Clinical trial NCT04525079
Conditions: SARS-CoV-2 Infection
Sponsor: Celltrion
Start date: 2020-07-18; Completion date: 2020-11-05
Enrollment: 32 participants; Allocation: RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
This is a Phase I study that randomized, double-blind, Placebo-controlled, Parallel Group, Single Ascending Dose Study to evaluate Safety, Tolerability and Pharmacokinetics of CT-P59 in Healthy Subjects.

Detailed description:
CT-P59 is a monoclonal antibody targeted against SARS-CoV-2 spike RBD as a treatment for SARS CoV 2 infection. CT-P59 is currently being developed by the Sponsor as a potential treatment for SARS-CoV-2 infection. In this study, safety, tolerability, and pharmacokinetics of CT-P59 will be evaluated in healthy subjects.

Arms: arm 1: Cohort 1 will receive a dose of CT-P59 or matching placebo arm 2: Cohort 2 will receive a dose of CT-P59 or matching placebo arm 3: Cohort 3 will receive a dose of CT-P59 or matching placebo arm 4: Cohort 4 will receive a dose of CT-P59 or matching placebo
Interventions: intervention 1: CT-P59 intervention 2: Placebo
Intervention descriptions: intervention 1: CT-P59 will be administered intervention 2: Placebo-matching CT-P59

Protocol documents:
Prot_000.pdf: 
CLINICAL STUDY PROTOCOL 
A Phase 1, Randomized, Double-blind, Placebo-controlled, Parallel Group, 
Single Ascending Dose Study to Evaluate the Safety, Tolerability and 
Pharmacokinetics of CT-P59 in Healthy Subjects 
PROTOCOL NUMBER CT-P59 1.1 
EudraCT Number: 
2020-003065-19 
Study Drug 
CT-P59 
Sponsor: 
CELLTRION, Inc. 
 
 
 
 
 
Sponsor Contact : 
 
 
 
 
 
SAE Reporting : 
Email: 
 
Version and Date of Protocol 
Protocol Version 1.3, 03 July 2020 
CONFIDENTIAL 
All financial and nonfinancial support for this study will be provided by CELLTRION, Inc. The concepts 
and information contained in this document or generated during the study are considered proprietary and 
may not be disclosed in whole or in part without the expressed, written consent of CELLTRION, Inc. The 
study will be conducted according to the protocol and in compliance with the International Council for 
Harmonisation harmonised tripartite guideline E6(R2): Good Clinical Practice and the Declaration of 
Helsinki (World Medical Association 2013). Throughout this document, symbols indicating proprietary 
names (®, ™) are not displayed. The appearance of product names without these symbols does not imply 
that these names are not protected. 




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Declaration of Investigator 
I have read and understood all sections of the protocol entitled ‘A Phase 1, Randomized, 
Double-blind, Placebo-controlled, Parallel Group, Single Ascending Dose Study to Evaluate 
the Safety, Tolerability and Pharmacokinetics of CT-P59 in Healthy Subjects’ and the 
accompanying current Investigator’s Brochure. 
I agree to supervise all aspects of the protocol and to conduct the clinical investigation in 
accordance with the Protocol Version 1.3, dated 03 July 2020, the International Council for 
Harmonisation harmonised tripartite guideline E6(R2): Good Clinical Practice, Declaration of 
Helsinki (World Medical Association 2013), and all applicable government regulations. I will 
not make changes to the protocol before consulting with CELLTRION, Inc. or implement 
protocol changes without Independent Ethics Committee (or Institutional Review Board) 
approval except to eliminate an immediate risk to subjects. I agree to administer study drug only 
to subjects under my personal supervision or the supervision of a Sub-Investigator. 
I will not supply the study drug to any person not authorized to receive it. Confidentiality will 
be protected. Subject identity will not be disclosed to third parties or appear in any study reports 
or publications. 
I will not disclose information regarding this clinical investigation or publish results of the 
investigation without authorization from CELLTRION, Inc. 
 
 
 
 
 
Signature of Principal Investigator 
 
Date 
 
 
 
 
 
 
Printed Name of Principal Investigator: 
 
Address: 
 
 
 
Phone:  
 
 
 
 


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TABLE OF CONTENTS 
CLINICAL STUDY PROTOCOL ............................................................................................. 1 
Protocol Approval ....................................................................................................................... 2 
TABLE OF CONTENTS ............................................................................................................ 4 
LIST OF TABLES ...................................................................................................................... 9 
LIST OF FIGURES .................................................................................................................... 9 
PROTOCOL SYNOPSIS ......................................................................................................... 10 
LIST OF ABBREVIATIONS ................................................................................................... 15 
1 Introduction ......................................................................................................................... 16 
1.1 
Background ............................................................................................................... 16 
1.2 
CT-P59 ...................................................................................................................... 17 
1.2.1 
Nonclinical Studies ........................................................................................... 17 
1.2.2 
Clinical Studies ................................................................................................. 17 
1.3 
Study Rationale ......................................................................................................... 18 
1.3.1 
Rationale for Study Population ......................................................................... 18 
1.4 
Benefit and Risk Assessment .................................................................................... 18 
2 Study Objectives and Endpoints ......................................................................................... 20 
2.1 
Study Objectives ....................................................................................................... 20 
2.1.1 
Primary Objective ............................................................................................. 20 
2.1.2 
Secondary Objectives........................................................................................ 20 
2.2 
Study Endpoints ........................................................................................................ 20 
2.2.1 
Primary Endpoints ............................................................................................ 20 
2.2.2 
Secondary Endpoints ........................................................................................ 20 
2.2.2.1 Safety Endpoints ........................................................................................... 21 
2.2.2.2 Pharmacokinetic Endpoints .......................................................................... 21 
3 Investigational Plan ............................................................................................................. 22 
3.1 
Study Design ............................................................................................................. 22 


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3.2 
Rationale for Study Design ....................................................................................... 23 
3.3 
Dose Escalation and Stopping Criteria ..................................................................... 23 
3.3.1 
Criteria for Proceeding from Sentinel Group to Remaining Group .................. 23 
3.3.2 
Dose Escalation Criteria ................................................................................... 24 
3.3.3 
Dose Stopping Rules ......................................................................................... 25 
3.4 
Study Overview ........................................................................................................ 25 
3.4.1 
Screening Period (Day -21 to Day -2) .............................................................. 25 
3.4.2 
Admission (Day -1)........................................................................................... 26 
3.4.3 
Study Period (Day 1 to prior to End-of-Study Visit) ........................................ 26 
3.4.4 
End-of-Study Visit (Day 90) ............................................................................. 26 
4 Subject Selection and Withdrawal Criteria ......................................................................... 27 
4.1 
Selection of Study Population ................................................................................... 27 
4.2 
Inclusion Criteria ...................................................................................................... 27 
4.3 
Exclusion Criteria ..................................................................................................... 28 
4.4 
Subject Withdrawal and Replacement ...................................................................... 30 
4.4.1 
Recruitment of Additional Subjects .................................................................. 31 
4.5 
Premature Termination of the Clinical Trial ............................................................. 31 
5 Study Treatment .................................................................................................................. 32 
5.1 
Method of Assigning Subjects to Treatment Group ................................................. 32 
5.2 
Treatment Administered ........................................................................................... 32 
5.2.1 
CT-P59 .............................................................................................................. 33 
5.2.2 
Placebo .............................................................................................................. 33 
5.2.3 
Rationale for Dose Selection ............................................................................ 33 
5.2.4 
Dose Modification ............................................................................................ 34 
5.3 
Management of Clinical Supplies ............................................................................. 34 
5.3.1 
Study Drug Packaging, Labeling, and Storage ................................................. 34 
5.3.2 
Study Drug Accountability ............................................................................... 35 
5.4 
Blinding..................................................................................................................... 36 


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5.5 
Breaking the Blind .................................................................................................... 36 
5.6 
Treatment Compliance .............................................................................................. 37 
5.7 
Prior, Concomitant, and Prohibited Medications ...................................................... 37 
5.8 
Restriction ................................................................................................................. 37 
5.8.1 
Dietary and Fluid Restrictions .......................................................................... 37 
5.8.2 
Other Restrictions ............................................................................................. 38 
6 Study Assessments and Procedures .................................................................................... 40 
6.1 
Safety Assessments ................................................................................................... 40 
6.1.1 
Medical History and Demographic Information ............................................... 40 
6.1.2 
Other Baseline Characteristics .......................................................................... 40 
6.1.2.1 SARS-CoV-2 Infection Test ......................................................................... 40 
6.1.2.2 Viral Serology Test ....................................................................................... 40 
6.1.2.3 Urine Drug Test ............................................................................................ 41 
6.1.2.4 Chest X-ray ................................................................................................... 41 
6.1.3 
Adverse Events ................................................................................................. 41 
6.1.3.1 Definition of Adverse Events ....................................................................... 41 
6.1.3.2 Assessment of Severity ................................................................................. 46 
6.1.3.3 Assessment of Causality ............................................................................... 46 
6.1.4 
Hypersensitivity Monitoring ............................................................................. 47 
6.1.5 
Vital Signs, Weight, and Height ....................................................................... 48 
6.1.6 
Electrocardiogram ............................................................................................. 48 
6.1.7 
Physical Examination........................................................................................ 49 
6.1.8 
Pregnancy .......................................................................................................... 49 
6.1.9 
Clinical Laboratory Tests .................................................................................. 50 
6.1.10 Immunogenicity Assessments ........................................................................... 50 
6.2 
Pharmacokinetic Assessments .................................................................................. 51 
6.3 
Sample Collection ..................................................................................................... 51 
6.3.1 
Pharmacokinetic Blood Sampling..................................................................... 52 


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6.3.2 
Immunogenicity Blood Sampling ..................................................................... 52 
6.3.3 
Safety Blood Sampling ..................................................................................... 52 
6.3.4 
Safety Urine Sampling ...................................................................................... 52 
6.4 
Labeling, Storage, and Transportation of Samples ................................................... 52 
6.4.1 
Sample Labeling ............................................................................................... 52 
6.4.2 
Sample Storage and Shipment .......................................................................... 52 
7 Statistical Analysis .............................................................................................................. 54 
7.1 
Sample Size Calculation ........................................................................................... 54 
7.2 
Analysis Sets ............................................................................................................. 54 
7.3 
Description of Subgroups to be analyzed ................................................................. 54 
7.4 
Statistical Analysis Methodology ............................................................................. 55 
7.4.1 
General Consideration ...................................................................................... 55 
7.4.2 
Study Population ............................................................................................... 55 
7.4.2.1 Disposition of Subjects ................................................................................. 55 
7.4.3 
Safety Analysis ................................................................................................. 55 
7.4.3.1 Demographic, Baseline, and Background Characteristics ............................ 55 
7.4.3.2 Adverse Events ............................................................................................. 55 
7.4.3.3 Clinical Laboratory and Pregnancy Tests ..................................................... 56 
7.4.3.4 Electrocardiogram, Physical Examination, and Vital Signs ......................... 56 
7.4.3.5 Prior and Concomitant Medications ............................................................. 57 
7.4.3.6 Immunogenicity Analysis ............................................................................. 57 
7.4.4 
Pharmacokinetic Analyses ................................................................................ 57 
7.5 
Interim Analysis ........................................................................................................ 57 
7.6 
Data Quality Assurance ............................................................................................ 57 
8 Investigator’s Obligations ................................................................................................... 59 
8.1 
Confidentiality .......................................................................................................... 59 
8.2 
Independent Ethics Committee ................................................................................. 59 
8.3 
Subject Information and Consent.............................................................................. 60 


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8.4 
Study Reporting Requirements ................................................................................. 61 
8.5 
Financial Disclosure and Obligations ....................................................................... 61 
8.6 
Investigator Documentation ...................................................................................... 62 
8.7 
Study Conduct ........................................................................................................... 63 
8.8 
Data Collection ......................................................................................................... 63 
8.8.1 
Electronic Case Report Forms and Source Documents .................................... 63 
8.9 
Adherence to Protocol............................................................................................... 63 
8.10 Investigator’s Final Report ....................................................................................... 63 
8.11 Record Retention ...................................................................................................... 64 
8.12 Subject Identification Register .................................................................................. 64 
8.13 Publications ............................................................................................................... 64 
9 Study Management ............................................................................................................. 65 
9.1 
Sponsor ..................................................................................................................... 65 
9.2 
Vendor Contact ......................................................................................................... 65 
9.3 
Central Analytical Facility ........................................................................................ 65 
9.4 
Monitoring ................................................................................................................ 66 
9.4.1 
Dose Escalation Committee .............................................................................. 66 
9.4.2 
Data and Safety Monitoring Board ................................................................... 66 
9.4.3 
Monitoring of the Study .................................................................................... 66 
9.4.4 
Inspection of Records ....................................................................................... 67 
9.5 
Management of Protocol Amendments and Deviations ........................................... 67 
9.5.1 
Modification of the Protocol ............................................................................. 67 
9.5.2 
Protocol Deviations ........................................................................................... 67 
9.6 
Study Termination .................................................................................................... 68 
9.7 
Final Report .............................................................................................................. 68 
10 
Reference List ................................................................................................................. 69 
11 
Appendices ...................................................................................................................... 71 
11.1 Schedule of Assessments .......................................................................................... 71 


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LIST OF TABLES 
Table 6-1 Schedule of Assessments for Hypersensitivity Monitoring ................................. 47 
Table 6-2 Blood Sampling Time Points for Pharmacokinetic Assessment .......................... 51 
Table 11-1 Schedule of Assessments .................................................................................... 71 
 
LIST OF FIGURES 
Figure 3-1 Study Overview ................................................................................................... 23 
 
 


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PROTOCOL SYNOPSIS 
Protocol Number: CT-P59 1.1 
Title: A Phase 1, Randomized, Double-blind, Placebo-controlled, Parallel Group, Single Ascending Dose Study 
to Evaluate the Safety, Tolerability and Pharmacokinetics of CT-P59 in Healthy Subjects 
Study Phase: Phase 1 
Sponsor: CELLTRION, Inc. 
Principal Investigator: 
 
Study Center: 
 
Test Drug Formulation, Dose, and Regimen: 
CT-P59 (960 mg/16 mL): 10 mg/kg, 20 mg/kg, 40 mg/kg or 80 mg/kg, intravenous (IV) infusion for 90 minutes 
(± 15 minutes) 
Reference Drug Formulation, Dose, and Regimen: 
Placebo (16 mL): matching in volume to each dose of CT-P59, IV infusion for 90 minutes (± 15 minutes) 
Objectives: 
Primary objective 
 
To evaluate the preliminary safety and tolerability of CT-P59 up to Day 14 of the last enrolled subject 
Secondary objectives 
 
To evaluate the pharmacokinetic (PK) of CT-P59 
 
To evaluate additional safety of CT-P59 including immunogenicity 
Main Selection Criteria: 
Healthy male or female subjects who are negative on the severe acute respiratory syndrome coronavirus 2 
(SARS-CoV-2) infection test with 19 to 55 years (both inclusive) of age, a body weight of ≥ 50 kg and a body 
mass index between 18.0 and 29.9 kg/m2 (both inclusive) will be considered for enrollment in the study if they 
meet all of inclusion criteria and none of the exclusion criteria. 
Inclusion Criteria: 
Each subject must meet all of the following criteria to be randomized in this study: 
1. Subject is a healthy male or female subject, aged between 19 to 55 years (both inclusive). Health is defined 
as no clinically relevant abnormalities identified by Investigator’s decision based on a detailed medical 
history, full physical examination, including blood pressure, heart rate, respiratory rate, and body 
temperature measurements, 12-lead electrocardiogram (ECG) and clinical laboratory tests prior to the study 
drug administration. 
2. Subject is confirmed as negative in SARS-CoV-2 infection test on screening and Day -1 visits. 
3. Subject with a body weight of ≥ 50 kg and a body mass index between 18.0 and 29.9 kg/m2 (both inclusive). 
4. Subject is able to understand and to comply with protocol requirements, instructions, and restrictions. 
5. Subject voluntarily agrees to participate in this study and has given a written informed consent prior to 
undergoing any of the screening procedures. 
6. Subjects and their partners of childbearing potential must agree to use a highly effective method of 
contraception or two acceptable methods of contraception until 6 months after the study drug administration 
as specified in Section 5.8.2. A man or woman is of childbearing potential if he or she is biologically capable 
of having children and is sexually active in the opinion of the Investigator. Subjects and their partners who 
have been surgically sterilized for less than 6 months prior to the date of informed consent must agree to use 
any medically acceptable methods of contraception. 
Exclusion Criteria: 
A Subject meeting any of the following criteria will be excluded from the study: 
1. Subject has a medical history or current presence of disease including one or more of the following(s): 
a. History of or current allergic reaction such as asthma, urticaria, angioedema, and eczematous dermatitis 
considered as clinically significant in the Investigator’s opinion or hypersensitivity including known or 
suspected clinically relevant drug hypersensitivity to any monoclonal antibody or any component of study 
drug 
b. History of or current medical condition including gastrointestinal, renal, endocrine, neurologic, 
autoimmune, hepatic, hematological metabolic (including known diabetes mellitus), cardiovascular, or 
psychiatric condition classed as clinically significant by the Investigator 


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c. History of or any concomitant active malignancy 
d. History of or current infection with human immunodeficiency, syphilis, hepatitis B or hepatitis C 
e. History of or current infection requiring a course of systemic anti-infective that was completed within 
28 days prior to the study drug administration or a serious infection (associated with hospitalization or 
which required IV antibiotics) within 6 months before the study drug administration 
f. History of an illness within 28 days prior to the study drug administration that is identified as clinically 
significant by the Investigator or requires hospitalization 
g. History of surgical intervention or an operation within 28 days prior to the study drug administration or 
plans to have a surgical procedure during the study period 
2. Subject had a history of or concurrent use of medications including any prior therapy of following(s): 
a. Prescription medication (excluding hormonal birth control), over-the-counter drug, dietary supplements or 
herbal remedies within 7 days or 5 half-lives (whichever is longer) prior to the study drug administration 
b. Any vaccination within 4 weeks prior to the study drug administration 
c. Treatment with any monoclonal antibody, fusion protein, or blood transfusion within 6 months or 
5 half-lives (which is longer) prior to the study drug administration or current use of biologics 
d. Treatment with any other investigational drug within 6 months or 5 half-lives (which is longer) prior to the 
study drug administration 
3. A male subject plans to father a child or donate sperm or a female subject is lactating or planning to be 
pregnant or to breastfeed within 6 months from the study drug administration. 
4. Subject shows reasonable evidence of drug/alcohol/nicotine abuse prior to the study drug administration as 
opinion of the Investigator or has following(s): 
a. Positive result for drug urine test during screening or Day -1 
b. History or presence of regular consumption exceeding an average weekly intake of > 14 units of alcohol 
in recent 3 months prior to the study drug administration 
c. Consuming more than 10 cigarettes or equivalent per day within a month prior to the study drug 
administration 
5. Subject is unwilling to avoid the use of alcohol or alcohol containing foods, medications, or beverage within 
48 hours prior to admission and 24 hours prior to each study visit throughout the study or unable to refrain 
from smoking during the in-house stays. 
6. Subject donated or lost 400 mL or more whole blood within 8 weeks (plasma/platelets donation within 4 
weeks) prior to the study drug administration. 
7. Subject shows evidence of a condition (psychological, emotional problems, any disorders or resultant 
therapy) that is likely to invalidate health information, consent, or limit the ability of the subject to comply 
with the protocol requirements in the opinion of the Investigator. 
8. Subject is vulnerable (e.g., employees of the clinical trial site or any other individuals involved with the 
conduct of the study, or immediate family members of such individuals, persons kept in prison or other 
institutionalized persons by law enforcement). 
9. Subject is not likely to complete the study for whatever reason other than criteria listed above in the opinion 
of the Investigator. 
Study Design: 
This is a randomized, double-blind, placebo-controlled, parallel group, single ascending dose, Phase 1 study to 
evaluate the safety, tolerability and PK of CT-P59 in healthy subjects. Approximately 32 subjects in 4 cohorts 
are planned for enrollment and each cohort will consist of 8 subjects, 6 of whom will receive CT-P59 and 2 of 
whom will receive a placebo. In cohorts 1 and 2, each cohort includes a sentinel group of 2 subjects and a 
remaining group of 6 subjects. In a sentinel group, 2 subjects will be randomized in a 1:1 ratio to receive CT-P59 
or placebo. In a remaining group, 6 subjects will be randomized in a 5:1 ratio to receive CT-P59 or placebo. In 
cohorts 3 and 4, 8 subjects will be randomized in 3:1 ratio to receive CT-P59 or placebo. 


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Figure S 1. Study Design Overview 
 
This study will be started with the lowest dose that will maximize safety and the dose levels will be escalated to 
the higher doses. In cohorts 1 and 2, the first study drug administration will be administered as IV infusion to 
the each sentinel group. In cohorts 3 and 4, all subjects in each cohort will randomly receive study drug without 
group sequence. Dose Escalation Committee will review all available safety data after an observation period of 
48 hours and will decide whether to proceed dosing of remaining group and next cohort. If any safety concern 
including predefined stopping rule is raised under decision of committee, the study will be temporarily stopped 
and Data and Safety Monitoring Board will evaluate and review all available data and evaluate the relationship 
to CT P59 of the event with unblinded manner and will make a decision on continuation of the study. 
This study is consist of screening period (Day -21 to Day -2), admission (Day -1), study period (Day 1 to prior 
to end-of-study visit), and end-of-study visit (Day 90). The total duration of this study will be approximately 16 
weeks for the individual subject. Subjects will sign the informed consent at screening visit and undergo 
procedures to determine eligibility. Eligible subjects will have admission visit on Day -1 and under go baseline 
assessments and recheck eligibility. Subjects will be randomized to receive a single dose of CT-P59 or placebo 
on Day 1. All subjects will be confined to the study center on Day -1 until completion of the 72-hour (Day 4) 
assessments after the study drug administration and confinement can be extended depending on the subjects’ 
and study center’s availability up to Day 14. The subsequent study visits will be carried out on an out-patient 
basis. Subjects will return to the study center on Day 90 and undergo predefined end-of-study visit assessments. 
Safety Assessments: 
Primary endpoints 
Primary endpoints will be analyzed based on the data up to Day 14 of the last enrolled subject. 
 
Treatment-emergent AEs (TEAEs) 
 
Treatment-emergent serious AEs (TESAEs) 
 
Treatment-emergent AE of special interest (TEAESI; infusion related reactions including 
hypersensitivity/anaphylactic reaction) 
 
Vital signs (blood pressure, heart rate, body temperature, and respiratory rate) 
 
Hypersensitivity monitoring 
 
Twelve-lead ECG 
 
Physical examination findings 
 
Clinical laboratory tests (clinical chemistry, hematology, and urinalysis) 
Secondary endpoints 
Secondary endpoints will be analyzed for whole study period. 
 
Treatment-emergent AEs (including TESAEs and TEAESI) 
 
Vital signs (blood pressure, heart rate, body temperature, and respiratory rate) 
 
Twelve-lead ECG 
 
Physical examination findings 
 
Clinical laboratory tests (clinical chemistry, hematology, and urinalysis) 
 
Incidence of anti-drug antibodies and neutralizing antibodies 


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Pharmacokinetic Assessments: 
Secondary endpoints 
 
Area under the concentration-time curve from time zero to infinity (AUC0-inf) 
 
Dose normalized AUC0-inf (AUC0-inf/Dose) 
 
Area under the concentration-time curve from time zero to the last quantifiable concentration (AUC0-last) 
 
Dose normalized AUC0-last (AUC0-last/Dose) 
 
Maximum serum concentration (Cmax) 
 
Dose normalized Cmax (Cmax/Dose) 
 
Time to Cmax (Tmax) 
 
Terminal half-life (t1/2) 
 
Percentage of AUC0-inf obtained by extrapolation (%AUCext) 
 
Terminal elimination rate constant (λz) 
 
Total body clearance (CL) 
 
Volume of distribution during the elimination phase (Vz) 
Sample Size: 
The total sample size of 32 subjects is not based on a formal statistical hypothesis. A sample size justification 
based on statistical hypotheses is not relevant in this study. The proposed number of 8 subjects (6 subjects for 
CT-P59 and 2 subjects for placebo) in each cohort is set empirically based on sample sizes in other Phase 1 
studies investigating the safety and tolerability of their study drugs and is considered to be sufficient to achieve 
the objectives of the study. 
Statistical Methods: 
Data Analyses 
The study will be unblinded for the reporting purposes after database lock for data up to Day 14 of the last 
enrolled subject. The unblinded team will be predefined and documented before performing the analyses. The 
study will remain blinded to the Investigators, subjects, predefined blinded study center staffs, blinded teams in 
the Sponsor, and contract research organization until all subject have completed the study and the database has 
been finalized for study termination. 
Statistical Analysis 
The statistical analysis will be performed using Statistical Analysis System Software Version 9.4 or higher (SAS 
institute Inc., Cary, North Carolina, US). The statistical methods for this study will be described in a detailed 
statistical analysis plan (SAP). Changes from analyses planned in this protocol will be documented in the SAP. 
Any deviations from the planned analysis as described in the SAP will be justified and recorded in the clinical 
study reports. 
Analysis Sets 
Intent-to-treat Set: The Intent-to-treat Set is defined as all randomly assigned subjects to study drug. 
Safety Set: The Safety Set will include all randomized subjects who received a full or partial dose of the study 
drug. 
Pharmacokinetic Set: The PK Set will include all subjects in the Safety Set who received a full dose of CT-P59 
and provide at least 1 evaluable post-treatment PK concentration result. 
Safety analysis 
All safety analyses including immunogenicity will be conducted on the Safety Set and will be listed and 
summarized by the cohort of CT-P59 groups and pooling of placebo group. Adverse events will be listed and 
summarized by severity and relationship to the study drug using system organ class and preferred term. Serious 
adverse events will be summarized separately. Terminology and severity grading of AEs will be recorded based 
on Common Terminology Criteria for Adverse Events Version 5.0. All reported terms for AEs will be coded 
using the Medical Dictionary for Regulatory Activities. Prior and concomitant medications will be coded using 
the World Health Organization Drug Dictionary. Safety data on results of vital signs, ECG, clinical laboratory 
tests, pregnancy test, hypersensitivity monitoring, and physical examination, prior and concomitant medications, 
and immunogenicity will be listed and summarized by visits as well as by the cohort of CT-P59 groups and 
pooling of placebo group. 
Pharmacokinetic analysis 
All PK analyses will be conducted in the PK set. The PK parameters of CT-P59 will be analyzed using 
noncompartmental methods based on the actual sampling time points. All parameters will be calculated using 
Phoenix WinNonlin (Pharsight, St Louis, Missouri, US). Pharmacokinetic parameters and PK concentrations 


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will be presented in listings and summarized in tables by cohort of CT-P59 groups. The tables will display the 
following descriptive statistics: n, mean, SD, median, minimum, maximum, geometric mean and coefficient of 
variation. 
 
 


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LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
%AUCext 
Percentage of AUC0-inf obtained by extrapolation  
ABV 
alcohol by volume 
ACE2 
angiotensin-converting enzyme 2 
ADA 
anti-drug antibody 
ADL 
activities of daily living  
AE 
adverse event 
AESI 
adverse events of special interest  
AUC 
area under the concentration-time curve  
AUC0-inf 
area under the concentration-time curve from time zero to infinity  
AUC0-last 
area under the concentration-time curve from time zero to the last quantifiable 
concentration  
BMI 
body mass index  
CL 
total body clearance  
Cmax 
maximum serum concentration  
COVID-19  
corona virus disease 19 
CRO 
contract research organization  
CSR 
clinical study report 
CTCAE 
Common Terminology Criteria for Adverse Event 
DEC 
Dose Escalation Committee  
DSMB 
Data and Safety Monitoring Board 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EDC 
Electronic Data Capture  
EOS 
end-of-study  
ESR 
erythrocyte sedimentation rate  
GCP 
Good Clinical Practice  
HBsAg 
hepatitis B surface antigen 
HIV 
human immunodeficiency virus 
IB 
Investigator’s brochure  
ICF  
informed consent form 
ICH 
International Council for Harmonisation 
IEC 
Independent Ethics Committee 
ITT 
Intent-to-treat  
IV 
intravenous  
NAb 
neutralizing antibody 
OTC 
over-the-counter 
PK 
pharmacokinetic 
RBD 
receptor binding protein 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SARS‑CoV‑2 
severe acute respiratory syndrome coronavirus 2 
SOP 
standard operating procedure 
t1/2 
Terminal half-life  
TEAE 
Treatment-emergent adverse event 
TEAESI 
Treatment-emergent adverse events of special interest 
TESAE 
Treatment-emergent serious adverse event 
Tmax 
Time to Cmax 
Vz 
Volume of distribution during the elimination phase 
λz 
Terminal elimination rate constant 


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1 Introduction 
1.1 Background 
Coronaviruses are single stranded ribonucleic acid viruses, capable of causing life threatening 
disease in humans and animals. The novel severe acute respiratory syndrome coronavirus 2 
(SARS-CoV-2) was initially identified during an outbreak of atypical viral pneumonia cases of 
unknown cause in the People’s Republic of China (hereafter “China”) in December 2019. Most 
of the initial infections outside of China were travel associated (i.e., from people who had 
travelled from the infected regions of China to other countries), although person to person 
transmission in other countries was quickly established. The disease caused by SARS-CoV-2 
has been designated as coronavirus disease 2019, known as COVID-19 (World Health 
Organization [WHO] disease outbreak news, 2020). 
Most people with SARS-CoV-2 infection develop only mild (40%) or moderate (40%) disease. 
However, approximately 15% develop severe disease that requires oxygen support, and 5% 
have critical disease with complications such as respiratory failure, acute respiratory distress 
syndrome, sepsis and septic shock, thromboembolism, and/or multiorgan failure, including 
acute kidney injury and cardiac injury. Older age, smoking and underlying noncommunicable 
diseases, such as diabetes, hypertension, cardiac disease, chronic lung disease, and cancer have 
been reported as risk factors for severe disease and death. 
Severe acute respiratory syndrome coronavirus 2 infection is also associated with mental and 
neurological manifestations, including delirium or encephalopathy, agitation, ischemic and 
hemorrhagic stroke, meningoencephalitis, impaired sense of smell or taste, anxiety, depression, 
and sleep problems. In many cases, neurological manifestations have been reported even 
without 
respiratory 
symptoms. 
Case 
reports 
of 
Guillain-Barré 
syndrome 
and 
meningoencephalitis among people with SARS-CoV-2 infection have also been reported. 
Clinical manifestations of SARS-CoV-2 infection are generally milder in children compared 
with adults. Relatively few cases of infants confirmed with SARS-CoV-2 infection have been 
reported. However, most recently a multisystem inflammatory syndrome temporally associated 
with SARS-CoV-2 infection in children and adolescents has been described (WHO Guidelines, 
2020). 
Coronavirus entry into host cells is an important determinant of viral infectivity and 
pathogenesis. It is also a major target for host immune surveillance and human intervention 
strategies. It has been established that SARS-CoV-2 binds via the angiotensin-converting 
enzyme 2 (ACE2) receptor located on epithelial and endothelial cells which traverse multiple 


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organs (Varga et al., 2020). SARS-CoV-2 infection is initiated by binding of the SARS-CoV-2 
spike protein to ACE2 via the receptor binding protein (RBD) of the spike protein, which 
mediates viral entry into the target cells. The virus is mutating, indicating that virulence and 
transmission will shift over time, and showing diversity in this critical surface protein. New 
evidence suggests there are 2 strains of SARS-CoV-2; L-type and S-type (Tang et al., 2020). 
S-type is the less aggressive (30%); the L-type is now the most prevalent strain (70%) and is 
more aggressive. Additionally, individuals appear to be affected to different degrees with 
varying symptoms and outcomes. These findings strongly support an urgent need for immediate 
comprehensive studies and robust validation of testing methods that combine genomic data, 
chart records and clinical symptoms, to help better understand the disease, enable risk 
assessment, triage and support public health resource planning. 
1.2 CT-P59 
CT-P59 is a monoclonal antibody targeted against SARS-CoV-2 spike RBD as a treatment for 
SARS-CoV-2 infection. The dosage form of CT-P59 is solution concentrate for dilution for 
administration in a single intravenous (IV) infusion. 
The main mechanism of action is binding to SARS-CoV-2 RBD and the cellular receptor, ACE2, 
thus blocking the SARS-CoV-2 infection. Although it is known that in many virus infections 
antibodies can remove the virus-infected cells via antibody Fc-dependent function such as 
antibody dependent cellular cytotoxicity, it’s unlikely that CT-P59 induces antibody 
Fc-dependent virus clearance, considering the life cycle of SARS-CoV-2 which is assembled 
inside cells and released via exocytosis. However, it is postulated that there are additional 
mechanisms of CT-P59 mediated virus clearance by opsonization and complement activation 
(i.e., antibody dependent, complement-dependent virolysis or antibody dependent 
phagocytosis). 
1.2.1 Nonclinical Studies 
The nonclinical program for CT-P59 has been designed to support clinical studies. Detailed 
information regarding the nonclinical pharmacology and toxicology of CT-P59 can be found in 
the Investigator’s brochure (IB). 
1.2.2 Clinical Studies 
CT-P59 has not been administered in humans yet. The current study is the first-in-human study. 


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1.3 Study Rationale 
There are currently no approved monoclonal antibody therapies available to treat coronaviruses 
such as SARS-CoV-2 and there is an urgent public health need for the rapid development of 
such interventions. On 11 March 2020, the WHO declared the SARS-CoV-2 infection outbreak 
a global pandemic as there were more than 118,000 cases in 114 countries, and 4,291 people 
had lost their lives. According to the WHO coronavirus disease situation report-135, about 6.28 
million people were confirmed to have SARS-CoV-2 infection in 216 countries and fatalities 
exceeded about 380,000. 
CT-P59 is currently being developed by the Sponsor as a potential treatment for SARS-CoV-2 
infection. The anticipated high affinity and targeted effect of CT-P59 is expected to enable 
antiviral activity. In this study, safety, tolerability, and pharmacokinetics of CT-P59 will be 
evaluated in healthy subjects. 
1.3.1 Rationale for Study Population 
Healthy subject is selected as study population since this healthy population allows for the 
collection of information which is not confounded by pathogens or medications likely used for 
treatment of the condition, easier access to a full pharmacokinetic profile, and higher internal 
validity of collected data due to lower variability of factors affecting the study subjects 
(Association of the British Pharmacology Industry, 2018). 
1.4 Benefit and Risk Assessment 
Despite the fact that numerous entities are under investigation, no potent and highly targeted 
antiviral options are available for treatment and/or prophylaxis of coronaviruses such as 
SARS-CoV-2 at present. 
CT-P59 has not been administered in humans yet, and therefore, the benefits or risks in humans 
are unknown at this time. 
There may not be benefits for an individual subject, there may be benefits to society if a safe, 
efficacious therapeutic agent can be identified during this global SARS-CoV-2 infection 
outbreak. 
A global independent Data and Safety Monitoring Board (DSMB) would monitor the 
preliminary analysis with safety data up to Day 14 of the last subject and available 
pharmacokinetic (PK) data (central) to evaluate initial safety of CT-P59. 
More detailed information about the known and expected benefits and risks and reasonably 
expected adverse events (AEs) of CT-P59 may be found in the current version of the IB. 


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The Sponsor will immediately notify the Principal Investigator if any additional safety or 
toxicology information becomes available during the study. 
This study will be performed in compliance with the protocol, International Council for 
Harmonisation (ICH) Good Clinical Practice (GCP) and applicable regulatory requirements. 
Aspects of the study concerned with the investigational medicinal product(s) will meet the 
requirements of European Union – Good Manufacturing Practice. 
The Sponsor and Investigator may take appropriate urgent safety measures in order to protect 
the subjects of a clinical study against any immediate hazard to their health or safety. If such 
measures are taken, the Sponsor shall immediately give written notice to the licensing authority 
and the relevant ethics committee of the measures taken and the circumstances giving rise to 
those measures. 


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2 Study Objectives and Endpoints 
2.1 Study Objectives 
2.1.1 Primary Objective 
 
To evaluate the preliminary safety and tolerability of CT-P59 up to Day 14 of the last 
enrolled subject 
2.1.2 Secondary Objectives 
 
To evaluate the PK of CT-P59 
 
To evaluate additional safety of CT-P59 including immunogenicity 
2.2 Study Endpoints 
2.2.1 Primary Endpoints 
Primary endpoints will be analyzed based on the data up to Day 14 of the last enrolled subject. 
 
Treatment-emergent adverse events (TEAEs) 
 
Treatment-emergent serious AEs (TESAEs) 
 
Treatment-emergent AEs of special interest (TEAESI; infusion related reactions including 
hypersensitivity/anaphylactic reaction) 
 
Vital signs (blood pressure, heart rate, body temperature, and respiratory rate) 
 
Hypersensitivity monitoring 
 
Twelve-lead electrocardiogram (ECG) 
 
Physical examination findings 
 
Clinical laboratory tests (clinical chemistry, hematology, and urinalysis) 
2.2.2 Secondary Endpoints 
Secondary safety and PK endpoints will be analyzed for whole study period. 


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2.2.2.1 Safety Endpoints 
 
Treatment-emergent AEs (including TESAE and TEAESI) 
 
Vital signs (blood pressure, heart rate, body temperature, and respiratory rate) 
 
Twelve-lead ECG 
 
Physical examination findings 
 
Clinical laboratory tests (clinical chemistry, hematology, and urinalysis) 
 
Incidence of anti-drug antibodies (ADAs) and neutralizing antibodies (NAbs) 
2.2.2.2 Pharmacokinetic Endpoints 
 
Area under the concentration-time curve (AUC) from time zero to infinity (AUC0-inf) 
 
Dose normalized AUC0-inf (AUC0-inf/Dose) 
 
Area under the concentration-time curve from time zero to the last quantifiable 
concentration (AUC0-last) 
 
Dose normalized AUC0-last (AUC0-last/Dose) 
 
Maximum serum concentration (Cmax) 
 
Dose normalized Cmax (Cmax/Dose) 
 
Time to Cmax (Tmax) 
 
Terminal half-life (t1/2) 
 
Percentage of AUC0-inf obtained by extrapolation (%AUCext) 
 
Terminal elimination rate constant (λz) 
 
Total body clearance (CL) 
 
Volume of distribution during the elimination phase (Vz) 


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3 Investigational Plan 
3.1 Study Design 
This is a randomized, double-blind, placebo-controlled, parallel group, single ascending dose, 
Phase 1 study to evaluate the safety, tolerability and PK of CT-P59 in healthy subjects. 
Approximately 32 subjects in 4 cohorts are planned for enrollment and each cohort will consist 
of 8 subjects, 6 of whom will receive CT-P59 and 2 of whom will receive a placebo. 
In cohorts 1 and 2, each cohort includes a sentinel group of 2 subjects and a remaining group of 
6 subjects. In a sentinel group, 2 subjects will be randomized in a 1:1 ratio to receive CT-P59 or 
placebo. In a remaining group, 6 subjects will be randomized in a 5:1 ratio to receive CT-P59 
or placebo. In cohorts 3 and 4, 8 subjects will be randomized in 3:1 ratio to receive CT-P59 or 
placebo. 
This study will be started with the lowest dose that will maximize safety and the dose levels 
will be escalated to the higher doses. 
Subjects will be admitted to the study center on Day -1 and will be discharged on Day 4 after 
completion of the 72-hour assessments after study drug administration to identify any 
subsequent reactions. 
In cohorts 1 and 2, the first study drug administration will be administered as IV infusion to the 
each sentinel group. In cohorts 3 and 4, all subjects in each cohort will randomly receive study 
drug without group sequence. The details of dose escalation and stopping criteria is specified in 
Section 3.2. 
The overview of the study is presented in Figure 3-1. 


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Figure 3-1 Study Overview 
 
The study will be performed in a double-blind manner. To minimize the risk of unblinding, the 
study drug will be dispensed by unblinded study center personnel. The unblinded personnel who 
are responsible for dispensing study drugs will not be permitted to conduct any subject 
assessments. 
3.2 Rationale for Study Design 
The design of this clinical trial follows the recommendation of the European Medicines Agency 
(EMA) Guideline on Strategies to identify and mitigate risks for first-in-human and early 
clinical trials with investigational medicinal product (EMA, 2017). 
In line with the standard approach to first-in-human studies, the Sponsor is planning an initial 
dose escalating Phase 1 study in healthy subjects to evaluate safety and tolerability of CT-P59. 
The dose escalation study has been designed to carefully assess the safety and tolerability of 
CT-P59 in healthy subjects, before progressing into the subsequent studies. 
3.3 Dose Escalation and Stopping Criteria 
3.3.1 Criteria for Proceeding from Sentinel Group to Remaining Group 
In cohorts 1 and 2, 2 subjects in sentinel group will receive study drug first. One subject will 
receive CT-P59 and the other subject will receive placebo. After an observation period of 48 
hours, all available safety data (including TEAE, vital signs, 12-lead ECG, hypersensitivity 
monitoring, and clinical laboratory tests, etc.) of subjects in sentinel group will be reviewed by 
the Dose Escalation Committee (DEC) and they will decide whether to proceed dosing of 
remaining group or stop dosing. If no safety or tolerability concern is observed, the 6 subjects 
of remaining group in same cohort will proceed to dosing. If any safety concern including 


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stopping rule specified in Section 3.3.3 is raised under decision of DEC, the study will be 
temporarily stopped and DSMB meeting will be held. The appointed DSMB members will 
evaluate the relationship to CT-P59 of the event with unblinded manner and review all available 
data and make a decision on continuation of the study. 
3.3.2 Dose Escalation Criteria 
When escalating dose to next cohort, DEC will review all available safety data of all subjects 
in current cohort, after an observation period of 48 hours after study drug administration. If no 
safety or tolerability concern is observed in the current cohort, dose will be escalating to next 
cohort. 
When escalating dose from cohort 1 to 2, DEC will review all available safety data of all 
subjects in the cohort 1, after an observation period of 48 hours after study drug administration 
of remaining group. If no safety or tolerability concern is observed in the cohorts 1, 2 subjects 
in sentinel group of cohort 2 will receive study drug.  
When escalating dose from cohort 2 to 3, DEC will review all available safety data of all 
subjects in the cohort 2, respectively, after an observation period of 48 hours after study drug 
administration of remaining group. If no safety or tolerability concern is observed in the cohort 
2, 8 subjects in cohort 3 will receive study drug. 
When escalating dose from cohorts 3 to 4, DEC will review all available safety data of all 
subjects in the cohort 3 after observation period of 48 hours after study drug administration of 
cohort 3. If no safety or tolerability concern is observed, 8 subjects in cohort 4 will receive study 
drug. 
If any safety concern including stopping rule specified in Section 3.3.3 is raised under decision 
of DEC, the dose escalation and study will be temporarily stopped and DSMB meeting will be 
held. The appointed DSMB members will evaluate the relationship to CT-P59 of the event with 
unblinded manner and review all available data and make a decision on continuation of the 
study. 
3.3.3 Dose Stopping Rules 
The continuation of dosing after the sentinel group or the dose escalation from a previous cohort 
to the next cohort will be stopped if one or more of the following stopping criteria are met: 
 
One or more subjects experience a study drug-related TESAE 


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 
Two or more subjects in one cohort experience study drug-related TEAEs of grade 3 or 
higher 
 
Four or more subjects in one cohort experience study drug-related TEAEs of grade 2 or 
higher 
If an event corresponding to the above criteria occurs within the observation period of 48 hours 
in each group and the dosing is temporarily stopped under the decision of DEC, DSMB will 
evaluate the relationship to CT-P59 of the event with unblinded manner and make a decision on 
continuation of the study. 
If an event corresponding to the above criteria occurs after observation period of 48 hours in 
the previous cohort, further progression to next group or cohort will be temporarily stopped and 
DSMB will review data and make a decision on continuation of the study. 
3.4 Study Overview 
The total duration of this study will be approximately 16 weeks for the individual subject, 
including Screening Period. All study procedures will be performed at the time points specified 
in Table 11-1. 
3.4.1 Screening Period (Day -21 to Day -2) 
Subjects will sign and date the informed consent form (ICF) and undergo procedures to 
determine eligibility. During the Screening Period, retest for screening is permitted only once 
by the Investigator’s judgement. If the repeated test result is again not suitable or indeterminate 
for inclusion, the subject will be screen failed. 
If screening visit date and the admission date (Day -1) are same, all assessments scheduled for 
the screening and Day -1 visit can be performed only once on the date. 
3.4.2 Admission (Day -1) 
Subjects who successfully complete the screening visit will be confined in the study centers as 
scheduled on Day -1. Eligible criteria will be reviewed to confirm subject eligibility. If it is 
concluded that the subject is not eligible in Day -1 assessments, the subject will be considered 
as a screening failure even if he was eligible based on assessments results performed during the 
screening visit. 


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3.4.3 Study Period (Day 1 to prior to End-of-Study Visit) 
Subjects will be randomized to receive a single dose of CT-P59 or placebo on Day 1. In cohorts 
1 and 2, 2 subjects will be randomized in a 1:1 ratio to receive CT-P59 or placebo in the sentinel 
group. If it is decided to proceed to remaining group based on criteria specified in Section 3.3.1, 
6 subjects in the remaining group of cohorts 1 and 2 will be randomized in a 5:1 ratio to receive 
CT-P59 or placebo. If it is decided to proceed to cohorts 3 and 4, 8 subjects will be randomized 
in 3:1 ratio to receive CT-P59 or placebo.  
All subjects will be confined to the study center until completion of the 72-hour (Day 4) 
assessments after the study drug administration and confinement can be extended depending on 
the subjects’ and study center’s availability up to Day 14. The subsequent study visits will be 
carried out on an out-patient basis. 
3.4.4 End-of-Study Visit (Day 90) 
End-of-study (EOS) visit assessments will be performed on Day 90. Subjects will undergo the 
assessments specified in Table 11-1. 
If a subject withdraws prematurely after study drug administration, the subject will be asked to 
return to the study center for the safety assessments predefined on EOS visit. If deemed 
necessary by the Investigator, the subject will be asked to return for the scheduled EOS visit. 


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4 Subject Selection and Withdrawal Criteria 
4.1 Selection of Study Population 
The study population will consist of healthy male or female subjects who are negative on 
SARS-CoV-2 infection test with 19 to 55 years (both inclusive) of age, a body weight of ≥ 50 kg 
and a body mass index (BMI) between 18.0 and 29.9 kg/m2 (both inclusive). Subjects must be 
able to provide written informed consent and meet all the inclusion criteria and none of the 
exclusion criteria, according to the criteria outlined below (Section 4.2 and Section 4.3). 
4.2 Inclusion Criteria 
Each subject must meet all of the following criteria to be randomized in this study: 
1. Subject is a healthy male or female subject, aged between 19 to 55 years (both inclusive). 
Health is defined as no clinically relevant abnormalities identified by Investigator’s decision 
based on a detailed medical history, full physical examination, including blood pressure, 
heart rate, respiratory rate, and body temperature measurements, 12-lead ECG and clinical 
laboratory tests prior to the study drug administration. 
2. Subject is confirmed as negative in SARS-CoV-2 infection test on screening and Day -1 
visits. 
3. Subject with a body weight of ≥ 50 kg and a BMI between 18.0 and 29.9 kg/m2 (both 
inclusive). 
4. Subject is able to understand and to comply with protocol requirements, instructions, and 
restrictions. 
5. Subject voluntarily agrees to participate in this study and has given a written informed 
consent prior to undergoing any of the screening procedures. 
6. Subjects and their partners of childbearing potential must agree to use a highly effective 
method of contraception or two acceptable methods of contraception until 6 months after 
the study drug administration as specified in Section 5.8.2. A man or woman is of 
childbearing potential if he or she is biologically capable of having children and is sexually 
active in the opinion of the Investigator. Subjects and their partners who have been surgically 
sterilized for less than 6 months prior to the date of informed consent must agree to use any 
medically acceptable methods of contraception. 


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4.3 Exclusion Criteria 
A subject meeting any of the following criteria will be excluded from the study: 
1. Subject has a medical history or current presence of disease including one or more of the 
following(s): 
a. History of or current allergic reaction such as asthma, urticaria, angioedema, and 
eczematous dermatitis considered as clinically significant in the Investigator’s opinion 
or hypersensitivity including known or suspected clinically relevant drug 
hypersensitivity to any monoclonal antibody or any component of study drug 
b. History of or current medical condition including gastrointestinal, renal, endocrine, 
neurologic, autoimmune, hepatic, hematological metabolic (including known diabetes 
mellitus), cardiovascular, or psychiatric condition classed as clinically significant by 
the Investigator 
c. History of or any concomitant active malignancy 
d. History of or current infection with human immunodeficiency (HIV), syphilis, hepatitis 
B or hepatitis C 
e. History of or current infection requiring a course of systemic anti-infective that was 
completed within 28 days prior to the study drug administration or a serious infection 
(associated with hospitalization or which required intravenous antibiotics) within 
6 months before the study drug administration 
f. 
History of an illness within 28 days prior to the study drug administration that is 
identified as clinically significant by the Investigator or requires hospitalization 
g. History of surgical intervention or an operation within 28 days prior to the study drug 
administration or plans to have a surgical procedure during the study period 
2. Subject had a history of or concurrent use of medications including any prior therapy of 
following(s): 
a. Prescription medication (excluding hormonal birth control), over-the-counter (OTC) 
drug, dietary supplements or herbal remedies from 7 days or 5 half-lives (whichever is 
longer) prior to the study drug administration 


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b. Any vaccination within 4 weeks prior to the study drug administration 
c. Treatment with any monoclonal antibody, fusion protein, or blood transfusion within 
6 months or 5 half-lives (which is longer) prior to the study drug administration or 
current use of biologics 
d. Treatment with any other investigational drug within 6 months or 5 half-lives (which is 
longer) prior to the study drug administration 
3. A male subject plans to father a child or donate sperm or a female subject is lactating or 
planning to be pregnant or to breastfeed within 6 months from the study drug administration. 
4. Subject shows reasonable evidence of drug/alcohol/nicotine abuse prior to the study drug 
administration as opinion of the Investigator or has following(s): 
a. Positive result for drug urine test during screening or Day -1 
b. History or presence of regular consumption exceeding an average weekly intake of 
> 14 units of alcohol in recent 3 months prior to the study drug administration 
c. Consuming more than 10 cigarettes or equivalent per day within a month prior to the 
study drug administration 
5. Subject is unwilling to avoid the use of alcohol or alcohol containing foods, medications, or 
beverage within 48 hours prior to admission and 24 hours prior to each study visit 
throughout the study or unable to refrain from smoking during the in-house stays. 
6. Subject donated or lost 400 mL or more whole blood within 8 weeks (plasma/platelets 
donation within 4 weeks) prior to the study drug administration. 
7. Subject shows evidence of a condition (psychological, emotional problems, any disorders 
or resultant therapy) that is likely to invalidate health information, consent, or limit the 
ability of the subject to comply with the protocol requirements in the opinion of the 
Investigator. 
8. Subject is vulnerable (e.g., employees of the clinical trial site or any other individuals 
involved with the conduct of the study, or immediate family members of such individuals, 
persons kept in prison or other institutionalized persons by law enforcement). 


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9. Subject is not likely to complete the study for whatever reason other than criteria listed 
above in the opinion of the Investigator. 
4.4 Subject Withdrawal and Replacement 
Subjects are free to withdraw from the study at any time for any reason. The Investigator may 
also discontinue the subject from the study at any time in the interest of subject safety.  
If premature withdrawal occurs for any reason, the Investigator must determine the primary 
reason for a subject’s premature withdrawal from the study and record this information in the 
subject’s medical record and in the electronic case report form (eCRF). The primary reasons for 
premature withdrawal are as following: 
 
Withdrawal of consent 
 
Lost to follow-up 
 
Adverse event 
 
Death 
 
Investigator’s decision 
 
Study termination by the Sponsor 
For subjects who are lost to follow-up (i.e., those subjects whose status is unclear because they 
fail to appear for study visits without stating an intention to withdraw), the Investigator should 
show due diligence by documenting in the source documents steps taken to contact the subjects, 
e.g., dates of telephone calls, registered letters, etc. Subjects who fail to return for final 
assessments will be contacted by the center in an attempt to have them comply with the protocol. 
The status of subjects who fail to complete final assessments will be documented in the eCRF. 
When possible, the Sponsor should be notified of the withdrawal of a subject from the study. If 
necessary, the investigator may discuss with the Sponsor or its designee any subject’s reason 
for withdrawal from the study. The Sponsor may be contacted if clarification is required on a 
case-by-case basis. All subjects who are terminated from the study will retain their subject 
identification number. 


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4.4.1 Recruitment of Additional Subjects 
Subjects who receive study drug and discontinue before the study completion will generally not 
be replaced. However, if a subject who receives study drug discontinues the study for a reason 
other than subject’s safety, additional subject can be recruited upon decision of DEC. If a subject 
who randomized but did not receive study drug decides to discontinue the study, this subject 
can be replaced. 
Subjects who failed screening, for any reason, can be rescreened only once. If there is unusual 
situation so that additional rescreening should be considered, the Investigator is recommended 
to discuss with the Sponsor. Rescreened subject will be assigned with new subject identification 
number. 
4.5 Premature Termination of the Clinical Trial 
The Sponsor reserves the right to terminate the study at any time for reasonable medical and/or 
administrative reasons. As far as possible, this should occur after mutual consultation. 
If the study is terminated prematurely by the Sponsor, all subjects will be kept fully informed 
and an appropriate follow-up examination of the subjects will be arranged. The investigator will 
inform the Independent Ethics Committee (IEC; or Institutional Review Board, where 
applicable) of any premature termination or suspension of the study. 


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5 Study Treatment 
5.1 Method of Assigning Subjects to Treatment Group 
The randomization code will be generated by unblinded statistician prior to the study, and will 
be provided to unblinded pharmacist in the study center. Enrolled subjects who meet all of the 
inclusion and none of the exclusion criteria will be randomly assigned to CT-P59 or placebo on 
Day 1. In cohorts 1 and 2, subjects will be randomized in a 1:1 ratio to receive CT-P59 or 
placebo in sentinel group and in a 5:1 ratio to receive CT-P59 or placebo in remaining group. In 
cohorts 3 and 4, 8 subjects will be randomized in a 3:1 ratio to receive CT-P59 or placebo. 
5.2 Treatment Administered 
On day 1, subjects who meet all of the inclusion and none of the exclusion criteria will be 
randomly assigned to one of 2 treatment groups, CT-P59 or placebo, according to randomization 
scheme. 
Subjects in each cohort will receive study drug as follows: 
 
Cohort 1: CT-P59 10 mg/kg or placebo 
 
Cohort 2: CT-P59 20 mg/kg or placebo 
 
Cohort 3: CT-P59 40 mg/kg or placebo 
 
Cohort 4: CT-P59 80 mg/kg or placebo 
A 250 mL infusion solution of 0.9% weight/volume sodium chloride will be used for subject 
infusion. The bag will be gently inverted to mix the solution in order to avoid foaming. 
Parenteral solutions will be inspected visually for particulates and discoloration prior to 
administration and administration will not be performed if any particulates and discoloration 
are found. The detailed method about mixing the solution will be described in the pharmacy 
manual. 
Study drug will be administered as an IV infusion for 90 minutes (±15 minutes) on Day 1. 
When calculating total volume of study drug to be administered, the body weight of each subject 
measured on Day -1 will be used. Placebo will be administered as in the same volume as the 
active dose used for CT-P59 in each cohort. 


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5.2.1 CT-P59 
CT-P59 is a monoclonal antibody which is being developed by the Sponsor as a potential 
treatment for SARS-CoV-2 infection. 
CT-P59 is supplied as a sterile, preservative-free solution of SARS-CoV-2 RBD binding 
monoclonal antibody in a 20 mL single use vial for IV infusion. CT-P59 is a clear to opalescent, 
colorless to pale yellow solution for injection, with a pH of 6.0 and 960 mg of SARS-CoV-2 
RBD binding monoclonal antibody in 16 mL for intravenous infusion. One vial (16 mL) delivers 
960 mg SARS-CoV-2 RBD binding monoclonal antibody, 13.12 mg of L-histidine, 15.84 mg 
of L-histidine monohydrochloride monohydrate, 8.0 mg of polysorbate 80, 505.584 mg of 
L-Arginine monohydrochloride, and water for injection. The container closure system includes 
type I borosilicate glass vial, Fluroetec Film coated rubber stopper and flip-off type aluminum 
cap. 
5.2.2 Placebo 
Placebo contains the same ingredient as the CT-P59 formulation listed in Section 5.2.1, 
excluding SARS-CoV-2 RBD binding monoclonal antibody. Each placebo vial contains 
13.12 mg of L-histidine, 15.84 mg of L-histidine monohydrochloride monohydrate, 8.0 mg of 
polysorbate 80, and 505.584 mg of L-Arginine monohydrochloride, and water for injection in 
16 mL. The pH of the placebo solution is 6.0. The container closure system includes type I 
borosilicate glass vial, Fluroetec Film coated rubber stopper and flip-off type aluminum cap. 
5.2.3 Rationale for Dose Selection 
In this study, there will be four dose levels and an approximate 2-fold increase between doses. 
The planned starting dose is 10 mg/kg and the proposed top dose is 80 mg/kg. 
The PK profile of CT-P59 is expected to be similar to those of CT-P27, an anti-influenza 
antibody drug to treat influenza under development by the Sponsor. CT-P27 drug product is a 
combination of the two human immunoglobulin G1 monoclonal antibodies. This is due to the 
structural similarity between the CT-P27 monoclonal antibodies and the CT-P59 monoclonal 
antibody, in that CT-P59 shares an identical human immunoglobulin G1 Fc region backbone 
with the two monoclonal antibodies of CT-P27. 
In the 2-week repeat dose nonhuman primate toxicity study of CT-P27, which included safety 
pharmacology endpoints (e.g., clinical observations, body temperature, respiratory rate, heart 
rate, blood pressure, and electrocardiogram) and full histopathology, there were no treatment 


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related adverse effects at IV doses up to 320 mg/kg. The main finding was a minimal to mild 
inflammatory response at the catheter infusion sites; however, the effects were fully reversible 
and not considered adverse. 
In this study, the first dose will be 10 mg/kg via IV infusion. The nonhuman primate repeat dose 
toxicity study of CT P27 had no-observed-adverse-effect level of 320 mg/kg, which was the 
highest dose tested and no adverse effects were observed. Applying a safety factor of 10, it is 
expected that a dose of up to 32 mg/kg could be supported as posing a very low risk of inducing 
adverse effects in this study as well. However, to maximize the safety in this first-in-human 
study, a lower dose of 10 mg/kg will be adapted as the starting dose. In addition, since this study 
is being conducted in healthy subjects, a pharmacologically-active dose is not relevant for the 
initial dose setting. 
The proposed top dose of 80 mg/kg is expected to ensure 2.8 times of the margin of exposure 
based on the CT-P27 studies results (AUC results of the no-observed-adverse-effect level in 
nonclinical study and expected AUC value of 80 mg/kg in a clinical study with healthy 
volunteers). 
CT-P59 will be administrated intravenously. Several human antibodies are approved for IV 
infusion, which is the same route of administration of CT-P59. 
The further nonclinical results of CT-P59 will be updated in the IB and will serve as the rationale 
behind dose selection. 
5.2.4 Dose Modification 
No dose modifications or dose omissions are permitted for CT-P59 or placebo. 
5.3 Management of Clinical Supplies 
5.3.1 Study Drug Packaging, Labeling, and Storage 
The Sponsor will provide the Investigator and study center with adequate quantities of CT-P59 
and placebo. A label will be attached to the outside of each subject kit, as well as to the 
immediate container. The text will be compliant with local regulatory requirements and may 
include some of the following information: 
 
Protocol number 
 
Subject number/site number 


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 
Contents and quantity 
 
Lot number 
 
Randomization code/kit number 
 
Investigator’s name 
 
Route of administration 
 
Directions for use 
 
Storage instructions 
 
Caution statement (for clinical study use only) 
 
Sponsor’s contact name and address 
 
Expiry date 
CT-P59 drug product in a vial should be stored in a refrigerator between 2°C and 8°C and not 
frozen. It should be kept in its original outer packaging to protect it from light and it should not 
be shaken. 
5.3.2 Study Drug Accountability 
It is the responsibility of the clinical Investigator to ensure that all study drug received at the 
study center will be inventoried and accounted for throughout the study and the result recorded 
in the drug accountability form maintained at the study center. The study drug accountability 
will be verified by the monitor during on-site monitoring visits. In case an on-site monitoring 
visit cannot be made because of the SARS-CoV-2 pandemic situation, the Sponsor and CRO 
will discussed with the Investigator. Study drug will be stored in a limited-access area or in a 
locked cabinet under appropriate environmental conditions. 
The Investigator agrees not to supply the study drug to any person other than sub-Investigators, 
designated staffs, and the subjects participating in the study. Study drug may not be relabeled 
or reassigned for use by another subjects unless approved by the Sponsor. 
The Investigator will return or destroy all study drugs according to the pharmacy manual. The 
Investigator will destroy empty or partially used vials in a blinded manner as well as its cartons 
after reconstitution per the center’s SOPs, and keep tear-off labels for accountability. This 


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authorization may also be granted to destroy used vials immediately after administering to 
subjects. The list of destroyed vials must be recorded. The Investigator agrees to neither 
dispense the study drug from, nor store it at, any study center other than the study center agreed 
upon with the Sponsor. Details on study drugs accountability and destruction will be followed 
according to the pharmacy manual. 
5.4 Blinding 
This study will be double-blind until the end of the study. The randomization codes will not be 
revealed to study subjects, Investigator, and study center personnel, except for delegated 
unblinded staff who will handle the study drug and predefined unblinded teams in the Sponsor 
and CRO until all final clinical data have been entered into the database and the database is 
locked and released for analysis. 
Pharmacy personnel (trained by a delegated pharmacist) at the study center who has no other 
subject contact and who are not directly involved with the clinical aspects of the study will 
prepare and dispense the study medication and will be aware of the randomization code. All 
study drugs will be delivered to the study center and will be assigned to treatment groups by the 
pharmacy personnel in accordance with the provided randomization schedule. The pharmacy 
personnel will also be provided Kit List that provides the kit number and corresponding 
treatment arm. The pharmacy personnel will select the kit based on the randomization and kit 
lists provided. All study drugs will be supplied to the trained clinical staff member in a sealed 
carton marked with the kit number. 
5.5 Breaking the Blind 
Under normal circumstances, the blind should not be broken. The blind should only be broken 
if specific emergency treatment would be dictated as knowing the study drug assignment is 
required for medical management. In such cases, the investigator may, in emergency, determine 
the identity of the study drug by using applicable procedure. 
The date, time and reason for the unblinding must be documented in the source document and 
the appropriate field of the eCRF and the medical monitor will be informed as soon as possible. 
All unblinding events will be reported to the medical monitor and the Sponsor. Any subjects for 
whom the blind is broken may continue in the study at the investigator’s discretion. 
The DSMB and the statistician(s) who provides the safety analyses for the DSMB will also be 
unblinded upon the request from DSMB members during closed session. 


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The overall randomization code will be broken only for reporting purposes. This will occur after 
database lock for data up to Day 14 of the last enrolled subject. The unblinded personnel will 
be predefined and documented before performing the analyses.  
5.6 Treatment Compliance 
Subject compliance will be determined based on drug accountability as well as source 
documents. The date and time of the study drug administration will be documented and every 
effort will be made to encourage the subjects’ compliance with the study visits. 
5.7 Prior, Concomitant, and Prohibited Medications 
Prior and concomitant medication use will be recorded for the 30 days prior to the subject signs 
the ICF (inclusive of the applicable periods for prohibited medication as defined in Section 4.3) 
until the EOS visit. Concomitant medication use is permitted if indicated by the Investigator for 
treatment of AE. 
Prohibited medications during the study include the following: 
 
Prescription medications (excluding hormonal birth control), OTC drugs, dietary 
supplements or herbal remedies 
 
Any vaccinations 
 
Treatment with any other investigational drug, any monoclonal antibody, fusion protein, or 
biologics, and blood transfusion. 
It is the Investigator’s responsibility to ensure that details regarding the medication are 
adequately recorded in both the source documents and eCRF. Any changes in concomitant 
medications will also be recorded in both the source documents and eCRF. 
5.8 Restriction 
The Investigator, or delegated clinical staff member, will check if subject is complying with 
these restraints during the study. 
5.8.1 Dietary and Fluid Restrictions 
Alcohol: 
Alcohol containing products (including alcohol, alcohol-containing foods, 
medications, or beverages) must be avoided from 48 hours before the 
study drug administration and 24 hours before any study visit and while 


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subjects are confined to the study center. Subjects must abstain from 
alcohol-containing products for 24 hours prior to each PK sampling time 
point. Subject will not exceed an alcohol consumption of 14 units per 
week until the end of the study period. One standard unit is equal to 
approximately 285 mL of full strength beer (4.8% alcohol by volume 
[ABV]), 30 mL of spirits (40% ABV), or 100 mL of wine (13.5% ABV). 
Caffeine: 
Subjects will not be permitted to drink caffeine or xanthine-containing 
products (e.g., coffee, black tea, cola, etc., or use caffeine or xanthine-
containing products) for 24 hours prior to the study drug administration 
and during the confinement period of the study. Subjects must abstain 
from caffeine or xanthine-containing products for 24 hours prior to each 
PK sampling time point. 
Nicotine: 
Subjects will be permitted to smoke less than 10 cigarettes or equivalent 
per day until the end of the study period, but will not be allowed to smoke 
during the confinement period of the study. 
Meals: 
Subjects must abstain from all food and drink (except water) at least 8 
hours prior to the study drug administration and at least 4 hours prior to 
any safety laboratory evaluations. Water is permitted until 1 hour prior to 
the study drug administration and may be consumed without restriction 
beginning 1 hour after the study drug administration. No outside food or 
drink is permitted at the study center. All meals will be provided by the 
study center. 
5.8.2 Other Restrictions 
Activity: 
Strenuous activity (e.g., heavy lifting, weight training, calisthenics, and 
aerobics) is prohibited from 96 hours prior to admission until discharge. 
After discharge, mild physical activity can be resumed, but strenuous 
physical activity is prohibited 96 hours prior to each study visit. 
Hygiene: 
Subjects should follow the country/local guideline for SARS-CoV-2 
infection prevention. 
Medications: 
Restrictions on medication during the study is described in Section 5.7. 


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Lactation: 
Female subjects are prohibited to breastfeed until 6 months from the study 
drug administration. 
Contraception: 
Subjects and their female partners of childbearing potential must agree to 
use a highly effective method of contraception or two acceptable methods 
of contraception (e.g., male or female condom AND additional hormonal 
or barrier contraceptive method by female partner) consistent with local 
regulations until 6 months after the study drug administration regardless 
of subject withdrawal. A highly effective method of birth control may be 
defined as those which result in a low failure rate (e.g., <1% per year, 
when used consistently and correctly). Examples of acceptable forms of 
highly effective contraception for females include: abstinence, 
simultaneous use of hormonal contraceptives starting at least 4 weeks 
prior to study drug administration and must agree to use the same 
hormonal contraceptive throughout the study and condom for the male 
partner, simultaneous use of intra-uterine contraceptive device placed at 
least 4 weeks prior to study drug administration and condom for the male 
partner, or a sterilized male partner (vasectomized since at least 6 months). 
Examples of acceptable forms of highly effective contraception for male 
subjects include: abstinence, simultaneous use of a male condom and, for 
the female partners include: combined (estrogen and progestogen 
containing) or progestogen-only hormonal contraceptives associated with 
inhibition of ovulation, intra-uterine or intrauterine hormone-releasing 
system (placed since at least 4 weeks). Examples of nonacceptable 
methods of contraception include solo use of a barrier method (including 
use of a diaphragm, cervical cap, or condom), periodic abstinence, the 
withdrawal method, or use of spermicide. Subjects are not permitted to 
donate sperm or plan to have a child until 6 months after the study drug 
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6 Study Assessments and Procedures 
Before performing any study procedures, all potential subjects will be informed of the full 
nature and purpose of the study, including possible risks and side effects, and given ample time 
and opportunity to read and understand this information, before signing and dating the ICF. The 
investigator will respond to any questions raised by the subject. The investigator will also sign 
the ICF. 
Subjects will undergo the procedures at the time points specified in Table 11-1. 
6.1 Safety Assessments 
Safety assessments include monitoring of AEs (including SAEs and AESI [infusion related 
reactions including hypersensitivity and anaphylactic reactions]), hypersensitivity monitoring, 
immunogenicity including ADAs and NAbs, vital sign assessments, physical examination, 
clinical laboratory tests, pregnancy test, 12-lead ECG, and prior and concomitant medications. 
6.1.1 Medical History and Demographic Information 
Medical history (general medical history and medication history) and demographic information 
(age, sex, ethnicity, and race) will be recorded on both the source documents and eCRF. 
6.1.2 Other Baseline Characteristics 
6.1.2.1 SARS-CoV-2 Infection Test 
A SARS-CoV-2 infection test will be performed at Screening and Day -1 visit to confirm a 
subject is not infected to SARS-CoV-2. Only subjects who are negative on both screening and 
Day -1 tests can be enrolled in study. If the scheduled SARS-CoV-2 infection test seemed 
unavailable on Day -1, it can be performed on Day -2 or Day -3 instead. 
6.1.2.2 Viral Serology Test 
Viral serology tests including hepatitis B surface antigen (HBsAg), hepatitis B core antibody 
(HBcAb), hepatitis C antibody, rapid plasma reagin and anti-HIV tests will be performed at 
screening visit. If the HBsAg test result is positive, the subject cannot be enrolled in the study. 
If the HBcAb test result is positive, the subject is also cannot be enrolled. If the hepatitis C 
antibody, rapid plasma reagin or anti-HIV test result is a positive, the subject also cannot be 
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6.1.2.3 Urine Drug Test 
A urine drug tests will be performed at screening and Day -1 visit. The screen for drug abuse 
includes methamphetamine, barbiturates, benzodiazepines, cocaine, tetrahydrocannabinol, and 
opiates. The urine test can be repeated once at the discretion of the Investigator. 
6.1.2.4 Chest X-ray 
A chest X-ray will be performed on screening visit for baseline data collection purposes. An 
additional assessment can be performed when the Investigator considers it is clinically necessary. 
6.1.3 Adverse Events 
6.1.3.1 Definition of Adverse Events 
An AE is defined as any untoward medical occurrence in any subject during the study which 
does not necessarily have a causal relationship with the study drug. Any new condition noted at 
Screening would be regarded as an AE, but not a TEAE. 
Adverse events requiring therapy must be treated with recognized standards of medical care to 
protect the health and well-being of the subject. Treatment due to an AE will be recorded. 
A TEAE includes any untoward medical occurrence in a subject after administration of a study 
drug, which does not necessarily have to have a causal relationship with this the study drug. A 
TEAE can therefore be any unfavorable and unintended sign (including an abnormal laboratory 
finding), symptom, or disease temporally associated with the use of the product, whether or not 
related to the study drug. 
Abnormal results of diagnostic procedures including laboratory test abnormalities are 
considered as AEs if they fulfill the following criteria: 
 
Result in discontinuation from the study drug 
 
Require treatment or any other therapeutic intervention 
 
Require further diagnostic evaluation (excluding a repetition of the same procedure to 
confirm the abnormality) 
 
Are clinically significant as evaluated by the investigator 


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Medical intervention such as surgery, diagnostic procedures, and therapeutic procedures are not 
AEs, but the action taken to treat the medical condition. They should be recorded as treatment(s) 
of the AEs. The event term of primary cause should be recorded and reported instead of the term 
of surgery, diagnostic procedure, or therapeutic procedure. 
6.1.3.1.1 Serious Adverse Events 
An SAE is defined as any untoward medical occurrence that at any dose: 
 
Results in death. 
 
Is life-threatening (refers to an AE in which the subject was at immediate risk of death at 
the time of event). It does not refer to an event which may have caused death, if it was more 
severe. 
 
Requires inpatient hospitalization or prolongation of existing hospitalization. 
 
Results in persistent or significant disability/incapacity. 
 
Is a congenital anomaly/birth defect. 
Medical and scientific judgment should be exercised in deciding whether expedited reporting is 
appropriate in other situations, such as important medical events that may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the subject or may 
require medical or surgical intervention to prevent one of the outcomes listed in the definition 
above. These should also be considered serious. Examples of such medical events include 
allergic bronchospasm requiring intensive treatment in an emergency room or at home, blood 
dyscrasias or convulsions that do not result in inpatient hospitalization, or the development of 
drug dependency or drug abuse. 
Adverse events associated with hospitalization or prolongations of hospitalization are 
considered as SAEs. Any admission (even if < 24 hours) to a healthcare facility meets these 
criteria. Admission also includes transfer within the hospital to an acute/intensive care unit (e.g., 
from the psychiatric wing to a medical floor, from medical floor to a coronary care unit, from 
neurological floor to a tuberculosis unit). 
Hospitalization or prolongation of hospitalization in the absence of a precipitating clinical AE 
is not in itself an SAE. Examples include the following: 


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 
Admission for treatment of a pre-existing condition not associated with the development of 
a new AE or worsening of the pre-existing condition (for work-up of persistent 
pre-treatment laboratory abnormality) 
 
Social admission (e.g., subject has no place to sleep) 
 
Purely for convenience (e.g., for easier performance of study assessments) 
 
Administrative admission (e.g., for yearly physical examination) 
 
Protocol-specified admission during a study (e.g., for a procedure required by the study 
protocol) 
 
Optional admission not associated with a precipitating clinical AE (e.g., for elective 
cosmetic surgery) 
 
Hospitalization for observation without a medical AE 
 
Pre-planned treatments or surgical procedures; these should be noted in the baseline 
documentation for the entire protocol and/or for the individual subject 
6.1.3.1.2 Unlisted (Unexpected) Serious Adverse Events 
An unlisted or unexpected SAE is defined as an event of which the nature or severity is not 
consistent with the applicable product information (e.g., IB) for an unapproved investigational 
product. 
6.1.3.1.3 Suspected Unexpected Serious Adverse Reactions 
The Sponsor will promptly evaluate all suspected unexpected serious adverse reactions against 
cumulative product experience to identify and expeditiously communicate possible new safety 
findings to Investigators, IECs, and applicable health authorities based on applicable legislation. 
To determine reporting requirements for single SAE cases, the Sponsor will assess the 
expectedness of these events using the applicable reference documents (e.g., IB). 
Reporting requirements will also be based on the Investigator’s assessment of causality and 
seriousness, with allowance for upgrading by the Sponsor as needed. 


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6.1.3.1.4 Adverse Events of Special Interest 
Infusion related reaction including hypersensitivity/anaphylactic reactions is considered as 
AESI and will be reported using the same process as for AEs. 
6.1.3.1.5 Eliciting and Documenting Adverse Events 
All AEs will be reported by the Investigator via eCRF from the date subjects signs the ICF until 
EOS visit, regardless of the relationship to the study drug. The condition of the subject will be 
monitored throughout the study for any signs or symptoms. 
At every study visit, subject will be asked a standard nonleading question to elicit any medically 
related changes in their well-being. They will also be asked if they have been hospitalized, had 
any accidents, used any new medications, or changed concomitant medication regimens (both 
prescription medications and OTC drugs). 
In addition to subject observations, AEs identified from any study data (e.g., laboratory values, 
physical examination findings, ECG changes) or identified from review of other documents that 
are relevant to subject safety will be documented on the AE page in the eCRF. 
6.1.3.1.6 Reporting Adverse Events 
All AEs reported or observed during the study will be recorded on the AE page in the eCRF and 
source documents. Information to be collected includes drug treatment, action taken with study 
drug, event term, date/time of onset and end date, Investigator-specified assessment of severity 
and relationship to study drug, seriousness of AE, any required treatment or evaluations, and 
outcome. 
Adverse events resulting from concurrent illness, reactions to concurrent illnesses, or reactions 
to concurrent medications must also be reported from the date subjects signs the ICF until EOS 
visit. Adverse events will be graded for severity according to the Common Terminology Criteria 
for Adverse Events (CTCAE) Version 5.0. The Medical Dictionary for Regulatory Activities 
will be used to code all AEs. 
Any medical condition that is present at the time that the subject is screened but does not 
deteriorate should not be reported as an AE. However, if it deteriorates at any time during the 
study, it should be recorded as an AE. 


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The Investigator’s assessment of an AE’s relationship to study drug is part of the documentation 
process, but it is not a factor in determining what is or is not reported in the study. If there is 
any doubt as to whether a clinical observation is an AE, the event will be reported. 
The severity and the relationship or association of the study drug in causing or contributing to 
the AE will be characterized as defined in Section 6.1.3.2 and Section 6.1.3.3, respectively. 
6.1.3.1.7 Reporting Serious Adverse Events 
Any AE considered serious by the Investigator or which meets SAE criteria (Section 6.1.3.1.1) 
must be reported to CRO within 24 hours from the time study center staff first learn about the 
event. Data entry should be completed in the remote data capture system by the Investigator 
within 24 hours of awareness of an SAE. In the event that this is not possible (e.g., system 
failure or access problems), the study center should complete an SAE report form and email it 
to 
 or via FAX (details on SAE report form) within 24 hours 
of awareness of the event. The remote data capture system should be updated as soon as it is 
available. Withdrawal from the study and all therapeutic measures will be at the discretion of 
the Principal Investigator or Sub-Investigator. All SAEs will be followed up as specified in 
Section 6.1.3.1.8. 
The Sponsor or its designee is responsible for reporting relevant SAEs to the competent 
authority, other applicable regulatory authorities, and participating Investigators, in accordance 
with European Clinical Trials Directive (Directive 2001/20/EC), International Council for 
Harmonisation (ICH) guidelines, and/or local regulatory requirements. 
The Sponsor or its designee is responsible for reporting fatal or life-threatening suspected 
unexpected serious adverse reaction (expedited reports) to the regulatory agencies and 
competent authorities within 7 calendar days after being notified of the event. The Sponsor or 
its designee should report other relevant SAEs associated with the use of the study drug to the 
appropriate competent authorities (according to local guidelines), Investigators, and IECs by a 
written safety report within 15 calendar days of notification. 
6.1.3.1.8 Follow-up of Adverse Events 
All reported AEs will be followed until one of the following: resolution or improvement from 
baseline, confirmed by the Investigator that no further improvement could be expected, no more 
collection of clinical or safety data, or final database closure. For subjects who withdraw from 
the study, the last assessed status of AEs will be collected. 


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6.1.3.2 Assessment of Severity 
The severity of an AE refers to the extent to which an AE affects the subject’s daily activities. 
The severity of the AE will be graded based on the CTCAE Version 5.0, based on the following 
general guidelines (a semicolon indicates “or” within each description): 
Grade 1: 
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations 
only; intervention not indicated 
Grade 2: 
Moderate; minimal, local or noninvasive intervention indicated; limiting 
age appropriate instrumental activities of daily living (ADL)1 
Grade 3: 
Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; 
limiting self-care ADL2 
Grade 4: 
Life-threatening consequences; urgent intervention indicated 
Grade 5: 
Death related to AE 
1. Instrumental ADL refer to preparing meals, shopping for groceries or clothes, using the telephone, managing money, etc. 
2. Self-care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not 
bedridden. 
Changes in the severity of an AE should be documented to allow an assessment of the duration 
of the event at each level of severity to be performed. If an AE upgrades in severity or changes 
from nonserious to serious, a new AE needs to be reported. If an AE downgrades in severity, it 
should not be reported as a new AE. Adverse events characterized as intermittent do not require 
documentation of onset and duration of each episode. 
6.1.3.3 Assessment of Causality 
As discussed in Section 6.1.3.1.6, the Investigator’s assessment of an AE’s relationship to study 
drug is part of the documentation process, but it is not a factor in determining what is or is not 
reported in the study. If there is any doubt as to whether a clinical observation is an AE, the 
event will be reported. 
The relationship or association of study drug in causing or contributing to the AE will be 
characterized using the following classification and criteria: 


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Unrelated: 
This relationship suggests that there is no association between the study drug 
and the reported event. 
Possible: 
This relationship suggests that treatment with the study drug caused or 
contributed to the AE, e.g., the events follows a reasonable temporal sequence 
from the time of drug administration or follows a known response pattern to 
the study drug but could also have been produced by other factors. 
Probable: 
This relationship suggests that a reasonable temporal sequence of the event 
with drug administration exists and, based upon the known pharmacological 
action of the drug, known or previously reported adverse reactions to the drug 
or class of drugs, or judgment based on the Investigator’s clinical experience, 
the association of the event with the study drug seems likely. The event 
disappears or decreases on cessation or reduction of the dose of study drug. 
Definite: 
This relationship suggests that a definite causal relationship exists between 
drug administration and the AE, and other conditions (concurrent illness, 
progression/expression of disease states, or concurrent medication reaction) 
do not appear to explain the event. The event reappears or worsens if the study 
drug is re-administered. 
6.1.4 Hypersensitivity Monitoring 
Hypersensitivity monitoring will be performed as specified in Table 6-1. 
Table 6-1 Schedule of Assessments for Hypersensitivity Monitoring 
Day 
Time points 
Window 
Day 1 
Predose (prior to dosing on Day 1) 
Within 30 minutes 
15 minutes from start of infusion 
± 5 minutes 
30 minutes from start of infusion 
60 minutes from start of infusion 
End of infusion 
2 hours from start of infusion 
± 15 minutes 
3 hours from start of infusion 
6 hours from start of infusion 
12 hours from start of infusion 
Day 2 
24 hours from start of infusion 
± 30 minutes 


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Hypersensitivity will be assessed by additional vital signs measurements including blood 
pressure, heart rate, respiratory rate, and body temperature. In addition, hypersensitivity will be 
monitored by routine continuous clinical monitoring. In case of hypersensitivity, emergency 
medication and equipment, such as adrenaline, antihistamines, corticosteroids, and respiratory 
support including inhalational therapy, oxygen, and/or artificial ventilation will be available and 
any type of ECG can be performed if a subject experiences cardiac symptoms. 
For subjects who experience or develop life threatening treatment-related hypersensitivity 
reactions, study drug must be stopped immediately. 
Details will be recorded in both the source documents and the eCRF. 
6.1.5 Vital Signs, Weight, and Height 
Vital signs and weight measurements will be performed at the time points specified in 
Table 11-1. Vital signs (including blood pressure, heart rates, respiratory rates, and body 
temperature) will be measured after the subject has rested quietly for at least 5 minutes. Body 
temperature will be measured using tympanic thermometer throughout the study. Height will be 
assessed at Screening only as a baseline measurement. Details will be recorded in both the 
eCRFs and source documents. 
Additional vital sign measurements will also be monitored before and after the study drug 
administration as part of the hypersensitivity monitoring (Section 6.1.4). 
6.1.6 Electrocardiogram 
A 12-lead ECG will be performed at the time points specified in Table 11-1 and if the subject 
experienced cardiac symptoms during study drug administration. All scheduled 12-lead ECGs 
will be performed after the subject has rested quietly for at least 5 minutes. If following the 
ECG review by the Investigator there are any ECG findings that would indicate cardiac 
insufficiency or QT prolongation or any other abnormalities, the subject will be referred to a 
cardiologist if required, to confirm the abnormality. The Investigator will then report the event 
in the eCRF and source documents. Regardless of 12-lead ECG result, further evaluation with 
a cardiologist can be performed at the Investigator’s discretion. 
In case of hypersensitivity monitoring, any type of ECG can be performed (Section 6.1.4). 


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6.1.7 Physical Examination 
Physical examinations will be performed at time points specified in Table 11-1. The physical 
examination includes an assessment of general appearance and a review of systems. Information 
about the physical examination will be recorded by the Investigator, or delegated clinical staff 
member, in both the source documents and the eCRF. Any abnormalities will be recorded in the 
source documents. Clinically significant findings and illnesses reported after the start of the 
study that meet the definition of an AE will be recorded as such in the source documents and 
eCRF. 
6.1.8 Pregnancy 
A serum pregnancy test will be performed at screening and EOS visits, and urine pregnancy test 
will be performed on female subjects with childbearing potential on Day -1 as specified in Table 
11-1. Only subjects who are confirmed as nonpregnant by both serum pregnancy test at 
screening and urine pregnancy test on Day -1 can be enrolled in the study. 
Throughout the study, a urine pregnancy test will be performed when there is any possibility of 
pregnancy, and a confirmatory serum pregnancy test will be performed if a urine pregnancy test 
result is positive or equivocal. 
The serum and urine pregnancy test samples will be analyzed at the local laboratory. 
In an event of unexpected pregnancy within 6 months after the study drug administration, 
subjects will be counselled to inform the investigator. If a female subject or a female subject or 
female partner of a male subject becomes pregnant, the pregnancy must be reported to the 
Sponsor and CRO within 24 hours of the study center’s knowledge of the likelihood of 
pregnancy while confirmation is pending. Once the pregnancy is confirmed with a serum 
pregnancy test, female subjects must be withdrawn from the study. The study center must 
complete the supplied pregnancy form and return it to the Sponsor and CRO within 24 hours of 
pregnancy being detected. 
Pregnant subjects or partners of subjects will be followed until the end of the pregnancy (e.g., 
delivery, stillbirth, miscarriage) and the mother and the baby will be followed for 1 year after 
the birth, provided consent is obtained. 
In female subjects or female partners of subjects, abnormal pregnancy outcomes (e.g., 
spontaneous abortion, fetal death, stillbirth, congenital anomalies, and ectopic pregnancy) are 
considered SAEs. Any SAE that occurs during pregnancy (e.g., maternal serious complications, 


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ectopic pregnancy, stillbirth, neonatal death, congenital anomaly, birth defect) must be reported 
within 24 hours in accordance with the procedure for reporting SAEs (Section 6.1.3.1.7). 
6.1.9 Clinical Laboratory Tests 
Blood and urine samples for clinical laboratory tests including clinical chemistry, hematology, 
and urinalysis will be collected at the time points specified in Table 11-1. Laboratory tests will 
be performed by the local laboratories. 
The following clinical laboratory tests will be performed. 
Clinical chemistry: 
Total protein, total bilirubin, alanine aminotransferase, aspartate 
aminotransferase, alkaline phosphatase, blood urea nitrogen, 
creatinine, creatine kinase, creatine kinase-myocardial band 
isoenzyme, troponin I, albumin, sodium, potassium, total calcium, 
chloride, 
phosphorus, 
glucose, 
lactate 
dehydrogenase, 
total 
cholesterol, 
gamma-glutamyltransferase, 
estimated 
glomerular 
filtration rate (eGFR), uric acid and C-reactive protein. 
(Direct bilirubin, troponin T, triglyceride and high-density lipoprotein 
cholesterol will be analyzed at screening visit and when the 
Investigator consider it is clinically necessary.) 
Hematology: 
Red blood cell count, white blood cell count, absolute neutrophil 
count, eosinophil count, lymphocyte count, monocyte count, basophil 
count, platelet, hemoglobin, mean corpuscular volume, mean 
corpuscular 
hemoglobin, 
mean 
corpuscular 
hemoglobin 
concentration, and hematocrit 
Urinalysis: 
Bilirubin, red blood cell, glucose, ketones, leukocytes, nitrite, pH, 
protein, specific gravity, urobilinogen, and microscopic examination 
of white blood cell count, red blood cell count, and bacteria 
6.1.10 Immunogenicity Assessments 
The immunogenicity of CT-59 will be assessed by ADA and NAb test in validated immunoassay. 
Blood samples for immunogenicity assessments will be collected at the time points specified in 
Table 11-1. If the blood sample is unable to be analyzed or is missing at certain time point, some 
blood samples collected for PK assessment at the same time point can be used for 


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immunogenicity 
assessment. Additional 
immunogenicity 
will 
be 
assessed 
when 
immune-related AEs occurs. 
Analysis will be performed at the central laboratory. 
6.2 Pharmacokinetic Assessments 
Details of blood sampling time points and acceptable tolerance windows for PK assessments 
are described in Table 6-2. 
Table 6-2 Blood Sampling Time Points for Pharmacokinetic Assessment 
Day 
Time point 
Window 
Day 1 
Predose 
Predose within the day 
End of infusion 
+ 5 minutes 
1 hour after end of infusion 
± 15 minutes 
4 hours after end of infusion 
8 hours after end of infusion 
12 hours after end of infusion 
Day 2 
24 hours after start of infusion 
± 1 hours 
Day 3 
48 hours after start of infusion 
Day 5 
96 hours after start of infusion 
± 4 hours 
Day 7 
144 hours after start of infusion 
Day 10 
216 hours after start of infusion 
Day 14 
312 hours after start of infusion 
± 1 day 
Day 28 
648 hours after start of infusion 
± 3 days 
Day 56 
1,320 hours after start of infusion 
± 5 days 
Day 90 
2,136 hours after start of infusion 
If the blood sample is unable to be analyzed or is missing at certain time point, some blood 
samples collected for immunogenicity assessment at same time point can be used for PK 
assessment. Analysis will be performed at the central laboratory. 
Instructions for the blood collection, storage, and shipment to the central laboratory is describe 
in Section 6.3 and Section 6.4. 
6.3 Sample Collection 
The total volume of blood collected for each assessment is discussed in each specific laboratory 
manual. The sample collection tube may be changed during the study and details will be 
provided in the laboratory manual. 


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6.3.1 Pharmacokinetic Blood Sampling 
Blood samples for PK assessments will be obtained in accordance with the laboratory manual 
from each subject at the time point specified in Table 6-2. All samples should be collected as 
close as possible to the scheduled time point. The actual sampling date and time will be recorded 
in both the eCRF and source documents. 
6.3.2 Immunogenicity Blood Sampling 
Blood samples for immunogenicity assessments will be obtained in accordance with the 
laboratory manual from each subject at the time point specified in Table 11-1 or when immune-
related AEs occur. All samples should be collected as close as possible to the scheduled time 
point. The actual sampling date and time will be recorded in both the eCRF and source 
documents. 
6.3.3 Safety Blood Sampling 
Blood samples for clinical chemistry, hematology and serum pregnancy tests will be collected 
for analysis throughout the study at the time points specified in Table 11-1. The actual sampling 
date will be recorded in both the eCRF and source documents. 
6.3.4 Safety Urine Sampling 
Urine samples for urinalysis and urine pregnancy test will be collected for analysis at the time 
points specified in Table 11-1. The actual sampling date will be recorded in both the eCRF and 
source documents. 
6.4 Labeling, Storage, and Transportation of Samples 
6.4.1 Sample Labeling 
Each sample tube will be clearly labeled with the following information: study number, subject 
number, tube identification and scheduled sampling time point. 
6.4.2 Sample Storage and Shipment 
During the study, blood samples will be collected for PK, immunogenicity, and safety analyses. 
Where appropriate, the serum should be transferred into a sufficient number of transfer tubes 
for transport to assigned testing facilities. Primary and back-up samples will be shipped to the 
central laboratory according to the laboratory manual, and primary samples should be shipped 
separately from the back-up samples. 


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Additionally, back-up samples for PK and immunogenicity will be retained at the central 
laboratory for up to 5 years after the end of the study in case additional analysis is required. If 
additional analysis for PK and immunogenicity is not required, the sample will be stored at the 
Sponsor or a designated biobank for a further 5 years (from the date the sample is transferred to 
the Sponsor/biobank) unless a specific authorization is given by the Sponsor to destroy the 
sample. Additional tests can be conducted at the Sponsor or the biobank if it is required from a 
regulatory or medical perspective. Procedures for storage and shipment will be followed 
according to the laboratory manual. 


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7 Statistical Analysis 
The statistical analysis will be performed using Statistical Analysis System Software Version 
9.4 or higher (SAS institute Inc., Cary, North Carolina, US). The statistical methods for this 
study will be described in a detailed SAP. Changes from analyses planned in this protocol will 
be documented in the SAP. Any deviations from the planned analysis as described in the SAP 
will be justified and recorded in the CSRs. 
Full details of the statistical methods will be described in the SAP. 
7.1 Sample Size Calculation 
The total sample size of 32 subjects is not based on a formal statistical hypothesis. A sample 
size justification based on statistical hypotheses is not relevant in this study. The proposed 
number of 8 subjects (6 subjects for CT-P59 and 2 subjects for placebo) in each cohort is set 
empirically based on sample sizes in other Phase 1 studies investigating the safety and 
tolerability of their study drugs and is considered to be sufficient to achieve the objectives of 
the study. 
7.2 Analysis Sets 
The following analysis sets will be used in the statistical analyses. 
Intent-to-treat (ITT) Set: The ITT Set is defined as all randomly assigned subjects to study 
drug. 
Safety Set: The Safety Set will include all randomized subjects who received a full or partial 
dose of the study drug. 
Pharmacokinetic Set: The PK Set will include all subjects in the Safety Set who received a 
full dose of CT-P59 and provide at least 1 evaluable post-treatment PK concentration result. 
7.3 Description of Subgroups to be analyzed 
Subgroup analysis can be implemented to reflect medical, regulatory, or ethnic consideration, 
if required. 


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7.4 Statistical Analysis Methodology 
7.4.1 General Consideration 
Continuous variables will be summarized by reporting the following descriptive statistics: the 
number of observations (n), mean, standard deviation (SD), median, minimum, and maximum. 
Categorical variables will be summarized using frequency tables showing the number and 
percentage of subjects within a particular category. Data will be listed in data listings. 
7.4.2 Study Population 
7.4.2.1 Disposition of Subjects 
The number and percentage of subjects entering and completing the clinical study will be 
presented by the cohort of CT-P59 groups and pooling of placebo group. 
The number of subjects who enroll in the study and the number and percentage of subjects who 
complete the study will be presented. Frequency and percentage of subjects who is withdrawn 
or discontinue from the study, and the reason for withdrawal or discontinuation, will also be 
summarized. 
7.4.3 Safety Analysis 
Safety analyses will be performed in the Safety Set, unless otherwise indicated. 
7.4.3.1 Demographic, Baseline, and Background Characteristics 
Baseline demographic and background variables will be summarized by the cohort of CT-P59 
groups and pooling of placebo group using the ITT Set. 
Demographics (including age, sex, ethnicity, and race) and baseline and background 
characteristics will be presented in summary tables. Qualitative data (e.g., medical history) will 
be summarized in contingency tables, and quantitative data (e.g., age) will be summarized using 
quantitative descriptive statistics. 
7.4.3.2 Adverse Events 
Adverse events will be recorded according to the CTCAE Version 5.0 and will be coded to 
system organ class and preferred term according to Medical Dictionary for Regulatory Activities. 
A TEAE is defined as described in Section 6.1.3.1. The following AE summaries will be 
reported by system organ class, preferred term, and the cohort of CT-P59 groups and pooling of 
placebo group, as appropriate: 


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 
Number and percentage of subjects reporting at least 1 TEAE 
 
Number and percentage of subjects reporting at least 1 TESAE 
 
Number and percentage of subjects discontinuing the study drug due to a TEAE 
 
Number and percentage of subjects with TEAESIs (infusion related reaction including 
hypersensitivity/anaphylaxis reaction) 
If more than 1 AE is recorded for a subject within any system organ class or preferred term, the 
subject will be counted only once within the respective summary. Adverse events will also be 
summarized by maximum intensity and relationship to study drug with the percentage of 
subjects in each category. All AE data will be presented in the data listings, and additional TEAE 
analyses may be performed as detailed in the SAP. 
7.4.3.3 Clinical Laboratory and Pregnancy Tests 
Actual values and changes from baseline for numeric clinical laboratory tests (clinical chemistry, 
hematology and urinalysis) results will be summarized by the cohort of CT-P59 groups and 
pooling of placebo group at each scheduled visit using descriptive statistics. Shift tables will be 
generated for categorical clinical laboratory tests results. 
Individual clinical laboratory and serum and urine pregnancy tests results will be presented in 
data listings. 
7.4.3.4 Electrocardiogram, Physical Examination, and Vital Signs 
Actual values and change from baseline for vital sign measurements will be summarized by the 
cohort of CT-P59 groups and pooling of placebo group at each scheduled visit using descriptive 
statistics. 
Shift tables comparing the categorical Investigator interpretation of 12-lead ECGs and physical 
examinations at each scheduled visit with those at baseline will be summarized by the cohort of 
CT-P59 groups and pooling of placebo group. 
Individual ECG results and the Investigator’s interpretation, physical examination findings, and 
vital sign measurements (including hypersensitivity monitoring) will be presented in data 
listings. 


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7.4.3.5 Prior and Concomitant Medications 
Prior and concomitant medications will be coded using the WHO Drug Dictionary. All prior and 
concomitant medications data will be listed and summarized by the cohort of CT-P59 groups 
and pooling of placebo group. 
7.4.3.6 Immunogenicity Analysis 
Immunogenicity test results will be summarized by the cohort of CT-P59 groups and pooling of 
placebo group at each scheduled visit and presented in a data listing. 
7.4.4 Pharmacokinetic Analyses 
All PK analyses will be conducted in the PK Set. The PK parameters of CT-P59 will be analyzed 
using noncompartmental methods based on the actual sampling time points. All parameters will 
be calculated using Phoenix WinNonlin (Pharsight, St Louis, Missouri, USA). 
Pharmacokinetic parameters of AUC0-inf, AUC0-inf /Dose, AUC0-last, AUC0-last/Dose, Cmax, Cmax 
/Dose, Tmax, t1/2, %AUCext, λz, CL, and Vz will be presented in data listings and summarized by 
the cohort of CT-P59 groups at each scheduled visit using descriptive statistics. 
Serum concentration data will be presented in data listings and summarized by the cohort of 
CT-P59 groups at each scheduled visit using descriptive statistics. 
7.5 Interim Analysis 
No formal interim analysis will be performed in this study. The Sponsor plans to prepare two 
CSRs (Section 9.7). 
7.6 Data Quality Assurance 
This study will be conducted according to the ICH E6(R2) risk and quality processes described 
in the applicable procedural documents. The quality management approach to be implemented 
in this study will be documented and will comply with the current ICH GCP guidelines on 
quality and risk management. 
Steps to be taken to ensure the accuracy and reliability of data include the selection of qualified 
Investigators and appropriate study center, review of protocol procedures with the Investigator 
and associated staff prior to the study, periodic monitoring visits by the Sponsor or its designee, 
and direct transmission of clinical laboratory data from central and/or local laboratories into the 
clinical database. The data will be collected via Electronic Data Capture (EDC) using eCRFs. 


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The study center will be responsible for data entry into the EDC system. The eCRF will be 
reviewed for accuracy and completeness by the monitor during on-site monitoring visits and 
after their return to the Sponsor or its designee. In the event of discrepant data, the Sponsor will 
request data clarification from the study center, which the study center will resolve 
electronically in the EDC system. The Sponsor will be responsible for the data management of 
this study, including quality checking of the data. 
Central laboratory data will be sent directly to the Sponsor using their standard procedures to 
handle and process the electronic transfer of these data. Quality assurance staff from the Sponsor 
or its designee may visit the study center to carry out an audit of the study in compliance with 
regulatory guidelines and company policy. Such audits will require access to all study records, 
including source documents, for inspection and comparison with the eCRF. Subject privacy 
must, however, be respected. Sufficient prior notice will be provided to allow the Investigator 
to prepare properly for the audit. 
Similar auditing procedures may also be conducted by agents of any regulatory body reviewing 
the results of this study in support of a licensing application. The Investigator should 
immediately notify the Sponsor or its designee if he or she has been contacted by a regulatory 
agency concerning an upcoming inspection. 


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8 Investigator’s Obligations 
The following administrative items are meant to guide the Investigator in the conduct of the 
study but may be subject to changed based on industry and government SOPs, working practice 
documents, or guidelines. Changes will be reported to the IEC but will not result in a protocol 
amendment. 
8.1 Confidentiality 
All laboratory specimens, evaluation forms, reports, and other records will be identified in a 
manner designed to maintain subject confidentiality. All records will be kept in a secure storage 
area with limited access. Clinical information will not be disclosed without the written 
permission of the subject (or the subject’s legal guardian), except as necessary for monitoring 
and auditing by the Sponsor, its designee, the regulatory authorities or the IEC. 
The Investigator, all employees, and coworkers involved with this study may not disclose or use 
for any purpose other than performance of the study, any data, record, or other unpublished, 
confidential information disclosed to those individuals for the purpose of the study. Prior written 
agreement from the Sponsor or its designee must be obtained for the disclosure of any said 
confidential information to other parties. 
8.2 Independent Ethics Committee 
Regulations and ICH guidelines require that approval be obtained from an IEC before 
participation of human subjects in research studies. Before study onset; the protocol, informed 
consent, advertisements to be used for the recruitment of study subjects, and any other written 
information regarding this study to be provided to the subject or the subject’s legal guardian, 
must be approved by the IEC. Documentation of all IEC approvals and of the IEC compliance 
with ICH harmonised tripartite guideline E6(R2): GCP will be maintained by the study center 
and will be available for review by the Sponsor or its designee. 
All IEC approvals should be signed by the IEC chairman or designee and must identify the IEC 
name and address, the clinical protocol by title or protocol number or both, and the data approval 
or a favorable opinion was granted. 
The Investigator is responsible for providing written summaries of the progress and status of 
the study at intervals not exceeding 1 year or otherwise specified by the IEC. The Investigator 
must promptly supply the Sponsor or its designee, the IEC, and, where applicable, the institution, 


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with written reports on any changes significantly affecting the conduct of the study or increasing 
risk to subjects. 
8.3 Subject Information and Consent 
A written informed consent in compliance with ICH E6(R2) guidelines will be obtained from 
each subject before entering the study or performing any unusual or nonroutine procedure that 
involves risk to the subject. An informed consent template may be provided by the Sponsor to 
the study center. If any institution-specific modifications to study-related procedures are 
proposed or made by the study center, the consent should be reviewed by the Sponsor or its 
designee or both before IEC submission. Once reviewed, the consent will be submitted by the 
Investigator to his or her IEC for review and approval before the start of the study. If the ICF is 
revised during the course of the study, all active participating subjects must sign the revised 
form in case new information becomes available that may be relevant to the subject’s 
willingness to continue participation in the clinical study. 
Before recruitment and enrollment, each prospective subject will be given a full explanation of 
the study and be allowed to read the approved ICF. Once the Investigator is assured that the 
subject understands the implications of participating in the study, the subject will be asked to 
give consent to participate in the study by signing the ICF. 
In addition to the standard requirements that physicians are currently obliged to observe when 
providing information, the following points must also be covered: 
 
A description of the objectives of the study and how it will be organized 
 
The type of treatment 
 
Any potential negative effects attributable to the study drug 
 
The freedom to ask for further information at any time 
 
The subject’s right to withdraw from the clinical study at any time without giving reason 
and without jeopardizing the subject’s further course of medical treatment 
 
The existence of subject insurance coverage and a summary of what is included in this 
coverage 
 
Adequate time and opportunity to satisfy questions will be given to the subjects. 


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The Investigator will be supplied with an adequate number of ICFs to be used. The forms will 
be signed and dated by both the Investigator or Sub-Investigator and the subject’s legal 
representatives (according to the local regulations) before the beginning of the study. The 
Investigator shall retain the signed original ICF(s) and give a copy of the signed original form 
to the subject or legal guardian. 
To ensure medical confidentiality and data protection, the signed ICFs will be stored in the 
Investigator’s study file. The Investigator will allow inspection of the forms by authorized 
representatives of the Sponsor, IEC members, and regulatory authorities. The Investigator will 
confirm, by signing and dating the eCRFs, that informed consent has been obtained. 
8.4 Study Reporting Requirements 
By participating in this study, the Principal Investigator or Sub-Investigator agrees to submit 
reports of SAEs according to the timeline and method outlined in Section 6.1.3.1.7. In addition, 
the Principal Investigator or Sub-Investigator agrees to submit annual report to his or her IEC 
as appropriate. 
8.5 Financial Disclosure and Obligations 
CELLTRION, Inc. is the Sponsor of the study and is funding the study. All financial details are 
provided in the separate contracts between the institution, Investigator, and CRO. The Sponsor 
maintains appropriate insurance coverage for clinical studies and will follow applicable local 
compensation laws. The Sponsor will indemnify all Investigators participating in this study 
against future claims by study subjects; the terms of this will be detailed within a separate letter 
of indemnification. The indemnity will only apply where all study procedures have been carried 
out according to this protocol. 
The Investigator is required to take out liability insurance for all subjects included in the study 
as required by local law and/or regulations and/or ICH GCP, whichever is applicable. 
The Investigator and the Sponsor will sign a clinical study agreement before the start of the 
study. The agreement will outline overall Sponsor and Investigator responsibilities in relation 
to the study. Financial remuneration will cover the costs based on the calculated expenses of 
performing the study assessments in accordance with the protocol and the specified terms of 
payment will be described in the contract. 
Investigators are required to provide financial disclosure information to allow the Sponsor to 
submit the complete and accurate certification or disclosure statements per regional 


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requirements. In addition, the Investigator must provide to the Sponsor a commitment to 
promptly update this information if any relevant changes occur during the course of the 
investigation and for 1 year following the completion of the study. 
Neither the Sponsor nor its designee is financially responsible for further testing or treatment or 
any medical condition that may be detected during the Screening process. In addition, in the 
absence of specific arrangements, neither the Sponsor nor its designee is financially responsible 
for further treatment of the subject’s pre-existing disease prior to study participation (Screening). 
The Sponsor undertakes to compensate the subject for injuries which are considered, on the 
balance of probabilities, to have arisen as a result of their participation in the trial 
8.6 Investigator Documentation 
Before beginning the study, the Investigator will be asked to comply with ICH E6(R2) 8.2 and 
Title 21 of the Code of Federal Regulations by providing the following essential documents, 
including but not limited to: 
 
Independent Ethics Committee approval 
 
Original Investigator-signed Investigator agreement page of the protocol 
 
Curriculum vitae for the Principal Investigator and each Sub-Investigator. Current licensure 
must be noted in the curriculum vitae. The curriculum vitae will be signed and dated by the 
Principal Investigators and Sub-Investigators at the study start-up, indicating that they are 
accurate and current 
 
Financial disclosure information to allow the Sponsor to submit complete and accurate 
certification or disclosure statements. In addition, the Investigators must provide to the 
Sponsor a commitment to promptly update this information if any relevant changes occur 
during the course of the investigation and for 1 year after the completion of the study 
 
Independent Ethics Committee-approved informed consent, samples of study center 
advertisements for recruitment for this study, and any other written information regarding 
this study that is to be provided to the subject or legal guardian 
 
Laboratory certifications and normal ranges for any local laboratories used by the study 
center 


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8.7 Study Conduct 
The Investigator agrees that the study will be conducted according to Declaration of Helsinki, 
the principles of ICH E6(R2) and all applicable regulations. The Investigator will conduct all 
aspects of this study in accordance with all national, state, and local laws or regulations. 
8.8 Data Collection 
8.8.1 Electronic Case Report Forms and Source Documents 
It is the intent of this study to acquire study data via electronic format. As part of the 
responsibilities assumed by participating in the study, the Principal Investigator or 
Sub-Investigator agrees to maintain adequate case histories for the subjects treated as part of 
the research under this protocol. The Principal Investigator or Sub-Investigator agrees to 
maintain source documentation (e.g., laboratory reports), enter subject data into the eCRF as 
accurately as possible, and respond to any reported discrepancies rapidly. 
The eCRFs are accessed through the appropriate system, which allows for on-site data entry 
and data management. Study center users will have access to read and write in the Sponsor’s 
database where the clinical data are collected. This provides immediate, direct data transfer to 
the database, as well as immediate detection of discrepancies, enabling study center 
coordinators to resolve and manage discrepancies in a timely manner. 
Each study center staff involved with the study at each study center will have an individual 
logon account and password that allow for record traceability. Thus, the system and 
subsequently any investigative reviews, can identify coordinators, Investigators and individuals 
who have entered or modified records. 
8.9 Adherence to Protocol 
The Investigator agrees to conduct the study as outlined in this protocol in accordance with ICH 
E6(R2) and all applicable guidelines and regulations. 
8.10 Investigator’s Final Report 
Upon completion of the study, the Investigator, where applicable, should inform the institution; 
the Investigator/institution should provide IEC with a summary of the study’s outcome and the 
Sponsor and regulatory authority(ies) with any reports required. 


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8.11 Record Retention 
Correspondence (e.g., with Sponsor, IEC, or clinical research associates) relating to this clinical 
study will be kept in appropriate file folders. Records of subjects, source documents, eCRFs, 
and drug inventory sheets pertaining to the study must be kept on file. 
Essential documents should be retained until at least 15 years after completion or 
discontinuation of the trial or at least 2 years after the granting of the last marketing 
authorization in the EU (when there are no pending or contemplated marketing applications in 
the EU) or for at least 2 years after formal discontinuation of clinical development of the 
investigational product, whichever is the longest. 
These documents can be retained for a longer period, if required by the applicable regulatory 
requirements or by an agreement with the Sponsor. It is the responsibility of the Sponsor to 
inform the Investigator/institution as to when these documents no longer need to be retained. 
If an Investigator moves, withdraws from an investigation, or retires, the responsibility for 
maintaining the records may be transferred to another person, who will accept the responsibility. 
Notice of transfer must be made to and agreed upon by the Sponsor. 
8.12 Subject Identification Register 
The Investigator agrees to complete a subject identification register, which will be used for the 
purpose of long-term follow-up, if needed. This form will be treated as confidential and will be 
filed by the Investigator in the Study Center Master File. Otherwise, all reports and 
communications relating to the study will identify subjects by assigned number only. 
8.13 Publications 
After completion of the study, the data may be considered for reporting at a scientific meeting 
or for publication in a scientific journal. In these cases, the Sponsor will be responsible for these 
activities and will work with the Principal Investigator and Sub-Investigator to determine how 
the manuscript is written and edited, the number and order of authors, the publication to which 
it will be submitted, and other related issues. The Sponsor has final approval authority over all 
such issues. 
Data are the property of the Sponsor and cannot be published without prior authorization from 
the Sponsor, but data publication thereof will not be unduly withheld. 


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9 Study Management 
9.1 Sponsor 
CELLTRION, Inc. 
 
 
 
 
 
Sponsor Representative 
 
 
 
 
 
9.2 Vendor Contact 
CRO 
 
 
 
 
SAE Reporting 
Email:
 
9.3 Central Analytical Facility 
Analyses of PK and immunogenicity samples will be performed in following central analytical 
facility: 
  
  
  
 


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Analytical facility and any procedures utilized for this study must be Good Laboratory Practice 
compliant. 
9.4 Monitoring 
9.4.1 Dose Escalation Committee 
The DEC is consist of Investigator, representatives of the Sponsor, and medical monitor of CRO. 
The DEC will be appointed for safety oversight and will make decision on continuation of next 
group dosing or dose escalation according to the criteria specified in Section 3.3. 
Further details will be provided in DEC charter. 
9.4.2 Data and Safety Monitoring Board 
This study will be monitored by an independent DSMB consisting of a PK specialist, statistician, 
chairing physician, and an independent physician. 
The appointed DSMB members will review the safety data and make a decision on continuation 
the study according to the criteria specified in Section 3.3. The DSMB will also review the data 
up to Day 14 of the last subject to evaluate preliminary safety and make recommendations on 
conduct of the study. 
Further details will be provided in the independent DSMB charter. 
9.4.3 Monitoring of the Study 
The clinical monitor, as a representative of the Sponsor, has the obligation to follow the study 
closely. In doing so, the monitor will visit the Investigator and study center at periodic intervals, 
in addition to maintaining necessary telephone and letter contact. The monitor will maintain 
current personal knowledge of the study through observation, review of study records and 
source documentation, and discussion of the conduct of the study with the Investigator and staff. 
In case where a monitoring visit cannot be made because of SARS-CoV-2 pandemic situation, 
the monitor will discuss with the Sponsor, CRO, and the Investigator for further plan. 
All aspects of the study will be carefully monitored, by the Sponsor or its designee, for 
compliance with applicable government regulation with respect to current ICH E6(R2) and 
SOPs. 


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9.4.4 Inspection of Records 
Investigators and institutions involved in the study will permit study-related monitoring, audits, 
IEC review, and regulatory inspections by providing direct access to all study records. In the 
event of an audit, the Investigator agrees to allow the Sponsor, representatives of the Sponsor, 
or a regulatory agency to access to all study records. 
The Investigator should promptly notify the Sponsor and CRO of any audits scheduled by any 
regulatory authorities. 
9.5 Management of Protocol Amendments and Deviations 
9.5.1 Modification of the Protocol 
Any changes in this research activity, except those necessary to remove an apparent, immediate 
hazard to the subject, must be reviewed and approved by the Sponsor or its designee. Substantial 
amendments to the protocol must be submitted in writing to the applicable IEC and Regulatory 
Authority for approval before subjects are enrolled under an amended protocol. This will be 
fully documented. 
The Investigator must not implement any deviation from or change to the protocol without 
discussion and agreement from the Sponsor or its designee, and prior review, documented 
approval, and favorable opinion of the amendment from the relevant IEC and/or regulatory 
authorities, except where it is necessary to eliminate an immediate hazard to subjects or where 
the changes involve only logistical or administrative aspects of the clinical study. The eCRF and 
source documents will describe any departure from the protocol and the circumstances requiring 
it. 
Protocol amendments will be submitted to the appropriate authorities as required by the 
applicable regulatory requirements. 
9.5.2 Protocol Deviations 
The Investigator or designee must document and explain in the subject’s source documentation 
any deviation from the approved protocol. The Investigator may implement a deviation from, 
or a change of, the protocol to eliminate an immediate hazard to study subjects without prior 
IEC approval. As soon as possible after such an occurrence, the implemented deviation or 
change, the reasons for it, and any proposed protocol amendments should be submitted to the 
IEC for review and approval, to the Sponsor for agreement and to the regulatory authorities, if 
required. 


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A deviation from the protocol is an unintended or unanticipated departure from the procedures 
or processes approved by the Sponsor and the IEC and agreed to by the Investigator. A 
significant deviation occurs when there is nonadherence to the protocol by the subject or 
Investigator that results in a significant and additional risk to the subject’s right, safety and 
well-being. Significant deviations may include nonadherence to inclusion or exclusion criteria, 
or nonadherence to regulations or ICH GCP guidelines. 
Protocol deviations will be documented by the clinical monitor throughout the course of 
monitoring visits. Deviations will be defined before unblinding. Principal Investigator will be 
notified in writing by the monitor of deviations. The IEC will be notified of protocol deviations, 
if applicable, in a timely manner. 
9.6 Study Termination 
Although the Sponsor has every intention of completing the study, the Sponsor reserves the 
right to discontinue the study at any time for clinical or administrative reasons. 
The end of the study is defined as the date of final database lock with no further database change 
for the final CSR. 
9.7 Final Report 
Whether the study is completed or prematurely terminated, the Sponsor will ensure that the 
CSRs are prepared and provided to the regulatory agency(ies) as required by the applicable 
regulatory requirement(s). The Sponsor will also ensure that the CSRs in marketing applications 
meet the standards of the ICH harmonised tripartite guideline E3: Structure and content of CSRs. 
The Sponsor plans to prepare two CSRs to report the following: 
 
First CSR: data up to Day 14 of the last enrolled subject 
 
Final CSR: all data after completion of the study 
If additional CSRs are required for regulatory or academic purposes, CSRs will be generated 
after the first database lock and unblinding process. 


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10 Reference List 
Association of the British Pharmacology Industry. Guidelines for Phase I clinical trials 2018 
edition. Available from: https://www.abpi.org.uk/media/4992/guidelines-for-phase-i-clinical-
trials-2018-edition-20180626.pdf 
European Medicines Agency. Committee for Medicinal Products for Human Use (CHMP). 
(2017). Guideline on strategies to identify and mitigate risks for first-in-human and early clinical 
trials with investigational medicinal products. London. EMEA/CHMP/SWP/28367/07 Rev. 1. 
Available from:  
https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-strategies-identify-
mitigate-risks-first-human-early-clinical-trials-investigational_en.pdf 
Food and Drug Administration. Code of Federal Regulations Title 21 (regulation 21 CFR 
320.38). Available from:  
https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=320.38 
Food and Drug Administration. Guidance for Industry: M3(R2) Nonclinical Safety Studies for 
the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals. 
January 2010. Available from: https://www.fda.gov/regulatory-information/search-fda-
guidance-documents/m3r2-nonclinical-safety-studies-conduct-human-clinical-trials-and-
marketing-authorization 
ICH Assembly. Integrated Addendum to ICH E6(R2): Guideline for good clinical practice 
E6(R2): ICH harmonised guideline. International Council for Harmonisation. 09 November 
2016. 
Tang X, Wu C, Li X, et al. On the origin and continuing evolution of SARS-CoV-2. National 
Science Review. 2020;0:1-12. 
US Department of Health and Human Services. (2010). National Institutes of Health, National 
Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. 
Available from: http://evs.nci.nih.gov/ftp1/CTCAE/About.html 
Varga Z, Flammer AJ, Steiger P, et al. Endothelial cell infection and endotheliitis in COVID-
19. Lancet. 2020 May 2;395:1417-18. 
World Health Organization. Coronavirus disease (COVID-19) Situation Report-135. 03 June 
2020. Available from: 
https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports/ 


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World Health Organization. Disease outbreak news. 05 January 2020. Available from: 
http://who.int/csr/don/05-january-2020-pneumonia-of-unkown-cause-china/en/ 
World Health Organization Guidelines. Infection prevention and control of epidemic- and 
pandemic-prone 
acute 
respiratory 
infections 
in 
health 
care. 
Available 
from: 
https://www.who.int/csr/bioriskreduction/infection_control/publication/en/ 


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11 Appendices 
11.1 Schedule of Assessments 
Table 11-1 Schedule of Assessments 
 
Screening1 
In-house stay 
Out-patient visit 
EOS2 
Study day 
-21 to -2 
-1 
1 
2 
3 
4 
5 
7 
10 
14 
28 
56 
90 
Visit window 
- 
 
 
 
 
 
- 
- 
- 
±1 
±3 
±5 
±5 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Demographic information 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion criteria3 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Weight and height4 
X 
X 
 
 
 
 
 
 
 
 
 
 
X 
Urine drug tests 5 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy test6 
X 
X 
 
 
 
 
 
 
 
 
 
 
X 
SARS-CoV-2 infection test 
X 
X18 
 
 
 
 
 
 
 
 
 
 
 
Viral serology test7 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Chest X-ray8 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Vital signs 
X 
X 
X9 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Randomization 
 
 
X9 
 
 
 
 
 
 
 
 
 
 
Study drug administration10 
 
 
X 
 
 
 
 
 
 
 
 
 
 
Hypersensitivity monitoring11 
 
 
X 
X 
 
 
 
 
 
 
 
 
 
Physical examination 
X 
X 
X9 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Clinical laboratory tests12 
X 
X 
 
X 
X 
 
 
X 
 
X 
X 
X 
X 
Twelve-lead electrocardiogram13 
X 
 
 
X 
 
 
 
X 
 
X 
X 
 
X 
Pharmacokinetic sampling14 
 
 
X 
X 
X 
 
X 
X  
X 
X 
X 
X 
X 
Immunogenicity sampling15 
 
 
X9 
 
 
 
 
X 
 
X 
X 
X 
X 
Restriction assessment 
X 
Prior and concomitant medication16 
X 
Adverse events17 
X 


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Abbreviations: BMI = body mass index; ECG = electrocardiogram; EOS = end-of-study; HBcAb = hepatitis B core antibody; HbsAg = hepatitis B surface antigen; HIV = human 
immunodeficiency virus; ICF = informed consent form; IV = intravenous; PK = pharmacokinetics; RPR = rapid plasma reagin; SARS-CoV-2 = severe acute respiratory syndrome 
coronavirus 2. 
1. 
If screening visit date and the admission date (Day -1) are same, all assessments scheduled for the screening and Day -1 visit will be performed only once on the date. 
2. 
End-of-study visit assessments will be performed on Day 90 (± 5 days). If a subject withdraws prematurely after study drug administration, the subject will be asked to return 
to the study center for the safety assessments predefined on EOS visit. If deemed necessary by the Investigator, the subject will be asked to return for the scheduled EOS visit. 
3. 
Inclusion and exclusion criteria will be confirmed at screening and will be rechecked on Day -1. 
4. 
Height will be measured only once at screening visit. BMI will be measured once at screening for eligibility check. 
5. 
Drug abuse testing includes drugs specified in Section 6.1.2.3. The urine test for drugs of abuse will be performed at screening and Day -1 visit. The urine test can be repeated 
once at the Investigator’s discretion. 
6. 
For female subjects with childbearing potential, a serum pregnancy test will be performed at screening and EOS visits, and urine pregnancy test will be performed on Day -1. 
Only subjects who are confirmed as nonpregnant by both serum pregnancy test at screening and urine pregnancy test on Day -1 can be enrolled in the study. A urine pregnancy 
test will be performed when there is any possibility of pregnancy, and a confirmatory serum pregnancy test will be performed if a urine pregnancy test result is positive or 
equivocal throughout the study. 
7. 
Viral serology test including HBsAg, HBcAb, hepatitis C antibody, RPR, and anti-HIV test must be assessed in all subjects (mandatory). If any of the test result is positive, the 
subject cannot be enrolled in the study. 
8. 
Chest X-ray will be performed at screening visit to collect baseline data. Additional chest X-ray assessments can be performed when the Investigator consider it is clinically 
necessary. 
9. 
These assessments should be performed on Day 1 prior to the study drug administration. 
10. Study drug will be administered as an IV infusion for 90 minutes (±15 minutes) on Day 1. When calculating total volume of study drug to be administered, the body weight of 
each subject measured on Day -1 will be used. 
11. Additional vital sign assessments will be evaluated for hypersensitivity monitoring purpose at the time point specified in Table 6-1. Any type of ECG will be performed if a 
subject experiences cardiac symptoms. Emergency equipment, such as adrenaline, antihistamines, corticosteroids, and respiratory support (inhalational therapy, oxygen and/or 
artificial ventilator) must be available. 
12. Hematology, clinical chemistry, and urinalysis will be performed and detail analyses are listed in Section 6.1.9. 
13. All scheduled 12-lead ECG assessments must be performed after the subject has rested quietly for at least 5 minutes in the supine position. Regardless of the 12-lead ECG result, 
further cardiological evaluation can be done at the Investigator’s discretion. 
14. Details of blood sampling time points and acceptable tolerance windows for PK assessments are described in Table 6-2. Analysis will be performed at the central laboratory. 
15. In addition to sampling time point specified, serum samples for immunogenicity testing may be collected if a subject experiences immune-related AEs. Analysis will be 
performed at the central laboratory. 
16. Prior and/or concomitant medication use will be recorded within 30 days before the signed date of ICF (inclusive of the applicable periods for prohibited medications as defined 
in Section 5.7) until the EOS visit. 
17. Adverse events will be assessed from the date the ICF is signed until up to EOS visit, regardless of the relationship to the study drug. 
18. If the scheduled SARS-CoV-2 infection test seemed unavailable on Day -1, it can be performed on Day -2 or Day -3 instead. 

SAP_001.pdf: 


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TABLE OF CONTENTS 
1. 
ADMINISTRATIVE STRUCTURE .......................................................................... 5 
2. 
INTRODUCTION........................................................................................................ 5 
3. 
STUDY OBJECTIVE .................................................................................................. 5 
3.1. 
Primary Objective .................................................................................................. 5 
3.2. 
Secondary Objectives............................................................................................. 6 
4. 
INVESTIGATIONAL PLAN ..................................................................................... 6 
4.1. 
Study Design and Plan ........................................................................................... 6 
5. 
GENERAL STATISTICAL CONSIDERATIONS .................................................. 7 
5.1. 
Software ................................................................................................................. 8 
5.2. 
Sample Size ............................................................................................................ 8 
5.3. 
Randomization, Stratification, and Blinding ......................................................... 9 
5.4. 
Analysis sets......................................................................................................... 10 
5.4.1. 
Intent-to-Treat (ITT) Set ................................................................................... 10 
5.4.2. 
Safety Set .......................................................................................................... 10 
5.4.3. 
Pharmacokinetic Set ......................................................................................... 10 
5.5. 
Definition of Baseline .......................................................................................... 10 
5.6. 
Protocol Deviations .............................................................................................. 10 
5.7. 
Outliers ................................................................................................................. 11 
6. 
SUBJECT DISPOSITION ........................................................................................ 11 
7. 
DEMOGRAPHICS, BASELINE, AND BACKGROUND 
CHARACTERISTICS ............................................................................................... 12 
7.1. 
Demographics ...................................................................................................... 12 
7.2. 
SARS-CoV-2 Infection Test ................................................................................ 12 
7.3. 
Viral Serology Test .............................................................................................. 13 
7.4. 
Urine Drug Test ................................................................................................... 13 
7.5. 
Chest X-ray .......................................................................................................... 13 
7.6. 
Medical History ................................................................................................... 13 
8. 
TREATMENTS AND MEDICATIONS .................................................................. 13 
8.1. 
Prior and Concomitant Medications .................................................................... 13 
8.2. 
Exposure to Study Drug ....................................................................................... 14 
8.3. 
Study Restriction Assessment .............................................................................. 14 
9. 
PHARMACOKINETIC ANALYSIS ....................................................................... 14 
9.1. 
Serum Concentrations .......................................................................................... 15 
9.2. 
Serum Pharmacokinetic Parameters .................................................................... 16 
10. 
SAFETY ANALYSIS................................................................................................. 17 
10.1. 
Adverse Events ................................................................................................. 17 
10.1.1. 
Incidence of Treatment-Emergent Adverse Events .......................................... 18 
10.1.2. 
Serious Adverse Events .................................................................................... 19 
10.1.3. 
Deaths ............................................................................................................... 19 


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10.1.4. 
Treatment-Emergent Adverse Events Leading to Discontinuation .................. 19 
10.1.5. 
Treatment-Emergent Adverse Events of Special Interest ................................. 19 
10.2. 
Clinical Laboratory Evaluations .......................................................................... 20 
10.3. 
Vital Signs and Weight ........................................................................................ 21 
10.4. 
Electrocardiogram ................................................................................................ 21 
10.5. 
Hypersensitivity Monitoring ................................................................................ 21 
10.6. 
Physical Examination........................................................................................... 22 
10.7. 
Pregnancy Test ..................................................................................................... 23 
10.8. 
Immunogenicity ................................................................................................... 23 
11. 
REFERENCE LIST ................................................................................................... 24 
12. 
APPENDIX ................................................................................................................. 25 
Appendix 1: Schedule of Assessments ................................................................................ 25 
Appendix 2: Tables, Listings, and Figures in the Initial Analysis (For first CSR) .............. 27 
Appendix 3: CTCAE v5.0 for Clinical Laboratory Test Results ......................................... 29 
 
 


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LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
%AUCext 
Percentage of AUC0-inf obtained by extrapolation 
ADA 
Anti-Drug Antibody 
AE 
Adverse Event 
ATC 
Anatomical Therapeutic Chemical 
AUC0-inf 
Area under the Concentration-Time Curve from Time zero to Infinity  
AUC0-last 
Area under the Concentration-Time Curve from time zero to the Last 
Quantifiable Concentration  
BLQ 
Below the Lower limit of Quantification 
BMI 
Body Mass Index  
AESI(s) 
Adverse Event(s) of Special Interest 
CI 
Confidence Interval 
CL 
total body clearance  
Cmax 
maximum serum concentration  
eCRF 
Electronic Case Report Form 
CSR 
Clinical Study Report 
CTCAE 
Common Terminology Criteria for Adverse Events 
%CV 
percent Coefficient of Variation 
DEC 
Dose Escalation Committee  
DRM 
Date Review Meeting 
DSMB 
Data and Safety Monitoring Board 
ECG 
electrocardiogram 
eCRF 
electronic Case Report Form 
EOS 
End-Of-Study  
GCP 
Good Clinical Practice 
HBsAg 
Hepatitis B Surface Antigen 
HBcAb 
Hepatitis B Core Antibody 
HIV 
Human Immunodeficiency Virus 
ICF  
Informed Consent Form 
ICH 
International Council for Harmonisation 
ITT 
Intent-to-treat 
IV 
intravenous  
LS 
Least Square 
NAb 
neutralizing antibody 
MedDRA 
Medical Dictionary for Regulatory Activities 
PK 
pharmacokinetic 
PT 
Preferred Term 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SARS‑CoV‑2 
Severe Acute Respiratory Syndrome Coronavirus 2 


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Abbreviation 
Definition 
SD 
Standard Deviation 
SOC 
System Organ Class 
t1/2 
Terminal half-life  
TEAE 
Treatment-emergent adverse event 
TEAESI 
Treatment-emergent adverse events of special interest 
TESAE 
Treatment-emergent serious adverse event 
TLF 
Table, Listing and Figure 
Tmax 
Time to Cmax 
Vz 
Volume of distribution during the elimination phase 
λz 
Terminal elimination rate constant 
WHO 
World Health Organization 
 
 


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1. ADMINISTRATIVE STRUCTURE 
This study is being conducted under the sponsorship of CELLTRION, Inc. (hereinafter referred 
to as “CELLTRION”). The clinical monitoring, medical writing, randomization and 
pharmacokinetic parameter calculation are being performed under contract with 
, in 
collaboration with CELLTRION. The bioanalytical lab analysis is being performed under 
contract with 
, in collaboration with CELLTRION. The data management and statistical 
analyses are being performed by CELLTRION. 
2. INTRODUCTION 
This Statistical Analysis Plan (SAP) defines the statistical methods to be used by CELLTRION 
Clinical Statistics team in the analysis and presentation of data from CELLTRION study 
number CT-P59 1.1, entitled as “A Phase 1, Randomized, Double-Blind, Placebo-controlled, 
Parallel-Group, Single Ascending Dose Study to Evaluate the Safety, Tolerability and 
Pharmacokinetics of CT-P59 in Healthy Subjects”. 
There are two clinical study reports (CSRs) planned for the following time points: 
 
First CSR: Data up to Day 14 of the last enrolled subject will be included, except for 
pharmacokinetic (PK) and immunogenicity data, which will include results up to Day 
7 of each subject. List of TLFs for the first CSR is presented in Appendix 2. 
 
Final CSR: All data after completion of the study 
If additional CSRs are required for regulatory or academic purposes, CSRs will be generated 
after the first database lock and unblinding process. 
This SAP covers all specified analyses and is based on the following documents: 
 
Study Protocol Version 1.3 – 03rd July 2020 
 
Unique Case Report Form Version 1.0 – 01st July 2020 
Table, Listing and Figure (TLF) mock shells will be provided as an addendum to this document. 
3. Study Objective 
Primary and secondary objectives are described as below. 
3.1. Primary Objective 
The primary objective is to evaluate the preliminary safety and tolerability of CT-P59 up to 
Day 14 of the last enrolled subject. 


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3.2. Secondary Objectives 
The secondary objectives are as follows: 
• 
To evaluate the PK of CT-P59 
• 
To evaluate additional safety of CT-P59 including immunogenicity 
4. INVESTIGATIONAL PLAN  
4.1. Study Design and Plan 
This study is a randomized, double-blind, placebo-controlled, parallel group, single ascending 
dose, Phase 1 study to evaluate the safety, tolerability and PK of CT-P59 in healthy subjects. 
Approximately 32 subjects in 4 cohorts are planned for enrollment and each cohort will consist 
of 8 subjects, 6 of whom will receive CT-P59 and 2 of whom will receive a placebo. In cohorts 
1 and 2, each cohort includes a sentinel group of 2 subjects and a remaining group of 6 subjects. 
In a sentinel group, 2 subjects will be randomized in a 1:1 ratio to receive CT-P59 or placebo. 
In a remaining group, 6 subjects will be randomized in a 5:1 ratio to receive CT-P59 or placebo. 
In cohorts 3 and 4, 8 subjects will be randomized in 3:1 ratio to receive CT-P59 or placebo. 
The study design overview is presented in Figure 1. 
Figure 1: Study Design Overview 
 
This study will be started with the lowest dose that will maximize safety and the dose levels 
will be escalated to the higher doses. In cohorts 1 and 2, the first study drug administration will 
be administered as intravenous (IV) infusion to each sentinel group. In cohorts 3 and 4, all 
subjects in each cohort will randomly receive study drug without group sequence. Dose 
Escalation Committee (DEC) will review all available safety data after an observation period 
of 48 hours and will decide whether to proceed dosing of remaining group and escalating dose 
to next cohort. If any safety concern including predefined stopping rule is raised under decision 


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of committee, the study will be temporarily stopped and Data and Safety Monitoring Board 
(DSMB) will review all available data and evaluate the relationship to CT-P59 of the event 
with unblinded manner and will make a decision on continuation of the study.  
This study consists of Screening period (Day -21 to Day -2), Admission (Day -1), Study period 
(Day 1 to prior to end-of-study visit), and end-of-study (EOS) visit (Day 90). The total duration 
of this study will be approximately 16 weeks for the individual subject. Subjects will sign the 
informed consent at screening visit and undergo procedures to determine eligibility. Eligible 
subjects will have admission visit on Day -1 and under go baseline assessments and recheck 
eligibility. If subjects are confirmed to be eligible, subjects will be randomized to receive a 
single dose of CT-P59 or placebo on Day 1. All subjects will be confined to the study center 
on Day -1 until completion of the 72-hour (Day 4) assessments after the study drug 
administration and confinement can be extended depending on subjects and study center’s 
availability up to Day 14. The subsequent study visits will be carried out on an out-patient basis. 
Subjects will return to the study center on Day 90 and undergo predefined End-of-Study (EOS) 
visit assessments. 
The schedule of assessments is presented in Appendix 1. 
 
5. GENERAL STATISTICAL CONSIDERATIONS 
Continuous data will be summarized using descriptive statistics: number of subjects (n), mean, 
standard deviation (SD), minimum, median and maximum, unless otherwise specified. The 
descriptive statistics will be calculated using raw data before rounding although rounded values 
are listed. The following rules will be followed with regards to the number of decimal places: 
 
Minimum and maximum will be presented to the same number of decimal places as 
reported. 
 
Mean, median, geometric mean and percent coefficient of variation (%CV) will be 
rounded to one more decimal place than the maximum decimal place of values in the 
source listing. 
 
SD will be rounded to one more decimal place than mean. 
 
Point estimate and confidence intervals (CI) obtained from statistical procedures will 
be displayed to two decimal places. 
Geometric mean will not be reported if the dataset includes zero values and %CV will not be 
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Categorical data will be summarized using frequency tables showing numbers and percentages 
of subjects. Percentages will be rounded to one decimal place and will be suppressed when the 
count is zero. The denominator for all percentages will be the number of subjects within each 
treatment group for the set of interest, unless otherwise specified. 
Unscheduled visit will not be summarized in visit-based tables, unless otherwise specified. 
However, all data will be displayed in listings. Unless otherwise specified, listings will be 
sorted by the treatment group, subject number and visit, if applicable. In cases where more 
ordering is required, other variables will be included in the sort order as applicable. 
When combining data from electronic Case Report Form (eCRF) and analytical facilities such 
as Central Laboratory for pharmacokinetics or immunogenicity, discrepancy will be handled 
as following: 
1) Recorded as sample collected in eCRF but no corresponding results from analytical 
facility – listing will display only sample collection visit/date from eCRF; 
2) No corresponding records in eCRF for results from analytical facility – listing will 
display only specimen collection visit/date and results from analytical facility; 
3) Discrepancy in sample collection date from eCRF and analytical facility – listing will 
display results from analytical facility and visit/date from eCRF if not missing; if 
sample collection date is missing in eCRF then use specimen collection visit/date from 
analytical facility. 
All available results from analytical facilities will be included in the summary table. 
This SAP could be updated after the Data Review Meeting (DRM) but prior to database hard 
lock to document any deviations. 
5.1. Software 
All statistical analyses will be conducted using 
 
 
 PK parameters will be computed by noncompartmental methods using appropriate 
validated software such as 
 
 
5.2. Sample Size 
The total sample size of 32 subjects is not based on a formal statistical hypothesis. A sample 
size justification based on statistical hypotheses is not relevant in this study. The proposed 
number of 8 subjects (6 subjects for CT-P59 and 2 subjects for placebo) in each cohort is set 
empirically based on sample sizes in other Phase 1 studies investigating the safety and 


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tolerability of their study drugs and is considered to be sufficient to achieve the objectives of 
the study. 
5.3. Randomization, Stratification, and Blinding 
On Day 1, eligible subjects will be randomly assigned to CT-P59 or placebo. In cohorts 1 and 
2, subjects will be randomized in a 1:1 ratio to receive CT-P59 or placebo in sentinel group 
and in a 5:1 ratio to receive CT-P59 or placebo in remaining group. In cohorts 3 and 4, 8 
subjects will be randomized in a 3:1 ratio to receive CT-P59 or placebo.  
Subjects who receive study drug and discontinue before the study completion will generally 
not be replaced. However, if a subject who receives study drug discontinues the study for a 
reason other than subject’s safety, additional subject can be recruited upon decision of DEC. If 
a subject who randomized but did not receive study drug decides to discontinue the study, this 
subject can be replaced.  
 will generate the randomization and kit schedules which contain the randomization and 
kit number, and corresponding treatment group using 
. The 
unblinded site pharmacist will use both the randomization and kit schedule provided by 
 
for treatment assignment. 
This study will be double-blind until the end of the study. The randomization codes will not be 
revealed to study subjects, investigator, and study center personnel, except for delegated 
unblinded site pharmacist who will handle the study drug and predefined unblinded teams in 
CELLTRION and 
 until all final data have been entered into the database and the 
database is locked and released for analysis. 
Under normal circumstances, the blind should not be broken. The blind should only be broken 
if specific emergency treatment would be dictated as knowing the study drug assignment is 
required for medical management. In such cases, the investigator may, in emergency, 
determine the identity of the study drug by using applicable procedure. The specified envelope, 
which contains randomization information, should be opened by principal investigator or its 
designee.  
The date, time, and reason for the unblinding must be documented in the “End of Study 
Participation” page of eCRF and the medical monitor will be informed as soon as possible. All 
unblinding events will be reported to the medical monitor and CELLTRION. Any subjects for 
whom the blind is broken may continue in the study at the investigator’s discretion. 
The overall randomization code will be broken only for reporting purposes. This will occur 
after database lock for data up to Day 14 of the last enrolled subject. The unblinded personnel 
will be predefined and documented before performing the analyses. 


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5.4. Analysis sets 
Analysis set and its definition are described in this section. The analysis set will be identified 
and included as a subtitle of each TLF. 
Subjects could be excluded from analysis set because of major protocol deviation described in 
Section 5.6. 
The following treatment groups will be used for analysis: CT-P59 10mg/kg, CT-P59 20mg/kg, 
CT-P59 40mg/kg, CT-P59 80mg/kg and Placebo. For placebo group, pooling of placebo 
subjects within each cohort is considered for analysis. 
For ITT set, subjects will be assigned to either “CT-P59 10mg/kg”, “CT-P59 20mg/kg”, “CT-
P59 40mg/kg”, “CT-P59 80 mg/kg” or Placebo treatment group according to the treatment they 
were randomized to. The PK and Safety sets will be analyzed according to actual treatment 
group. Subjects receiving at least one kit of CT-P59 will be assigned to the actual treatment 
group of CT-P59 of corresponding cohort, even if the subject is randomized to Placebo group. 
The number of subjects in all sets will be tabulated by the treatment group on ITT set. A listing 
will also be produced displaying data on ITT set. 
5.4.1. Intent-to-Treat (ITT) Set 
The ITT set is defined as all subjects enrolled and randomly assigned to receive a dose of either 
of the study drugs, regardless of whether or not any study drug dosing was completed.  
5.4.2. Safety Set 
The safety set will consist of all subjects who receive a full or partial dose of the study drugs.  
5.4.3. Pharmacokinetic Set 
The PK set will consist of all subjects who receive a full dose of CT-P59 and have at least 1 
evaluable post-treatment PK concentration result. 
5.5. Definition of Baseline 
The baseline value will be considered to be the last non-missing measurement before the study 
drug administration. Post-baseline values will be considered to be all measurements collected 
after the study drug administration. 
5.6. Protocol Deviations 
Protocol deviation will be categorized as “major” or “minor”. A major protocol deviation is 
one that may affect the interpretation of study results or the subject’s rights, safety or welfare, 


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and will be identified prior to study unblinding. Major protocol deviations include, but are not 
limited to, the following: 
 
Mis-randomization (defined as subjects who received treatment other than randomly 
assigned treatment) 
 
Non-adherence to Inclusion or Exclusion criteria (to be identified through review of 
data) 
 
Significant Good Clinical Practice (GCP) non-compliance 
A listing of major protocol deviations for each subject will be provided by treatment group for 
the ITT set. 
5.7. Outliers 
Any outliers that are detected during the review of the data will be investigated and discussed 
during the DRM. In general, outliers will not be excluded. 
6. SUBJECT DISPOSITION 
The number of subjects who were screened and failed at screening will be displayed along with 
the primary reason for screening failure based on the ‘Eligibility Criteria’ page of eCRF.  
The number and percentage of subjects who were randomized, initiated study treatment, 
discontinued from the study and completed the study will also be displayed for the ITT set by 
treatment group. 
Subject disposition will be defined as follows: 
• 
A subject will be considered to have failed the Screening if the subject was considered 
as not eligible to be enrolled in the study based on the ‘Eligibility Criteria’ page of 
eCRF. 
• 
A subject will be considered to be randomized if a randomization ID was allocated to 
the subject based on the ‘Randomization’ page of eCRF. 
• 
A subject will be considered to be initiated study if it is recorded that the subject was 
administered the study drug (‘Yes’ box checked) on the ‘Study Drug Administration’ 
page of eCRF. 
• 
A subject will be considered to have completed the study if it is recorded that the 
subject completed the study (‘Yes’ box checked) on the ‘End of Study Participation’ 
page of eCRF. 


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• 
A subject will be considered to have discontinued the study if it is recorded that the 
subject was discontinued from the study (‘No’ box checked) on the ‘End of Study 
Participation’ page of eCRF. 
The number and percentage of subjects who discontinued the study will be displayed by 
primary reason for discontinuation based on the “End of Study Participation” page of eCRF 
and treatment group. In addition, time on study prior to discontinuation will also be displayed 
using descriptive statistics, for those subjects who initiate the study treatment and discontinue 
for the ITT set. The study duration in days will be calculated as (study discontinuation date – 
study drug administration date +1). The study discontinuation date and study drug 
administration date will be taken as the date on the ‘End of Study Participation’ page and on 
the ‘Study Drug Administration’ page of eCRF, respectively. 
Subject randomization and subject disposition data will be listed in separate listings for the ITT 
set by treatment group. A listing of subjects reported as screening failures will also be provided. 
 
7. DEMOGRAPHICS, BASELINE, AND BACKGROUND CHARACTERISTICS 
7.1. Demographics 
The following demographic measures will be summarized for the ITT set: Age (years); Sex 
(Male, Female); Fertility Status (Pre-Menarche, Surgically Sterilized, Post-Menopausal, 
Potentially Able to Bear Children for female subject only); Race (White, Black or African 
American, American Indian or Alaska Native, Asian, Native Hawaiian or Other Pacific 
Islander, Not Allowed by Investigator Country Regulations, Other); Ethnicity (Hispanic or 
Latino, Non-Hispanic or Non-Latino, Unknown); Screening Height (cm), Day -1 Weight (kg) 
and Screening Body Mass Index (BMI) (kg/m2). 
Age will be automatically calculated in eCRF system based on the date of the informed consent 
day and the year of birth considering whether birth date has passed the informed consent date 
or not. 
Demographics will be presented for the ITT set by treatment group. 
7.2. SARS-CoV-2 Infection Test 
A Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection test will be 
performed at Screening and Day -1 visit to confirm a subject is not infected to SARS-CoV-2. 
Only subjects who are negative on both screening and Day -1 tests can be enrolled in the study. 
If the scheduled SARS-CoV-2 infection test seemed unavailable on Day -1, it can be performed 
on Day -2 or Day -3 instead. All SARS-CoV-2 infection test results will be listed for the ITT 
set by treatment group. 


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7.3. Viral Serology Test 
At Screening, the following assessments for serologic markers will be performed: 
 
Hepatitis B Surface Antigen (HBsAg) 
 
Hepatitis B Core Antibody (HBcAb) 
 
Hepatitis C Antibody 
 
Anti-Human Immunodeficiency Virus (HIV) 
 
Rapid Plasma Reagin 
If any of the test result is positive, the subject cannot be enrolled in the study. All viral serology 
test results will be listed for the ITT set by treatment group. 
7.4. Urine Drug Test 
A urine drug tests will be performed at screening and Day -1 visit. The screen for drug abuse 
includes methamphetamine, barbiturates, benzodiazepines, cocaine, tetrahydrocannabinol and 
opiates. The urine test can be repeated once at the discretion of the Investigator. All urine drug 
test results will be listed for the ITT set by treatment group. 
7.5. Chest X-ray 
A chest X-ray will be performed on screening visit for baseline data collection purposes. An 
additional assessment can be performed when the Investigator considers it is clinically 
necessary. Results for Chest X-ray will be classified as either “Normal”, “Abnormal, Not 
Clinically Significant” or “Abnormal, Clinically Significant”. All Chest X-ray data will be 
listed for the ITT set by treatment group. 
7.6. Medical History 
Medical history is captured at Screening and Day -1 visit, and will be coded using Medical 
Dictionary for Regulatory Activities (MedDRA Version 23.0 or the later version). Medical 
history will be summarized by treatment group, system organ class (SOC) and preferred term 
(PT) for the ITT set. Medical history will be listed for the ITT set by treatment group. 
8. TREATMENTS AND MEDICATIONS 
8.1. Prior and Concomitant Medications 
All medications used during the study, taken within 30 days before the subject signs the 
Informed Consent Form (ICF) until the EOS visit will be collected on the eCRF. All 
medications will be coded according to the World Health Organization drug dictionary (WHO 


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Drug Dictionary March 2020 or the later version). Medications will be classified as either prior 
or concomitant.  
A prior medication is defined as following, and all other medications will be defined as 
concomitant medication. 
 
A medication checked as “Yes” to “If stop date is unknown, was this drug stopped 
before the study drug administration (Day 1)?” on eCRF or    
 
A medication having actual stop date of medication before the date of study drug 
administration. 
The prior medications will be summarized by treatment group, drug class (using Anatomical 
Therapeutic Chemical [ATC] level 2), and PT along with the total number of prior medications 
and the number and percentage of subjects with at least one prior medication for the Safety set. 
The separate tables will be also generated for the concomitant medications by treatment group, 
drug class (using ATC level 2), and PT along with the total number of concomitant medications 
and the number and percentage of subjects with at least one concomitant medication for the 
Safety set. At each level of summarization, a subject is counted only once if the subject reported 
one or more medications at that level. When ATC Level 2 for drug class is not available, Level 
1 will be used instead. 
All prior and concomitant medications will be listed separately by treatment group for the 
Safety set. 
8.2. Exposure to Study Drug 
The number and percentage of subjects who received the study drug will be summarized by 
treatment group for the Safety set. The prescribed and actual administered dose (mg) of study 
drug will also be summarized using descriptive statistics. 
A listing will be provided by treatment group for the ITT set showing the details collected on 
the “Study Drug Administration” page of eCRF. 
8.3. Study Restriction Assessment 
Subjects who follow or not any of the study restriction will be listed for the Safety set by 
treatment group, visit and category. 
9. PHARMACOKINETIC ANALYSIS 
All PK analyses will be conducted on the PK set unless otherwise specified. 


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9.1. Serum Concentrations 
Blood samples for PK analyses will be collected from all subjects at the time points specified 
in PK Blood Sampling Time Points and acceptable tolerance windows (Table 1 ). If the PK 
blood sample is unable to be analyzed or is missing at certain time point, some blood samples 
collected for immunogenicity assessment at same time point can be used for PK assessment. 
 
Descriptive statistics (n, mean, SD, geometric mean, %CV, minimum, median, and maximum) 
for serum concentrations will be summarized by cohort of CT-P59 groups at each scheduled 
visit and time point. Individual serum concentrations, collection date/time, and deviations from 
scheduled time will be listed for the Safety set by cohort of CT-P59 groups, visit and time 
points. 
 
Below the lower limit of quantification (BLQ) prior to the study drug administration will be 
treated as zero (0), and all other BLQ values will be treated as to missing for serum PK 
concentrations and PK parameter estimation. Measurable concentrations after consecutive 
BLQs during the terminal phase will also be set to missing. 
 
The mean (±SD) serum concentration versus scheduled sample time profiles for the CT-P59 
will be presented graphically on both linear and semi-logarithmic scales by cohort of CT-P59 
groups. In addition, the spaghetti plot of serum concentrations versus scheduled sample time 
profiles will be presented graphically on both linear and semi-logarithmic scales by cohort of 
CT-P59 groups. 
 
Table 1 Blood Sampling Time Points for Pharmacokinetic Assessment 
The first CSR will present PK serum concentration results up to Day 7 of each subject. 
 
Day 
Time point 
Window 
Day 1 
Predose 
Predose within the day 
End of infusion 
+ 5 minutes 
1 hour after end of infusion 
± 15 minutes 
4 hour after end of infusion 
8 hour after end of infusion 
12 hour after end of infusion 
Day 2 
24 hour after start of infusion 
±1 hours 
Day 3 
48 hour after start of infusion 
Day 5 
96 hour after start of infusion 
±4 hours 
Day 7 
144 hour after start of infusion 
Day 10 
216 hour after start of infusion 
Day 14 
312 hour after start of infusion 
±1 day 
Day 28 
648 hour after start of infusion 
±3 days 
Day 56 
1,320 hour after start of infusion 
±5 days 
Day 90 
2,136 hour after start of infusion 


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9.2. Serum Pharmacokinetic Parameters 
The following serum PK parameters will be calculated by noncompartmental methods based 
on the actual sampling time points using 
 
. 
 
 
Pharmacokinetic parameters will be summarized by cohort of CT-P59 groups using descriptive 
statistics (n, mean, SD, geometric mean, %CV, minimum, median, and maximum values for 
all parameters).  
 
All data for the PK parameters will be listed by cohort of CT-P59 groups using the following 
rules: Cmax and Cmax/Dose will be presented to same level of precision as the PK concentration 
results, Tmax will be presented to 2 decimal places, and all other PK parameters will be 
presented to 3 significant digits. 
 
Scatter plots of individual values and geometric mean versus dose (mg/kg) will be presented 
for AUC0-inf, AUC0-last, Cmax, and the corresponding dose-normalized parameters. 
 
Dose proportionality of the PK parameters, AUC0-inf, AUC0-last, and Cmax, over the administered 
dose range (mg/kg) will be quantified using the following power model: 
Parameter 
Definition 
AUC0-inf 
Area under the serum concentration-time curve from time zero to infinity, calculated 
using the linear up and low down trapezoidal rule 
AUC0-inf/Dose 
Dose normalized AUC0-inf (normalized to total body dose and dose/body weight) 
AUC0-last 
Area under the serum concentration-time curve from time zero to the last quantifiable 
concentration, calculated using the linear up and log down trapezoidal rule 
AUC0-last/Dose 
Dose normalized AUC0-last (normalized to total body dose and dose/body weight) 
Cmax 
Maximum observed serum concentration 
Cmax/Dose 
Dose normalized Cmax (normalized to total body dose and dose/body weight) 
Tmax 
Time to Cmax 
t1/2 
Terminal elimination half-life, calculated as: 
t1/2 = ln2/λz   
%AUCext 
Percentage of the area extrapolated for calculation of AUC0-inf. 
λz 
Terminal elimination rate constant estimated from the linear regression of the natural 
log-transformed concentration over time at the terminal phase. At least 3 time points 
(excluding Cmax) and in general, adjusted correlation coefficient (r2) greater than or 
equal to 0.85 is needed to calculate and retain λz and its associated parameters (t1/2, 
AUC0-inf, AUC0-inf/Dose, CL, and Vz). Values of adjusted r2 less than 0.85 will be 
examined on a case-by-case basis for reliability to calculate and retain λz and its 
associated parameters (t1/2, AUC0-inf, AUC0-inf/Dose, CL, and Vz). Pharmacokinetic 
parameters that do not meet this criterion will be listed but not summarized 
CL 
Total body clearance, calculated as: 
CL = Dose/AUC0-inf  where Dose is the total body dose 
Vz 
Volume of distribution during the terminal phase, calculated as: 
Vz = (CL)/λz 


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log (parameter) = a + b * log (dose) 
 
 
where ‘a’ is the intercept and ‘b’ is the slope. 
The power model parameters (slope and intercept) along with the corresponding 90% CIs will 
be estimated using least-squares (LS) regression or an equivalent method, and will be presented 
in tabular format and graphically.   
 
The first CSR will present only Cmax and Tmax derived from serum concentration up to Day 7 
and scatter plots and dose proportionality assessment only for Cmax using 
 
. 
 
10. SAFETY ANALYSIS 
All Safety analyses will be conducted on the Safety set unless otherwise stated. 
10.1. 
Adverse Events 
An adverse event (AE) is defined as any untoward medical occurrence in any subject during 
the study which does not necessarily have a causal relationship with the study drug. Any new 
condition noted at Screening would be regarded as an AE, but not a treatment-emergent adverse 
event (TEAE). 
 
A TEAE includes any untoward medical occurrence in a subject after administration of a study 
drug, which does not necessarily have to have a causal relationship with this the study drug. A 
TEAE can therefore be any unfavorable and unintended sign (including an abnormal laboratory 
finding), symptom, or disease temporally associated with the use of the product, whether or not 
related to the study drug. 
 
All AEs will be collected from the date subjects signs ICF until EOS visit, and graded for 
intensity according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0, 
and coded to system organ class (SOC) and preferred term (PT) according to MedDRA Version 
23.0 or later 
 
If the stop date of an AE is incomplete or unknown, the following rules will be applied. 
 
 
Missing day (e.g. XXJUL2020): Assume the last day of the month. (e.g. 31JUL2020) 
 
 
Missing day and month (e.g. XXXXX2020): Assume December 31st. (e.g. 
31DEC2020) 
 
 
Missing day, month and year (e.g. XXXXXXXXX): Leave it as Missing. 
 
In case a subject dies during the study, the stop date will be imputed with the date of death if 
the imputed stop date is after the date of death. 
 
If the start date of an AE is incomplete or unknown, the following rules will be applied. If the 
stop date of the AE is incomplete, imputed stop date will be used instead of reported stop date. 
 


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 
If the day is missing (e.g. XXJUN2020), the month and year of the incomplete date 
will be compared to the date of the study drug administration.  
 
o If the month and year are equal for both dates, the AE start date will be imputed 
as the earlier of: (i) the date of study drug administration, and (ii) the end date of 
the AE. 
 
o If the month and year are not equal, the AE start date will be imputed as the first 
day of the month (e.g. 01JUN2020). 
 
 
If the day and month are missing (e.g. XXXXX2020), the year of the incomplete date 
will be compared to the date of the study drug administration. 
 
o If the years of both dates are equal, start date will be imputed as earlier date of: (i) 
the date of the study drug administration, and (ii) the end date of the AE. 
 
o If the year is not equal, start date will be imputed as the 1st of January of the 
incomplete date year (e.g. 01JAN2020).  
 
 
If the AE start date is missing (e.g. XXXXXXXXX), start date will be imputed as the 
earlier date of: (i) the date of the study drug administration, and (ii) the end date of the 
AE. 
 
All AEs recorded will be presented in a data listing. Listings for AEs will include the following 
information: SOC, PT and Verbatim term; start and stop date/time; Time to Occurrence 
[calculated as (AE start date – date of study drug administration +1)]; TEAE flag; intensity 
(CTCAE 
Grade 
1 
to 
5); 
outcome 
(recovered/resolved, 
recovering/resolving, 
recovered/resolved with sequelae, not recovered/not resolved, fatal, unknown); relationship 
with study drug (unrelated, possible, probable, definite); action taken with study drug (dose not 
changed, drug interrupted, drug withdrawn, not applicable); any treatment received (no, 
medication, non-medication treatment, both medication and non-medication treatment); 
whether the event was serious (yes, no); whether the AE is classified as Infusion Related 
Reactions (IRR) including Hypersensitivity and Anaphylactic Reactions (yes, no).  
 
In summaries, AEs will be considered to be related if the relationship is possible, probable, or 
definite. If relationship or intensity is missing, it will be summarized separately under a missing 
category. 
10.1.1. 
Incidence of Treatment-Emergent Adverse Events 
All TEAEs will be summarized by treatment group, SOC, PT, relationship and intensity, 
displaying the number and percentage of subjects with at least one TEAE using only the worst 
intensity recorded at each level of summarization. The total number of events and number of 
subjects with at least one TEAE over all SOCs will also be displayed. 
 


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10.1.2. 
Serious Adverse Events 
A serious adverse event (SAE) is defined as any event that results in death, is life threatening, 
requires inpatient hospitalization or prolongation of existing hospitalization, results in 
persistent or significant disability/incapacity, or is a congenital anomaly/birth defect. Important 
medical events that may not result in death, be life threatening, or require hospitalization may 
be considered an SAE when, based upon appropriate medical and scientific judgment, they 
may jeopardize the subject or may require medical or surgical intervention to prevent one of 
the outcomes listed in this definition. 
 
Treatment-emergent serious adverse events (TESAEs) will be summarized by treatment group, 
SOC, PT, relationship and intensity, displaying the number and percentage of subjects with at 
least one TESAE using only the most severe intensity recorded at each level of summarization. 
The total number of events and number of subjects with at least one TESAE over all SOCs will 
also be displayed. All SAEs will be listed including serious criteria, SAE description and 
additional information. 
10.1.3. 
Deaths 
Subjects who have a SAE with serious criteria of “Death” will be presented in a separate listing 
and the following variables will be included: date of study drug administration, date of last 
visit, date of death, time (days) to death from study drug administration, TEAE flag, SOC/PT, 
whether an autopsy was performed (yes, no), whether a death certificate was completed (yes, 
no) and relationship to study drug. Time to death from the study drug administration will be 
calculated as (date of death – date of study drug administration+1).  
10.1.4. 
Treatment-Emergent Adverse Events Leading to Discontinuation  
All subjects who have a TEAE with an action taken with study drug of “Drug Withdrawn” will 
be summarized by treatment group, SOC, PT, relationship and intensity, displaying the number 
and percentage of subjects with at least one TEAE leading to study drug discontinuation, using 
only the most severe TEAE recorded at each level of summarization. The total number of 
events and subjects with at least one TEAE which led to study drug discontinuation will also 
be displayed.   
10.1.5. 
Treatment-Emergent Adverse Events of Special Interest 
The AEs checked as ‘Yes’ to ‘Is Adverse event classified Infusion Related Reactions including 
Hypersensitivity and Anaphylactic Reactions?’ on the ‘Adverse Event’ page of eCRF will be 
classified as Infusion Related Reaction (IRR) including Hypersensitivity and Anaphylactic 
Reaction, and considered as adverse events of special interest (AESI) because AE is related to 
infusion related reactions (hypersensitivity/anaphylactic reactions). 
Treatment emergent adverse events of special interest (TEAESI) will be summarized by 
treatment group, SOC, PT, relationship and intensity, displaying number and percentage of 
subjects with at least one TEAESI using only the most severe TEAESI recorded at each levels 
of summarization. The total number of events and number of subjects with at least one TEAESI 
over all SOCs will also be displayed. Additionally, table for signs and symptoms of TEAESI 


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will be provided separately by SOC, PT and intensity. Experienced signs and symptoms of 
TEAESI will be presented in additional information listing for TEAESI. 
10.2. 
Clinical Laboratory Evaluations 
Blood and urine samples for clinical laboratory testing (hematology, clinical chemistry, and 
urinalysis) will be collected at each scheduled visit specified in Appendix 1. The analysis will 
be performed at the local laboratory. All summaries and listings will be based on the SI (System 
International) units. The following clinical laboratory assessments will be performed and only 
the parameters specified will be summarized and listed: 
Clinical 
chemistry: 
Total protein, total bilirubin, alanine aminotransferase, aspartate 
aminotransferase, alkaline phosphatase, blood urea nitrogen, creatinine, 
creatine kinase, creatine kinase-myocardial band isoenzyme, troponin I, 
albumin, sodium, potassium, total calcium, chloride, phosphorus, glucose, 
lactate dehydrogenase, total cholesterol, gamma-glutamyltransferase, 
estimated glomerular filtration rate (eGFR), uric acid and C-reactive 
protein 
 
(Direct bilirubin, troponin T, triglyceride and high-density lipoprotein 
cholesterol will be analyzed when the investigator consider it is clinically 
necessary) 
 
Hematology: 
Red blood cell count, white blood cell count, absolute neutrophil 
count, eosinophil count, lymphocyte count, monocyte count, basophil 
count, platelet, hemoglobin, mean corpuscular volume, mean 
corpuscular hemoglobin, mean corpuscular hemoglobin 
concentration, and hematocrit 
Urinalysis: 
Bilirubin, red blood cell, glucose, ketones, leukocytes, nitrite, pH, 
protein, specific gravity, urobilinogen, and microscopic examination 
of white blood cell count, red blood cell count, and bacteria 
 
Abnormal numeric clinical laboratory values will be flagged as either “High” or “Low” based 
on the reference ranges for each laboratory parameter. The investigator will determine whether 
any of the abnormal clinical laboratory values are clinically significant or not clinically 
significant. 
Some numeric parameters will be labeled with a CTCAE term, and grading will be applied to 
post-baseline values for numeric parameters where possible according to CTCAE version 5.0. 
Grades that require clinical input only will not be assigned to these parameters. Grades which 
are part numeric and part clinical input will be assigned based on the numeric portion only. If 
different grades share the same criteria due to exclusion of clinical input, lower grade will be 
used. The CTCAE terms and grades for applicable parameters are listed in Appendix 3. The 
CTCAE grades for this analysis will be Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (Severe) 
and Grade 4 (Life-threatening). The CTCAE Grade 5 (Death) will not be applied in this analysis 
since death cannot be determined from a numeric laboratory result. If the post-baseline result 
for a subject does not satisfy any CTCAE grade, it will be classified as “No Grade”. 


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Actual values and changes from baseline of numeric laboratory parameters except for direct 
bilirubin, troponin T, triglyceride and high-density lipoprotein cholesterol will be summarized 
by treatment group, parameter and scheduled visit using descriptive statistics in separate tables 
by laboratory category. All numeric values recorded BLQ or above the upper limit of 
qualification are set to the respective limit for all summaries. 
The number and percentage of subjects for clinical laboratory test results except for direct 
bilirubin, troponin T, triglyceride and high-density lipoprotein cholesterol will be summarized 
by treatment group, parameter and scheduled visit using {“Normal”, “Abnormal, Not 
Clinically Significant”, “Abnormal, Clinically Significant”} categories as appropriate, in 
separate tables by laboratory category in the form of a shift table to detect changes from 
baseline. 
 
The number and percentage of subjects with a result for each CTCAE grade will be summarized 
by treatment group, laboratory category, CTCAE term and scheduled visit. Additional tables 
will be generated using the most severe grade after study drug administration. The most severe 
grade will be selected including all post-baseline scheduled and unscheduled visits. 
All clinical laboratory test results of hematology, clinical chemistry, and urinalysis will be 
presented in separate listings by laboratory category. For values that are outside the normal 
range, high and low flags and clinical significance as evaluated by the investigator will be 
presented if applicable, and CTCAE results will also be presented for applicable parameters. 
10.3. 
Vital Signs and Weight 
Vital signs (systolic and diastolic blood pressures, heart rate, respiratory rate and body 
temperature) and weight measurements will be assessed at the each scheduled visit specified 
in Appendix 1. 
All vital signs will be summarized using descriptive statistics of actual value and change from 
baseline by treatment group and parameter at each scheduled visit. All vital signs data including 
weight, except for hypersensitivity monitoring results will be listed for each subject by 
treatment group, parameter and visit. 
10.4. 
Electrocardiogram 
12-lead Electrocardiograms (ECGs) will be performed at each scheduled visit specified in 
Appendix 1 and if the subject experienced cardiac symptoms during study drug administration. 
The investigator will interpret the 12-lead ECG and the findings of 12-lead ECG will be 
classified as either “Normal”, “Abnormal, Not Clinically Significant”, or “Abnormal, 
Clinically Significant”.  
The number and percentage of subjects will be summarized by treatment group and scheduled 
visit, in the form of a shift table to detect changes from baseline. All ECG data will be listed 
for each subject by treatment group and visit. 
10.5. 
Hypersensitivity Monitoring 
For hypersensitivity monitoring, additional vital signs measurements including systolic and 


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diastolic blood pressure, heart rate, respiratory rate and body temperature will be assessed at 
the following time points in Table 2. 
Table 2 Scheduled of Assessments for Hypersensitivity Monitoring 
Day 
Time points 
Window 
Day 1 
Predose (prior to dosing on Day 1) 
Within 30 minutes 
15 minutes from start of infusion 
± 5 minutes 
30 minutes from start of infusion 
60 minutes from start of infusion 
End of infusion 
2 hours from start of infusion 
± 15 minutes 
3 hours from start of infusion 
6 hours from start of infusion 
12 hours from start of infusion 
Day 2 
24 hours from start of infusion 
± 30 minutes 
The number and percentage of subjects who have clinically notable hypersensitivity result will 
be summarized in a table by treatment group, scheduled visit, time points and parameter. The 
criteria for clinically notable results are defined as follows: 
 
Parameter 
Low 
High 
Systolic blood pressure (mmHg) 
≤ 90 
≥ 160 
Diastolic blood pressure (mmHg) 
≤ 50 
≥ 90 
Heart rate (beats per minute) 
≤ 50 
≥ 100 
Respiratory rate (breaths per minute) 
≤ 12 
≥ 20 
Body temperature (oC) 
≤ 35.0 
≥ 38.0 
All vital signs data for hypersensitivity monitoring will be listed for each subject by treatment 
group, parameter and time point. High and low flags will be presented in the listing to show 
whether a hypersensitivity reaction result is outside of normal range. 
10.6. 
Physical Examination 
A physical examination will be performed on each scheduled visit specified in Appendix 1. 
The examination will include assessment of general appearance, head and neck, skin, 
cardiovascular, respiratory, abdominal, neurological, musculoskeletal and lymphatic systems. 
Findings of physical examination will be classified as either “Normal”, “Abnormal, Not 
Clinically Significant”, or “Abnormal, Clinically Significant”. 
The number and percentage of subjects will be summarized by treatment group, scheduled visit 
and category, in the form of a shift table to detect changes from baseline. All physical 
examination data will be listed for each subject by treatment group, category and visit. 


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10.7. 
Pregnancy Test 
Pregnancy tests consist of serum and urine pregnancy tests. Serum pregnancy tests will be 
performed at Screening and EOS, and urine pregnancy test will be performed on female 
subjects with childbearing potential on Day -1. The serum and urine pregnancy test samples 
will be analyzed at the local laboratory. The result of serum test will be either “Negative” or 
“Positive” and urine test will be “Negative”, “Positive” or “Equivocal”.  
The number and percentage of the results of serum and urine pregnancy test will be summarized 
by treatment group and scheduled visit. All pregnancy test results will be listed for each subject 
tested by treatment group and visit 
10.8. 
Immunogenicity 
The immunogenicity will be assessed by Anti-Drug Antibody (ADA) and neutralizing antibody 
(NAb) in validated immunoassay. Blood samples for immunogenicity assessment will be 
collected at each scheduled visit specified in Appendix 1. If the blood sample for 
immunogenicity is unable to be analyzed or is missing at certain time point, some blood 
samples collected for PK assessment at the same time point can be used for immunogenicity 
assessment. Additional samples for immunogenicity assessment may be collected if a subject 
experiences immune-related AEs. The analysis will be performed at the central laboratory. 
The ADA assay will follow a three-tiered approach consisting of (i) screening assay, (ii) 
confirmatory assay, and (iii) titration. Sample that are “Potential Positive” in the screening 
assay will undergo further test in the confirmatory assay to determine if subjects are true 
positive. The test outcome for the overall assay will be either “Positive” or “Negative”. For 
further characterization, the antibody level will be assessed by titration in confirmed positive 
samples. Samples that are positive in the ADA confirmatory assay will be analyzed further to 
conduct a NAb assessment. The test outcome for the screening NAb assay will be either 
“Positive” or “Negative”.  
The number and percentage of subjects for the results of the final ADA and the screening NAb 
assay will be summarized by treatment group and test at each scheduled visit. The descriptive 
statistics of ADA titration results for each treatment group will also be presented by scheduled 
visit. All immunogenicity data will be listed for each subject by treatment group, test and 
scheduled visit.  
The first CSR will present only results of ADA screening and confirmatory assay up to Day 7 
of each subject. 
 
 


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11. Reference List 
International Council for Harmonisation (ICH) Assembly. ICH E9: Statistical principles for 
clinical trials – Step 5. 01 September 1998. 
US Department of Health and Human Services. (2010). National Institutes of Health, 
National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE) 
version 5.0. Available from: http://evs.nci.nih.gov/ftp1/CTCAE/About.html 


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12. APPENDIX 
Appendix 1: Schedule of Assessments 
 
Screening1 
In-house stay 
Out-patient visit 
EOS2 
Study day 
-21 to -2 
-1 
1 
2 
3 
4 
5 
7 
10 
14 
28 
56 
90 
Visit window 
- 
 
 
 
 
 
- 
- 
- 
±1 
±3 
±5 
±5 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Demographic information 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion criteria3 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Weight and height4 
X 
X 
 
 
 
 
 
 
 
 
 
 
X 
Urine drug tests 5 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy test6 
X 
X 
 
 
 
 
 
 
 
 
 
 
X 
SARS-CoV-2 infection test 
X 
X18 
 
 
 
 
 
 
 
 
 
 
 
Viral serology test7 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Chest X-ray8 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Vital signs 
X 
X 
X9 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Randomization 
 
 
X9 
 
 
 
 
 
 
 
 
 
 
Study drug administration10 
 
 
X 
 
 
 
 
 
 
 
 
 
 
Hypersensitivity monitoring11 
 
 
X 
X 
 
 
 
 
 
 
 
 
 
Physical examination 
X 
X 
X9 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Clinical laboratory tests12 
X 
X 
 
X 
X 
 
 
X 
 
X 
X 
X 
X 
Twelve-lead electrocardiogram13 
X 
 
 
X 
 
 
 
X 
 
X 
X 
 
X 
Pharmacokinetic sampling14 
 
 
X 
X 
X 
 
X 
X  
X 
X 
X 
X 
X 
Immunogenicity sampling15 
 
 
X9 
 
 
 
 
X 
 
X 
X 
X 
X 
Restriction assessment 
X 
Prior and concomitant medication16 
X 
Adverse events17 
X 


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Abbreviations: BMI = body mass index; ECG = electrocardiogram; EOS = end-of-study; HBcAb = hepatitis B core antibody; HbsAg = hepatitis B surface antigen; HIV = human 
immunodeficiency virus; ICF = informed consent form; IV = intravenous; PK = pharmacokinetics; RPR = rapid plasma reagin; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 
2. 
1. 
If screening visit date and the admission date (Day -1) are same, all assessments scheduled for the screening and Day -1 visit will be performed only once on the date. 
2. 
End-of-study visit assessments will be performed on Day 90 (± 5 days). If a subject withdraws prematurely after study drug administration, the subject will be asked to return to the study 
center for the safety assessments predefined on EOS visit. If deemed necessary by the Investigator, the subject will be asked to return for the scheduled EOS visit. 
3. 
Inclusion and exclusion criteria will be confirmed at screening and will be rechecked on Day -1. 
4. 
Height will be measured only once at screening visit. BMI will be measured once at screening for eligibility check. 
5. 
Drug abuse testing includes drugs specified in Section 6.1.2.3 (in protocol V1.3). The urine test for drugs of abuse will be performed at screening and Day -1 visit. The urine test can be 
repeated once at the Investigator’s discretion. 
6. 
For female subjects with childbearing potential, a serum pregnancy test will be performed at screening and EOS visits, and urine pregnancy test will be performed on Day -1. Only subjects 
who are confirmed as nonpregnant by both serum pregnancy test at screening and urine pregnancy test on Day -1 can be enrolled in the study. A urine pregnancy test will be performed 
when there is any possibility of pregnancy, and a confirmatory serum pregnancy test will be performed if a urine pregnancy test result is positive or equivocal throughout the study. 
7. 
Viral serology test including HBsAg, HBcAb, hepatitis C antibody, RPR, and anti-HIV test must be assessed in all subjects (mandatory). If any of the test result is positive, the subject 
cannot be enrolled in the study. 
8. 
Chest X-ray will be performed at screening visit to collect baseline data. Additional chest X-ray assessments can be performed when the Investigator consider it is clinically necessary. 
9. 
These assessments should be performed on Day 1 prior to the study drug administration. 
10. Study drug will be administered as an IV infusion for 90 minutes (±15 minutes) on Day 1. When calculating total volume of study drug to be administered, the body weight of each subject 
measured on Day -1 will be used. 
11. Additional vital sign assessments will be evaluated for hypersensitivity monitoring purpose at the time point specified in Table 6-1 (in protocol V1.3). Any type of ECG will be performed 
if a subject experiences cardiac symptoms. Emergency equipment, such as adrenaline, antihistamines, corticosteroids, and respiratory support (inhalational therapy, oxygen and/or artificial 
ventilator) must be available. 
12. Hematology, clinical chemistry, and urinalysis will be performed and detail analyses are listed in Section 6.1.9 (in protocol V1.3). 
13. All scheduled 12-lead ECG assessments must be performed after the subject has rested quietly for at least 5 minutes in the supine position. Regardless of the 12-lead ECG result, further 
cardiological evaluation can be done at the Investigator’s discretion. 
14. Details of blood sampling time points and acceptable tolerance windows for PK assessments are described in Table 6-2 (in protocol V1.3). Analysis will be performed at the central 
laboratory. 
15. In addition to sampling time point specified, serum samples for immunogenicity testing may be collected if a subject experiences immune-related AEs. Analysis will be performed at the 
central laboratory. 
16. Prior and/or concomitant medication use will be recorded within 30 days before the signed date of ICF (inclusive of the applicable periods for prohibited medications as defined in Section 
5.7 (in protocol V1.3)) until the EOS visit. 
17. Adverse events will be assessed from the date the ICF is signed until up to EOS visit, regardless of the relationship to the study drug. 
18. If the scheduled SARS-CoV-2 infection test seemed unavailable on Day -1, it can be performed on Day -2 or Day -3 instead. 
 
 


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Appendix 2: Tables, Listings, and Figures in the Initial Analysis (For first CSR) 
Output Number 
Title 
Analysis set 
Listings: 
Listing 16.2.1.1 
Subject Disposition 
ITT set 
Listing 16.2.2.1 
Analysis Sets 
ITT set 
Listing 16.2.2.2 
Major Protocol Deviations 
ITT set 
Listing 16.2.2.3 
Screening Failures 
 
Listing 16.2.4.1 
Demographics 
ITT set 
Listing 16.2.4.6 
Medical History 
ITT set 
Listing 16.2.4.7 
Prior Medication 
Safety set 
Listing 16.2.4.8 
Concomitant Medication 
Safety set 
Listing 16.2.5.1 
Study Drug Administration 
Safety set 
Listing 16.2.6.1 
Individual Serum Concentration (Unit) 
Safety set 
Listing 16.2.6.2 
Individual Serum Pharmacokinetic Parameters 
PK set 
Listing 16.2.7.1 
Adverse Events 
Safety set 
Listing 14.3.2.1 
Deaths 
Safety set 
Listing 14.3.2.2 
Serious Adverse Events: Additional Information 
Safety set 
Listing 14.3.2.3 
Infusion Related Reaction including hypersensitivity/anaphylactic reactions: Additional 
Information 
Safety set 
Listing 16.2.8.1 
Hematology 
Safety set 
Listing 16.2.8.2 
Clinical Chemistry 
Safety set 
Listing 16.2.8.3 
Urinalysis 
Safety set 
Listing 16.2.9.1 
Vital Signs and Weight 
Safety set 
Listing 16.2.9.2 
Vital Signs for Hypersensitivity Monitoring 
Safety set 
Listing 16.2.9.3 
Electrocardiograms 
Safety set 
Listing 16.2.9.4 
Physical Examinations 
Safety set 
Listing 16.2.9.6 
Immunogenicity Results 
Safety set 
Tables: 
Table 14.1.1 
Summary of Subject Disposition 
ITT set 


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Table 14.1.2 
Analysis Sets 
ITT set 
Table 14.1.3 
Summary of Demographics 
ITT set 
Table 14.1.7 
Study Drug Administration 
Safety set 
Table 14.2.1.1 
Summary of Serum Concentration 
PK set 
Table 14.2.1.2 
Summary of Serum Pharmacokinetic Parameters 
PK set 
Table 14.2.1.3 
Statistical Analysis to Assess Dose Proportionality 
PK set 
Table 14.3.1.1 
Treatment-Emergent Adverse Events by Intensity 
Safety set 
Table 14.3.1.2 
Treatment-Emergent Serious Adverse Events by Intensity 
Safety set 
Table 14.3.1.4 
Treatment-Emergent Adverse Events classified as Infusion related reaction including 
hypersensitivity/anaphylactic reactions 
Safety set 
Table 14.3.1.5 
Signs and Symptoms of Treatment-Emergent Adverse Events Classified as Infusion 
Related Reaction including hypersensitivity/anaphylactic reactions 
Safety set 
Table 14.3.6.6 
Summary of Immunogenicity 
Safety set 
Figures: 
Figure 14.2.1.1 
Mean (+/- SD) Serum Concentration of CT-P59 (unit) 
PK set 
Figure 14.2.1.2 
Individual Serum Concentration of CT-P59 (unit) 
PK set 
Figure 14.2.1.3 
Scatter plot of PK Parameter versus Dose 
PK set 
 
 
 


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Appendix 3: CTCAE v5.0 for Clinical Laboratory Test Results 
CTCAE Term 
Laboratory Parameter 
Level 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Alanine aminotransferase 
increased 
Alanine 
Aminotransferase (ALT) 
High 
>ULN - 3.0 x ULN if 
baseline was normal; 
1.5 - 3.0 x baseline if 
baseline was 
abnormal 
>3.0 - 5.0 x ULN if 
baseline was normal; 
>3.0 - 5.0 x baseline 
if baseline was 
abnormal 
>5.0 - 20.0 x ULN if 
baseline was normal; 
>5.0 - 20.0 x baseline 
if baseline was 
abnormal 
>20.0 x ULN if 
baseline was normal; 
>20.0 x baseline if 
baseline was 
abnormal 
Hypoalbuminemia 
Albumin 
Low 
<LLN - 3 g/dL; 
<LLN - 30 g/L 
<3 - 2 g/dL; 
<30 - 20 g/L 
<2 g/dL; <20 g/L 
- 
Alkaline phosphatase increased 
Alkaline phosphatase 
(ALP) 
High 
>ULN - 2.5 x ULN if 
baseline was normal; 
2.0 - 2.5 x baseline if 
baseline was 
abnormal 
>2.5 - 5.0 x ULN if 
baseline was normal; 
>2.5 - 5.0 x baseline 
if baseline was 
abnormal 
>5.0 - 20.0 x ULN if 
baseline was normal; 
>5.0 - 20.0 x baseline 
if baseline was 
abnormal 
>20.0 x ULN if 
baseline was normal; 
>20.0 x baseline if 
baseline was 
abnormal 
Aspartate aminotransferase 
increased 
Aspartate 
Aminotransferase (AST) 
High 
>ULN - 3.0 x ULN if 
baseline was normal; 
1.5 - 3.0 x baseline if 
baseline was 
abnormal 
>3.0 - 5.0 x ULN if 
baseline was normal; 
>3.0 - 5.0 x baseline 
if baseline was 
abnormal 
>5.0 - 20.0 x ULN if 
baseline was normal; 
>5.0 - 20.0 x baseline 
if baseline was 
abnormal 
>20.0 x ULN if 
baseline was normal; 
>20.0 x baseline if 
baseline was 
abnormal 
Blood bilirubin increased 
Total Bilirubin 
High 
>ULN - 1.5 x ULN if 
baseline was normal; 
> 1.0 - 1.5 x baseline 
if baseline was 
abnormal 
>1.5 - 3.0 x ULN if 
baseline was normal; 
>1.5 - 3.0 x baseline 
if baseline was 
abnormal 
>3.0 - 10.0 x ULN if 
baseline was normal; 
>3.0 - 10.0 x baseline 
if baseline was 
abnormal 
>10.0 x ULN if 
baseline was normal; 
>10.0 x baseline if 
baseline was 
abnormal 
Leukocytosis 
White Blood Cells 
High 
- 
- 
>100,000/mm3 
- 
White blood cell decreased 
White Blood Cells 
Low 
<LLN - 3000/mm3; 
<LLN - 3.0 x 10e9 /L 
<3000 - 2000/mm3; 
<3.0 - 2.0 x 10e9 /L 
<2000 - 1000/mm3; 
<2.0 - 1.0 x 10e9 /L 
<1000/mm3; 
<1.0 x 10e9 /L 
Creatinine increased 1) 
Creatinine 
High 
>ULN - 1.5 x ULN 
>1.5 - 3.0 x baseline; 
>1.5 - 3.0 x ULN 
>3.0 x baseline; 
>3.0 - 6.0 x ULN 
>6.0 x ULN 
Eosinophilia 
Eosinophils (Absolute 
Ct) 
High 
>ULN and >Baseline 
- 
- 
- 
GGT increased 
Gamma Glutamyl 
Transferase (GGT) 
High 
>ULN - 2.5 x ULN if 
baseline was normal; 
2.0 - 2.5 x baseline if 
>2.5 - 5.0 x ULN if 
baseline was normal; 
>2.5 - 5.0 x baseline 
>5.0 - 20.0 x ULN if 
baseline was normal; 
>5.0 - 20.0 x baseline 
>20.0 x ULN if 
baseline was normal; 
>20.0 x baseline if 


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baseline was 
abnormal 
if baseline was 
abnormal 
if baseline was 
abnormal 
baseline was 
abnormal 
Hypercalcemia 
Calcium 
High 
Corrected serum 
calcium of >ULN - 
11.5 mg/dL; >ULN - 
2.9 mmol/L; @ 
Corrected serum 
calcium of >11.5 - 
12.5 mg/dL; >2.9 - 
3.1 mmol/L; @ 
Corrected serum 
calcium of >12.5 - 
13.5 mg/dL; >3.1 - 
3.4 mmol/L; @ 
Corrected serum 
calcium of >13.5 
mg/dL; >3.4 mmol/L; 
@ 
Hypocalcemia 
Calcium 
Low 
Corrected serum 
calcium of <LLN – 
8.0 mg/dL; <LLN - 
2.0 mmol/L; @ 
Corrected serum 
calcium of <8.0 – 7.0 
mg/dL; <2.0 – 1.75 
mmol/L; @ 
Corrected serum 
calcium of <7.0 – 6.0 
mg/dL; <1.75 – 1.5 
mmol/L; @ 
Corrected serum 
calcium of <6.0 
mg/dL; <1.5 mmol/L; 
@ 
Hypoglycemia 
Glucose 
Low 
<LLN - 55 mg/dL; 
<LLN - 3.0 mmol/L 
<55 – 40 mg/dL; 
<3.0 – 2.2 mmol/L 
<40 – 30 mg/dL; 
<2.2 – 1.7 mmol/L 
<30 mg/dL;  
<1.7 mmol/L 
Anemia 
Hemoglobin 
Low 
<LLN - 10.0 g/dL; 
<LLN – 6.2 mmol/L; 
<LLN - 100 g/L 
<10.0 - 8.0 g/dL; 
<6.2 - 4.9 mmol/L; 
<100 – 80 g/L 
<8.0 g/dL;  
<4.9 mmol/L; 
<80 g/L 
- 
Hemoglobin increased 
Hemoglobin 
High 
Increase in >0 – 2 
g/dL from ULN or 
above baseline if 
baseline is above 
ULN 
Increase in >2 - 4 
g/dL from ULN or 
above baseline if 
baseline is above 
ULN 
Increase in >4 g/dL 
from ULN or above 
baseline if baseline is 
above ULN 
- 
Blood lactate dehydrogenase 
increased 
Lactate Dehydrogenase 
(LDH) 
High 
>ULN 
- 
- 
- 
Lymphocyte count decreased 
WBC Differential, 
Lymphocytes 
Low 
<LLN - 800/mm3; 
<LLN - 0.8 x 10e9/L 
<800 - 500/mm3; 
<0.8 - 0.5 x 10e9 /L 
<500 - 200/mm3; 
<0.5 - 0.2 x 10e9 /L 
<200/mm3; 
<0.2 x 10e9 /L 
Lymphocyte count increased 
WBC Differential, 
Lymphocytes 
High 
- 
>4000/mm3 - 
20,000/mm3 
>20,000/mm3 
- 
Platelet count decreased 
Platelet count 
Low 
<LLN - 75,000/mm3; 
<LLN - 75.0 x 10e9 /L 
<75,000-50,000/mm3; 
<75.0 - 50.0 x 10e9 /L 
<50,000-25,000/mm3; 
<50.0 - 25.0 x 10e9 /L 
<25,000/mm3; 
<25.0 x 10e9 /L 
Hyperkalemia 
Potassium 
High 
>ULN - 5.5 mmol/L 
>5.5 - 6.0 mmol/L 
>6.0 - 7.0 mmol/L 
>7.0 mmol/L 
Hypokalemia 
Potassium 
Low 
<LLN - 3.0 mmol/L 
 
<3.0 - 2.5 mmol/L 
<2.5 mmol/L 
Hypernatremia 
Sodium 
High 
>ULN - 150 mmol/L 
>150 - 155 mmol/L 
>155 - 160 mmol/L; 
>160 mmol/L 
Hyponatremia 
Sodium 
Low 
<LLN - 130 mmol/L 
125-129 mmol/L 
120-124 mmol/L 
regardless of 
symptoms 
<120 mmol/L 


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Cholesterol high 
Total Cholesterol 
High 
>ULN - 300 mg/dL; 
>ULN - 7.75 mmol/L 
>300 - 400 mg/dL; 
>7.75 - 10.34 mmol/L 
>400 - 500 mg/dL; 
>10.34 - 12.92 
mmol/L 
>500 mg/dL; 
>12.92 mmol/L 
Neutrophil count decreased 
WBC Differential, 
Neutrophils 
Low 
<LLN - 1500/mm3; 
<LLN - 1.5 x 10e9 /L 
<1500 - 1000/mm3; 
<1.5 - 1.0 x 10e9 /L 
<1000 - 500/mm3; 
<1.0 - 0.5 x 10e9 /L 
<500/mm3; 
<0.5 x 10e9 /L 
Hypertriglyceridemia 
Triglyceride 
High 
150 mg/dL - 300 
mg/dL; 
1.71 mmol/L - 3.42 
mmol/L 
>300 mg/dL - 500 
mg/dL; 
>3.42 mmol/L - 5.7 
mmol/L 
>500 mg/dL - 1000 
mg/dL;  
>5.7 mmol/L - 11.4 
mmol/L 
>1000 mg/dL;  
>11.4 mmol/L 
 
LLN = lower limit of normal, ULN = upper limit of normal. 
1) The most severe grade is counted if the CTCAE grade is discrepant by multiple definitions. 
Note: In case both clinical input and numeric value for grading can be used for grading (e.g. Hypokalemia), CTCAE grade which includes numeric value 
will only be applied, because abnormal laboratory value with clinical input was reported as an adverse event and graded accordingly.  
@ indicates that calcium (mg/dL) = measured total calcium (mg/dL) + 0.8 (4.0 – serum albumin [g/dL]), where 4.0 represents the average albumin level.