Investigator 
In Jin Jang MD, PhD 
Sponsor 
ImmuneMed, Inc. 
Statistical Analysis Plan Ver. 
1.0 (2019/11/29) 
 
 
 


Protocol No. IM_hzVSF_v13-0001 
Statistical Analysis Plan Ver. 1.0 (29Nov2019) 
CONFIDENTIAL 
2 
Prepared by 
 
 
 
 
 
Name 
Statistician, SNUH 
 
Signature 
 
Date (YYYY/MM/DD) 
 
Reviewed by 
 
 
 
 
 
 
Name 
STAT manager, SNUH 
 
Signature 
 
Date (YYYY/MM/DD) 
 
 
 
 
 
 
Name 
Sub-Investigator, SNUH 
 
Signature 
 
Date (YYYY/MM/DD) 
 
 
Approved by  
 
 
 
 
 
Name 
Principal Investigator, SNUH 
 
Signature 
 
Date (YYYY/MM/DD) 
 
 
 
 
 
 
Name 
CEO, ImmuneMed, Inc.  
 
Signature 
 
Date (YYYY/MM/DD) 
 
 
 


Protocol No. IM_hzVSF_v13-0001 
Statistical Analysis Plan Ver. 1.0 (29Nov2019) 
CONFIDENTIAL 
3 
Revision History 
Version 
No. 
Effective Date 
(YYYY/MM/DD) 
Description of Changes 
Revised by 
1.0 
2019/11/29 
Initial version 
N.A. 
 
 
 
 
 
 
 
 
 
 
 


Protocol No. IM_hzVSF_v13-0001 
Statistical Analysis Plan Ver. 1.0 (29Nov2019) 
CONFIDENTIAL 
4 
Table of Contents 
Revision History .................................................................................................................................... 3 
Table of Contents .................................................................................................................................. 4 
1. 
Introduction ................................................................................................................................... 6 
2. 
Study Objectives ............................................................................................................................ 6 
2.1. 
Primary Objective .................................................................................................................. 6 
2.2. 
Secondary Objective ............................................................................................................... 6 
3. 
Investigational Plan ...................................................................................................................... 6 
3.1. 
Overall Study Design .............................................................................................................. 6 
3.2. 
Drug Administration .............................................................................................................. 7 
3.3. 
Schedule of Study ................................................................................................................... 8 
3.4. 
Determination of the Sample Size ....................................................................................... 10 
4. 
Documentation of Variables ....................................................................................................... 10 
4.1. 
Safety Variables .................................................................................................................... 10 
4.1.1. 
Adverse Events .............................................................................................................. 10 
4.1.2. 
Vital Signs ...................................................................................................................... 11 
4.1.3. 
Clinical Laboratory Test .............................................................................................. 11 
4.1.4. 
12-Lead Electrocardiogram Test ................................................................................. 11 
4.1.5. 
Physical Examination .................................................................................................... 11 
4.1.6. 
Immunogenicity Test .................................................................................................... 12 
4.2. 
Pharmacokinetic Variables .................................................................................................. 12 
4.2.1. 
Pharmacokinetic Measurements .................................................................................. 12 
4.2.2. 
Pharmacokinetic Parameters ....................................................................................... 12 
5. 
Definitions of the Analysis Sets .................................................................................................. 13 
5.1. 
Screened Set .......................................................................................................................... 13 
5.2. 
Randomized Set .................................................................................................................... 13 
5.3. 
Safety Analysis Set ................................................................................................................ 13 
5.4. 
Pharmacokinetic Analysis Set ............................................................................................. 13 
6. 
General Presentation of Summaries and Analyses .................................................................. 13 
6.1. 
Summary Statistics ............................................................................................................... 13 
6.2. 
Definition of Subgroups for Analysis .................................................................................. 13 
6.2.1. 
Dose Group .................................................................................................................... 13 
6.2.2. 
Treatment Group .......................................................................................................... 13 
6.3. 
Baseline .................................................................................................................................. 14 


Protocol No. IM_hzVSF_v13-0001 
Statistical Analysis Plan Ver. 1.0 (29Nov2019) 
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6.4. 
Handling of Missing Data .................................................................................................... 14 
6.5. 
Software for Statistical Analysis ......................................................................................... 14 
6.6. 
Significance Level ................................................................................................................. 14 
7. 
Methods for Analyses.................................................................................................................. 14 
7.1. 
Disposition and Protocol Deviations ................................................................................... 14 
7.1.1. 
Subject Disposition ........................................................................................................ 14 
7.1.2. 
Summary for Analysis Sets........................................................................................... 14 
7.1.3. 
Protocol Deviations ....................................................................................................... 14 
7.2. 
Demographics and Baseline Characteristics ...................................................................... 15 
7.2.1. 
Demographics ................................................................................................................ 15 
7.2.2. 
Medical History ............................................................................................................. 15 
7.2.3. 
Concomitant Medication .............................................................................................. 15 
7.3. 
Safety Evaluation .................................................................................................................. 15 
7.3.1. 
Adverse Events .............................................................................................................. 15 
7.3.2. 
Vital Signs ...................................................................................................................... 16 
7.3.3. 
Clinical Laboratory Test .............................................................................................. 16 
7.3.4. 
12-Lead Electrocardiogram Test ................................................................................. 16 
7.3.5. 
Physical Examination .................................................................................................... 16 
7.4. 
Pharmacokinetics ................................................................................................................. 16 
7.4.1. 
Pharmacokinetic Measurements .................................................................................. 16 
7.4.2. 
Pharmacokinetic Profiles .............................................................................................. 17 
7.4.3. 
Pharmacokinetic Parameters ....................................................................................... 17 
7.5. 
Immunogenecity ................................................................................................................... 17 
7.5.1. 
Immunogenicity measurements ................................................................................... 17 
7.5.2. 
Immunogenicity profiles ............................................................................................... 17 
8. 
Sensitivity Analysis ..................................................................................................................... 17 
9. 
Interim Analysis .......................................................................................................................... 17 
10. Change from Protocol ................................................................................................................. 18 
11. References .................................................................................................................................... 19 
12. Appendix: List of Tables, Figures, and Listings....................................................................... 20 
12.1. 
List of Tables ..................................................................................................................... 20 
12.2. 
List of Figures.................................................................................................................... 21 
12.3. 
List of Listings ................................................................................................................... 21 
 


Protocol No. IM_hzVSF_v13-0001 
Statistical Analysis Plan Ver. 1.0 (29Nov2019) 
CONFIDENTIAL 
6 
1. Introduction 
 This statistical analysis plan (statistical analysis plan) presents details on the clinical 
characteristic analysis method of the pharmacokinetic and safety/tolerability data described in the 
hzVSF-v13 protocol of ImmuneMed, Inc., for describe the method and procedure to evaluate the 
purpose of the clinical trials.  
 
2. Study Objectives 
2.1. Primary Objective 
 The safety and tolerability were evaluated after intravenous(IV) administration of a single dose 
of the study drug hzVSF-v13 in healthy male subjects. 
2.2. Secondary Objective 
 The pharmacokinetic characteristics were evaluated after intravenous(IV) administration of a 
single dose of the study drug hzVSF-v13 in healthy male subjects. 
 
3. Investigational Plan 
3.1. Overall Study Design 
 This is a Phase 1, dose blocked-randomized, double-blind, placebo controlled, single dosing, 
dose-escalation study to investigate the safety, tolerability, pharmacokinetic characteristics of 
hzVSF-v13 after intravenous(IV) administration in healthy male subjects. 
 
 
 


Protocol No. IM_hzVSF_v13-0001 
Statistical Analysis Plan Ver. 1.0 (29Nov2019) 
CONFIDENTIAL 
7 
3.2. Drug Administration 
 Dose Group 
The number of subjects 
Group 1 (10 mg IV) 
hzVSF-v13: 3 
Placebo: 1 
Group 2 (20 mg IV) 
hzVSF-v13: 3 
Placebo: 1 
Group 3 (50 mg IV) 
hzVSF-v13: 6 
Placebo: 2 
Group 4 (100 mg IV) 
hzVSF-v13: 6 
Placebo: 2 
Group 5 (200 mg IV) 
hzVSF-v13: 6 
Placebo: 2 
Group 6 (400 mg IV) 
hzVSF-v13: 6 
Placebo: 2 
Group 7 (800 mg IV) 
hzVSF-v13: 6 
Placebo: 2 
Group 8 (1200 mg IV) 
hzVSF-v13: 6 
Placebo: 2 
 
 
 


Protocol No. IM_hzVSF_v13-0001 
Statistical Analysis Plan Ver. 1.0 (29Nov2019) 
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3.3. Schedule of Study 
◆  Flow Chart  
 Schedule 
Screening 
Hospitalization Period 
Outpatient Period 
Day (d) 
Item 
-28 ~ -2 
-2 
-1 
1 
2 ~ 7 
8 
9 ~ 92 
Obtaining an informed consent 
form 
● 
 
 
 
 
 
 
Checking 
demographic 
information/medical history 
● 
 
 
 
 
 
 
Serology1 
● 
 
 
 
 
 
 
Urine drug test2 
● 
 
 
 
 
 
 
Checking the inclusion/exclusion 
criteria 
● 
 
 
 
 
 
 
Assigning 
the 
randomization/subject numbers3 
 
 
● 
 
 
 
 
Admission4 
 
● 
 
 
 
 
 
Discharge5 
 
 
 
 
 
● 
 
Skin test6 
 
 
● 
 
 
 
 
Administration 
of 
the 
investigational product7 
 
 
 
● 
 
 
 
Physical examination8 
● 
 
 
● 
 
● 
● 
Vital signs9 
● 
 
 
● 
● 
● 
● 
Electrocardiography 
(12-lead 
ECG)10 
● 
 
 
● 
 
● 
● 
Clinical laboratory tests11 
● 
 
 
● 
● 
● 
● 
Blood 
collection 
for 
pharmacokinetics12 
 
 
 
● 
● 
● 
● 
Immunogenicity test13 
● 
 
 
 
 
● 
● 
Monitoring of adverse events 
 
● 
● 
● 
● 
● 
● 
Checking on the concomitant 
medications 
● 
● 
● 
● 
● 
● 
● 
Tolerability/safety assessments14 
 
 
 
 
 
 
● 
 
1 Serology: Hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) tests shall be performed 
only at the screening. 
2 Urine drug test: It shall be performed only at the screening (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, opiates). 
3 Assigning the randomization/subject numbers: The randomization and subject numbers shall be assigned after the skin test at −1 d. 
4 Admission: Subjects shall be admitted in the afternoon at −2 d. 
5 Discharge: Subjects shall be discharged after completing all scheduled tasks in the morning at 8 d. 
6 Skin test: The skin test shall be performed at 9 a.m. at −1 d. 
7 Administration of the investigational product: HzVSF-v13 (or the placebo) shall be administered intravenously at 9 a.m. at 1 d.  
8 Physical examination: It shall be performed at the screening, 1 d 0 h (pre-dose), 168 (8 d 0 h), 336 (15 d 0 h), 504 (22d 0h), 672 (29 d 0 h), 
840 (36 d 0 h), 1,176 (50 d 0 h), 1,512 (64 d 0 h), 1,848 (78 d 0 h) and 2,184 h (92 d 0 h; post-dose). 
9 Vital signs: It shall be performed at the screening, 1 d 0 h (pre-dose), 0.5, 1, 2, 4, 6, 8, 10, 12, 24 (2 d 0 h), 36 (2 d 12 h), 48 (3 d 0 h), 60 (3 
d 12 h), 72 (4 d 0 h), 96 (5 d 0 h), 120 (6 d 0 h), 144 (7 d 0 h), 168 (8 d 0 h), 336 (15 d 0 h), 504 (22 d 0 h), 672 (29 d 0 h), 840 (36 d 0 h), 
1,176 (50 d 0 h), 1,512 (64 d 0 h), 1,848 (78 d 0 h) and 2,184 h (92 d 0 h; post-dose) (systolic blood pressure, diastolic blood pressure, pulse 
rate, and temperature). 


Protocol No. IM_hzVSF_v13-0001 
Statistical Analysis Plan Ver. 1.0 (29Nov2019) 
CONFIDENTIAL 
9 
10 Electrocardiography (12-lead ECG): It shall be performed at the screening, 1 d 0 h (pre-dose), 168 (8 d 0 h), 336 (15 d 0 h), 504 (22 d 0 h), 
672 (29 d 0 h), 840 (36 d 0 h), 1,176 (50 d 0 h), 1,512 (64 d 0 h), 1,848 (78 d 0 h) and 2,184 h (92 d 0 h; post-dose). 
11 Clinical laboratory tests: It shall be performed at the screening, 1 d 0 h (pre-dose), 24 (2 d 0 h), 72 (4 d 0 h), 168 (8 d 0 h), 336 (15 d 0 h), 
504 (22 d 0 h), 672 (29 d 0 h), 840 (36 d 0 h), 1,176 (50 d 0 h), 1,512 (64 d 0 h), 1,848 (78 d 0 h) and 2,184 h (92 d 0 h; post-dose) (hematology, 
blood chemistry, and urinalysis). 
12 Blood collection for pharmacokinetics: It shall be performed at 1 d 0 h (pre-dose), 0.5, 1, 2, 4, 6, 8, 10, 12, 24 (2 d 0 h), 36 (2 d 12 h), 48 (3 
d 0 h), 60 (3 d 12 h), 72 (4 d 0 h), 96 (5 d 0 h), 120 (6 d 0 h), 144 (7 d 0 h), 168 (8 d 0 h), 336 (15 d 0 h), 504 (22 d 0 h), 672 (29 d 0 h), 840 
(36 d 0 h), 1,176 (50 d 0 h), 1,512 (64 d 0 h), 1,848 (78 d 0 h) and 2,184 h (92 d 0 h; post-dose). 
13 Immunogenicity test: It shall be performed at the screening, 168 (8 d 0 h), 336 (15 d 0 h), 672 (29 d 0 h), 1,344 (57 d 0 h) and 2,184 h (92 
d 0 h; post-dose). 
14 Tolerability/safety assessments: The tolerance and safety of the relevant dose group were evaluated after completing all scheduled tests up 
to 15 d in order to determine whether to proceed to the next dose group. 


Protocol No. IM_hzVSF_v13-0001 
Statistical Analysis Plan Ver. 1.0 (29Nov2019) 
CONFIDENTIAL 
10 
3.4. Determination of the Sample Size 
 The purpose of the study was exploratory which was not to verify statistical hypotheses, and in 
the case of clinical studies conducted using new drugs for which safety is not established, it is 
ethically desirable to conduct the study in the minimum number of subjects while satisfying the study 
objectives. In addition, dose groups had a certain ratio of subjects who received the placebo to enable 
double-blind for an objective safety and tolerability review. In this study, for the low dose groups 
(Groups 1 and 2), the sentinel dose groups, the target number of subjects per dose group had been 
set to 4 subjects per dose group, and the target number of subjects for other dose groups had been 
set to 8 subjects per dose group. 
 
4. Documentation of Variables 
4.1. Safety Variables 
4.1.1. 
Adverse Events 
4.1.1.1. Adverse Events (AE) 
It refers to undesirable and unintended symptoms (including signs, abnormalities in laboratory 
test results, etc.), symptoms, or diseases that occurred to a subject after administration of an 
investigational product and not necessarily have a causal relationship with the investigational 
product. 
4.1.1.2. Adverse Drug Reaction (ADR) 
It refers to any hazardous and unintended reaction that occurs at any dose of an investigational 
product, where the causal relationship with the investigational product cannot be excluded. 
4.1.1.3. Serious Adverse Event (SAE) 
It is defined as occurrence that adverse events or adverse drug reaction: 
①  Results in death or life-threatening. 
Life-threatening cases means emergency situations that can lead to death if medical treatment 
is not performed (eg, hepatic necrosis requiring liver transplantation, anaphylactic shock 
requiring emergency resuscitation, etc.). 
②  Requires inpatient hospitalization or prolongation of existing hospitalization 
Hospitalization is also considered at the discretion of the investigator if medical treatment is 
received in an emergency room other than in the hospital room (eg, acute allergic reaction). 
Hospitalization for the following is not considered a serious adverse event. 


Protocol No. IM_hzVSF_v13-0001 
Statistical Analysis Plan Ver. 1.0 (29Nov2019) 
CONFIDENTIAL 
11 
· 
Examination for the hospitalization or diagnosis during the Pharmacokinetic Sampling 
period or routine treatment or monitoring that is not related to deterioration of the 
condition, such as training for test drug administration. 
· 
Hospitalization for pre-scheduled treatment and surgery for a condition that is not related 
to the indication in clinical trial and does not deteriorated. 
③ Results in persistent or significant disability/incapacity 
④ Results in a congenital anomaly/birth defect 
If pregnancy occurs in a partner of the test subject during the clinical trial, it should be reported 
immediately to the monitor (or person in charge) of ImmunMed, but this is not a serious adverse 
events and it should be reported as serious adverse event in case of miscarriage, deformed child, 
developmental abnormality. 
⑤ Results in an important medical event 
4.1.2. 
Vital Signs 
Systolic blood pressure, B. 
Diastolic blood pressure, Pulse Rate, Body temperature 
4.1.3. 
Clinical Laboratory Test 
4.1.3.1. Hematology Test 
• WBC with differential count (neutrophil(seg.), lymphocyte, monocyte, eosinophil, basophil), 
RBC, Hemoglobin, Hematocrit, Platelet 
4.1.3.2. Blood Chemistry Test 
•  Sodium, Potassium, Chloride, Calcium, Phosphorus, BUN, Creatinine, Total protein, 
Albumin, Total bilirubin, Alkaline phosphatase, AST, ALT, γ-GT, LDH, CPK, Glucose, Cholesterol, 
LDH, Uric acid, Amylase, Lipase, 
Triglyceride 
4.1.3.3. Urine Test 
• Color, Specific gravity, pH, WBC(s), Nitrite, Albumin, Glucose, Ketone, Urobilinogen, 
Bilirubin, Occult blood with Microscopy 
4.1.4. 
12-Lead Electrocardiogram Test 
Ventricular rate, PR interval, QRS, QT, QTc 
4.1.5. 
Physical Examination 
During the screening tests, all signs and symptoms of physical examination are recorded in the 
case report form (CRF), and newly observed abnormalities or any changes to previously observed 


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abnormalities (deterioration or improvement) in subsequent tests are recorded in the case report form 
(CRF). 
4.1.6. 
Immunogenicity Test 
 Immunogenicity was evaluated by confirming the production of antibodies against hzVSF-v13 
4.2. Pharmacokinetic Variables 
4.2.1. 
Pharmacokinetic Measurements 
 Blood samples are collected to assess the pharmacokinetics of hzVSF-v13 until 2,184 hours 
after administration of the investigational product. 
- Blood collection time: 1d 0h (pre-dose), 0.5, 1, 2, 4, 6, 8, 10, 12, 24(2d 0h), 36(2d 12h), 48(3d 
0h), 60(3d 12h), 72(4d 0h), 96(5d 0h), 120(6d 0h), 144(7d 0h), 168(8d 0h), 336(15d 0h), 504(22d 
0h), 672(29d 0h), 840(36d 0h), 1176(50d 0h), 1512(64d 0h), 1848(78d 0h), 2184h(92d 0h) (post-
dose) 
4.2.2. 
Pharmacokinetic Parameters 
Parameter 
Unit 
Definition 
Calculation Method 
Tmax 
h 
Time to reach maximum blood 
levels after administration 
Direct observation in data 
Cmax 
mg/L 
Maximum blood concentration after 
administration of a single dose 
Direct observation in data 
AUClast 
mg·h/L 
Area under the blood concentration-
time curve from administration to 
the last blood collection point 
Linear up/Log down (calculated by 
applying the linear trapezoidal rule 
for 
the 
increase 
in 
blood 
concentration and the logarithmic 
trapezoidal rule for the decrease in 
blood concentration) 
AUCinf 
mg·h/L 
 Area 
under 
the 
blood 
concentration–time 
curve 
extrapolated to infinity after 
administration of a single dose. 
AUCinf = AUClast + Clast / z 
AUClast+Clast/λz 
t1/2 
h 
 Elimination half-life 
ln(2)/λz 
CL 
L/h 
Clearance after administration of a 
single dose. CL = Dose / AUClast, 
Dose/AUCinf 


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Vd 
L 
Volume 
of 
distribution 
after 
administration of a single dose. Vd = CL 
/ λz 
Dose/(AUCinf*λz) 
Clast:  Blood concentration at last quantifiable blood collection time point 
λz: Loss rate constant obtained by linear regression analysis in the log-linear plot of the part corresponding to the terminal 
phase of the blood concentration-time curve 
 
5. Definitions of the Analysis Sets 
5.1. Screened Set 
All subjects who signed on the consent and be given the screening number. 
5.2. Randomized Set 
All subjects who randomized (Intention-To-Treat, ITT). 
5.3. Safety Analysis Set  
Subjects who are administered the investigational product at least once were analyzed. 
5.4. Pharmacokinetic Analysis Set 
It is intended for the subjects (Per Protocol) who have completed a as per the protocol without 
significant protocol violations that may affect the pharmacokinetic results. However, it can refered 
to the information of the subject who dropped out during the pharmacokinetic evaluation. 
 
6. General Presentation of Summaries and Analyses 
6.1. Summary Statistics 
Unless other statement, continuous data (number of subjects, mean, standard deviation, 
coefficient of variation [%], minimum, median, maximum) is suggested by descriptive statistics. 
Categorical data suggested by frequency (N) and ratio (%). 
6.2. Definition of Subgroups for Analysis 
6.2.1. 
Dose Group  
The subjects who are assigned on the dose group (10 mg, 20 mg, 50 mg, 100 mg, 200 mg, 400 
mg, 800 mg, 1200 mg). 
6.2.2. 
Treatment Group  


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The subjects who are administered the investigational products indeed (Placebo, 10 mg, 20 mg, 
50 mg, 100 mg, 200 mg, 400 mg, 800 mg, 1200 mg). 
6.3. Baseline 
Unless other statement, the baseline is defined as the first value of prior to administration. 
6.4. Handling of Missing Data 
Unless otherwise stated, missing data (missing values) are not replaced with other values. 
6.5. Software for Statistical Analysis 
Statistical analysis is performed using SAS® (version 9.4 or most recent version available), etc. 
6.6. Significance Level 
Unless otherwise stated, statistical analysis is performed under the significance level of 0.05. 
 
7. Methods for Analyses 
7.1. Disposition and Protocol Deviations 
7.1.1. 
Subject Disposition 
 An assessment of clinical study participation status is done for the screened set. The following 
are summarized and tabulated for each treatment group in each dose group: screened subjects, 
subjects that failed screening, randomized subjects, subjects that received and did not receive 
investigational product administration after randomization, subjects dropped out after receiving 
investigational product administration, and subjects that completed the clinical study. 
The clinical study participation status data of each subject will be presented as a listing for all 
randomized subjects (randomized set). 
7.1.2. 
Summary for Analysis Sets 
The subjects included in each analysis group (Randomized Set, Safety Analysis Set, 
Pharmacokinetic Analysis Set) are summarized by dose group and treatment group. 
7.1.3. 
Protocol Deviations 
The evaluation of violation of the protocol is conducted for the Randomized Set. Each violations 
of protocol are summarized by the number of subjects, percentage (%), and number of occurrences 
by treatment group, and data of each subject are presented in a listing. 


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7.2. Demographics and Baseline Characteristics 
7.2.1. 
Demographics 
The subjects’ demographic characteristics for the following items are summarized by the overall 
subjects, by dose group, and by treatment group. 
- 
 Age, height, weight, BMI 
- 
 Alcohol use history, smoking history, caffeine consumption 
For the following items, each subject data is presented in a listing. 
- 
Demographics 
- 
Interview 
- 
Urine Drug Screening 
- 
Serology 
7.2.2. 
Medical History 
Evaluation of medical history is conducted for the Safety Analysis Set. All medical history are 
standardized as System Organ Class (SOC) and Preferred Term (PT) by using MedDRA® (version 
21.1 or most recent version). For each treatment group and all subjects, each evaluation item is 
summarized in terms of the number of subjects, ratio (%), and number of occurrence cases. The data 
of each subject are presented as a listing. 
7.2.3. 
Concomitant Medication 
Evaluation of concomitant drug is conducted for the Safety Analysis Set. Concomitant drugs are 
coded into Anatomical main group (Level 1) and Therapeutic subgroup (Level 2) using WHO-DD 
(World Health Organization Drug Dictionary) (version 2018 or recent version), and summarize by 
number of subjects, percentage (%), and number of occurrences. Each subject data is presented as a 
listing. 
 
7.3. Safety Evaluation 
Safety evaluation is carried out for the safety set. 
7.3.1. 
Adverse Events 
All reported TEAEs/ADRs are standardized as SOC and PT by using MedDRA® (version 21.1 
or most recent version). For each treatment group and all subjects, each evaluation item (severity, 
seriousness, causal relationship, actions taken, outcomes, treatment) are summarized in terms of the 


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number of subjects, ratio (%), and number of occurrence cases. If necessary, statistical testing using 
Fisher’s exact test is performed to evaluate the differences in the pattern of adverse event occurrences 
between the treatment groups. The data of each subject are presented as a listing. 
7.3.2. 
Vital Signs 
Vital signs are reviewed comprehensively and were described in the clinical study report if there 
was clinical significance, and their relationship to the investigational product is determined. For 
blood pressure, pulse rate, and temperature, the quantity changes compared to the results at each 
point of testing, as well as compared to the baseline were summarized by treatment group. The data 
of each subject are presented as a listing. 
7.3.3. 
Clinical Laboratory Test 
Clinical laboratory test results are reviewed comprehensively and are described in the clinical 
study report if there is clinical significance, and their relationship to the investigational product is 
determined. For hematology and blood chemistry, the quantity changes compared to the results at 
each point of testing, as well as compared to the baseline are summarized by treatment group. The 
data of each subject are presented as a listing 
7.3.4. 
12-Lead Electrocardiogram Test 
 Electrocardiography results are reviewed comprehensively and are described in the clinical 
study report if there is clinical significance, and their relationship to the investigational product is 
determined. The quantity changes compared to the results at each point of electrocardiography, as 
well as compared to the baseline are summarized by treatment group. The data of each subject are 
presented as a listing. 
7.3.5. 
Physical Examination 
Physical examination results are reviewed comprehensively and were described in the clinical 
study report if there is clinical significance, and their relationship to the investigational product was 
determined. The data of each subject are presented as a listing. 
7.4. Pharmacokinetics 
Pharmacokinetic evaluation is performed on the Pharmacokinetic Analysis Set. 
7.4.1. 
Pharmacokinetic Measurements 
The blood concentration of hzVSF-v13 is summarized as the nominal time for each dose group 
of the test drug. And the blood concentration of each subject is presented as a listing. 


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7.4.2. 
Pharmacokinetic Profiles 
The average blood concentration-time pattern of hzVSF-v13 is shown in linear and log-linear 
graphs for each dose group of the investigational product, and the individual blood concentration-
time graph of each subject is also shown in the same way. 
7.4.3. 
Pharmacokinetic Parameters 
The pharmacokinetic parameters of hzVSF-v13 are summarized by dose group, and the 
pharmacokinetic parameters of each subject are presented as a listing.  
To confirm dose-proportionality of the study drug, the Cmax and AUC parameters of hzVSF-
v13 is shown as a graph of each administration dose of the study drug, and a regression analysis is 
performed using the power model. 
 
7.5. Immunogenecity 
7.5.1. 
Immunogenicity measurements 
The immunogenicity test of hzVSF-v13 is summarized according to the nominal time of blood 
collection for each dose group. The immunogenicity test of each subjects is presented as listing. 
7.5.2. 
Immunogenicity profiles 
The average blood immunogenic titer-time pattern of hzVSF-v13 is shown in linear and log-
linear graphs for each dose group of test drug. In addition, the individual blood concentration-time 
graph of each subject is also shown in the same way. If necessary, statistical tests can be performed 
to confirm differences between dose groups. 
 
8. Sensitivity Analysis 
Sensitivity analysis is not performed in this study. 
 
9. Interim Analysis 
No interim analysis other than the tolerability and safety evaluation to determine whether to 
proceed to the next dose group is performed. However, to confirm the safety of the subject, a 
statistical analysis can be performed by combining the tolerability and safety evaluation. 


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10. Change from Protocol 
N.A. 
 
 
 


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11. References 
N.A. 
 


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12. Appendix: List of Tables, Figures, and Listings 
12.1. List of Tables 
Table 1-1. Disposition at Study Entry 
Table 1-2-1. Disposition by Analysis Set by Dose Group 
Table 1-2-2. Disposition by Analysis Set by Treatment Group 
Table 2. Summary of Protocol Violation  
Table 3-1-1. Summary of Demographics by Dose Group 
Table 3-1-2. Summary of Demographics by Treatment Group 
Table 3-2-1. Summary of Substance Use by Dose Group 
Table 3-2-2. Summary of Substance Use by Treatment Group 
Table 4. Summary of Medical History 
Table 5. Summary of Concomitant Medication 
Table 6-1. Overview of Treatment-Emergent Adverse Events (TEAEs) 
Table 6-2. Overview of Adverse Drug Reactions (ADRs) 
Table 7-1. Incidence of Treatment-Emergent Adverse Events (TEAEs) by SOC and PT 
Table 7-2. Incidence of Adverse Drug Reactions (ADRs) by SOC and PT 
Table 8. Summary of Vital Signs 
Table 9-1. Summary of Hematology 
Table 9-2. Summary of Blood Chemistry 
Table 10. Summary of 12-Lead Electrocardiogram 
Table 11. Summary of hzVSF-v13 Concentration for Nominal Time 
Table 12. Summary of Pharmacokinetic Parameters of hzVSF-v13 
Table 13. Dose-Proportionality Assessment using Power Model 
 
 


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12.2. List of Figures 
Figure 1. Subject Disposition 
Figure 2-1. Mean Concentration-Time Profile of hzVSF-v13 
Figure 2-2. Individual Concentration-Time Profiles of hzVSF-v13 
Figure 2-3. Scatter Plot of Pharmacokinetic Parameters by Dose Group 
 
12.3. List of Listings 
Listing 1. Subject Enrollment Status 
Listing 2. Missing or Deviations 
Listing 3-1. Demographics 
Listing 3-2. Interview 
Listing 3-3. Urine Drug Screening 
Listing 3-4. Serology 
Listing 4. Medical History 
Listing 5. Concomitant Medication 
Listing 6. Adverse Events 
Listing 7. Vital Signs 
Listing 8-1. Clinical Laboratory (Hematology) 
Listing 8-2. Clinical Laboratory (Blood Chemistry) 
Listing 8-3. Clinical Laboratory (Urinalysis) 
Listing 9. ECG 
Listing 10. Physical Examination 
Listing 11-1. Individual Concentration of hzVSF-v13 
Listing 12-2. Individual Pharmacokinetic Parameters of hzVSF-v13