A Randomized, Active-Controlled, Double-Blind, Phase 3 Study to Compare Efficacy and Safety of Two Intravenous Infusion Formulations of Tocilizumab (CT-P47 and RoActemra) When Co-administered With Methotrexate in Patients With Rheumatoid Arthritis
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Sponsor: Celltrion

CLINICAL STUDY PROTOCOL 
 
A Randomized, Active-Controlled, Double-Blind, Phase 3 Study to 
Compare Efficacy and Safety of Two Intravenous Infusion Formulations 
of Tocilizumab (CT-P47 and RoActemra) when Co-administered with 
Methotrexate in Patients with Moderate to Severe Active Rheumatoid 
Arthritis 
Protocol Number CT-P47 3.1 
EudraCT Number:  
 
2022-001066-36 
Sponsor: 
CELLTRION, Inc. 
23, Academy-ro, 
Yeonsu-Gu, Incheon, 22014, South Korea 
Phone: +82 32 850 5000 
Fax: +82 32 850 5050 
E-mail: contact@celltrion.com 
Sponsor Contact: 
  
 
 
SAE Reporting: 
EastHORN Clinical Services 
Panska 73 Str./804 00-834 Warsaw, Poland 
SAE email: safety.22101@easthorn.eu 
Protocol Version and Date:  
Version 1.1, including country specific A.0, 07 July 
2022  
 
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 guideline E6(R2): Good Clinical Practice with 
the Declaration of Helsinki (WMA 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. 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Declaration of Investigator 
I have read and understood all sections of the protocol entitled “A Randomized, Active-
Controlled, Double-Blind, Phase 3 Study to Compare Efficacy and Safety of Two 
Intravenous Infusion Formulations of Tocilizumab (CT-P47 and RoActemra) when Co-
administered with Methotrexate in Patients with Moderate to Severe Active Rheumatoid 
Arthritis” and the accompanying investigator’s brochure. 
I agree to supervise all aspects of the protocol and to conduct the clinical investigation in 
accordance with the Protocol Version 1.1, including country specific A.0, dated 07 July 
2022, the International Council for Harmonisation harmonised guideline E6(R2): Good 
Clinical Practice 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 approval except to eliminate an immediate risk to 
patients. I agree to administer study drug only to patients under my personal supervision 
or the supervision of a sub-investigator. 
I will not supply the investigational drug to any person not authorized to receive it. 
Confidentiality will be protected. Patient 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 
 
 
 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 4 
Table of Contents 
Protocol Approval .............................................................................................................. 2 
Declaration of Investigator................................................................................................ 3 
Table of Contents ............................................................................................................... 4 
List of Tables ....................................................................................................................... 9 
List of Figures ..................................................................................................................... 9 
Protocol Synopsis ............................................................................................................. 10 
List of Abbreviations ........................................................................................................ 18 
1 
Introduction .............................................................................................................. 21 
1.1 
Background ...................................................................................................... 21 
1.2 
CT-P47 ............................................................................................................. 22 
1.3 
Pre-clinical Studies .......................................................................................... 22 
1.4 
Clinical Studies ................................................................................................ 22 
1.5 
Study Rationale ................................................................................................ 24 
1.6 
Benefit and Risk Assessment ........................................................................... 25 
1.6.1 Risk Assessment During COVID-19 Pandemic .................................. 26 
1.6.1.1 
Benefit and Risk Assessment on Study Population ............. 26 
1.6.1.2 
Mitigation Plans ................................................................... 26 
2 
Study Objectives ....................................................................................................... 30 
2.1 
Primary Objective ............................................................................................ 30 
2.2 
Secondary Objective ........................................................................................ 30 
3 
Investigational Plan .................................................................................................. 31 
3.1 
Study Design .................................................................................................... 31 
3.1.1 Screening Period .................................................................................. 32 
3.1.2 Treatment Periods ................................................................................ 32 
3.1.3 End-of-Study Visit ............................................................................... 32 
4 
Patient Selection and Withdrawal Criteria ............................................................ 33 
4.1 
Selection of Study Population .......................................................................... 33 
4.1.1 Inclusion Criteria ................................................................................. 33 
4.1.2 Exclusion Criteria ................................................................................ 35 
4.2 
Study Drug Discontinuation and Study Termination ....................................... 39 
4.2.1 Recruitment of Additional Patients ...................................................... 40 
4.3 
Premature Termination of the Study ................................................................ 40 
5 
Study Treatment ....................................................................................................... 42 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 5 
5.1 
Method of Assigning Patients to Treatment Groups ........................................ 42 
5.2 
Treatments Administered ................................................................................. 42 
5.2.1 Co-administration of Methotrexate and Folic Acid ............................. 43 
5.2.2 Dosage Modification and Treatment Interruption or Discontinuation . 43 
5.2.2.1 
Elevated Liver Enzyme (ALT and/or AST) ......................... 43 
5.2.2.2 
Low Absolute Neutrophil count ........................................... 44 
5.2.2.3 
Low Platelet Count .............................................................. 44 
5.3 
Identity of Investigational Product................................................................... 44 
5.4 
Management of Clinical Supplies .................................................................... 45 
5.4.1 Study Drug Packaging, Labelling, and Storage ................................... 45 
5.4.2 Study Drug Accountability .................................................................. 45 
5.5 
Blinding............................................................................................................ 46 
5.5.1 Breaking the Blind ............................................................................... 46 
5.6 
Treatment Compliance ..................................................................................... 47 
5.7 
Prior, Concomitant, and Subsequent Therapy .................................................. 47 
5.8 
Rescue Therapy ................................................................................................ 48 
5.9 
Prohibited Therapy ........................................................................................... 49 
6 
Study Assessments and Procedures ........................................................................ 50 
6.1 
Demographics, Baseline, and Background Characteristics ............................. 50 
6.2 
Efficacy Assessments ....................................................................................... 50 
6.2.1 Joint Count Assessment ....................................................................... 50 
6.2.2 Disease Activity Score Using 28 Joint Counts .................................... 51 
6.2.3 American College of Rheumatology Criteria and Individual 
Components ......................................................................................... 51 
6.2.4 Simplified Disease Activity Index and Clinical Disease Activity Index
.............................................................................................................. 52 
6.2.5 ACR/EULAR remission (Boolean-based definition) .......................... 52 
6.2.6 Quality of Life...................................................................................... 52 
6.2.7 Joint Damage Progression.................................................................... 52 
6.3 
Pharmacokinetic Assessments ......................................................................... 53 
6.4 
Safety Assessments .......................................................................................... 53 
6.4.1 Adverse Events .................................................................................... 53 
6.4.1.1 
Definitions of Adverse Events ............................................. 53 
6.4.1.1.1 
Adverse Events of Special Interest .................. 54 
6.4.1.1.2 
Serious Adverse Events.................................... 54 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 6 
6.4.1.1.3 
Suspected Unexpected Serious Adverse 
Reactions .......................................................... 56 
6.4.1.2 
Eliciting and Documenting Adverse Events ........................ 56 
6.4.1.3 
Reporting Adverse Events.................................................... 56 
6.4.1.4 
Reporting Serious Adverse Events ....................................... 57 
6.4.1.5 
Assessment of Severity ........................................................ 58 
6.4.1.6 
Assessment of Causality ...................................................... 58 
6.4.1.7 
Follow-Up of Patients Reporting Adverse Events ............... 59 
6.4.2 Clinical Laboratory Testing ................................................................. 59 
6.4.2.1 
Hepatitis B and Hepatitis C and Human Immunodeficiency 
Virus ..................................................................................... 60 
6.4.3 Other Safety Assessment...................................................................... 61 
6.4.3.1 
Immunogenicity Testing ...................................................... 61 
6.4.3.2 
Hypersensitivity Monitoring ................................................ 62 
6.4.3.3 
Vital Signs and Weight ......................................................... 63 
6.4.3.4 
Physical Examination........................................................... 63 
6.4.3.5 
Pregnancy ............................................................................. 64 
6.4.3.6 
Electrocardiogram ................................................................ 64 
6.4.3.7 
Tuberculosis Assessment ..................................................... 65 
6.4.3.7.1 
Chest X-Ray ..................................................... 66 
6.4.3.7.2 
Interferon- γ Release Assay ............................. 66 
6.5 
Sample Collections .......................................................................................... 66 
6.6 
Sample Labelling, Storage, and Shipment ....................................................... 66 
6.6.1 Sample Labelling ................................................................................. 66 
6.6.2 Sample Storage and Shipment ............................................................. 67 
7 
Statistical Considerations ........................................................................................ 68 
7.1 
Sample Size Calculation .................................................................................. 68 
7.2 
Analysis Sets .................................................................................................... 68 
7.3 
Demographics, Baseline, and Background Characteristics ............................. 69 
7.4 
Efficacy Analyses ............................................................................................. 69 
7.4.1 Primary Efficacy Analysis ................................................................... 69 
7.4.1.1 
DAS28 (ESR)....................................................................... 70 
7.4.1.2 
Sensitivity Analysis for Primary Efficacy Endpoint ............ 71 
7.4.2 Secondary Efficacy Analysis ............................................................... 71 
7.4.2.1 
ACR20, ACR50, ACR70 and Individual Components ........ 72 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 7 
7.4.2.1.1 
Health Assessment Questionnaire Disability 
Index ................................................................ 72 
7.4.2.2 
Hybrid ACR Response ......................................................... 73 
7.4.2.3 
DAS28 (CRP) ...................................................................... 73 
7.4.2.4 
EULAR Response Criteria ................................................... 74 
7.4.2.5 
Simplified Disease Activity Index and Clinical Disease 
Activity Index ...................................................................... 74 
7.4.2.6 
ACR/EULAR remission (Boolean-based definition) .......... 75 
7.4.2.7 
Short-Form Health Survey ................................................... 75 
7.4.2.8 
Joint Damage Progression.................................................... 75 
7.5 
Pharmacokinetic Analyses ............................................................................... 76 
7.6 
Safety Analyses ................................................................................................ 76 
7.6.1 Adverse Events .................................................................................... 76 
7.6.2 Clinical Laboratory Tests ..................................................................... 77 
7.6.3 Immunogenicity ................................................................................... 77 
7.6.4 Prior and Concomitant Medications .................................................... 77 
7.6.5 Other Safety Analyses .......................................................................... 77 
7.7 
Interim Analyses .............................................................................................. 78 
7.8 
Data Quality Assurance.................................................................................... 78 
8 
Investigator’s Obligations ........................................................................................ 79 
8.1 
Confidentiality ................................................................................................. 79 
8.2 
Independent Ethics Committee ........................................................................ 79 
8.3 
Patient Information and Consent ..................................................................... 80 
8.4 
Study Reporting Requirements ........................................................................ 81 
8.5 
Financial Disclosure and Obligations .............................................................. 81 
8.6 
Investigator Documentation ............................................................................. 81 
8.7 
Study Conduct .................................................................................................. 82 
8.8 
Data Collection ................................................................................................ 83 
8.8.1 Electronic Case Report Forms and Source Documents ....................... 83 
8.9 
Adherence to Protocol...................................................................................... 83 
8.10 Investigator’s Final Report .............................................................................. 83 
8.11 Records Retention ............................................................................................ 83 
8.12 Publications ...................................................................................................... 84 
9 
Study Management................................................................................................... 85 
9.1 
Sponsor ............................................................................................................ 85 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 8 
9.2 
Vendor Contact................................................................................................. 85 
9.3 
Analytical Facilities ......................................................................................... 85 
9.4 
Monitoring ....................................................................................................... 86 
9.4.1 Independent Data Monitoring Committee ........................................... 86 
9.4.2 Monitoring of the Study ....................................................................... 86 
9.4.3 Inspection of Records .......................................................................... 86 
9.5 
Management of Protocol Amendments and Deviations................................... 87 
9.5.1 Modification of the Protocol ................................................................ 87 
9.5.2 Protocol Deviations .............................................................................. 87 
9.6 
Study Termination ............................................................................................ 88 
9.7 
Clinical Study Report ....................................................................................... 88 
10 Reference List ........................................................................................................... 89 
11 Appendices ................................................................................................................ 93 
11.1 Schedule of Event ............................................................................................ 93 
11.2 ACR Revised Criteria for Classification of Functional Status in RA .............. 98 
11.3 VAS Patient’s Global Assessment of Disease Activity .................................... 98 
11.4 VAS Physician Global Assessment of Disease Activity .................................. 99 
11.5 VAS Patient’s Assessment of Pain ................................................................... 99 
11.6 Health Assessment Questionnaire and Scoring of the Health Assessment 
Questionnaire ................................................................................................. 100 
11.7 General Health Status (Medical Outcomes Study Short-Form Health Survey)
........................................................................................................................ 102 
11.8 DAS28............................................................................................................ 105 
 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 9 
List of Tables 
Table 6-1 
Eligibility based on Serologic Markers for Hepatitis B Infection ............. 61 
Table 7-1 
Scoring Method for the Hybrid ACR ......................................................... 73 
Table 7-2 
EULAR Response Criteria ......................................................................... 74 
Table 7-3 
Calculation of Disease Activity Indices ..................................................... 74 
Table 11-1 
Schedule of Events ..................................................................................... 94 
 
List of Figures 
Figure 3-1 
Study Design Overview ............................................................................. 31 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 10 
Protocol Synopsis 
Protocol Number: CT-P47 3.1 
Title: A Randomized, Active-Controlled, Double-Blind, Phase 3 Study to Compare Efficacy and Safety 
of Two Intravenous Infusion Formulations of Tocilizumab (CT-P47 and RoActemra) when Co-
administered with Methotrexate in Patients with Moderate to Severe Active Rheumatoid Arthritis 
Study Phase: Phase 3 
Study Centers: Approximately 22 study centers in Poland 
Test Drug, Dose and Regimen: CT-P47, 8 mg/kg (not exceeding 800 mg/dose) by intravenous (IV) 
infusion every 4 weeks (Q4W), co-administered with methotrexate (MTX) between 10 to 25 mg/week, 
oral or parenteral dose (dose and route must be maintained from the beginning to the end of the study) 
and folic acid (≥5 mg/week, oral dose) 
Reference Drug, Dose and Regimen: EU-approved RoActemra, 8 mg/kg (not exceeding 800 mg/dose) 
by IV infusion Q4W, co-administered with MTX between 10 to 25 mg/week, oral or parenteral dose 
(dose and route must be maintained from the beginning to the end of the study) and folic acid (≥5 
mg/week, oral dose) 
Objectives: 
Primary Objective 
• 
To demonstrate that CT-P47 is equivalent to RoActemra, in terms of efficacy as determined by 
clinical response according to the change from baseline in disease activity measured by Disease 
Activity Score using 28 joint counts (DAS28) (Erythrocyte-Sedimentation Rate [ESR]) at 
Week 24. 
Secondary Objective 
• 
To evaluate additional efficacy, pharmacokinetics (PK), and overall safety, including 
immunogenicity. 
Main selection criteria: Male or female patient with moderate to severe active rheumatoid arthritis 
(RA) diagnosed according to the 2010 American College of Rheumatology (ACR)/European Alliance of 
Associations for Rheumatology (EULAR) classification criteria (Aletaha et al., 2010) for at least 24 
weeks, who have inadequate response to one or more disease-modifying antirheumatic drugs 
(DMARDs), will be considered for enrollment in the study if they meet all of the inclusion criteria and 
none of the exclusion criteria. 
Inclusion Criteria: 
Each patient must meet all of the following criteria to be enrolled in this study: 
1. Patient is male or female aged 18 to 75 years old, both inclusive. 
2. Patient has had a diagnosis of RA according to the 2010 ACR/EULAR classification criteria 
(Aletaha et al., 2010) for at least 24 weeks prior to the first administration of the study drug (Day 1). 
3. Patient must have moderate to severe disease activity as defined by all of the following at Screening: 
• 
6 or more swollen joints (of 66 assessed)  
• 
6 or more tender joints (of 68 assessed)  
• 
either an ESR ≥28 mm/hour or a serum C-reactive protein (CRP) concentration ≥1.0 mg/dL 
(≥10 mg/L) 
• 
DAS28 (ESR or CRP) ≥3.2 
4. Patient who has been receiving oral or parenteral MTX for at least 12 weeks and who has been on a 
stable dose and route of MTX between 10 to 25 mg/week for at least 8 weeks prior to the first 
administration of the study drug (Day 1). 
5. Patient has adequate renal and hepatic function at Screening as defined by the following clinical 
chemistry results: 
• 
Serum creatinine ≤1.5 × upper limit of normal (ULN) or an estimated creatinine clearance level 
>50 mL/min (by Cockcroft-Gault formula) (SI [Système International d'Unités] units: 
0.84 mL/s) 
• 
Serum alanine aminotransferase ≤2.0 × ULN 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 11 
• 
Serum aspartate aminotransferase ≤2.0 × ULN 
• 
Serum total bilirubin ≤1.5 × ULN 
6. Patient has the following hematology laboratory test results at Screening: 
• 
Absolute neutrophil count ≥2,000/mm3 (2.0×103/µL) 
• 
Platelet count ≥100,000/mm3 (100.0×103/µL) 
7. Patient and their partner of childbearing potential must agree to use following highly effective 
method of contraception consistent with local regulations throughout the study and for 6 months 
after the last dose of assigned treatment. A man or woman is of childbearing potential if, in the 
opinion of the investigator, he or she is biologically capable of having children and is sexually active 
(i.e., a man is fertile after puberty unless permanently sterile by bilateral orchidectomy or a woman 
is fertile, following menarche and until becoming postmenopausal unless permanently sterile). 
 
Combined (estrogen and progestogen containing) or progestogen-only hormonal contraceptives 
associated with inhibition of ovulation 
 
Intrauterine device or system  
 
True abstinence, when this is in line with the preferred and usual lifestyle of the patient. 
Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), 
declaration of abstinence for the duration of exposure to investigational drug, and withdrawal 
are not acceptable methods of contraception. 
 
Double contraceptive methods (e.g., male condom in addition to use of hormonal or barrier 
method in female); for male patient with his female partner of childbearing potential only. 
If patient or their partner has been surgically sterilized for less than 24 weeks prior to the date of 
informed consent, they must agree to use any medically acceptable methods of contraception. 
Postmenopausal females must have experienced their last menstrual period more than 1 year prior to 
the date of informed consent without an alternative medical cause to be classified as not of 
childbearing potential. 
8. Patient (or legal guardian, if applicable) is informed of the full nature and purpose of the study, 
including possible risks and side effects, has the ability to cooperate with the investigator and is 
given ample time and opportunity to read and understand verbal and/or written instructions, and 
signs the written informed consent form with date prior to participation in the study. 
Exclusion Criteria: 
A patient meeting any of the following criteria will be excluded from the study: 
1. Patient who has previously received investigational or licensed product; targeted synthetic 
DMARD(s) (e.g., tofacitinib, baricitinib) for the treatment of RA and/or an interleukin-6 (IL-6) 
inhibitor for any purposes. 
2. Patient who has previously received more than 1 biologic agents approved for the treatment of RA.  
Note. Patient with 1 biologic agent for the treatment of RA can be enrolled after sufficient wash-out 
period of at least 3 months or 5 half-lives (whichever is longer) prior to the first administration of 
the study drug (Day 1), except for etanercept and anakinra where only a 1 month washout prior to 
the first administration of study drug (Day 1) is necessary. Patients who have been treated with 
rituximab or a biosimilar of rituximab will not be allowed to enroll in the study. 
3. Patient who has allergies to any of the excipients of study drug or any other murine and human 
proteins, or patient with a hypersensitivity to immunoglobulin products. 
4. Patient who currently has, or has a history of, any of the following infections: 
• 
A known infection with hepatitis B (active or carrier of hepatitis B) or hepatitis C, or 
infection with human immunodeficiency virus (HIV). However, a patient with past 
hepatitis B virus is allowed if resolved (confirmed by negative HBsAg and HBV DNA). 
• 
Acute infection requiring oral antibiotics within 2 weeks or parenteral injection of 
antibiotics within 4 weeks prior to the first administration of the study drug (Day 1) 
• 
Recurrent herpes zoster or other chronic or recurrent infection within 6 weeks prior to the 
first administration of the study drug (Day 1) 
• 
Past or current granulomatous infections or other severe or chronic infections (such as 
sepsis, abscess, opportunistic infections, or invasive fungal infections such as 
histoplasmosis). However, a patient who has a past diagnosis with sufficient documentation 
of complete resolution of the infection can be enrolled in the study. 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 12 
• 
Other serious infections within 24 weeks prior to the first administration of the study drug 
(Day 1) 
5. Patient who currently has, or has a history of, any of the following tuberculosis (TB): 
• 
Patient who has current or a history of active TB. Patient who has any evidence of history 
of active TB cannot be enrolled despite sufficient documentation of complete resolution of 
active TB. 
• 
Patient who has signs or symptoms suggestive of active TB. 
• 
Patient who has had exposure to a person with active TB such as first-degree family 
members or co-workers within 16 weeks prior to the first administration of the study drug 
(Day 1).  
• 
Patient who has a past diagnosis of latent TB unless they have documentation of 
completing TB prophylaxis, or have received at least the first 3 weeks of country-specific 
TB prophylaxis prior to the first administration of the study drug (Day 1) and intends to 
complete its entire course can be enrolled. 
• 
Patient who has a current diagnosis of latent TB (defined as a positive result of interferon-γ 
release assay [IGRA] with a negative examination of chest X-ray) at Screening without a 
history of active TB or latent TB. However, a patient who has received at least the first 3 
weeks of country-specific TB prophylaxis prior to the first administration of the study drug 
(Day 1) and intends to complete its entire course can be enrolled. 
• 
Patient who is without a history of active TB or latent TB and has an indeterminate result of 
IGRA with a negative examination of chest X-ray at Screening. If the result of IGRA is 
indeterminate at Screening, 1 retest will be allowed during the Screening Period. 
Depending on the result of retest, the enrollment will be determined as follows:  
- 
If the repeated IGRA result is negative, the patient can be enrolled. 
- 
If the repeated IGRA result is positive, the patient who has received at least the first 3 
weeks of country-specific TB prophylaxis prior to the first administration of the study 
drug (Day 1) and intends to complete its entire course can be enrolled. 
- 
If the repeated IGRA result is again indeterminate, the patient cannot be enrolled. 
6. Patient who has a medical condition including one or more of the following: 
• 
Current uncontrolled diabetes mellitus, even after insulin treatment 
• 
Current uncontrolled hypertension (as defined by systolic blood pressure [BP] ≥160 mmHg 
or diastolic BP ≥100 mmHg) 
• 
Any other current inflammatory or rheumatic diseases, including but not limited to psoriatic 
arthritis, ankylosing spondylitis, spondyloarthritis, systemic lupus erythematosus, Lyme 
disease, or fibromyalgia, that may confound the evaluation of the effect of the study drug 
• 
Current significant systemic RA involvement (e.g., Sjögren’s syndrome, vasculitis, 
pulmonary fibrosis), which would put the patient at risk if they are enrolled 
• 
Current or history of diverticulitis, chronic ulcerative lower gastrointestinal tract disease or 
any other gastrointestinal condition that may predispose to perforation. 
• 
A known malignancy within the previous 5 years prior to the first administration of the 
study drug (Day 1) except completely excised and cured squamous carcinoma of the uterine 
cervix in situ, cutaneous basal cell carcinoma, or cutaneous squamous cell carcinoma 
• 
Current or past history of severe uncontrolled cardiac disease (unstable angina, New York 
Heart Association [NYHA] Class III or IV heart failure or clinically significant 
electrocardiogram [ECG] abnormalities judged by the investigator) including 
cardiovascular disorders or myocardial infarction within 24 weeks prior to the first 
administration of the study drug (Day 1) 
• 
History of organ transplantation, including corneal graft/transplantation 
• 
Any current respiratory disease that can be judged as clinically significant at the 
investigator’s discretion, including but not limited to chronic obstructive pulmonary 
disease, asthma, or pleural effusion 
• 
Previous diagnosis or symptoms suggestive of demyelinating disorders, including multiple 
sclerosis and Guillain-Barre syndrome 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 13 
• 
Any other current or history of serious acute or chronic medical or psychiatric condition 
that could increase the risk associated with study participation or study drug administration 
or that could interfere with the interpretation of study results 
• 
History or evidence of any other clinically significant disorder, condition, or disease that, in 
the opinion of the investigator, would pose a risk to patient safety or interfere with the 
study evaluation, procedures, or completion 
7. Patient who has received or plans to receive any of the following prohibited medications or 
treatment: 
• 
Intra-articular corticosteroids within 4 weeks prior to the first administration of the study 
drug (Day 1). A patient is permitted to receive one injection of intra-articular corticosteroid 
(≤40 mg of methylprednisolone or equivalent) from Week 36 (after all Week 36 
assessments have been performed) and until the end of the study. A patient is permitted to 
receive either oral or parenteral glucocorticoids (≤10 mg daily of prednisone/prednisolone 
or equivalent) and non-steroidal anti-inflammatory drug, if they have received a stable dose 
for at least 4 weeks prior to the first administration of the study drug (Day 1) and the same 
dose must be maintained until 24 weeks after the first administration of the study drug 
(Day 1). In addition, a patient is permitted to receive low-potency topical, inhaled, otic, and 
ophthalmic glucocorticoid preparations provided, if the preparations are administered per 
the instructions on the product label. 
• 
Conventional DMARDs, other than MTX, including hydroxychloroquine, chloroquine, or 
sulfasalazine within 4 weeks prior to the first administration of the study drug (Day 1). A 
patient who discontinued leflunomide and have had successful chelation with 8 g of 
cholestyramine (3 times daily) for 11 days must wait 4 weeks after the last dose of 
cholestyramine prior to the first administration of the study drug (Day 1). A patient who 
discontinued leflunomide and did not have cholestyramine washout must wait 12 weeks 
after the last dose of leflunomide prior to the first administration of the study drug (Day 1) 
• 
Any other investigational device or medical product within 4 weeks prior to the first 
administration of the study drug (Day 1) or 5 half-lives, whichever is longer 
• 
Alkylating agents within 1 year prior to the first administration of the study drug (Day 1) 
• 
Herbal treatment within 2 weeks prior to the first administration of the study drug (Day 1) 
• 
Live or live-attenuated vaccine within 4 weeks prior to the first administration of the study 
drug (Day 1), or any planned live or live-attenuated vaccination during the study period 
• 
Any surgical procedure, including bone or joint surgery or synovectomy (including joint 
fusion or replacement) within 12 weeks prior to the first administration of the study drug 
(Day 1) or planned within 36 weeks after the first administration of the study drug (Day 1) 
8. Severe physical incapacitation (severely limited in ability to perform routine self-care, has RA ACR 
global functional status Class IV [Hochberg et al., 1992], or who cannot benefit from medication). 
9. Female patient who is currently pregnant or breastfeeding, or plans to become pregnant or 
breastfeed within 6 months of the last dose of study drug. Male patient who is planning to donate 
sperm or father a child within 6 months of the last dose of study drug.  
10. Patient who currently abuses alcohol or drugs or has a history of alcohol or drug abuse within 
1 years from Screening. 
11. Patient is vulnerable (e.g., employee of the study center 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). 
12. Patient who, in the opinion of the investigator, should not participate in the study. 
Study Design: 
This study is a randomized, active-controlled, double-blind, multicenter, Phase 3 study designed to 
evaluate efficacy, PK, and overall safety including immunogenicity of multiple dose (8 mg/kg, not 
exceeding 800 mg/dose) of either CT-P47 or RoActemra administered by IV Q4W in combination with 
MTX (between 10 to 25 mg/week, oral or parenteral [intramuscular or SC] dose) and folic acid 
(≥5 mg/week, oral dose). The MTX dose and route must be maintained from the beginning to the end of 
the study. Approximately 448 male and female patients with moderate to severe active RA will be 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 14 
enrolled in a 1:1 ratio (approximately 224 patients per treatment group) into the CT-P47 or RoActemra 
treatment groups. 
The first randomization to treatment assignment will be stratified by the followings: 
• 
Body weight (<100 kg or ≥100kg) measured on Day 1 
• 
Disease activity by DAS28 (ESR) score at Screening (>5.1 or ≤5.1) 
• 
Prior biologic use approved for RA treatment (yes or no) 
Patients will receive CT-P47 or RoActemra Q4W up to Week 20. Prior to dosing at Week 24, patients in 
the RoActemra treatment group will be randomly assigned in a ratio of 1:1 to either continue with 
RoActemra (Cohort 2) or undergo transition to CT-P47 (Cohort 3). All patients who are initially 
assigned to CT-P47 treatment group at Day 1 (Week 0) will continue their treatment with CT-P47 
(Cohort 1) until Week 48. Second randomization process will also be conducted in Cohort 1 prior to 
dosing at Week 24 to maintain the study blind. 
The second randomization to Cohorts 2 or 3 will be stratified by the following: 
• 
Disease activity by DAS28 (ESR) score at Week 20; <2.6 vs. ≥2.6 
The study design and patient assessment overview is presented in Figure S1. 
Figure S1 
Study Design Overview  
 
Abbreviations: EOS, end-of-study; IV, intravenous; Q4W, every 4 weeks. 
* Prior to dosing at Week 24, all patients will undergo a second randomization process. Patients who are initially 
randomized to RoActemra will be randomized again in a ratio of 1:1 to either continue with RoActemra or undergo 
transition to CT-P47. Patients who are randomized to CT-P47 or RoActemra will receive assigned study drug Q4W 
from Week 24 and thereafter up to Week 48.  
1 The EOS assessments will be performed at Week 52 for all patients who completed or discontinued study drug. 
The patients who early discontinued from the study drug will also visit the study center until Week 52 by regular 
scheduled time interval for efficacy and safety assessments, even if they change their RA medication (including 
those prohibited by the protocol). 
2 An independent joint count assessor assigned to each study center will assess joint counts. If possible, it is 
recommended that the joint count assessments are performed independently by the same person, at each study 
center throughout the entire study period. 
 
After database lock for data up to 32 weeks for all patients, the study will be unblinded for reporting 
purposes and efficacy, PK, and safety endpoints will be evaluated by the pre-defined unblinded sponsor 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 15 
and Contract Research Organization (CRO) teams. The investigators, patients, and other sponsor and 
CRO teams will remain blinded until the end of the study. 
 
Study Schedule: The study will include a Screening Period, Treatment Period (I and II), and End-of-
Study (EOS) visit. 
 
Screening Period:  
Screening will take place between Day –42 and Day –1 (6 weeks), prior to the first study drug 
administration.  
 
Treatment Period:  
• 
Treatment Period I (from Week 0 [Day 1] to Week 24 Predose) 
• 
Treatment Period II (from Week 24 to Prior to Week 52 [EOS visit]) 
 
On Day 1, Week 0, patients who meet all of the inclusion criteria and none of the exclusion criteria will 
be enrolled in the study and randomly assigned to receive either CT-P47 or RoActemra prior to 
treatment. The patient will receive either CT-P47 or RoActemra, as per first and second randomization, 
by IV infusion Q4W, co-administered with MTX between 10 to 25 mg/week, oral or parenteral dose 
(intramuscular [IM] or SC; dose and route must be maintained from beginning to EOS) and folic acid 
(≥5 mg/week, oral dose). Patients will comply with all appropriate visits and assessments. At each visit, 
the patient will be questioned about adverse events (AEs) and concomitant medications and will be 
monitored for the clinical signs and symptoms of TB. 
 
Rescue therapy will be allowed to patients who meet the following criteria: 
• 
From Week 16 and thereafter, patients who have less than a 20% improvement in both swollen 
and tender joint counts (of 66/68 assessed) compared to baseline may receive rescue treatment 
at the discretion of the investigator by initiating or increasing background RA medications 
(including those prohibited by the protocol). The choice of medication is at the discretion of 
the investigator. The patient will be discontinued from the study drug and treated according to 
standard of care and at the discretion of the investigator. Patients receiving rescue treatment 
will attend all visits until Week 52.  
 
End-of-Study (Week 52) visit:  
An EOS visit will occur at Week 52 for all patients who completed or discontinued study drug. The 
patients who early discontinued from the study drug will also visit the study center until Week 52 by 
regular scheduled time interval for efficacy and safety assessments, even if they change their RA 
medication (including those prohibited by the protocol). 
Efficacy Assessments: 
Primary Endpoint 
• 
Mean change from baseline of DAS28 (ESR) at Week 24 
Secondary Endpoints 
The following secondary efficacy endpoints will be assessed up to Week 52: 
• 
ACR20, ACR50 and ACR70  
• 
Individual components of the ACR  
• 
Hybrid ACR response  
• 
DAS28 (CRP) 
• 
DAS28 (ESR) (except for Week 24) 
• 
Individual components of the DAS28 
• 
EULAR response 
• 
Simplified disease activity index (SDAI) and clinical disease activity index (CDAI) 
• 
ACR/EULAR remission (Boolean-based definition)  

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 16 
• 
36-item short form health survey (SF-36)  
• 
Joint damage progression based on radiographic evaluations 
Pharmacokinetic Assessment: 
Secondary Endpoint 
• 
Serum tocilizumab concentration at each time point will be assessed up to Week 52 
Safety Assessments: 
Safety assessments will be performed on AEs (including serious AEs), AEs of special interest (AESI) 
(infection, hypersensitivity including anaphylaxis, hepatic event, haemorrhage, gastrointestinal 
perforation, malignancy, and demyelinating disorder), immunogenicity, hypersensitivity monitoring (via 
monitoring of vital signs, includes BP, heart and respiratory rates, and body temperature), vital sign and 
weight measurement, ECGs, physical examination findings, IGRA, chest X-ray, hepatitis B and hepatitis 
C and HIV status, pregnancy testing, clinical laboratory analyses, signs and symptoms of TB, and prior 
and concomitant medications monitored throughout the study.  
Sample Size: 
A sample size of 336 patients (168 patients in each treatment group of CT-P47 and RoActemra) leads to 
at least 85% statistical power to demonstrate equivalence of CT-P47 and RoActemra based on the two-
sided 90% confidence interval for the difference of mean change from baseline of DAS28 (ESR) score at 
Week 24. In the sample size calculation, equivalence margin of -0.6 to 0.5, two one-sided 5% 
significance level, standard deviation of 1.53 and actual difference of 0 in mean change from baseline at 
Week 24 was assumed. The drop-out rate has been hypothesized at 25%; therefore, approximately 
448 patients (224 patients in each treatment group of CT-P47 and RoActemra) will be randomized. The 
sample size with sufficient number of patients remaining at the time of single transition was also 
considered. 
Statistical Analysis: 
The statistical analysis will be performed using SAS software Version 9.4 or later (SAS Institute, Inc., 
Cary, North Carolina). The statistical methods for this study will be described in a detailed statistical 
analysis plan (SAP), which will be finalized prior to database lock. The data documented in this study 
and the clinical parameters measured will be described using descriptive statistics (n, mean, median, 
standard deviation, minimum, and maximum) for quantitative variables and frequency counts and 
percentages for qualitative variables.  
 
Definition of Analysis Set:  
• 
Intent-to-treat (ITT) Set: The ITT Set is defined as all patients randomly assigned to receive 
study drugs (CT-P47 or RoActemra) 
• 
ITT-Treatment Period II subset: The ITT–Treatment Period II subset is defined as all patients 
in ITT set who are randomly assigned to receive study drug (CT-P47 or RoActemra) prior to 
dosing at Week 24. 
• 
Per-Protocol Set (PPS): The PPS is defined as all randomly assigned patients who are 
compliant with therapy (defined to be ≥80% of planned cumulative doses up to Week 20) and 
have a DAS28 (ESR) assessment at baseline and Week 24 and do not have any major protocol 
deviation affecting primary endpoint. Patients who received rescue therapy before Week 24 will 
be excluded. Final determinations of the PPS will be made at the blinded data review meeting 
(DRM) for the efficacy primary endpoint before unblinding.  
• 
Pharmacokinetic (PK) Set: The PK Set is defined as all randomly assigned patients who 
receive at least 1 full 8 mg/kg dose of study drug (CT-P47 or RoActemra) and who have at least 
1 post-treatment PK result. If any patient is found to be non-compliant with respect to dosing, a 
determination of the PK Set will be made on a case-by-case basis at the blinded DRM. 
• 
PK-Treatment Period II subset: The PK–Treatment Period II subset will consist of all 
patients in PK set who receive at least 1 full 8 mg/kg dose of either of study drug (CT-P47 or 
RoActemra) and have at least 1 post-treatment PK result at or after Week 24. 
• 
Safety Set: The Safety Set is defined as all randomly assigned patients who receive at least 1 
dose (full or partial) of study drug (CT-P47 or RoActemra).  

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 17 
• 
Safety–Treatment Period II subset: The Safety–Treatment Period II subset will consist of all 
patients in Safety set who receive at least 1 dose (full or partial) of study drug (CT-P47 or 
RoActemra) at or after Week 24. 
Efficacy Analysis 
• 
Primary endpoint: The difference of mean change from baseline of DAS28 (ESR) score at 
Week 24 will be analyzed using an ANCOVA model with Multiple imputation (MI) under the 
Missing At Random (MAR) assumption for missing data handling. Missing values will be 
imputed using regression method with treatment, body weight (<100 kg or ≥100 kg) measured 
on Day 1, disease activity by DAS28 (ESR) score at Screening (>5.1 or ≤5.1), and prior 
biologic use approved for RA treatment (yes or no) as covariates. The multiple imputed datasets 
are then analyzed by using ANCOVA with treatment as a fixed effect using covariates as above. 
Final determination of covariates and details will be described in the SAP. The two-sided 90% 
confidence interval (CI) for the difference between the 2 treatment groups (CT-P47 and 
RoActemra) will be produced. Therapeutic equivalence of treatment difference in the change 
from baseline of DAS28 (ESR) at Week 24 by the ANCOVA analysis will be concluded if the 
90% CIs for the treatment difference is entirely within –0.6 to 0.5.  
The primary population of primary endpoint is ITT Set evaluated under a treatment policy 
estimand. For the treatment policy estimand, all available data will be included in the primary 
analysis regardless of intercurrent events such as study drug discontinuation, switch to rescue 
therapy or protocol violation. A supportive analysis for the primary efficacy endpoint will be 
conducted using the PPS. Additionally, the sensitivity analysis to evaluate the impact of missing 
data will be conducted on the ITT Set.  
• 
Secondary endpoints: The secondary efficacy endpoints will be descriptively summarized 
using the ITT Set and PPS and data for Treatment Period II will be summarized on the ITT-
Treatment Period II subset, unless otherwise specified.  
Pharmacokinetic Analysis 
Serum concentrations for Treatment Period I will be summarized on PK Set and data for Treatment 
Period II will be summarized on PK-Treatment Period II subset, unless otherwise specified. Serum 
concentrations will be summarized using quantitative descriptive statistics (including geometric mean 
and percent coefficient of variation [CV%], as appropriate). 
Safety Analysis 
Adverse events will be coded to system organ class (SOC) and preferred term (PT) according to the 
Medical Dictionary for Regulatory Activities (MedDRA). Adverse events will be graded for intensity 
according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Prior and 
concomitant medication will be coded to drug class and PT using the World Health Organization (WHO) 
drug dictionary. All safety data including immunogenicity will be listed and summarized by treatment 
groups as appropriate for the Safety Set and data for Treatment Period II will be summarized on Safety–
Treatment Period II subset, unless otherwise specified. The safety endpoints will be evaluated under a 
treatment policy estimand, and for AESI, evaluation will be under both treatment policy estimand and 
‘while on treatment’ estimand.  
 
 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 18 
List of Abbreviations 
Abbreviation 
Definition 
ACR 
American College of Rheumatology 
ACR20 
American College of Rheumatology 20% improvement 
ACR50 
American College of Rheumatology 50% improvement 
ACR70 
American College of Rheumatology 70% improvement 
ADA 
Anti-drug antibody 
AE 
Adverse event 
AESI 
Adverse event of special interest 
ALT 
Alanine aminotransferase 
ANC 
Absolute neutrophil count 
Anti-CCP 
Anti-cyclic citrullinated peptide 
AST 
Aspartate aminotransferase 
bDMARD 
Biological disease-modifying antirheumatic drug 
BP 
Blood pressure 
CDAI 
Clinical disease activity index 
CEE 
Central and Eastern Europe 
CFR 
Code of Federal Regulations 
CI 
Confidence interval 
COVID-19 
Coronavirus disease 2019 
CRO 
CRP 
Contract research organization 
C-reactive protein 
CSR 
Clinical study report 
CTCAE 
Common Terminology Criteria for Adverse Events 
CV 
Curriculum vitae 
CV% 
DAS28 
Percent coefficient of variation 
Disease Activity Score 28 
DMARD 
DRM 
Disease-modifying antirheumatic drug 
Data review meeting 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
EMA 
European Medicines Agency 
EOS 
End-of-study 
EPAR 
European public assessment report 
ESR 
Erythrocyte sedimentation rate 
EU 
European Union 
EULAR 
European Alliance of Associations for Rheumatology 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HAQ 
Health assessment questionnaire 
HBcAb 
Hepatitis B core antibody 
HBsAb 
Hepatitis B surface antibody 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 19 
Abbreviation 
Definition 
HBsAg 
Hepatitis B surface antigen 
HBV 
Hepatitis B virus 
HIV 
Human immunodeficiency virus 
IB 
Investigator’s brochure 
ICF 
Informed consent form 
ICH 
International Council for Harmonisation 
IDMC 
Independent Data Monitoring Committee 
IEC 
Independent ethics committee 
IGRA 
Interferon-gamma release assays 
IL 
Interleukin 
IL-6R 
Interleukin-6 receptor 
IM 
Intramuscular 
ITT 
Intent-to-treat 
IWRS 
Interactive web response system 
MAR 
Missing at random 
MedDRA 
Medical Dictionary for Regulatory Activities 
MI 
Multiple imputation 
MNAR 
Missing not at random 
MTX 
Methotrexate 
NSAID 
NYHA 
Non-steroidal anti-inflammatory drug 
New York Heart Association 
PK 
Pharmacokinetic 
PP 
Per-protocol 
PT 
Preferred term 
RA 
RF 
Rheumatoid arthritis 
Rheumatoid factor 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SC 
Subcutaneous 
SD 
SDAI 
SI 
Standard deviation 
Simplified disease activity index 
Système International d’Unités 
SF-36 
36-item short form health survey 
sIL-6R 
Soluble interleukin-6 receptor 
SJC 
SOC 
Swollen joint count 
System organ class 
SOP 
Standard operating procedure 
SUSAR 
Suspected unexpected serious adverse reaction 
TB 
Tuberculosis 
TEAE 
Treatment-emergent adverse event 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 20 
Abbreviation 
Definition 
TJC 
TNF 
Tender joint count 
Tumor necrosis factor 
ULN 
Upper limit of normal 
US 
United States 
VAS 
Visual analogue scale 
WHO 
World Health Organizations 
 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 21 
1 Introduction 
1.1 
Background 
Rheumatoid arthritis (RA) is the most common autoimmune inflammatory arthritis in 
adults, occurring in approximately 0.5 to 1.0% of the global population (Silman and 
Pearson, 2002; Singh et al., 2015). It is characterized by synovial inflammation and 
hyperplasia, autoantibody production, cartilage and bone destruction, and systemic 
features (Mcinnes and Schett, 2011). It has a significant negative impact on the ability to 
perform daily activities and health-related quality of life, and it increases mortality (Singh 
et al., 2015). The goals of RA treatment are to improve patients’ quality of life by 
reducing symptoms, reducing functional limitations, preventing joint damage, and 
decreasing complications of the disease. The mainstays of treatment have been 
conventional synthetic disease-modifying anti-rheumatic drugs (DMARDs) such as 
methotrexate (MTX) and sulfasalazine. An array of targeted biologic therapies have now 
been approved to treat RA (ACR, 2018). 
Interleukin (IL)-6 (IL-6) is a pleiotropic cytokine that is over-expressed in synovial tissue 
in patients with RA, with raised concentrations in serum and synovial fluid. IL-6 affects 
the function of neutrophils, T cells, B cells, monocytes, and osteoclasts cells that are 
highly activated in RA and is the major inducer of the hepatic acute phase response, 
which is also a key feature of RA that is correlated with disease activity and joint 
destruction (Smolen et al., 2008). An interleukin-6 receptor (IL-6R) inhibitor biological 
DMARD (bDMARD) approved for the treatment of RA includes tocilizumab and 
sarilumab (Smolen et al., 2020; Fraenkel et al., 2021). 
Tocilizumab is a recombinant humanized immunoglobulin (Ig) G1 monoclonal antibody 
(mAb) directed against the IL-6R that binds specifically to both soluble and membrane-
bound IL-6R, thereby inhibiting IL-6-mediated signaling (RoActemra EPAR, 2018). 
Tocilizumab was originally approved as RoActemra in the European Union (EU) in 
January 2009 and as Actemra in the United States (US) in January 2010. Tocilizumab is 
available in 2 different pharmaceutical forms to allow either administration by 
intravenous (IV) infusion or by subcutaneous (SC) injection. Both pharmaceutical forms 
of tocilizumab are approved in both the EU and US, for the treatment of RA in adults, for 
the treatment of polyarticular juvenile idiopathic arthritis in patients 2 years of age and 
older, and for the treatment of systemic juvenile idiopathic polyarthritis in patients 2 years 
of age and older. The SC formulation of tocilizumab is also approved for the treatment of 
giant cell arteritis in adult patients and systemic sclerosis-associated interstitial lung 
disease (US only). The IV formulation of tocilizumab is also approved for the treatment 
of chimeric antigen receptor T cell-induced severe or life-threatening cytokine release 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 22 
syndrome in adults and pediatric patients 2 years of age and older (RoActemra SmPC, 
2022; Actemra USPI, 2022). 
1.2 
CT-P47 
CT-P47, containing the active ingredient tocilizumab, is a recombinant humanized Ig G1 
mAb directed against the IL-6R that binds specifically to both soluble and membrane-
bound IL-6R, thereby inhibiting IL-6-mediated signaling.  
CT-P47 is being developed by CELLTRION, Inc (hereafter, the sponsor) as a proposed 
biosimilar to the reference products, EU-approved RoActemra and US-licensed Actemra 
(hereafter referred to as RoActemra and Actemra, respectively). CT-P47 is manufactured 
using a Chinese hamster ovary cell line. The primary amino acid sequences of 
tocilizumab in CT-P47 are identical to those of the reference products. 
CT-P47 will be supplied as a sterile, preservative-free, colorless to pale yellowish solution 
at a concentration of 20 mg/mL in 400 mg (20 mL) vials for IV infusion. The CT-P47 
drug product will have the same pharmaceutical liquid formulation form and strength as 
the reference products for IV infusion and is intended to have a highly similar quality 
profile to the reference products. 
The sponsor plans to seek approval for all indications for which the reference products 
has been approved by demonstrating similarity of CT-P47 with the reference products 
through an extensive array of quality, nonclinical, and clinical comparability assessments. 
1.3 
Pre-clinical Studies 
Detailed information regarding the non-clinical pharmacology and toxicology of CT-P47 
can be found in the investigator’s brochure (IB). 
1.4 
Clinical Studies 
The PK and safety of CT-P47 will be evaluated in two phase 1 clinical studies; Study CT-
P47 1.1 will compare CT-P47 and RoActemra SC in healthy subjects and CT-P47 1.2 will 
compare CT-P47, RoActemra, and Actemra IV in healthy subjects. The study results are 
not yet available. 
The efficacy and safety of the reference products (RoActemra or Actemra) administered 
by IV infusion in RA patients were assessed in several randomized clinical trials. Of 
these, a brief description of the 5 pivotal double-blind, randomized, parallel group phase 3 
studies is provided below. 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 23 
Study WA17822 (OPTION) assessed the therapeutic effects of tocilizumab in 623 RA 
patients. The patients were randomized to receive tocilizumab 8mg/kg (n=205), 
tocilizumab 4mg/kg (n=214), or placebo (n=204) intravenously every 4 weeks (Q4W), 
with MTX at stable doses (10-25 mg/week). At Week 24, American College of 
Rheumatology 20% improvement (ACR20) responses were seen in more patients 
receiving tocilizumab than in those receiving placebo (59% patients in the 8mg/kg group, 
48% in the 4mg/kg group, and 26% in the placebo group). The study demonstrated that 
tocilizumab could be an effective therapeutic approach in patients with moderate to 
severe active RA (Smolen et al., 2008). 
Study WA18062 (RADIATE) evaluated efficacy and safety of tocilizumab in patients 
with RA refractory to tumor necrosis factor (TNF) antagonist therapy. A total of 499 
patients were randomly assigned to receive tocilizumab 8mg/kg (n=170), tocilizumab 
4mg/kg (n=161), or placebo (n=158) intravenously Q4W with stable MTX (10-25 
mg/week) for 24 weeks. ACR20 was achieved at 24 weeks by 50.0%, 30.4% and 10.1% 
of patients in the 8 mg/kg, 4 mg/kg and control groups, respectively. Disease activity 
score 28 (DAS28) remission (DAS28 <2.6) rates at Week 24 were clearly dose related, 
being achieved by 30.1%, 7.6% and 1.6% of 8 mg/kg, 4 mg/kg and control groups. 
Tocilizumab plus MTX is effective in achieving rapid and sustained improvements in 
signs and symptoms of RA in patients with inadequate response to TNF antagonists and 
had a manageable safety profile (Emery et al., 2008). 
Study WA18063 (TOWARD) examined efficacy and safety of tocilizumab combined with 
conventional DMARDs in patients with RA. A total of 1,220 patients were randomized 
(2:1 ratio) and the patients remained on stable doses of DMARDs and received 
tocilizumab 8mg/kg (n=805) or placebo (n=415) every 4 weeks. At Week 24, the 
proportion of patients achieving ACR20 response was greater in the tocilizumab plus 
DMARD group than in the placebo group (61% versus 25%). Tocilizumab combined with 
any of the DMARDs evaluated was safe and effective in reducing articular and systemic 
symptoms in patients with an inadequate response to these agents (Genovese et al., 2008). 
Study WA17824 (AMBITION) evaluated the efficacy and safety of tocilizumab 
monotherapy versus MTX in patients with RA for whom previous treatment with 
MTX/biological agents had not failed. This study randomized 673 patients to either 
tocilizumab 8mg/kg every 4 weeks (n=288), or MTX starting at 7.5 mg/week and titrated 
to 20 mg/week within 8 weeks (n=284), or placebo for 8 weeks followed by tocilizumab 
8mg/kg (n=101). The intention-to-treat analysis demonstrated that tocilizumab was better 
than MTX treatment with a higher ACR20 response (69.9 vs 52.5%), and DAS28 <2.6 
rate (33.6 vs 12.1%) at Week 24 (Jones et al., 2010). 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 24 
Study WA17823 (LITHE) assessed the efficacy and safety of tocilizumab plus MTX 
versus MTX alone in preventing structural joint damage and improving physical function 
and disease activity in patients with RA and inadequate responses to MTX. A total of 
1,196 patients were randomized to receive tocilizumab 8 mg/kg (n=398), 4 mg/kg 
(n=399), or placebo (n=393) every 4 weeks plus MTX (10-25 mg/week). Mean change in 
the total Genant-modified Sharp score was 0.29 and 0.34 with tocilizumab 8 mg/kg plus 
MTX and 4 mg/kg plus MTX, respectively, versus 1.13 with placebo plus MTX. Analysis 
of variance of the area under the curve for change from baseline in the disability index of 
the Health Assessment Questionnaire (HAQ) showed greater decreases with tocilizumab 
8 mg/kg and 4 mg/kg (-144.1 and -128.4 units, respectively) than with placebo (-58.1 
units). Proportions of patients with ACR20, 50, and 70 and with DAS28 remission were 
higher in those receiving 8 mg/kg tocilizumab than in those receiving placebo. The safety 
profile of tocilizumab was consistent with the profiles in previous studies (Kremer et al., 
2011). 
1.5 
Study Rationale 
CT-P47 is currently being developed by Sponsor, and is intended to be developed as a 
biosimilar to RoActemra and Actemra. For a biosimilar to be approved, it must be proven 
that there are no clinically meaningful differences between the two products. The 
stepwise ‘totality of evidence’ approach adopted by regulatory authorities for biosimilars 
means that the type of clinical studies needed varies on a case-by-case basis. However, 
statistically proven equivalence between biosimilar and reference product in both 
pharmacokinetics (PK) and efficacy are usually required, as is a demonstration of 
acceptable safety and immunogenicity. Therefore, the PK profile of both IV and SC 
formulations of CT-P47 and the reference products will be compared to demonstrate PK 
equivalence in two phase 1 studies in healthy volunteers, respectively. 
In conjunction with IV and SC phase 1 studies, this study will evaluate the similarity in 
efficacy, PK, safety, and immunogenicity using IV formulation in patients with moderate 
to severe active RA. CT-P47 or RoActemra 8 mg/kg (not exceeding 800 mg/dose) will be 
administered Q4W for up to 48 weeks. The proposed dosing regimen is in line with the 
approved labeling for RoActemra (RoActemra SmPC, 2022; Actemra USPI, 2022). The 
route of IV administration has been chosen for this study based on comparable efficacy, 
safety, and immunogenicity results between the SC and IV administration of tocilizumab 
demonstrated from extensive clinical experiences. 
Comparable efficacy was demonstrated between tocilizumab 162 mg administered SC 
weekly and 8 mg/kg administered IV Q4W in patients with RA. The safety profiles were 
similar, with the exception of a higher incidence of injection site reaction, which were 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 25 
more common with SC administration (Burmester et al., 2014). Low and comparable 
immunogenicity of SC and IV administration has been observed for tocilizumab 
(RoActemra EPAR, 2014). Anti-drug antibody (ADA) positivity rates in patients 
administered tocilizumab SC and IV were 1.2% and 1.5%, respectively, based on a pooled 
analysis data from 8,974 patients in 5 tocilizumab SC and 8 tocilizumab IV phase 3 
studies, indicating overall low risk of tocilizumab immunogenicity. The development of 
ADA did not correlate with PK or safety events, including hypersensitivity or injection-
site reactions, and no patients who developed ADAs had loss of efficacy (Burmester et 
al., 2017). 
International regulations (EMA, 2010; FDA, 2015) suggest that proposed biosimilars 
should be tested in a population representative of approved therapeutic indications of the 
reference product and sufficiently sensitive for detecting potential differences between the 
biosimilar and the reference product. Consequently, RA has been selected as indication 
for the comparative clinical trial, due to the relatively high magnitude of the treatment 
effect observed in the tocilizumab clinical studies in this indication and approved standard 
doses; thus, facilitating the detection of potential differences between CT-P47 and the 
reference products. 
1.6 
Benefit and Risk Assessment 
RoActemra has been studied extensively and has been shown to be effective at reducing 
symptoms in patients with RA (RoActemra SmPC, 2022; Actemra USPI, 2022). 
Taking into account the results of the analytical similarity, pharmacological, and 
toxicological profiles of CT-P47 in non-clinical studies, the clinical findings for CT-P47 
are expected to be in line with those of RoActemra/Actemra, specifically in terms of 
clinical pharmacology, efficacy, and safety.  
The design of this study contains adequate measures to mitigate risks and adequate safety 
monitoring to protect the patients. Nonresponders from Week 16 and thereafter, will be 
offered to receive a rescue therapy at the discretion of the investigator (see Section 5.8). 
An independent data monitoring committee (IDMC) appointed to the study will provide 
an additional level of risk mitigation. The proposed safety monitoring is deemed to be 
sufficient to monitor potential risks of CT-P47 administration. 
Based upon the clinical evidence (Section 1.4) as well as the proven safety profile of 
RoActemra, the benefits of the conduct of the proposed clinical study outweigh the 
associated risks. 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 26 
1.6.1 Risk Assessment During COVID-19 Pandemic 
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 in December 2019 and the disease caused by SARS-CoV-2 
has been designated as coronavirus disease 2019 (COVID-19). On 11 March 2020, World 
Health Organization (WHO) declared the SARS-CoV-2 infection outbreak a global 
pandemic as there are now in excess of 6 million deaths have been reported globally 
(WHO COVID-19 Dashboard, 2022). 
Due to the global impact of the COVID-19 pandemic, the sponsor is taking proactive 
measures to guarantee that all site staff and patients involved in trial are secure and the 
patients remain in the study until their last visit, with continuation of treatment during 
study period. 
1.6.1.1 Benefit and Risk Assessment on Study Population 
To date, there is no evidence that patients with RA face more risk of contracting COVID-
19 than individuals without RA, nor that they have a worse prognosis when they contract 
it. Patients with RA should in general be advised to comply with the same preventive and 
control measures prescribed by the health authorities in their countries. Patients with RA 
who do not have suspected or confirmed COVID-19 should be advised to continue their 
treatment unchanged, namely NSAIDs, glucocorticoids, synthetic DMARDs, bDMARDs, 
osteoporosis medications and analgesics, among others during the COVID-19 outbreak 
(Landewé et al., 2020).  
Basically, the quarantine of COVID-19 should be carried out based on the SOP of each 
site and local regulatory guidelines. Taking this into account, the risk of COVID-19 
infection for each patient is not expected to increase by participating in this study. Yet due 
to the possibility of increasing the safety risk by being involved in the study, a systematic 
risk assessment will be conducted during the study by the sponsor through a sufficient 
discussion with the Investigators and IDMC. 
1.6.1.2 Mitigation Plans 
Investigational Medical Product Management 
To better cope with the sudden imposition of movement restriction and/or increase 
shipment lead time due to frequent flight cancellation and limited staff at customs, 
sufficient investigational medicinal product (IMP) will be supplied to cover patient visit 
for longer period. Inter-country study drug transfer using regional airways will be 
considered in case intercontinental flights are repeatedly cancelled. In addition, sponsor 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 27 
will prepare site-to-site transfer of study drug from nearby clinical sites in case agile 
resupply is required (e.g., patients are enrolled in a site more than anticipated but 
additional supplied IMP could not be sufficient). 
COVID-19 vaccination during the study period 
According to the ACR guidance for COVID-19 vaccination in patients with rheumatic 
and musculoskeletal diseases (Curtis et al., 2021), no modification is required in the use 
and timing of treatment with IL-6R inhibitors. However, patients receiving MTX is 
advised to hold MTX for 1 week after each of the 2 mRNA vaccine dose with the 
exception for those with well-controlled disease, or to withhold MTX for 2 weeks after 
single-dose COVID-19 vaccination, for those with well-controlled disease. 
Patients will be allowed to receive an authorized COVID-19 vaccine of non-live 
attenuated types (e.g., mRNA, viral vector) at least >7 days apart from the previous and 
next study drug administration. Dose modification of MTX will be at the discretion of the 
investigator and in accordance with local regulatory requirements. 
Rescheduling of Visit and Study Drug Administration Schedule of Patients 
The COVID-19 screening tests will be performed locally based on each site and/or local 
regulatory guidelines upon the investigator’s discretion throughout the study period. If 
COVID-19 is confirmed positive during the Screening period, the patient should not be 
enrolled in this study until confirmation of complete recover from COVID-19 as per site 
and/or local regulatory guidelines. Although patients can be screened only once in normal 
circumstance as specified in Section 4.2.1, additional rescreening can be performed only 
in limited cases considering COVID-19. If COVID-19 is confirmed after randomization, 
the investigators will discuss a case-by-case about the position of patient with the sponsor. 
In case of patient who has contact with COVID-19 patients within 14 days from any site 
visit, investigator will reconsider the enrollment or visit schedule following the site 
and/local regulatory guidelines 
Investigators will promptly notify to the sponsor if any unfavorable situation is occurred 
in relation to local COVID-19 status (e.g., site shut down, lock down of city, cohort 
isolation, etc.). For sites where the patients are unable to travel or use public 
transportation, the sponsor will support the patients with alternative transportation or 
reimbursement for travel to ensure the visits can be made within the window or the visit 
can be proceeded at the earliest. Pre-approval is required for reimbursement. 
The patients require face-to-face interactions for study drug administration. Therefore, in 
the event patients cannot visit the study center on the scheduled day for administration, 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 28 
the treatment schedule will be adjusted following Section 5.6. However, if study drug 
administration cannot be done within an allowed visit window or missed dose is expected, 
whether to continue with the subsequent study drug will be discussed with the sponsor, 
ensuring the compliance with the trial protocol to such an extent that an ongoing benefit-
risk assessment for the clinical trial and patients is still possible.  
Even if study visit cannot be made, possible data will be collected via phone call and 
during the next visit, if applicable. Investigator will keep following up with patients 
regarding any safety issues by phone call before the patients visit the site. 
Although the COVID-19 pandemic situation is likely to introduce more protocol 
deviations than normal circumstance, protocol deviations will be managed in accordance 
with the standard procedures. The number and type of deviations will be monitored 
periodically to assess whether a protocol amendment or other modifications are needed. 
Site Monitoring and Audit 
In case where a monitoring visit cannot be made because of the situation of COVID-19, 
centralized monitoring will be performed by the sponsor and/or contract research 
organization (CRO) as alternatives particularly considering the situation of the site, for 
the sites where the first patient is randomized but the first monitoring visit is not 
performed. Manual data review on electronic case report form (eCRF) will be performed 
and if any mistakes or deviations are observed, proper guidance will be provided to avoid 
them in the future on the site. Sponsor and/or CRO will review the data entered in CRF 
continuously and ensure raising queries and support the sites as necessary. If necessary, 
sponsor will create and review a report based on the eCRF data to check whether visits, 
assessments and administrations of study drug are in progress according to protocol and 
the same will be shared with CRO for site management. 
Audits are needed as part of implementing quality assurance throughout the study period 
in order to evaluate trial conduct and compliance with the protocol, SOPs, GCP, and the 
applicable regulatory requirements. In case where an audit cannot be made due to 
COVID-19 pandemic situation, sponsor will postpone audits or consider the remote audits 
after careful consideration of COVID-19 pandemic situation according to Guidance on 
the management of clinical trials during the COVID-19 Pandemic (EMA, 2021). Audits 
will be conducted only when permitted under national, local and/or organizational social 
distancing restrictions. 
Handling of Missing Data 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 29 
To assess any possible risks on data collection, data will be routinely reviewed according 
to Centralized monitoring plan and Risk based monitoring plan. After data collection, 
missing data on the primary analysis due to COVID-19 will be handled equally as 
specified in Section 7.4.1 as other missing cases. However, if a different approach is 
required for missing data due to COVID-19, it will be discussed at the masked data 
review meeting in a case-by-case manner and method of handling missing data will be 
specified in the SAP. 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 30 
2 Study Objectives 
2.1 
Primary Objective 
• To demonstrate that CT-P47 is equivalent to RoActemra, in terms of efficacy as 
determined by clinical response according to the change from baseline in disease 
activity measured by DAS28 (Erythrocyte-Sedimentation Rate [ESR]) at Week 
24. 
2.2 
Secondary Objective 
• To evaluate additional efficacy, PK, and overall safety, including immunogenicity. 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 31 
3 Investigational Plan 
3.1 
Study Design 
This study is a randomized, active-controlled, double-blind, multicenter, Phase 3 study 
designed to evaluate efficacy, PK, and overall safety including immunogenicity of 
multiple dose (8 mg/kg, not exceeding 800 mg/dose) of either CT-P47 or RoActemra 
administered by IV Q4W in combination with MTX (between 10 to 25 mg/week, oral or 
parenteral; intramuscular [IM] or SC dose) and folic acid (≥5 mg/week, oral dose). The 
MTX dose and route must be maintained from the beginning to the end of the study.  
Approximately 448 male and female patients with moderate to severe active RA will be 
enrolled in a 1:1 ratio (approximately 224 patients per treatment group) into the CT-P47 
or RoActemra treatment groups. 
The duration of the study will be up to 58 weeks, which includes Screening (up to 
6 weeks) and the last dose at 48 weeks plus the following 4 weeks off-dose period, prior 
to the End-of-Study (EOS) visit. 
The study design and patient assessment overview is presented in Figure 3-1. 
 
Figure 3-1 
Study Design Overview 
Abbreviations: EOS, end-of-study; IV, intravenous; Q4W, every 4 weeks. 
* Prior to dosing at Week 24, all patients will undergo a second randomization process. Patients who are initially 
randomized to RoActemra will be randomized again in a ratio of 1:1 to either continue with RoActemra or undergo 
transition to CT-P47. Patients who are randomized to CT-P47 or RoActemra will receive assigned study drug Q4W 
from Week 24 and thereafter up to Week 48.  

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 32 
1 The EOS assessments will be performed at Week 52 for all patients who completed or discontinued study drug. The 
patients who early discontinued from the study drug will also visit the study center until Week 52 by regular 
scheduled time interval for efficacy and safety assessments, even if they change their RA medication (including those 
prohibited by the protocol). 
2 An independent joint count assessor assigned to each study center will assess joint counts. If possible, it is 
recommended that the joint count assessments are performed independently by the same person, at each study center 
throughout the entire study period. 
3.1.1 Screening Period 
Screening will take place between Day –42 and Day –1 (6 weeks), prior to the first study 
drug administration (Day 1). The Day 0 will not be used in the study day counting. The 
date immediately before the study drug administration will be counted as Day -1. 
3.1.2 Treatment Periods 
• Treatment Period I (from Week 0 [Day 1] to Week 24 Predose) 
• Treatment Period II (from Week 24 to Prior to Week 52 [EOS visit]) 
The study will comprise 2 treatment periods (I and II). During Treatment Periods I and II, 
patients will receive either CT-P47 or RoActemra 8 mg/kg (not exceeding 800 mg/dose), 
as per first and second randomization, by IV infusion Q4W, co-administered with MTX 
between 10 to 25 mg/week, oral or parenteral dose (IM or SC; dose and route must be 
maintained from beginning to EOS) and folic acid (≥5 mg/week, oral dose). 
On Day 1, Week 0, patients who meet all of the inclusion criteria and none of the 
exclusion criteria will be enrolled in the study and randomly assigned to receive either 
CT-P47 or RoActemra prior to treatment. 
Patients will comply with all appropriate visits and assessments that will be performed at 
the time points specified in the schedule of events (Table 11-1). At each visit, the patient 
will be questioned about AEs and concomitant medications and will be monitored for the 
clinical signs and symptoms of tuberculosis (TB). 
3.1.3 End-of-Study Visit 
An EOS visit will occur at Week 52 for all patients who completed or discontinued study 
drug. The patients who early discontinued from the study drug will also visit the study 
center until Week 52 by regular scheduled time interval for efficacy and safety 
assessments, even if they change their RA medication (including those prohibited by the 
protocol). 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 33 
4 Patient Selection and Withdrawal Criteria 
4.1 
Selection of Study Population 
It is expected that approximately 448 patients will be enrolled at approximately 22 study 
centers in Poland. Male or female patients with moderate to severe active RA diagnosed 
according to the 2010 ACR/European Alliance of Associations for Rheumatology 
(EULAR) classification criteria (Aletaha et al., 2010) for at least 24 weeks, who have 
inadequate response to one or more DMARDs, will be considered for enrollment in the 
study if they meet all of the inclusion criteria and none of the exclusion criteria. 
4.1.1 Inclusion Criteria 
Each patient must meet all of the following criteria to be enrolled in this study: 
1. Patient is male or female aged 18 to 75 years old, both inclusive. 
2. Patient has had a diagnosis of RA according to the 2010 ACR/EULAR classification 
criteria (Aletaha et al., 2010) for at least 24 weeks prior to the first administration of 
the study drug (Day 1). 
3. Patient must have moderate to severe disease activity as defined by all of the 
following at Screening: 
• 
6 or more swollen joints (of 66 assessed) 
• 
6 or more tender joints (of 68 assessed) 
• 
either an ESR ≥28 mm/hour or a serum C-reactive protein (CRP) concentration 
≥1.0 mg/dL (≥10 mg/L) 
• 
DAS28 (ESR or CRP) ≥3.2 
4. Patient who has been receiving oral or parenteral MTX for at least 12 weeks and who 
has been on a stable dose and route of MTX between 10 to 25 mg/week for at least 8 
weeks prior to the first administration of the study drug (Day 1). 
5. Patient has adequate renal and hepatic function at Screening as defined by the 
following clinical chemistry results: 
 Serum creatinine ≤1.5 × upper limit of normal (ULN) or an estimated creatinine 
clearance level >50 mL/min (by Cockcroft-Gault formula) (SI [Système 
International d'Unités] units: 0.84 mL/s) 
 Serum alanine aminotransferase (ALT) ≤2.0 × ULN 
 Serum aspartate aminotransferase (AST) ≤2.0 × ULN 
 Serum total bilirubin ≤1.5 × ULN 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 34 
6. Patient has the following hematology laboratory test results at Screening: 
 Absolute neutrophil count (ANC) ≥2,000/mm3 (2.0×103/µL) 
 Platelet count ≥100,000/mm3 (100.0×103/µL) 
7. Patient and their partner of childbearing potential must agree to use following highly 
effective method of contraception consistent with local regulations throughout the 
study and for 6 months after the last dose of assigned treatment. A man or woman is 
of childbearing potential if, in the opinion of the investigator, he or she is biologically 
capable of having children and is sexually active (i.e., a man is fertile after puberty 
unless permanently sterile by bilateral orchidectomy or a woman is fertile, following 
menarche and until becoming postmenopausal unless permanently sterile). 
 Combined (estrogen and progestogen containing) or progestogen-only hormonal 
contraceptives associated with inhibition of ovulation 
 Intrauterine device or system  
 True abstinence, when this is in line with the preferred and usual lifestyle of the 
patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-
ovulation methods), declaration of abstinence for the duration of exposure to 
investigational drug, and withdrawal are not acceptable methods of contraception. 
 Double contraceptive methods (e.g., male condom in addition to use of hormonal 
or barrier method in female); for male patient with his female partner of 
childbearing potential only. 
If patient or their partner has been surgically sterilized for less than 24 weeks prior to 
the date of informed consent, they must agree to use any medically acceptable 
methods of contraception. Postmenopausal females must have experienced their last 
menstrual period more than 1 year prior to the date of informed consent without an 
alternative medical cause to be classified as not of childbearing potential. 
8. Patient (or legal guardian, if applicable) is informed of the full nature and purpose of 
the study, including possible risks and side effects, has the ability to cooperate with 
the investigator and is given ample time and opportunity to read and understand 
verbal and/or written instructions, and signs the written informed consent form with 
date prior to participation in the study. 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 35 
4.1.2 Exclusion Criteria 
A patient meeting any of the following criteria will be excluded from the study: 
1. Patient who has previously received investigational or licensed product; targeted 
synthetic DMARD(s) (e.g., tofacitinib, baricitinib) for the treatment of RA and/or an 
IL-6 inhibitor for any purposes. 
2. Patient who has previously received more than 1 biologic agents approved for the 
treatment of RA.  
Note. Patient with 1 biologic agent for the treatment of RA can be enrolled after 
sufficient wash-out period of at least 3 months or 5 half-lives (whichever is longer) 
prior to the first administration of the study drug (Day 1), except for etanercept and 
anakinra where only a 1 month washout prior to the first administration of study drug 
(Day 1) is necessary. Patients who have been treated with rituximab or a biosimilar of 
rituximab will not be allowed to enroll in the study. 
3. Patient who has allergies to any of the excipients of study drug or any other murine 
and human proteins, or patient with a hypersensitivity to immunoglobulin products. 
4. Patient who currently has, or has a history of, any of the following infections: 
 A known infection with hepatitis B (active or carrier of hepatitis B) or hepatitis C, 
or infection with human immunodeficiency virus (HIV). However, a patient with 
past hepatitis B virus is allowed if resolved (confirmed by negative HBsAg and 
HBV DNA). 
 Acute infection requiring oral antibiotics within 2 weeks or parenteral injection of 
antibiotics within 4 weeks prior to the first administration of the study drug 
(Day 1) 
 Recurrent herpes zoster or other chronic or recurrent infection within 6 weeks 
prior to the first administration of the study drug (Day 1) 
 Past or current granulomatous infections or other severe or chronic infections 
(such as sepsis, abscess, opportunistic infections, or invasive fungal infections 
such as histoplasmosis). However, a patient who has a past diagnosis with 
sufficient documentation of complete resolution of the infection can be enrolled in 
the study. 
 Other serious infections within 24 weeks prior to the first administration of the 
study drug (Day 1) 
5. Patient who currently has, or has a history of, any of the following tuberculosis (TB): 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 36 
 Patient who has current or a history of active TB. Patient who has any evidence of 
history of active TB cannot be enrolled despite sufficient documentation of 
complete resolution of active TB. 
 Patient who has signs or symptoms suggestive of active TB. 
 Patient who has had exposure to a person with active TB such as first-degree 
family members or co-workers within 16 weeks prior to the first administration of 
the study drug (Day 1).  
 Patient who has a past diagnosis of latent TB unless they have documentation of 
completing TB prophylaxis, or have received at least the first 3 weeks of country-
specific TB prophylaxis prior to the first administration of the study drug (Day 1) 
and intends to complete its entire course can be enrolled. 
 Patient who has a current diagnosis of latent TB (defined as a positive result of 
interferon-γ release assay [IGRA] with a negative examination of chest X-ray) at 
Screening without a history of active TB or latent TB. However, a patient who has 
received at least the first 3 weeks of country-specific TB prophylaxis prior to the 
first administration of the study drug (Day 1) and intends to complete its entire 
course can be enrolled. 
 Patient who is without a history of active TB or latent TB and has an 
indeterminate result of IGRA with a negative examination of chest X-ray at 
Screening. If the result of IGRA is indeterminate at Screening, 1 retest will be 
allowed during the Screening Period. Depending on the result of retest, the 
enrollment will be determined as follows:  
- 
If the repeated IGRA result is negative, the patient can be enrolled. 
- 
If the repeated IGRA result is positive, the patient who has received at least 
the first 3 weeks of country-specific TB prophylaxis prior to the first 
administration of the study drug (Day 1) and intends to complete its entire 
course can be enrolled. 
- 
If the repeated IGRA result is again indeterminate, the patient cannot be 
enrolled. 
6. Patient who has a medical condition including one or more of the following: 
 Current uncontrolled diabetes mellitus, even after insulin treatment 
 Current uncontrolled hypertension (as defined by systolic blood pressure [BP] 
≥160 mmHg or diastolic BP ≥100 mmHg) 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 37 
 Any other current inflammatory or rheumatic diseases, including but not limited to 
psoriatic arthritis, ankylosing spondylitis, spondyloarthritis, systemic lupus 
erythematosus, Lyme disease, or fibromyalgia, that may confound the evaluation 
of the effect of the study drug 
 Current significant systemic RA involvement (e.g., Sjögren’s syndrome, 
vasculitis, pulmonary fibrosis), which would put the patient at risk if they are 
enrolled 
 Current or history of diverticulitis, chronic ulcerative lower gastrointestinal tract 
disease or any other gastrointestinal condition that may predispose to perforation. 
A known malignancy within the previous 5 years prior to the first administration 
of the study drug (Day 1) except completely excised and cured squamous 
carcinoma of the uterine cervix in situ, cutaneous basal cell carcinoma, or 
cutaneous squamous cell carcinoma 
 Current or past history of severe uncontrolled cardiac disease (unstable angina, 
New York Heart Association [NYHA] Class III or IV heart failure, or clinically 
significant electrocardiogram [ECG] abnormalities judged by the investigator) 
including cardiovascular disorders or myocardial infarction within 24 weeks prior 
to the first administration of the study drug (Day 1) 
 History of organ transplantation, including corneal graft/transplantation 
 Any current respiratory disease that can be judged as clinically significant at the 
investigator’s discretion, including but not limited to chronic obstructive 
pulmonary disease, asthma, or pleural effusion 
 Previous diagnosis or symptoms suggestive of demyelinating disorders, including 
multiple sclerosis and Guillain-Barre syndrome 
 Any other current or history of serious acute or chronic medical or psychiatric 
condition that could increase the risk associated with study participation or study 
drug administration or that could interfere with the interpretation of study results 
 History or evidence of any other clinically significant disorder, condition, or 
disease that, in the opinion of the investigator, would pose a risk to patient safety 
or interfere with the study evaluation, procedures, or completion 
7. Patient who has received or plans to receive any of the following prohibited 
medications or treatment: 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 38 
 Intra-articular corticosteroids within 4 weeks prior to the first administration of 
the study drug (Day 1). A patient is permitted to receive one injection of intra-
articular corticosteroid (≤40 mg of methylprednisolone or equivalent) from Week 
36 (after all Week 36 assessments have been performed) and until the end of the 
study. A patient is permitted to receive either oral or parenteral glucocorticoids 
(≤10 mg daily of prednisone/prednisolone or equivalent) and NSAID, if they have 
received a stable dose for at least 4 weeks prior to the first administration of the 
study drug (Day 1) and the same dose must be maintained until 24 weeks after the 
first administration of the study drug (Day 1). In addition, a patient is permitted to 
receive low-potency topical, inhaled, otic, and ophthalmic glucocorticoid 
preparations provided, if the preparations are administered per the instructions on 
the product label. 
 Conventional DMARDs, other than MTX, including hydroxychloroquine, 
chloroquine, or sulfasalazine within 4 weeks prior to the first administration of the 
study drug (Day 1). A patient who discontinued leflunomide and have had 
successful chelation with 8 g of cholestyramine (3 times daily) for 11 days must 
wait 4 weeks after the last dose of cholestyramine prior to the first administration 
of the study drug (Day 1). A patient who discontinued leflunomide and did not 
have cholestyramine washout must wait 12 weeks after the last dose of 
leflunomide prior to the first administration of the study drug (Day 1) 
 Any other investigational device or medical product within 4 weeks prior to the 
first administration of the study drug (Day 1) or 5 half-lives, whichever is longer 
 Alkylating agents within 1 year prior to the first administration of the study drug 
(Day 1) 
 Herbal treatment within 2 weeks prior to the first administration of the study drug 
(Day 1) 
 Live or live-attenuated vaccine within 4 weeks prior to the first administration of 
the study drug (Day 1), or any planned live or live-attenuated vaccination during 
the study period 
 Any surgical procedure, including bone or joint surgery or synovectomy 
(including joint fusion or replacement) within 12 weeks prior to the first 
administration of the study drug (Day 1) or planned within 36 weeks after the first 
administration of the study drug (Day 1) 
8. Severe physical incapacitation (severely limited in ability to perform routine self-care, 
has RA ACR global functional status Class IV [Hochberg et al., 1992], or who cannot 
benefit from medication). 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 39 
9. Female patient who is currently pregnant or breastfeeding, or plans to become 
pregnant or breastfeed within 6 months of the last dose of study drug. Male patient 
who is planning to donate sperm or father a child within 6 months of the last dose of 
study drug. 
10. Patient who currently abuses alcohol or drugs or has a history of alcohol or drug 
abuse within 1 years from Screening. 
11. Patient is vulnerable (e.g., employee of the study center 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). 
12. Patient who, in the opinion of the investigator, should not participate in the study. 
4.2 
Study Drug Discontinuation and Study Termination  
Patients are free to withdraw consent for treatment or participation in the study at any 
time for any reason. The investigator may also discontinue the study drug at any time in 
the interest of patient safety. Study drug discontinuation should not be considered as study 
termination. The primary reasons for the study drug discontinuation and study termination 
must be recorded in the patient’s medical record and in the eCRF, with any comments 
(spontaneous or elicited) or complaints made by the patient. Reasons for study drug 
discontinuation include the following: 
• Patient has any AE that would compromise his or her safety if he or she continues 
the study drug.  
Note. Patient experiences abnormal laboratory results (who meet discontinuation 
condition), or anaphylaxis or other serious treatment-related hypersensitivity 
reactions as described in Section 5.2.2.  
• Patient shows inadequate efficacy or disease progression in the judgement of the 
investigator. 
• Patient has a significant protocol deviation(s). 
• Patient is pregnant. 
• Investigator’s decision. 
• Patient withdraws consent for treatment: Patients will continue off treatment in the 
study until EOS or until withdraws consent for participation. 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 40 
• Patient dies 
• Patient is lost to follow-up 
If the patient does not visit the study center without contacting and is not responsive to 
the telephone contact by the site, the site will try to contact to patient’s family member(s) 
by telephone, using contact information available on file at the site. The contact 
information will only be collected if the patient and patient’s family member(s) agreed in 
advance. For all patients who discontinue study drug early, every effort should be made to 
complete regularly scheduled visits for efficacy and safety assessments, even if they 
change their RA medication (including those prohibited by the protocol). If a patient 
cannot or is unwilling to attend any visit(s), a safety follow-up will be conducted by 
telephone according to the study visit schedule.  
Reasons for study termination include the following: 
• Patient withdraws consent or refuses to procedures/observations. 
• Patient is lost to follow-up. 
• Patient dies. 
If necessary, the investigator may discuss with sponsor or its designee any patient’s 
reason for study drug discontinuation or study termination. The sponsor may be contacted 
if clarification is required on a case-by-case basis. All patients who terminated from the 
study will retain their patient number.  
4.2.1 Recruitment of Additional Patients 
Patients who receive study drug and terminate prior to study completion will not be 
replaced. Patients who are failed at Screening, for any reason, can be rescreened only 
once. If there is unusual situation that justifies consideration for additional rescreening, 
the investigator is recommended to discuss with the sponsor. Rescreened patient will be 
assigned with new patient identification number. 
4.3 
Premature Termination of the Study 
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.  

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 41 
During the study period, IDMC members will review and evaluate accumulating data 
including safety according to Section 9.4.1. IDMC members will recommend trial 
continuation or stop considering the safety of study patients and/or unfavorable results. 
If the study is terminated prematurely by the sponsor, all patients will be kept fully 
informed and an appropriate follow-up examination of the patients will be arranged. The 
investigator will inform the independent ethics committee (IEC) of any premature 
termination or suspension of the study, where applicable. 
 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 42 
5 Study Treatment 
5.1 
Method of Assigning Patients to Treatment Groups 
An interactive web response system (IWRS) will be used for the randomization. 
Biostatistician will generate the randomization schedule for IWRS, which will link 
sequential patient randomization numbers to treatment codes. 
Approximately 448 male and female patients with moderate to severe active RA will be 
enrolled in a 1:1 ratio (approximately 224 patients per treatment group) into the CT-P47 
or RoActemra treatment groups. 
The first randomization to treatment assignment will be stratified by the followings;  
• Body weight (<100 kg or ≥100kg) measured on Day 1 
• Disease activity by DAS28 (ESR) score at Screening (>5.1 or ≤5.1) 
• Prior biologic use approved for RA treatment (yes or no) 
Patients will receive CT-P47 or RoActemra Q4W up to Week 20. Prior to dosing at Week 
24, patients in the RoActemra treatment group will be randomly assigned in a ratio of 1:1 
to either continue with RoActemra (Cohort 2) or undergo transition to CT-P47 (Cohort 3). 
All patients who are initially assigned to CT-P47 treatment group at Day 1 (Week 0) will 
continue their treatment with CT-P47 (Cohort 1) until Week 48. Second randomization 
process will also be conducted in Cohort 1 prior to dosing at Week 24 to maintain the 
study blind. 
The second randomization to Cohorts 2 or 3 will be stratified by the following: 
• Disease activity by DAS28 (ESR) score at Week 20; <2.6 vs. ≥2.6 
The details of stratification factors will be described in the randomization specification 
document, which will be provided in a separate document. 
5.2 
Treatments Administered 
Patients will receive either CT-P47 or RoActemra 8 mg/kg (not exceeding 800 mg/dose) 
by IV infusion Q4W. The study drug should be diluted to a final volume of 100 ml with 
sterile, non-pyrogenic sodium chloride 9 mg/ml (0.9%) solution and infused over 1 hour 
(+15 minutes). Patients will be dosed at specific time points as detailed in the schedule of 
events (Table 11-1).  

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 43 
5.2.1 Co-administration of Methotrexate and Folic Acid 
All patients should have been receiving oral or parenteral (IM or SC) MTX at a dose of 
between 10 to 25 mg/week, for at least 12 weeks and have been on a stable dose and route 
of MTX for at least 8 weeks prior to the first administration of the study drug (Day 1). 
The same dose and route should be maintained throughout the study. 
Methotrexate with folic acid is co-administered to minimize or prevent AEs related to 
MTX side effects. Patients are required to take folic acid (≥5 mg/week, oral dose) 
throughout the duration of the study (Whittle and Hughes, 2004).  
Methotrexate and folic acid should be given according to a weekly schedule on the day 
recommended by the investigator and details will be recorded in the source documents 
and the eCRF.  
5.2.2 Dosage Modification and Treatment Interruption or 
Discontinuation 
For patients who experienced anaphylaxis or other serious treatment-related 
hypersensitivity reaction, study drug must be stopped immediately and discontinue study 
drug. If patients develop laboratory abnormalities in liver enzyme (ALT and/or AST), 
ANC, or platelet, or develops a serious infection, an opportunistic infection, or sepsis, the 
dose of concomitant DMARDs should be modified or dosing stopped and/or study drug 
(CT-P47 or RoActemra) dosing modified until the clinical situation has been evaluated 
and controlled. The window for dose delay should be followed according to Section 5.6.   
5.2.2.1 Elevated Liver Enzyme (ALT and/or AST) 
Laboratory Value 
Action 
>1 to 3 × Upper 
Limit of Normal 
(ULN)  
Dose modify concomitant MTX if appropriate.  
For persistent increases in this range (e.g., if lab abnormality occurs at ≥2 
consecutive visits or by investigator’s decision), reduce dose to 4 mg/kg or 
hold CT-P47 or RoActemra until ALT or AST have normalized.   
Restart with 4 mg/kg or 8 mg/kg, as clinically appropriate. 
>3 to 5 × ULN  
Interrupt CT-P47 or RoActemra dosing until <3 × ULN and follow 
recommendations above for >1 to 3 × ULN.  
For persistent increases >3 × ULN (confirmed by repeat testing) (e.g., if lab 
abnormality occurs at ≥2 consecutive visits or by investigator’s decision), 
discontinue CT-P47 or RoActemra.  
>5 × ULN  
Discontinue CT-P47 or RoActemra.  
References: RoActemra SmPC, 2022; Actemra USPI, 2022. 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 44 
5.2.2.2 Low Absolute Neutrophil count 
Laboratory Value 
(cells x 109/L) 
Action 
ANC >1  
Maintain dose.  
ANC 0.5 to 1  
Interrupt CT-P47 or RoActemra dosing.  
When ANC increases >1 × 109/L, resume CT-P47 or RoActemra at 4 mg/kg 
and increase to 8 mg/kg as clinically appropriate.  
ANC <0.5  
Discontinue CT-P47 or RoActemra.  
References: RoActemra SmPC, 2022; Actemra USPI, 2022. 
5.2.2.3 Low Platelet Count 
Laboratory Value 
(cells x 103/μL) 
Action 
Platelet 50 to 100 
Interrupt CT-P47 or RoActemra dosing.  
When platelet count >100 × 103/μL, resume CT-P47 or RoActemra at 4 mg/kg 
and increase to 8 mg/kg as clinically appropriate. 
Platelet <50 
Discontinue CT-P47 or RoActemra.  
References: RoActemra SmPC, 2022; Actemra USPI, 2022. 
5.3 
Identity of Investigational Product 
CT-P47 is a humanized mAb that is being developed as a proposed biosimilar medicinal 
product to RoActemra and Actemra.  
The International Non-proprietary Name of the commercially available reference material 
(RoActemra/Actemra) is tocilizumab and the Anatomical Therapeutic Chemical 
Classification System code is L04AC07.  
The reference product, RoActemra, is supplied as a sterile concentrate for solution for IV 
infusion. RoActemra is a clear to opalescent, colorless to pale yellow solution 
(RoActemra SmPC, 2022). 
CT-P47 drug product will be supplied as a sterile, preservative-free, colorless to pale 
yellowish solution with a pH 5.5-6.5. CT-P47 for IV use in clinical study is formulated at 
400 mg/20 mL in single-dose vial. 
The following drug supplies will be used in the study: 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 45 
Product 
Supplied as: 
CT-P47 
Vial containing 20 mL (400 mg/20 mL) concentrate of 
CT-P47 for solution for infusion  
RoActemra 
Vial containing 20 mL (400 mg/20 mL) concentrate of 
tocilizumab for solution for infusion 
5.4 
Management of Clinical Supplies 
5.4.1 Study Drug Packaging, Labelling, and Storage 
The appropriate number of study drug will be allocated to each patient via the IWRS 
system at each visit. 
A label will be attached to the outside of each patient 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 
• Patient number 
• Contents  
• Lot number 
• Randomization code/kit number 
• Investigator’s name 
• Storage instructions 
• Caution statement (for study use only) 
• Sponsor’s contact name and address 
• Expiry date 
All study drug supplies must be stored in a secured area (e.g., a locked cabinet), protected 
from light. Both CT-P47 and RoActemra must be kept at a controlled refrigerated 
temperature between 2°C and 8°C (36°F to 46°F) and it must not be frozen.  
5.4.2 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 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 46 
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. 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 staff, and the patients participating in the study. Study drug 
may not be relabeled or reassigned for use by other patients unless approved by sponsor. 
During the study, unused study drug vials should be returned to the depot of origin. 
Accountability of the product must be completed at the site level and discrepancies, if 
any, need to be resolved prior to return. Only if it is written in standard operating 
procedures or documentation in place, the used vials can be destroyed locally. 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 centers agreed upon with 
sponsor. 
Details in study drugs accountability and destruction will be followed according to the 
pharmacy manual.  
5.5 
Blinding 
This study will be double-blind. 
5.5.1 Breaking the Blind 
Under normal circumstances, the blind should not be broken. The blind should be broken 
only 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 an 
emergency, determine the identity of the study drug by using the applicable procedure in 
the IWRS (see study manual, which is provided as a separate document). 
The date, time and reason for the unblinding must be documented in the appropriate field 
of the eCRF and the medical monitor will be informed as soon as possible. All calls 
resulting in an unblinding event will be recorded and reported by the IWRS to the 
medical monitor and the sponsor. Any patients for whom the blind is broken may 
continue in the study and receive the study drug at the investigator’s discretion. 
For regulatory reporting purposes, the randomization code will be broken for a suspected 
unexpected serious adverse reaction (SUSAR) before submission, if required. 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 47 
The overall randomization code will be broken only for reporting purposes. Unblinding 
will occur after database lock for data up to 32 weeks for all patients. The unblinded team 
will be pre-defined and documented prior to performing the analyses. The study will 
remain blinded to the investigators, patients, and pre-defined sponsor and EastHORN 
blinded teams until all patients have completed the study and the database has been 
finalized for study termination. 
5.6 
Treatment Compliance 
CT-P47 and RoActemra will be diluted by a designated staff, and will be supplied to the 
treating staff or designee in the blinded manner. The study drug should be administered as 
a 1-hour infusion (+15 minutes). The start and end time of the infusion as well as any 
deviations from the planned infusion time will be recorded in both the source documents 
and the eCRF. 
Every effort will be made to encourage patients’ compliance with the study visits during 
study period. Particularly, patients are encouraged to visit study center at Week 20 within 
visit window for efficacy assessment which will be used for second randomization 
process at Week 24. If patient is unable to visit the study center at all at Week 20 for 
efficacy assessment, the investigator should contact the sponsor for further discussion.  
A dose visit window of ±3 days is allowed from Dose 2 (Week 4) to Dose 13 (last dose at 
Week 48). If the dose visit window exceeds >3 days but ≤13 days from the scheduled visit 
date due to lab abnormality (Section 5.2.2) or other safety concerns for dosing by the 
investigators’ discretion, it should be considered as ‘dose delay’ and the subsequent visit 
schedule should be readjusted to every 4 weeks from the time of last study drug 
administration. However, for other cases (e.g., patient’s personal reasons), original 
scheduled visit (Table 11-1) should be followed for the subsequent visits. If the dose visit 
window exceeds >13 days from the scheduled visit date (e.g., dosing interval is over 6-
week) regardless of the reasons, it should be considered as ‘dose skip’ and the next dose 
should be administered as soon as possible. The subsequent visit schedule should be 
readjusted to every 4 weeks from the time of last study drug administration. For study 
visits at which the study drug dosing is held, all other study assessments should be 
performed as per study schedule, if possible. 
5.7 
Prior, Concomitant, and Subsequent Therapy 
Aside from MTX and folic acid, which should be administered throughout the study as 
described in Section 5.2.1, a patient is permitted to receive either oral or parenteral 
glucocorticoids (≤10 mg daily of prednisone/prednisolone or equivalent) and NSAID, if 
they have received a stable dose for at least 4 weeks prior to the first administration of the 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 48 
study drug (Day 1) and the same dose must be maintained until 24 weeks after the first 
administration of the study drug (Day 1). Any changes before Week 24, in terms of dose, 
need to be reported to and discussed with the medical monitors of sponsor or its designee 
in advance. In addition, patients are permitted to receive low-potency topical, inhaled, 
otic, and ophthalmic glucocorticoid preparations provided, if the preparations are 
administered per the instructions on the product label. 
Killed vaccinations are acceptable during the study. 
Use of all prior and concomitant medications for the treatment of RA, from the diagnosis 
of disease until the EOS visit (Week 52), will be recorded in the patient’s eCRF. 
Use of all medications for other purposes, taken from 42 days prior to the first 
administration of study drug until the EOS visit, will be recorded in the patient’s eCRF. 
However, in order to check eligibility, prior medications will be reviewed from date 
specified in Section 4.1.2. This will include all prescription drugs, vitamins, minerals, and 
over-the-counter medications. Any changes in concomitant medications also will be 
recorded in the patient’s eCRF. 
Any concomitant medication deemed necessary for the welfare of the patient during the 
study may be given at the discretion of the investigator. However, it is the responsibility 
of the investigator to ensure that details regarding the medication are recorded in full in 
the eCRF. 
5.8 
Rescue Therapy 
For the duration of the study, rescue therapy will be allowed to patients who meet the 
following criteria.  
From Week 16 and thereafter, patients who have less than a 20% improvement in both 
swollen and tender joint counts compared to baseline may receive rescue treatment at the 
discretion of the investigator by initiating or increasing background RA medications 
(including those prohibited by the protocol). The choice of medication is at the discretion 
of the investigator. The information about the rescue therapy use will be reported in the 
patient’s eCRF. 
The patient will be discontinued from the study drug and treated according to standard of 
care and at the discretion of the investigator. Patients receiving rescue treatment will 
attend all visits until Week 52. 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 49 
5.9 
Prohibited Therapy 
The following medications, treatments, or procedures during the study period are 
prohibited. Patients who have received or plan to receive these prohibited medications or 
treatments will not be enrolled in the study (Section 4.1.2). Patients who receive any 
prohibited therapy during the Screening period should be considered a screen failure. 
Intake of any of the following prohibited therapy by the patients after randomization will 
be considered as protocol deviation (except patient receives prohibited medication for 
rescue therapy specified in Section 5.8). 
• Any biologic agents approved for the treatment of RA or IL-6 inhibitor for any 
purposes 
• Conventional DMARDs other than MTX or targeted synthetic DMARDs  
Intra-articular corticosteroids (From Week 36 [after all Week 36 assessments have 
been performed], one injection of ≤ 40 mg of methylprednisolone or equivalent is 
allowed until the end of the study)  
• Any other investigational device or medical product  
• Alkylating agents 
• Herbal treatments 
• Live or live-attenuated vaccine. Inactivated vaccines are acceptable during the 
study.  
Note. Authorized COVID-19 vaccines of non live-attenuated types are allowed 
(e.g., mRNA, viral vector), if patients receive COVID-19 vaccine at least >7 days 
apart from the previous and next study drug administration (refer to Section 
1.6.1.2). 
• 
Any surgical procedure, including bone or joint surgery or synovectomy 
(including joint fusion or replacement) are not allowed until 36 weeks after the 
first administration of the study drug (Day 1) 
 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 50 
6 Study Assessments and Procedures 
Prior to performing any study procedures, all potential patients will sign an informed 
consent form (ICF). Patients will have the opportunity to have any questions answered 
prior to signing the ICF. The investigator must address all questions raised by the patient. 
The investigator or designee will also sign the ICF. 
All patients will return to the study center by regular scheduled time intervals for clinical 
assessments and blood samplings. Patients will undergo the procedures at the time points 
specified in the schedule of events (Table 11-1). 
6.1 
Demographics, Baseline, and Background Characteristics 
At screening, medical history (general medical history and medication history), 
demographic data (age, gender, ethnicity, and race), and height will be collected and 
reported in the eCRF. 
Blood samples for rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) 
will be collected only at screening, at the same time as the clinical laboratory blood 
samples. The blood samples will be tested in the central laboratory. 
6.2 
Efficacy Assessments 
Efficacy will be assessed by the evaluation of the DAS28 (DAS28 [ESR], DAS28 [CRP], 
and individual components) score, ACR criteria (individual components, ACR20, ACR50, 
and ACR70, and hybrid ACR response), EULAR response criteria, simplified disease 
activity index (SDAI), clinical disease activity index (CDAI), ACR/EULAR remission 
(Boolean-based definition), quality of life (SF-36), and joint damage progression at the 
time points specified in the schedule of events (Table 11-1). 
6.2.1 Joint Count Assessment 
An independent joint count assessor will be assigned to each study center. If possible, it is 
recommended that the joint count assessments are performed independently by the same 
person, at each study center throughout the entire study period. Any joint injected with 
intra-articular corticosteroids or that has undergone any surgical procedure including joint 
surgery or synovectomy (including joint fusion or replacement) will not be included in 
the joint count from all subsequent assessments. For assessment, the independent joint 
assessor will be informed about the history of the patient’s joint surgery with the name of 
the surgery, date, and location. Standardized training will be provided to all joint count 
assessors and evidence of such training will be recorded in the joint assessor’s training 
records. 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 51 
6.2.2 Disease Activity Score Using 28 Joint Counts 
Disease Activity Score using 28 joint counts (ESR) and DAS28 (CRP) will be evaluated 
at time points specified in the schedule of events (Table 11-1). The core set of variables 
for DAS28 for this study include the following: 
• Number of tender and swollen joints with a total of 28 joints assessed for 
tenderness and 28 for swelling  
• Patient’s global assessment of disease activity measured using visual analogue 
scale (VAS) (Appendix 11.3) 
• ESR 
• CRP 
6.2.3 American College of Rheumatology Criteria and Individual 
Components 
The ACR criteria are a series of individual assessments used for the calculation of 
ACR20, ACR50, ACR70, and hybrid ACR response (American College of Rheumatology 
Committee to Reevaluate Improvement Criteria, 2007). The ACR core set of variables 
(individual components) for this study include the following: 
• Number of tender and swollen joints with a total of 68 joints assessed for 
tenderness and 66 for swelling 
• Patient’s and physician’s global assessment of disease activity measured on VAS 
(Appendices 11.3 and 11.4) 
• Patient’s assessment of pain measured on VAS (Appendix 11.5) 
• Health Assessment Questionnaire (HAQ) estimate of physical ability 
(Appendix 11.6) 
• ESR 
• CRP 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 52 
6.2.4 Simplified Disease Activity Index and Clinical Disease Activity 
Index 
Simplified and clinical disease activity will be measured using SDAI and CDAI (Aletaha 
and Smolen, 2009). The core set of variables for SDAI and CDAI for this study include 
the following: 
• Number of tender and swollen joints with a total of 28 joints assessed for 
tenderness and 28 joints assessed for swelling  
• Patient’s global assessment of disease activity (VAS) (Appendix 11.3) 
• Evaluator/physician global assessment of disease activity (VAS) (Appendix 11.4) 
• CRP (for SDAI only) 
6.2.5 ACR/EULAR remission (Boolean-based definition) 
ACR/EULAR remission will be evaluated using the Boolean-based definition. The 
variables include the following: 
• 
Number of tender and swollen joints with a total of 28 joints assessed for 
tenderness and 28 joints assessed for swelling  
• 
CRP 
• 
Patient’s global assessment of disease activity (VAS) (Appendix 11.3) 
6.2.6 Quality of Life 
Quality of life will be assessed using the 36-item short form health survey (SF-36) 
questionnaire at the time points specified in the schedule of events (Table 11-1). 
6.2.7 Joint Damage Progression 
One image of each hand and each foot (both the right and left hands and feet, a total of 
4 images) for analysis of efficacy will be obtained at the time points specified in the 
schedule of events (Table 11-1). Joint damage, progression as determined by radiography, 
will be assessed in the central laboratory by the change in total Sharp score using the 
modified total Sharp scoring system (Plant et al., 1994; Sharp et al., 1971; Sharp et al., 
1985) and the blind regarding the time point at which the displayed images will be 
obtained. The baseline radiographs will be assessed within 42 days prior to the first 
administration of the study drug (Day 1). 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 53 
6.3 
Pharmacokinetic Assessments 
For all patients, blood samples for the determination of serum concentration of study drug 
will be collected prior to dosing at the time points specified in the schedule of events 
(Table 11-1). If the blood sample is unable to be analyzed or is missing, extra blood 
samples collected for immunogenicity assessment at the same time point can be used for 
the PK assessment. The PK of CT-P47 and RoActemra will be assessed using a validated 
method for serum concentration. It will be specified in a separate validation document. 
Sample analysis will be performed at the bioanalytical laboratory. 
6.4 
Safety Assessments 
Safety assessments will include the followings, at time points specified in the schedule of 
events (Table 11-1): AEs, clinical laboratory testing, and other safety assessments.  
6.4.1 Adverse Events 
Patients will be instructed to contact the investigator immediately if any symptoms 
develop from the time the ICF is signed until the end of the patient’s participation in the 
study. The investigator is responsible for reporting all AEs that are observed and/or 
reported by the patient during the study through the eCRF.  
6.4.1.1 Definitions of Adverse Events 
An AE is defined as any untoward medical occurrence in a patient associated with the use 
of a medicinal product, whether or not considered related to the medicinal product. An AE 
can therefore be any unfavorable and unintended sign, symptom, or disease temporally 
associated with the use of a medicinal product. This includes any event that is new in 
onset or has aggravated in severity or frequency compared with baseline. 
A treatment-emergent adverse event (TEAE) is defined as any event not present prior to 
exposure to study drug or any event already present that worsens in either severity or 
frequency after exposure to study drug. This includes any occurrence that is new in onset 
or aggravated in severity or frequency from the baseline condition; abnormal results of 
diagnostic procedures including laboratory test abnormalities are considered AEs if they 
fulfill the following: 
• Result in discontinuation from the study 
• Require treatment or any other therapeutic intervention 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 54 
• Require further diagnostic evaluation (excluding a repetition of the same 
procedure to confirm the abnormality) 
• Are associated with clinical signs or symptoms judged by the investigator to have 
a significant clinical impact 
If the patient’s RA worsens temporarily, disease aggravation will be captured as the 
(S)AE(s) term. However, if disease has worsened continuously in the judgment of the 
investigator (e.g., worsened for >8 weeks), this will be considered disease progression 
and not disease aggravation; disease progression will not be captured as an (S)AE. If 
disease progression is decided by the investigator, the patient will be discontinued from 
the study drug by investigator’s judgement and the disease aggravation reported in the 
previous visit will be deleted in the eCRF. 
Medical interventions 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 in the eCRF instead of the term of surgery, diagnostic procedure, or therapeutic 
procedure.  
6.4.1.1.1 Adverse Events of Special Interest 
An adverse event of special interest (AESI) is an AE that is designated to be of special 
interest and will be reported by the study center following the same process as for AEs: 
• 
Infection 
• 
Hypersensitivity, including anaphylaxis 
• 
Hepatic event 
• 
Hemorrhage (medically significant bleeding events) 
• 
Gastrointestinal perforation 
• 
Malignancy 
• 
Demyelinating disorder 
6.4.1.1.2 Serious Adverse Events 
An SAE is defined as any untoward medical occurrence that at any dose: 
• Results in death 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 55 
• Is immediately life threatening: Refers to an AE in which the patient was at 
immediate risk of death at the time of the event. It does not refer to an event which 
hypothetically might have caused death, if it were more severe. 
• Requires inpatient hospitalization or prolongation of existing hospitalization 
• Results in persistent or significant disability/incapacity 
• Is a congenital anomaly/birth defect 
Important medical events that may not result in death, be life threatening, or require 
hospitalization may be considered SAEs when, based upon appropriate medical judgment, 
they may jeopardize the patient or may require medical or surgical intervention to prevent 
one of the outcomes listed in this definition. 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 SAEs. Any initial admission (even if less than 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 TB unit). 
Hospitalization or prolongation of hospitalization in the absence of a precipitating clinical 
AE is not in itself an SAE. Examples include the following: 
• 
Admission for treatment of a preexisting condition not associated with the 
development of a new AE or worsening of the preexisting condition (e.g., for work-up 
of persistent pre-treatment laboratory abnormality) 
• 
Social admission (e.g., patient has no place to sleep) 
• 
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 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 56 
• 
Hospitalization purely for convenience (e.g., for easier performance of study 
assessments) 
• 
Pre-planned treatments or surgical procedures; these should be noted in the baseline 
documentation for the entire protocol and/or for the individual patient 
6.4.1.1.3 Suspected Unexpected Serious Adverse Reactions 
A suspected unexpected serious adverse reaction (SUSAR) is defined as an event of 
which the nature or severity is not consistent with the applicable Reference Safety 
Information (e.g., IB). Assessment of expectedness will be made with the use of the IB. 
Therefore, if a treatment-related SAE occurs and it was not mentioned in the applicable 
Reference Safety Information of the product information, it will be reported as a SUSAR. 
6.4.1.2 Eliciting and Documenting Adverse Events 
Adverse events will be assessed from the date the patient signs the ICF until the end of 
the patient’s participation in the study. Adverse events of special interest will be closely 
monitored by the investigator. 
Throughout the study, patients will be asked a standard 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 and over-the-counter medications). 
In addition to patient observations, AEs identified from any study data (e.g., laboratory 
values, physical examination findings, ECG changes) or other data collected that are 
relevant to patient safety will be documented on the AE page in the eCRF. 
6.4.1.3 Reporting Adverse Events 
All AEs reported or observed during the study will be recorded on the AE page in the 
eCRF. Information to be collected includes drug treatment, dose, event term, time of 
onset, investigator-specified assessment of severity and relationship to study drug, time of 
resolution of the event, seriousness, action taken with study drug, any required treatment 
or evaluations, and outcome. 
Adverse events resulting from concurrent illnesses, reactions to concurrent illnesses, or 
reactions to concurrent medications must also be reported.  
Any medical condition that is present at the time that the patient is screened but does not 
deteriorate should not considered as an AE. However, if a preexisting condition 
deteriorates at any time during the study, this is considered an AE and must be reported. 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 57 
The investigator’s assessment of an AE’s severity and 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. The severity and the relationship or association of the study drug in causing 
or contributing to the AE will be characterized as defined in Sections 6.4.1.5 and 6.4.1.6, 
respectively. 
Adverse events (and SAEs) should be reported until the EOS visit regardless of the 
relationship to the study drug. 
6.4.1.4 Reporting Serious Adverse Events 
Any AE considered serious by the investigator or which meets SAE criteria (Section 
6.4.1.1.2) must be reported to EastHORN immediately (within 24 hours after the study 
center staff first notices 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 EastHORN within 24 hours of awareness of the event. The remote data capture 
system should be updated as soon as it is available. If the patient is hospitalized during an 
SAE or because of an SAE, a copy of the hospital discharge summary will be e-mailed to 
EastHORN as soon as it becomes available. Withdrawal from the study and all 
therapeutic measures will be at the discretion of the principal investigator or sub-
investigator.  
The following contact information is to be used for SAE reporting in case reporting via 
remote data capture system is not available: 
EastHORN Pharmacovigilance Department 
SAE E-mail: safety.22101@easthorn.eu 
SAE Fax (to be used only if e-mail is inaccessible): +420 244 462 271  
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), the FDA’s 
Code of Federal Regulations (CFR) (21 CFR part 312.32), International Council for 
Hamonisation (ICH) guidelines, and/or local regulatory requirements. 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 58 
6.4.1.5 Assessment of Severity 
The severity of an AE will be graded by the investigator according to the Common 
Terminology Criteria for Adverse Events (CTCAE) v5.0. For assessing severity for AEs 
that are not specifically listed in the CTCAE v5.0, the following general guideline will be 
used (a semicolon indicates “or” within each description): 
Grade 1: 
Mild AE (asymptomatic or mild symptoms; clinical or diagnostic observations 
only; intervention not indicated) 
Grade 2: 
Moderate AE (minimal, local or non-invasive intervention indicated; limiting 
age-appropriate instrumental activities of daily living.) 
Grade 3: 
Severe or medically significant but not immediately life threatening 
(hospitalization or prolongation of hospitalization indicated; disabling; limiting 
self-care activities of daily living) 
Grade 4: 
Life-threatening consequences (urgent intervention indicated) 
Grade 5: 
Death related to AE 
The investigator will assess of the maximum intensity that occurred over the duration of 
the event. However, if an existing AE before study drug administration exacerbates after 
study drug administration or if an AE changes from a nonserious to a serious event, a new 
AE needs to be reported separately. Adverse events characterized as intermittent do not 
require documentation of onset and duration of each episode. 
6.4.1.6 Assessment of Causality 
The causality or relatedness of an AE refers to whether or not the investigator deems the 
AE to be related to the study drug. The investigator’s assessment of an AE’s relationship 
to the study drug is part of the source documentation process and should be reported in 
the eCRF, regardless of the suggested causality.  
The causal relationship of an AE to the study drug will be characterized using the 
following classification: 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 59 
Unrelated: 
There is no association between the study drug and the reported event. 
Possible: 
Treatment with the study drug caused or contributed to the AE, i.e., the event 
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: 
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 of 
study drug. 
 
Definite: 
A definite causal relationship exists between drug administration and the AE, 
and other conditions (e.g., concurrent illness, progression of disease state, 
concurrent medication reaction, etc.) do not appear to explain the event.  
6.4.1.7 Follow-Up of Patients Reporting Adverse Events 
All AEs will be followed until resolution or improvement to baseline, death, confirmed by 
the investigator that no further improvement could be expected, or until the end of the 
patient’s participation in the study.  
6.4.2 Clinical Laboratory Testing 
The standard clinical laboratory analyses will be performed by the central laboratory 
according to validated methods and procedures, except for ESR (local laboratory using 
kits supplied centrally).  
The following clinical laboratory assessments will be performed (Table 11-1): 
Clinical chemistry 
Total protein, serum bilirubin (total, direct), ALT, AST, alkaline 
phosphatase, γ-glutamyltransferase, blood urea nitrogen, 
creatinine, albumin, sodium, potassium, calcium, chloride, 
inorganic phosphorus, glucose, magnesium, lactate 
dehydrogenase, total cholesterol, triglyceride, low-density 
lipoprotein cholesterol, high-density lipoprotein cholesterol, 
Creatine kinase, Creatine kinase-MB, CRP, ESR, and uric acid 
Hematology 
Hematocrit, hemoglobin, red blood cells, total and differential 
white blood cell count, ANC, and platelet count 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 60 
Viral Serology 
Anti-HIV (HIV-1 and HIV-2) antibodies, hepatitis B surface 
antigen (HBsAg), hepatitis B surface antibody (HBsAb), hepatitis 
B core antibody (HBcAb) (total or IgG), hepatitis C antibody 
(HCAb) 
Other 
IGRA, soluble interleukin-6 receptor (sIL-6R) 
Urinalysis 
bilirubin, blood, color, glucose, ketones, leukocytes, nitrite, pH, 
protein, specific gravity, and urobilinogen 
Creatinine clearance (by Cockcroft-Gault formula) will be calculated using serum 
creatinine level only at Screening for inclusion.  
During the study period, liver enzymes (ALT and AST), ANC and platelets will be closely 
monitored considering dose related laboratory abnormalities as specified in Section 5.2.2. 
The laboratory results from previous visit will be used to determine if dose modification 
or discontinuation is needed. If the investigator confirms that the previous laboratory 
results of liver enzymes, ANC or platelet are within abnormal range, additional sample 
should be collected in advance (≤7 days prior to the next dose administration as 
unscheduled visit) to facilitate rapid clinical decision making. Test results will be 
recorded in the eCRF and source documents.   
It is the investigator’s responsibility to review all laboratory findings. Any value that falls 
outside of the normal reference range will be flagged for review and the investigator will 
indicate whether or not the value is deemed clinically significant. If any of the screening 
results are indicated as clinically significant, the patient will be considered ineligible and 
not be allowed into the study without permission of the sponsor. However, a retest during 
the screening period is permitted once by the investigator’s judgment. Additional testing 
during the study may be performed if medically indicated. If a clinically significant 
abnormality is observed during the study, as defined in Section 6.4.1.1, this should be 
recorded as an AE and the patient will be followed up until the test have normalized or 
stabilized.  
6.4.2.1 Hepatitis B and Hepatitis C and Human Immunodeficiency 
Virus 
At Screening, HBsAg, HBsAb, and HBcAb (total or IgG) will be assessed in all patients 
as specified in Table 6-1. 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 61 
Table 6-1 
Eligibility based on Serologic Markers for Hepatitis B Infection 
Test Results 
Eligibility 
HBsAg 
HBsAb 
HBcAb 
HBV DNA 
+ 
+/– 
+/– 
Not applicable 
Not eligible 
– 
+/– 
+ 
+ 
Not eligible 
– 
Eligible1 
– 
+/– 
– 
Not applicable 
Eligible 
Abbreviations: DNA, DeoxyriboNucleic Acid; EOS, end of study; HBcAb, hepatitis B core antibody; 
HBsAb, hepatitis B surface antibody; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus. 
1. Testing of HBsAg, HBsAb, HBV DNA, ALT, AST, and total bilirubin will be performed at Week 24 
and EOS visit. 
If a patient has HBsAg (negative), HBsAb (negative or positive), and HBcAb (positive), a 
HBV DNA test will be performed at Screening. If the HBV DNA test result is positive, 
the patient will be excluded from the study; if the HBV DNA test result is negative, the 
patient can be included in the study. For patients who are enrolled based on the HBV 
DNA test, testing of HBsAg, HBsAb, HBV DNA, ALT, AST, and total bilirubin will be 
performed at the Week 24 and EOS visits. Hepatitis B analysis will be performed at the 
central laboratory. If the patient develops hepatitis B reactivation, the patient will be 
discontinued from the study drug. 
Hepatitis C antibody and HIV will be assessed at Screening in all patients. If hepatitis C 
or HIV test result is positive, the patient will be excluded from the study. Hepatitis and 
HIV analysis will be performed at the central laboratory. 
6.4.3 Other Safety Assessment 
6.4.3.1 Immunogenicity Testing 
The immunogenicity of CT-P47 and RoActemra will be assessed by ADA and 
neutralizing antibody (NAb) test in validated immunoassay. It will be specified in a 
separate validation document.  
Blood samples for immunogenicity assessments of CT-P47 and RoActemra will be 
collected from all patients at the time points specified in the schedule of events 
(Table 11-1). The immunogenicity samples will be drawn at the same time as samples for 
PK and/or for clinical laboratory testing, where possible. If the blood sample is unable to 
be analyzed or is missing, extra blood samples collected for PK assessment at the same 
time point can be used for the immunogenicity assessment. Additional immunogenicity 
will be assessed when immune-related AEs (e.g., hypersensitivity) occur. 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 62 
6.4.3.2 Hypersensitivity Monitoring 
For hypersensitivity monitoring, vital signs (including systolic and diastolic BP, heart 
rate, respiratory rate, and body temperature) will be monitored before beginning of the 
study drug administration (within 15 minutes) and at 1 hour (±15 minutes) after the end 
of the study drug infusion.  
In addition, any type of ECG will be performed for hypersensitivity monitoring 1 hour 
(±15 minutes) after the end of the study drug infusion. Emergency equipment, such as 
adrenaline, antihistamines, corticosteroids, and respiratory support including inhalational 
therapy, oxygen, and artificial ventilator will be available. For patient who early 
discontinued study drug, monitoring of hypersensitivity is unnecessary after the 
discontinuation. 
For patients who experience anaphylaxis or other serious treatment-related 
hypersensitivity reaction, study drug must be stopped immediately and the patient 
discontinued from the study drug. 
Anaphylaxis will be identified according to Sampson criteria as following.  
Anaphylactic reactions  
Anaphylaxis will be identified according to Sampson criteria (Sampson et al., 2006). 
Anaphylaxis is likely when any 1 of the 3 criteria are fulfilled.  
1. Acute onset of an illness (minutes to several hours) with involvement of the skin, 
mucosal tissue, or both (e.g., generalized hives, pruritus or flushing, swollen lips- 
tongue-uvula) and at least one of the following:  
a. Respiratory compromise (e.g., dyspnea, wheeze or bronchospasm, stridor, 
reduced peak expiratory flow, hypoxemia)  
b. Reduced BP or associated symptoms of end-organ dysfunction (e.g., hypotonia 
[collapse], syncope, incontinence)  
2. Two or more of the following that occur rapidly after exposure to a likely allergen for 
that patient (minutes to several hours):  
a. Involvement of the skin-mucosal tissue (e.g., generalized hives, itch-flush, 
swollen lips-tongue-uvula)  
b. Respiratory compromise (e.g., dyspnea, wheeze-bronchospasm, stridor, reduced 
peak expiratory flow, hypoxemia)  
c. Reduced BP or associated symptoms (e.g., hypotonia [collapse], syncope, 
incontinence)  

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 63 
d. Persistent gastrointestinal symptoms (e.g., crampy abdominal pain, vomiting)  
3. Reduced BP after exposure to known allergen for that patient (minutes to several 
hours):  
a. Adults: Systolic BP of less than 90 mmHg or greater than 30% decrease from 
that person’s baseline. 
Details will be recorded in both the source documents and the eCRF. 
6.4.3.3 Vital Signs and Weight 
Vital signs will be measured at the time points indicated in the schedule of events 
(Table 11-1). The following vital signs will be measured:  
• 
Blood pressure (systolic and diastolic [mmHg]) 
• 
Heart rate (beats per minute) 
• 
Body temperature (°C) 
• 
Respiratory rate (breaths per minute) 
Blood pressure and HR will be measured using consistent methods for each patient and 
after the patient has been resting for at least 5 minutes. The same route of temperature 
recording should be used for each patient. All measurements will be documented at each 
visit, and the details will be recorded in both the source documents and the eCRF. 
Vital sign measurements will also be monitored before and after study drug 
administration as part of hypersensitivity monitoring (Section 6.4.3.2). 
Body weight (in kg, wearing only light clothes, no shoes) will be measured according to 
the schedule of events (Table 11-1) to determine dose of study drug.  
6.4.3.4 Physical Examination 
A physical examination will be performed at the time points indicated in the schedule of 
events (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. 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 64 
6.4.3.5 Pregnancy 
For women of childbearing potential who have not been surgically sterilized, a serum 
pregnancy test will be conducted at Screening and EOS visit by central laboratory and 
urine pregnancy test will be used to confirm patients are not pregnant prior to dosing on 
each scheduled visit specified in the schedule of events (Table 11-1) or more frequently if 
required by country-specific legislation. Only patients with a negative serum pregnancy 
test results can be enrolled in the study (i.e., patients with inconclusive serum pregnancy 
test results at first result are not considered inclusion). A urine pregnancy test will be 
performed locally. If a urine pregnancy test result is positive, a confirmatory serum 
pregnancy test will be performed at the central laboratory.   
In an event of unexpected pregnancy during study participation and for 6 months after the 
last dose of study drug, patients will be counselled to inform the investigator. If a female 
patient becomes pregnant, the study drug must be discontinued immediately. If a female 
patient or the partner of a male patient becomes pregnant, the pregnancy must be reported 
to sponsor and EastHORN pharmacovigilance department within 24 hours of the study 
center’s knowledge of the pregnancy while confirmation is pending. Once the pregnancy 
is confirmed with a serum pregnancy test, female patients must permanently discontinue 
the study drug. The study center must complete the supplied pregnancy form (female 
patient or partner of a male patient) and return it to sponsor and EastHORN within 
24 hours after acquisition of the consent for the pregnancy form.  
Pregnant patients or the pregnant partners of male patients 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. Pregnancy alone will 
not be regarded as an AE unless there is a suspicion that the study drug may have 
interfered with the effectiveness of a contraceptive medication. Elective abortions without 
complications should not be handled as AEs, unless they are therapeutic abortions. 
Hospitalization for normal delivery of a healthy newborn should not be considered as 
SAE. Any SAE that occurs during pregnancy (e.g., maternal serious complications, 
ectopic pregnancy, stillbirth, neonatal death, congenital anomaly, birth defect) must be 
reported within 24 hours in accordance with the procedure for reporting SAEs 
(Section 6.4.1.4). 
6.4.3.6 Electrocardiogram 
12-lead ECGs will be performed locally after the patient has rested quietly for at least 5 
minutes in supine position at the time points indicated in the schedule of events 
(Table 11-1).  

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 65 
If patients have signs and symptoms of hypersensitivity or other cardiac origin, a 12-lead 
ECG could be performed at any time during the study period by investigator’s discretion. 
If, following ECG review by the investigator, there are any ECG findings that would 
indicate cardiac insufficiency or QT prolongation, the patients will be referred to a 
cardiologist and the event will be recorded in the source documents and the eCRF. 
Regardless of the ECG result, further evaluation with a cardiologist can be performed at 
the discretion of the investigator. 
In addition, any type of ECG will be performed for hypersensitivity monitoring 1 hour 
(±15 minutes) after the end of the study drug infusion (Section 6.4.3.2). 
6.4.3.7 Tuberculosis Assessment 
Patients who currently have, or have a history of, or experience any of TB related 
situation as specified in Section 4.1.2, will result in exclusion from the study. 
Throughout the study, patients will be monitored for the clinical signs and symptoms of 
TB, as specified in the schedule of events (Table 11-1). Patients with active TB based on 
the imaging, microbiology results and/or the clinical signs and symptoms will be 
discontinued from the study drug or terminate the study at discretion of the investigator.  
If the result of the IGRA is positive during the study, patients will be referred to the 
clinician immediately to investigate the presence of active TB based on medical history 
and any clinical signs and symptoms including chest X-ray result. Even in the absence of 
clinical suspicion for active TB, study drug administration will be temporarily stopped. It 
is recommended that study drug administration is resumed in patients who have received 
at least 3 weeks of country-specific TB therapy and who intend to complete the entire 
course of TB therapy. However, study drug administration can be resumed simultaneously 
with the start of country-specific TB therapy after discussion with the medical monitors 
of sponsor or its designee in advance. 
If the patient is exposed to a person with active TB during the study period, an IGRA test 
will be done immediately and country-specific TB therapy will be initiated immediately 
regardless of the IGRA test result being negative or positive. The IGRA test will be 
repeated 8 weeks after the initial IGRA test and country-specific TB therapy can be 
discontinued if the repeated result is negative. 
No further IGRA testing is required during the treatment period for the following patients:  
• 
Patient who has a history of latent TB with sufficient documentation of complete TB 
prophylaxis. 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 66 
• 
Patient who has confirmed latent TB at Screening and enrolled after at least 3 weeks 
of latent TB prophylaxis. This patient should have sufficient documentation of 
complete TB prophylaxis. 
• 
Patient with a positive result of IGRA during the study. 
6.4.3.7.1 Chest X-Ray 
A chest X-ray (both posterior–anterior and lateral views) should be taken during 
Screening and read by a qualified radiologist or pulmonary physician to specifically look 
for evidence of current or previous active or latent TB. If a chest X-ray within 42 days 
prior to the first administration of the study drug (Day 1) is available, a chest X-ray is not 
required at Screening, and the result will be recorded in both the source documents and 
the eCRF. 
Radiographic findings suggestive of healed TB or active TB may include but are not 
limited to pulmonary nodules, fibrotic scars, calcified granulomas, upper lobe infiltrates, 
cavitations, and pleural effusions. Any abnormal X-ray changes should be discussed with 
the medical monitor prior to the first administration of the study drug (Day 1). The chest 
X-ray should be available to the investigator for review prior to the first administration of 
the study drug (Day 1) of the patient. 
6.4.3.7.2 Interferon- γ Release Assay 
An IGRA will be used to identify positive conversion of negative results for patients. 
Samples for this analysis will be obtained at the time points specified in the schedule of 
events (Table 11-1). The IGRA will be performed at the central laboratory. 
6.5 
Sample Collections 
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. 
6.6 
Sample Labelling, Storage, and Shipment 
6.6.1 Sample Labelling 
Each sample tube will be clearly labelled with the following information: study number, 
patient number, tube identification, and scheduled sampling time point. 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 67 
6.6.2 Sample Storage and Shipment 
During the study, blood samples will be collected for PK, immunogenicity, and/or 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. 
Additionally, back-up samples for PK and/or immunogenicity will be retained at the 
central laboratory as a backup for up to 5 years after the end of the study in case 
additional analysis is required, however, samples can be destroyed at any time with 
sponsor’s approval even within 5 years. If additional analysis for PK and/or 
immunogenicity is not required, the sample will be stored at Sponsor or a designated 
biobank for a further 5 years (from the date the sample is transferred to the biobank) 
unless a specific authorization is given by sponsor to destroy the sample. Additional tests 
can be conducted at sponsor or the biobank if it is required from a regulatory or medical 
perspective. Details in storage and shipment will be followed according to the laboratory 
manual. 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 68 
7 Statistical Considerations 
The statistical analysis will be performed using SAS software Version 9.4 or later (SAS 
Institute Inc., Cary, North Carolina, USA). The statistical methods for this study will be 
described in a detailed SAP, which will be finalized prior to database lock. 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 study 
report. 
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 patients within a particular category. Data will be listed in data 
listings. 
7.1 
Sample Size Calculation 
A sample size of 336 patients (168 patients in each treatment group of CT-P47 and 
RoActemra) leads to at least 85% statistical power to demonstrate equivalence of CT-P47 
and RoActemra based on the two-sided 90% confidence interval for the difference of 
mean change from baseline of DAS28 (ESR) score at Week 24. In the sample size 
calculation, equivalence margin of -0.6 to 0.5, two one-sided 5% significance level, 
standard deviation of 1.53 and actual difference of 0 in mean change from baseline at 
Week 24 was assumed. The drop-out rate has been hypothesized at 25%; therefore, 
approximately 448 patients (224 patients in each treatment group of CT-P47 and 
RoActemra) will be randomized. The sample size with sufficient number of patients 
remaining at the time of single transition was also considered. 
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 patients randomly assigned to 
receive study drugs (CT-P47 or RoActemra) 
ITT-Treatment Period II subset: The ITT–Treatment Period II subset is defined as all 
patients in ITT set who are randomly assigned to receive study drug (CT-P47 or 
RoActemra) prior to dosing at Week 24. 
Per-Protocol Set (PPS): The PPS is defined as all randomly assigned patients who are 
compliant with therapy (defined to be ≥80% of planned cumulative doses up to Week 20) 
and have a DAS28 (ESR) assessment at baseline and Week 24 and do not have any major 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 69 
protocol deviation affecting primary endpoint. Patients who received rescue therapy 
before Week 24 will be excluded. Final determinations of the PPS will be made at the 
blinded data review meeting (DRM) for the efficacy primary endpoint before unblinding.  
Pharmacokinetic (PK) Set: The PK Set is defined as all randomly assigned patients who 
receive at least 1 full 8 mg/kg dose of study drug (CT-P47 or RoActemra) and who have 
at least 1 post-treatment PK result. If any patient is found to be non-compliant with 
respect to dosing, a determination of the PK Set will be made on a case-by-case basis at 
the blinded DRM. 
PK-Treatment Period II subset: The PK–Treatment Period II subset will consist of all 
patients in PK set who receive at least 1 full 8 mg/kg dose of either of study drug (CT-P47 
or RoActemra) and have at least 1 post-treatment PK result at or after Week 24. 
Safety Set: The Safety Set is defined as all randomly assigned patients who receive at 
least 1 dose (full or partial) of study drug (CT-P47 or RoActemra).  
Safety–Treatment Period II subset: The Safety–Treatment Period II subset will consist 
of all patients in Safety set who receive at least 1 dose (full or partial) of study drug (CT-
P47 or RoActemra) at or after Week 24. 
7.3 
Demographics, Baseline, and Background Characteristics 
Demographics (including age, gender, ethnicity, and race) and baseline and background 
characteristics (including medical history, RA history, RF, and anti-CCP) 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.  
Listings will be provided by treatment group showing the demographics, baseline, and 
background characteristics in ITT set. In addition, a listing of patients whose trial 
participation is impacted by COVID-19 with details of the impact, will be prepared, if 
applicable. 
7.4 
Efficacy Analyses 
7.4.1 Primary Efficacy Analysis 
The difference of mean change from baseline of DAS28 (ESR) score at Week 24 will be 
analyzed using an ANCOVA model with Multiple imputation (MI) under the Missing At 
Random (MAR) assumption for missing data handling. Missing values will be imputed 
using regression method with treatment, body weight (<100 kg or ≥100 kg) measured on 
Day 1, disease activity by DAS28 (ESR) score at Screening (>5.1 or ≤5.1), and prior 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 70 
biologic use approved for RA treatment (yes or no) as covariates. The 10 imputed datasets 
will be created. These multiple imputed datasets are then analyzed by using ANCOVA 
with treatment as a fixed effect and body weight (<100 kg or ≥100 kg) measured on Day 
1, disease activity by DAS28 (ESR) score at Screening (>5.1 or ≤5.1), and prior biologic 
use approved for RA treatment (yes or no) as covariates. The results from each set of 
imputed datasets will then be pooled using PROC MIANALYZE procedure in SAS®, 
aggregating the results for the final statistical inference using Rubin’s method. Final 
determination of covariates and details will be described in the SAP. The two-sided 90% 
confidence interval (CI) for the difference between the 2 treatment groups (CT-P47 and 
RoActemra) will be produced. Therapeutic equivalence of treatment difference in the 
change from baseline of DAS28 (ESR) at Week 24 by the ANCOVA analysis will be 
concluded if the 90% CIs for the treatment difference is entirely within –0.6 to 0.5.   
The primary population of primary endpoint is ITT Set evaluated under a treatment policy 
estimand. For the treatment policy estimand, all available data will be included in the 
primary analysis regardless of intercurrent events such as study drug discontinuation, 
switch to rescue therapy or protocol violation. A supportive analysis for the primary 
efficacy endpoint will be conducted using the PPS. Definition of each analysis set is 
described in Section 7.2. Additionally, the sensitivity analysis to evaluate the impact of 
missing data will be conducted on the ITT Set as described in Section 7.4.1.2. 
7.4.1.1 DAS28 (ESR) 
Disease activity score in 28 joints (ESR) (Appendix 11.8) will be assessed using the 
following equation: 
𝐷𝐷𝐷𝐷𝐷𝐷28 (𝐸𝐸𝐸𝐸𝐸𝐸) = ൫0.56 × ඥ𝑇𝑇𝑇𝑇𝑇𝑇28൯+ ൫0.28 × ඥ𝑆𝑆𝑆𝑆𝑆𝑆28൯+ (0.70 × ln[𝐸𝐸𝐸𝐸𝐸𝐸]) + (0.014 × 𝐺𝐺𝐺𝐺)  
Where: 
• TJC28 = number of tender joints (0-28): tender joint count (TJC) 
• SJC28 = number of swollen joints (0-28): swollen joint count (SJC) 
• ESR = ESR measurement (mm/hour) 
• GH = patient’s global disease activity measured on 100 mm VAS (Appendix 11.3) 
Descriptive statistics for actual value and change from baseline of DAS28 (ESR) will be 
summarized by treatment group. 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 71 
7.4.1.2 Sensitivity Analysis for Primary Efficacy Endpoint 
Sensitivity analysis using tipping point approach will be conducted for the primary 
efficacy endpoint in the ITT set. Tipping point analysis will be performed under the 
Missing Not At Random (MNAR) assumption. Imputed values by MI will be shifted 
gradually to make MNAR scenarios. A 90% CI for the treatment difference will be 
obtained from ANCOVA under these scenarios, and the scenario which the confidence 
interval no longer be included in the equivalent margin of -0.6 to 0.5 will be displayed. 
All the MNAR scenarios and corresponding CIs will be provided. 
7.4.2 Secondary Efficacy Analysis 
The secondary efficacy endpoints will be descriptively summarized using the ITT Set and 
PPS and data for Treatment Period II will be summarized on the ITT-Treatment Period II 
subset, unless otherwise specified. These will be summarized by treatment group as 
appropriate and listed. The following secondary efficacy endpoints will be assessed for all 
patients during the study: 
• ACR20, ACR50 and ACR70  
• Individual components of the ACR  
• Hybrid ACR response  
• DAS28 (CRP) 
• DAS28 (ESR) (except for Week 24) 
• Individual components of the DAS28 
• EULAR response 
• Simplified disease activity index (SDAI) and clinical disease activity index 
(CDAI)  
• ACR/EULAR remission (Boolean-based definition) 
• 36-item short form health survey (SF-36)  
• Joint damage progression based on radiographic evaluations 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 72 
7.4.2.1 ACR20, ACR50, ACR70 and Individual Components 
A patient is defined as a responder according to ACR20/ACR50/ACR70 criteria if the 
following are fulfilled: 
• A decrease of at least 20%/50%/70% in the number of tender joints (based on 
68 joints) 
• A decrease of at least 20%/50%/70% in the number of swollen joints (based on 
66 joints), and 
• A 20%/50%/70% improvement in at least 3 of the following: 
o Patient’s assessment of pain on the VAS 
o Patient’s global assessment of disease activity (VAS) 
o Physician’s global assessment of disease activity (VAS) 
o HAQ estimate of physical ability 
o Serum CRP concentration or ESR 
The VAS range is from 0 to 100 mm, with higher scores indicating poorer status or more 
severe pain (therefore an improvement in status or pain is reflected by a decrease in 
VAS). 
The proportion of patients demonstrating ACR20, ACR50 and ACR70 will be 
summarized by treatment. Descriptive statistics for actual value and change from baseline 
of components of the ACR will be summarized by treatment group. 
7.4.2.1.1 Health Assessment Questionnaire Disability Index 
General health status will be assessed using the Health Assessment Questionnaire (HAQ) 
(Appendix 11.6). Descriptive statistics for actual value and change from baseline of HAQ 
index will be summarized by treatment group.  
The following are the 8 categories within the HAQ: 
• Dressing and grooming (Questions 1, 2) 
• Arising (Questions 3, 4) 
• Eating (Questions 5, 6, 7) 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 73 
• Walking (Questions 8, 9) 
• Hygiene (Questions 10, 11, 12) 
• Reach (Questions 13, 14) 
• Grip (Questions 15, 16, 17) 
• Activities (Questions 18, 19, 20) 
7.4.2.2 Hybrid ACR Response 
The hybrid ACR is an outcome measure that combines the ACR20, the ACR50, the 
ACR70, and a continuous score of the mean improvement in core set measures (American 
College of Rheumatology Committee to Reevaluate Improvement Criteria, 2007). The 
hybrid ACR will be summarized by treatment using descriptive statistics. The possible 
scores are displayed in Table 7-1. 
Table 7-1 
Scoring Method for the Hybrid ACR 
ACR Status 
Mean % Change in Core Set Measures 
<20 
≥20, <50 
≥50, <70 
≥70 
Not ACR20 
Mean % change 
19.99 
19.99 
19.99 
ACR20 but not ACR50 
20 
Mean % change 
49.99 
49.99 
ACR50 but not ACR70 
50 
50 
Mean % change 
69.99 
ACR70 
70 
70 
70 
Mean % change 
Abbreviations: ACR, American College of Rheumatology; ACR20, ACR 20% improvement criteria; 
ACR50, ACR 50% improvement criteria; ACR70, ACR 70% improvement criteria. 
Reference: American College of Rheumatology Committee to Reevaluate Improvement Criteria, 2007. 
7.4.2.3 DAS28 (CRP) 
See Section 7.4.1.1 for DAS28 (ESR).  
Disease activity score in 28 joints (CRP) (Appendix 11.8) will be assessed using the 
following equation: 
𝐷𝐷𝐷𝐷𝐷𝐷28 (𝐶𝐶𝐶𝐶𝐶𝐶) = ൫0.56 × ඥ𝑇𝑇𝑇𝑇𝑇𝑇28൯+ ൫0.28 × ඥ𝑆𝑆𝑆𝑆𝑆𝑆28൯
+ (0.36 × ln[𝐶𝐶𝐶𝐶𝐶𝐶+ 1]) + (0.014 × 𝐺𝐺𝐺𝐺) + 0.96 
Where: 
• TJC28 = number of tender joints (0-28): tender joint count (TJC) 
• SJC28 = number of swollen joints (0-28): swollen joint count (SJC) 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 74 
• CRP = CRP measurement (mg/L) 
• GH = patient’s global disease activity measured on 100 mm VAS (Appendix 11.3) 
Descriptive statistics for actual value and change from baseline of DAS28 (CRP) and 
components of the DAS28 (ESR and CRP) will be summarized by treatment group. 
7.4.2.4 EULAR Response Criteria 
Response criteria according to EULAR are measured using DAS28 (ESR and CRP) 
according to Table 7-2. The proportion of patients achieving the EULAR response 
categories will be summarized by treatment group. 
Table 7-2 
EULAR Response Criteria 
Present DAS28 
DAS28 Improvement 
>1.2 
>0.6 to ≤1.2 
≤0.6 
≤3.2 
Good response 
Moderate response 
No response 
>3.2 to ≤5.1 
Moderate response 
Moderate response 
No response 
>5.1 
Moderate response 
No response 
No response 
Abbreviations: DAS28, disease activity score in 28 joints; EULAR, European Alliance of Associations 
for Rheumatology. 
Reference: Fransen and van Riel, 2005.  
7.4.2.5 Simplified Disease Activity Index and Clinical Disease Activity 
Index 
Simplified and clinical disease activity will be measured using SDAI and CDAI 
calculated from the formulas presented in Table 7-3. Descriptive statistics for actual value 
and change from baseline of SDAI and CDAI will be summarized by treatment group. 
Table 7-3 
Calculation of Disease Activity Indices 
Index 
Formula 
SDAI 
SJC28 + TJC28 + PGA + EGA + CRP 
CDAI 
SJC28 + TJC28 + PGA + EGA 
SJC28 = swollen joint count (0-28) 
TJC28 = tender joint count (0-28) 
PGA = patient global assessment of disease activity (VAS: 0-10 cm) 
EGA = evaluator/physician global assessment of disease activity (VAS: 0-10 cm) 
CRP = C-reactive protein (mg/dL) 
Abbreviations: CDAI, Clinical Disease Activity Index; CRP, C-reactive protein; EGA, evaluator’s global 
assessment of disease activity (physician global assessment); PGA, patient global assessment of disease 
activity; SDAI, Simplified Disease Activity Index; SJC, swollen joint count; TJC, tender joint count; 
VAS, visual analogue scale. 
Reference: Aletaha and Smolen, 2009. 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 75 
7.4.2.6 ACR/EULAR remission (Boolean-based definition) 
ACR/EULAR remission will be evaluated using the Boolean-based definition. 
Patient must satisfy all of the following: 
• 
Tender joint count ≤ 1 (of 28 assessed) 
• 
Swollen joint count ≤ 1 (of 28 assessed) 
• 
CRP ≤ 1 mg/dL 
• 
Patient’s global assessment of disease activity (VAS) ≤ 1 (when converted to 0-10 
scale) 
7.4.2.7 Short-Form Health Survey 
General health status will be assessed using the SF-36 version 2 (Appendix 11.7). The 
following 8 aspects of the health status will be assessed: 
• General and mental health 
• Physical function 
• Social function 
• Physical and emotional health 
• Pain 
• Vitality 
The score on each subscale ranges from 0 (worst) to 100 (best). The individual aspects of 
the survey will be grouped into a physical component and a mental component summary 
score, each of which will be assigned a mean (±SD) score of 50 with an SD of 10 on the 
basis of an assessment of the general population without chronic conditions. Individual 
scores will be compared with the normalized scores for the general population. 
Descriptive statistics for actual value and change from baseline of SF-36 score will be 
summarized by treatment group. 
7.4.2.8 Joint Damage Progression 
Joint damage progression based on radiographic evaluations (1 image of both the right 
and left hands and both the right and left feet, a total of 4 images) will be assessed by the 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 76 
change in the total Sharp score using the modified total Sharp scoring system (Plant et al., 
1994; Sharp et al., 1971; Sharp et al., 1985) at EOS visit. Descriptive statistics for actual 
value and change from baseline of joint damage progression will be summarized by 
treatment group. 
7.5 
Pharmacokinetic Analyses 
Serum concentrations will be summarized using quantitative descriptive statistics 
(including geometric mean and percent coefficient of variation [CV%], as appropriate) by 
treatment group, study visit, and time point. 
Serum concentrations for Treatment Period I will be summarized on PK Set and data for 
Treatment Period II will be summarized on PK-Treatment Period II subset, unless 
otherwise specified. 
7.6 
Safety Analyses 
Safety analyses will be performed on the Safety Set and data for Treatment Period II will 
be performed on Safety-Treatment Period II subset, unless otherwise specified. The safety 
endpoints will be evaluated under a treatment policy estimand, and for AESI, evaluation 
will be under both treatment policy estimand and ‘while on treatment’ estimand. For the 
treatment policy estimand, all available data will be included in the safety analysis 
regardless of intercurrent events such as study drug discontinuation, switch to rescue 
therapy or protocol violation. For the ‘while on treatment’ estimand, only collected data 
until a fixed timepoint after permanent treatment discontinuation will be included. The 
fixed timepoint is defined as the earliest of the following events.   
• 28 days after last study drug administration 
• Start date of rescue therapy 
• Date of EOS (Week 52)  
• Start date of any other intercurrent event: intercurrent event is defined as events 
occurring after treatment initiation that affect either the interpretation or the 
existence of the measurements associated with the clinical question of interest.   
7.6.1 Adverse Events 
Adverse events will be graded for severity according to the CTCAE v5.0 and will be 
coded to system organ class (SOC) and preferred term (PT) according to MedDRA. 
Safety analysis will focus on TEAEs, as described in Section 6.4.1.1.  

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 77 
The following TEAE summaries will be reported by SOC, PT, and treatment group, as 
appropriate: 
• Number and percentage of patients reporting at least 1 TEAE 
• Number and percentage of patients reporting at least 1 treatment-emergent SAE 
• Number and percentage of patients discontinuing the study drug due to a TEAE 
• Number and percentage of patients with AESIs (infection, hypersensitivity 
including anaphylaxis, hepatic event, haemorrhage, gastrointestinal perforation, 
malignancy, and demyelinating disorder) 
At each level of summarization for the number of patients with an event, a patient is 
counted only once if they reported one or more events and only the worst intensity will be 
counted at each level of summarization. All AE data will be presented in the data listings. 
7.6.2 Clinical Laboratory Tests 
Clinical laboratory tests will be summarized by treatment group at each scheduled 
collection time. Actual values and changes from baseline for clinical laboratory test 
results will be summarized by treatment arm at each time point using descriptive 
statistics. Shift tables will be generated for clinical laboratory test results. Individual 
clinical laboratory test results will also be presented in data listings. 
7.6.3 Immunogenicity 
The number and percentage of patients with ADA and NAb results will be listed and 
summarized by treatment group and visit. 
7.6.4 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 treatment group 
as appropriate. 
7.6.5 Other Safety Analyses 
Actual values and change from baseline for vital signs measurements will be summarized 
by treatment arm at each time point using descriptive statistics. 
A shift table of physical examination from baseline to each scheduled post-baseline 
timepoint for each body system will be summarized by treatment arm. 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 78 
Individual 12-lead ECG results will be summarized using a frequency table by treatment 
arm. 
Individual 12-lead ECG results, physical examination findings, and vital sign 
measurements (including hypersensitivity monitoring) will be presented in data listings. 
IGRA will be summarized and listed by treatment at each scheduled collection time. 
All other safety data will be listed and summarized by treatment arm as appropriate. 
7.7 
Interim Analyses 
No interim analyses are planned for this study. 
7.8 
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 
Good Clinical Practice (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 centers, review of protocol procedures with 
the investigator and associated staff prior to the study, periodic monitoring visits by 
sponsor or its designee, and direct transmission of clinical laboratory data from a central 
laboratory into the clinical database. The eCRF will be reviewed for accuracy and 
completeness by the monitor during on-site monitoring visits and after their return to 
sponsor or its designee; any discrepancies will be resolved with the investigator or 
designees, as appropriate. The data will be entered into the clinical study database and 
verified for accuracy. 
Quality assurance staff from 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. Patient 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 sponsor or its designee if he or she has been contacted by a 
regulatory agency concerning an upcoming inspection. 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 79 
8 Investigator’s Obligations 
The following administrative items are meant to guide the investigator in the conduct of 
the study but may be changed based on industry and government SOPs, working practice 
documents, or guidelines. Changes will be reported to the IEC but will not result in 
protocol amendments. 
8.1 
Confidentiality 
All laboratory specimens, evaluation forms, reports, and other records will be identified 
in a manner designed to maintain patient confidentiality. All records will be kept in a 
secure storage area with limited access. Clinical information will not be released without 
the written permission of the patient (or the patient’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 the ICH guidelines require that approval be obtained from an IEC prior 
to participation of human patients in research studies. Prior to study onset, the protocol, 
informed consent, advertisements to be used for the recruitment of study patients, and any 
other written information regarding this study to be provided to the patient or the patient’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 date 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, with written reports on any changes significantly affecting the 
conduct of the study or increasing the risk to patients. 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 80 
8.3 
Patient Information and Consent 
A written informed consent in compliance with the ICH E6(R2) guidelines shall be 
obtained from each patient prior to entering the study or performing any unusual or non-
routine procedure that involves risk to the patient. An informed consent template may be 
provided by the sponsor to the study centers. 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 prior to IEC submission. Once reviewed, 
the consent will be submitted by the investigator to his or her IEC for review and 
approval prior to the start of the study. If the ICF is revised during the course of the study, 
all active participating patients must sign the revised form. 
Prior to recruitment and enrollment, each prospective patient or his or her legal guardian 
will be given a full explanation of the study and be allowed to read the approved ICF. 
Once the investigator is assured that the patient/legal guardian understands the 
implications of participating in the study, the patient/legal guardian 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 patient’s right to withdraw from the clinical study at any time without giving 
reasons and without jeopardizing the patient’s further course of medical treatment 
• The existence of patient insurance coverage and a summary of what is included in 
this coverage 
• Adequate time and opportunity to satisfy questions will be given to the patients. 
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 patient or 
patient’s legal representatives (according to the local regulations) prior to 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 patient or legal guardian. 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 81 
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 eCRF, 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 6.4.1.4. 
In addition, the principal investigator or sub-investigator agrees to submit annual reports 
to his or her IEC as appropriate. 
8.5 
Financial Disclosure and Obligations 
Investigators are required to provide financial disclosure information to allow the sponsor 
to submit the complete and accurate certification or disclosure statements per regional 
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 EastHORN is financially responsible for further testing or 
treatment of any medical condition that may be detected during the Screening process. In 
addition, in the absence of specific arrangements, neither the sponsor nor EastHORN is 
financially responsible for further treatment of the patient’s disease. 
8.6 
Investigator Documentation 
Prior to beginning the study, the investigator will be asked to comply with ICH E6(R2) 
8.2 and Title 21 of the CFR by providing the following essential documents, including but 
not limited to: 
• IEC approval 
• Original investigator-signed investigator agreement page of the protocol 
• Curriculum vitae (CV) for the principal investigator and each sub-investigator. 
Current licensure must be noted on the CV. The CV will be signed and dated by 
the principal investigators and sub-investigators at study start-up, indicating that 
they are accurate and current. 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 82 
• 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. 
• IEC-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 patient or legal guardian, and 
• Laboratory certifications and normal ranges for any local laboratories used by the 
study center. 
8.7 
Study Conduct 
The investigator agrees that the study will be conducted according to the principles of 
ICH E6(R2). The investigator will conduct all aspects of this study in accordance with all 
national, state, and local laws or regulations. The analytical assays will be conducted 
according to the general principles of the Organization for Economic Cooperation and 
Development Principles of Good Laboratory Practice for testing of chemicals 
C(81)30(Final). 
Prior to the study onset, the protocol, informed consent, advertisements to be used for 
patient recruitment and any other written information regarding this study to be provided 
to the patient or the patient’s legal guardian must be approved by the IEC. Documentation 
of all IEC approvals and of the IEC compliance with the ICH E6(R2) guidelines will be 
maintained by the study center and will be available for review by the sponsor or its 
designee. 
All IEC approvals will be signed by the IEC chairman or designee and must identify the 
IEC name and address, the clinical protocol by title and/or protocol number and the date 
approval and/or favorable opinion was granted. 
The principal investigator or designated sub-investigator is responsible for obtaining 
continued review of the clinical research at intervals not exceeding 1 year or otherwise 
specified by the IEC. The principal investigator or designated sub-investigator must 
supply the sponsor or its designee with written documentation of continued review of the 
clinical research. 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 83 
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 patients 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 patient data into the 
eCRF as accurately as possible, and respond to any reported discrepancies rapidly. These 
source documents may include diaries, laboratory reports, ECG strips, etc. 
The analysis data sets will be a combination of these data and data from other sources 
(e.g., laboratory data). 
An eCRF is accessed through the appropriate system, which allows for on-site data entry 
and data management. Study center users can read from and write to 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 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 the IEC with a summary of the 
study’s outcome and the sponsor and regulatory authority(ies) with any reports required. 
8.11 Records Retention 
All correspondence (e.g., with sponsor, IEC, or clinical research associates) relating to 
this clinical study will be kept in appropriate file folders. Records of patients, source 
documents, eCRF, and drug inventory sheets pertaining to the study must be kept on file. 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 84 
Essential documents should be retained until at least 15 years after the date on which the 
results of the study are submitted to the regulatory authorities in support of an allocation 
for a research or marketing permit, or completion date for study by approval or 
disapproval of any application, whichever is later. These documents should be retained 
for a longer period, however, 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 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 may work with the investigators to determine how the 
manuscript is written and edited, the number and order of authors based on SOPs of 
sponsor, 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 and publication thereof will not be unduly withheld. 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 85 
9 Study Management 
9.1 
Sponsor 
CELLTRION, Inc. 
23 Academy-ro, Yeonsu-gu, Incheon, 22014, South Korea 
Phone: +82 32 850 5000 
Fax: +82 32 850 5050 
E-mail: contact@celltrion.com 
Sponsor Representative 
YunJu Bae 
Clinical Planning Department 1 Leader 
Phone: +82 32 850 4160 
Fax: +82 32 850 1202 
E-mail: yunju.bae@celltrion.com 
9.2 
Vendor Contact 
EastHORN Clinical Services in CEE, Limited. 
Zinonos Sozou 11, Office 303, 1075 Nicosia, Cyprus 
Phone: +44 7801 058660 
The names and addresses of the investigators and clinical study centers involved in the 
study are presented separately together with the investigators’ signatures. 
9.3 
Analytical Facilities 
Any analytical facilities and procedures utilized for this study must be Good Laboratory 
Practice compliant. The following analytical facilities will be used: 
Central Laboratories 
Medicover Integrated Clinical Services 
Palio Office Park, Building A, Marynarki Polskiej 197, 80-868 Gdańsk, Poland 
Phone: +48 602 443 552 
Laboratories for Pharmacokinetic and Immunogenicity Testing 
Syneos Health, Inc. 
Ligand Binding R&D, 301D College Road East, Princeton, NJ 08540 
Phone: +1 609 951 0005 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 86 
Laboratories for X-Ray Image analysis 
Clario 
211 Carnegie Center Drive, Princeton, NJ 08540 
Phone: +1 609 936 2600 
9.4 
Monitoring 
9.4.1 Independent Data Monitoring Committee 
This study will be monitored by an independent data monitoring committee (IDMC) 
consisting of a PK specialist, statistician, independent physician, and an independent 
chairing physician. The IDMC will review and evaluate accumulating safety data to 
ensure the safety of study patients. 
Additionally, study results when the clinical study report (CSR) is available will be 
reviewed by the IDMC. 
Further details will be provided in the independent IDMC charter. 
9.4.2 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 the pandemic situation of COVID-19 the monitor will discuss with the 
sponsor, CRO, and the investigator for further plan, which is specified in Section 1.6.1.2.  
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 current SOPs. 
9.4.3 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 access to all study records. 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 87 
The investigator should promptly notify the sponsor and EastHORN 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 patient, must be reviewed and approved by the sponsor or its 
designee. Amendments to the protocol must be submitted in writing to the investigator’s 
IEC for approval before patients 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 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 patients 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 patient’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 patients 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. 
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 major deviation occurs when there is non-adherence to the protocol by the 
patient or investigator that may results in a significant impact on the completeness, 
accuracy, reliability of study data, or additional risk to the patient’s rights, safety, and 
well-being. Major protocol deviations include the followings, and can lead to the patient 
being withdrawn from the study (Section 4.2) or exclusion from the statistical analysis 
according to SAP.  

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 88 
• Mis-randomization (defined as patients who received the opposite treatment to 
which they were assigned at any point during the study) 
• Non-adherence to Inclusion or Exclusion criteria 
• Significant ICH GCP non-compliance 
• Receipt of prohibited therapy (Section 5.9)   
Protocol deviations will be documented by the clinical monitor throughout the course of 
monitoring visits. Deviations will be defined prior to unblinding. Principal investigators 
will be notified in writing by the monitor of deviations. The IEC should be notified of all 
protocol deviations in a timely manner. 
9.6 
Study Termination 
Although sponsor has every intention of completing the study, sponsor reserves the right 
to discontinue the study at any time for clinical or administrative reasons. 
The completion of the study is defined as the date of final database is locked. 
9.7 
Clinical Study 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. 
Sponsor plans to prepare 2 CSRs, but additional CSRs will be generated upon 
requirements for regulatory or academic purposes, including but not limited to the 
following: 
• Data for each patient up to 32 weeks 
• All data after completion of the study (up to Week 52) 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 89 
10 Reference List 
Actemra (tocilizumab) [Prescribing information]. Genentech, Inc. USA; 02/2022. 
Available   from: 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/125276s134lbl.pdf 
American College of Rheumatology Committee to Reevaluate Improvement Criteria. A 
proposed revision to the ACR20: the hybrid measure of American College of 
Rheumatology response. Arthritis Rheum. 2007 Mar 15;57(2):193-202. Available from: 
https://www.rheumatology.org/Portals/0/Files/A%20Proposed%20Revision%20to%20the
%20ACR20.pdf 
American College of Rheumatology. Updated Guideline for the Management of 
Rheumatoid Arthritis. Project Plan – October 2018. Available from: 
https://www.rheumatology.org/Portals/0/Files/Rheumatoid-Arthritis-Guideline-Project-
Plan.pdf 
Aletaha D, Neogi T, Silman AJ, et al. 2010 Rheumatoid arthritis classification criteria: an 
American College of Rheumatology/European League Against Rheumatism collaborative 
initiative. Ann Rheum Dis. 2010;69:1580-8. 
Aletaha D, Smolen JS. The Simplified Disease Activity Index and Clinical Disease 
Activity Index to monitor patients in standard clinical care. Rheum Dis Clin North Am. 
2009;35(4):759-72. 
Burmester GR, Choy E, Kivitz A, et al. Low immunogenicity of tocilizumab in patients 
with rheumatoid arthritis. Ann Rheum Dis. 2017 Jun;76(6):1078-1085. 
Burmester GR, Rubbert-Roth A, Cantagrel A, et al. A randomised, double-blind, parallel-
group study of the safety and efficacy of subcutaneous tocilizumab versus intravenous 
tocilizumab in combination with traditional disease-modifying antirheumatic drugs in 
patients with moderate to severe rheumatoid arthritis (SUMMACTA study). Ann Rheum 
Dis. 2014 Jan;73(1):69-74. 
Curtis JR, Johnson SR, Anthony DD, et al. American College of Rheumatology. 
American College of Rheumatology Guidance for COVID-19 Vaccination in Patients 
With Rheumatic and Musculoskeletal Diseases: Version 1. Arthritis Rheumatol. 2021 
Jul;73(7):1093-1107. 
DAS28 form. MW Word DAS28. Available from:  
https://www.das-score.nl/das28/DAScalculators/DAS28frm%20v26-7-2012.doc 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 90 
Emery P, Keystone E, Tony HP, et al. IL-6 receptor inhibition with tocilizumab improves 
treatment outcomes in patients with rheumatoid arthritis refractory to anti-tumour 
necrosis factor biologicals: results from a 24-week multicentre randomised placebo-
controlled trial. Ann Rheum Dis. 2008 Nov;67(11):1516-23. 
European Medicines Agency (EMA). Directive 2001/20/EC of the European parliament 
and of the council of 04 April 2001. Available from: 
https://ec.europa.eu/health/sites/default/files/files/eudralex/vol-
1/dir_2001_20/dir_2001_20_en.pdf 
European Medicines Agency (EMA). Draft guidance. Guideline on similar biological 
medicinal products containing monoclonal antibodies. 18 Nov 2010. Available from: 
http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2010/11/
WC500099361.pdf 
European Medicines Agency (EMA). RoActemra: European public assessment report. 
EMEA/H/C/000955/II/0032; 2014. Available from: 
https://www.ema.europa.eu/en/documents/variation-report/roactemra-h-c-955-ii-0032-
epar-assessment-report-variation_en.pdf 
European Medicines Agency (EMA). RoActemra: European public assessment report. 
EMEA/H/C/000955/II/0076; 2018. Available from: 
https://www.ema.europa.eu/en/documents/variation-report/roactemra-h-c-955-ii-0076-
epar-assessment-report-variation_en.pdf 
European Medicines Agency (EMA). Guidance on the Management of Clinical Trials 
during the COVID-19 (Coronavirus) Pandemic. Version 5. 10/02/2022. Available from: 
https://ec.europa.eu/health/sites/default/files/files/eudralex/vol-
10/guidanceclinicaltrials_covid19_en.pdf 
Food and Drug Administration (FDA), Department of Health and Human Services (US). 
Guidance for Industry: Scientific considerations in demonstrating biosimilarity to a 
reference product. Apr 2015. Available from: 
https://www.fda.gov/downloads/drugs/guidances/ucm291128.pdf 
Food and Drug Administration (FDA). Code of Federal Regulations Title 21, Volume 5. 
Sec. 312.32 IND safety reporting (21CFR312.32). April 1, 2020. Available from: 
https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?fr=312.32 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 91 
Fraenkel L, Bathon JM, England BR, et al. 2021 American College of Rheumatology 
Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Care Res (Hoboken). 2021 
Jul;73(7):924-939. 
Fransen J, van Riel PLCM. The Disease Activity Score and the EULAR response criteria. 
Clin Exp Rheumatol. 2005;23(Suppl. 39):S93-9.  
Genovese MC, McKay JD, Nasonov EL, et al. Interleukin-6 receptor inhibition with 
tocilizumab reduces disease activity in rheumatoid arthritis with inadequate response to 
disease-modifying antirheumatic drugs: the tocilizumab in combination with traditional 
disease-modifying antirheumatic drug therapy study. Arthritis Rheum. 2008 
Oct;58(10):2968-80. 
Hochberg MC, Change RW, Dwosh I, et al. The American College of Rheumatology 
1991 revised criteria for the criteria for the classification of global functional status in 
rheumatoid arthritis. Arthritis Rheum. 1992;35:498-502. 
Jones G, Sebba A, Lowenstein MB, et al. Comparison of tocilizumab monotherapy versus 
methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: the 
AMBITION study. Ann Rheum Dis. 2010 Jan;69(1):88-96. 
Kremer JM, Blanco R, Brzoski M, et al. Tocilizumab inhibits structural joint damage in 
rheumatoid arthritis patients with inadequate responses to methotrexate: results from the 
double-blind treatment phase of a randomized placebo-controlled trial of tocilizumab 
safety and prevention of structural joint damage at one year. Arthritis Rheum. 2011 
Mar;63(3):609-21. 
Landewé RBM, Machado PM, Kroon F, et al. EULAR provisional recommendations for 
the management of rheumatic and musculoskeletal diseases in the context of SARS-CoV-
2. Ann Rheum Dis. 2020 Jul;79(7):851-858. 
Mcinnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med. 2011 
Dec8;365(23):2205-19. 
Plant MJ, Saklatvala J, Borg AA, et al. Measurement and prediction of radiological 
progression in early rheumatoid arthritis. J Rheumatol. 1994;21:1808-13. 
RoActemra (tocilizumab) [Summary of product characteristics]. Roche Registration 
GmbH. Germany; Feb 2022. Available from: 
https://www.ema.europa.eu/en/documents/product-information/roactemra-epar-product-
information_en.pdf 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 92 
Sampson HA, Munoz-Furlong A, Campbell RL, et al. Second symposium on the 
definition and management of anaphylaxis: Summary Report-Second National Institute of 
Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network Symposium. J 
Allergy Clin Immunol 2006;117(2):391-97. 
Sharp JT, Lidsky MD, Collins LC, Moreland J. Methods of scoring the progression of 
radiologic changes in rheumatoid arthritis: correlation of radiologic, clinical and 
laboratory abnormalities. Arthritis Rheum. 1971;14:706-20. 
Sharp JT, Young DY, Bluhm GB, Brook A, Brower AC, Corbett M, et al. How many 
joints in the hands and wrists should be included in a score of radiologic abnormalities 
used to assess rheumatoid arthritis? Arthritis Rheum. 1985;28:1326-35. 
Silman AJ, Pearson JE. Epidemiology and genetics of rheumatoid arthritis. Arthritis Res. 
2002;4 Suppl 3:S265-72. 
Singh JA, Saag KG, Bridges SL Jr, et al. 2015 American College of Rheumatology 
guideline for the treatment of rheumatoid arthritis. Arthritis Rheumatol. 2016 
Jan;68(1):1-26. 
Smolen JS, Beaulieu A, Rubbert-Roth A, et al. Effect of interleukin-6 receptor inhibition 
with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, 
placebo-controlled, randomised trial. Lancet. 2008 Mar 22;371(9617):987-97.  
Smolen JS, Landewé RBM, Bijlsma JWJ, et al. EULAR recommendations for the 
management of rheumatoid arthritis with synthetic and biological disease-modifying 
antirheumatic drugs: 2019 update. Ann Rheum Dis. 2020 Jun;79(6):685-699. 
Whittle SL, Hughes RA. Folate supplementation and methotrexate treatment in 
rheumatoid arthritis: a review. Rheumatology. 2004; 43(3):267-71. 
World Health Organization. Coronavirus (COVID-19) Dashboard. Available from: 
https://covid19.who.int 
World Medical Association Declaration of Helsinki: ethical principles for medical 
research involving human patients. JAMA. 2013 Nov 27;310(20):2191-4. 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 93 
11 Appendices 
11.1 Schedule of Event

CELLTRION, Inc 
Confidential 
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 94 
Table 11-1 
Schedule of Events 
Procedure 
Screening 
Study Period 
Treatment Period I 
Treatment Period II 
EOS1 
Dose 
1 
Dose 
2 
Dose 
3 
Dose  
4 
Dose 
5 
Dose  
6 
Dose 
7 
Dose 
8 
Dose 
9 
Dose 
10 
Dose 
11 
Dose 
12 
Dose 
13 
Study visit (Week) 
–6 
0 
4 
8 
12 
16 
20 
24 
28 
32 
36 
40 
44 
48 
52 
Study visit (Day) 
–42 to –1 
1 
29 
57 
85 
113 
141 
169 
197 
225 
253 
281 
309 
337 
365 
Visit Window (days)2 
 
 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
Screening/Baseline assessments 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics, height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history3 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
X4 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hepatitis B test5 
X 
 
 
 
 
 
 
(X4) 
 
 
 
 
 
 
(X) 
Hepatitis C and HIV-test6 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum pregnancy test7 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Chest X-ray8 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Interferon-γ release assay9 
X 
 
 
 
 
 
 
X4 
 
 
 
 
 
 
X 
Rheumatoid factor 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Anti-CCP 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization10 
 
X4 
 
 
 
 
 
X4 
 
 
 
 
 
 
 
Study drug administration11 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Efficacy assessments 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Swollen joint count12 
(28 joints/66 joints) 
X 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X 
Tender joint count12 
(28 joints/68 joints) 
X 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X 
CRP13 
X 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X 
ESR (local)13 
X 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X 
VAS global assessment of disease 
activity (patient/physician) scores 
X 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X 
VAS pain score 
X 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X 
Health assessment questionnaire 
X 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X 
QoL (SF-36) assessment 
X 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X 
Hand and foot x-ray14 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 

CELLTRION, Inc 
Confidential 
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 95 
Procedure 
Screening 
Study Period 
Treatment Period I 
Treatment Period II 
EOS1 
Dose 
1 
Dose 
2 
Dose 
3 
Dose  
4 
Dose 
5 
Dose  
6 
Dose 
7 
Dose 
8 
Dose 
9 
Dose 
10 
Dose 
11 
Dose 
12 
Dose 
13 
Study visit (Week) 
–6 
0 
4 
8 
12 
16 
20 
24 
28 
32 
36 
40 
44 
48 
52 
Study visit (Day) 
–42 to –1 
1 
29 
57 
85 
113 
141 
169 
197 
225 
253 
281 
309 
337 
365 
Visit Window (days)2 
 
 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
PK/Immunogenicity assessments 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pharmacokinetic blood sampling15 
 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X 
Immunogenicity blood sampling16 
 
X4 
X4 
X4 
X4 
X4 
 
X4 
 
X4 
 
X4 
 
X4 
X 
Safety and other assessments  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital signs, body weight 
X 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X 
Physical examination 
X 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X 
Clinical chemistry, hematology, 
urinalysis17 
X 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X 
Soluble interleukin-6 receptor 
 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X 
Urine pregnancy test7 
 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
 
12-lead ECG18 
X 
X4 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Hypersensitivity monitoring19 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Prior, concomitant medications20 
X 
TB clinical monitoring21 
X 
AEs22 
X 
Abbreviations: AE, adverse event(s); ANC, absolute neutrophil count; Anti-CCP, anti-cyclic citrullinated peptide antibody; CRP, C-reactive protein; DNA, DeoxyriboNucleic Acid; ECG, 
electrocardiogram; eCRF, electronic case report forms; EOS, end-of-study; ESR, erythrocyte sedimentation rate; HIV, human immunodeficiency virus; IGRA, Interferon-Gamma Release 
Assays; ICF, informed consent form; IM, intramuscular; PK pharmacokinetic; QoL, quality of life; Q4W, every 4 week;  SC, subcutaneous; TB, tuberculosis; VAS, visual analogue scale. 
1. 
An EOS visit will occur at Week 52 for all patients who completed or discontinued study drug.   
2. 
A dose visit window of 3 days is allowed based on the Day 1 visit throughout the study period, including EOS visit. Details of dose delay/skip criteria is described in Section 5.6. 
3. 
Rheumatoid arthritis history including 2010 ACR/EULAR classification criteria and ACR global functional status at Screening will also be collected. 
4. 
Procedures will be performed at the study center prior to the study drug administration. 
5. 
At Screening, HBsAg, HBsAb, and HBcAb must be assessed in all patients (mandatory). If the HBsAg test result is positive, the patient must be excluded from the study. If a patient has 
HBsAg (negative), HBsAb (negative or positive), and HBcAb (positive), a HBV DNA test will be performed at Screening. If the HBV DNA test result is positive, the patient will be 
excluded from the study; if the HBV DNA test result is negative, the patient can be included in the study. For patients who are enrolled based on the HBV DNA test, testing of HBsAg, 
HBsAb, HBV DNA, ALT, AST, and total bilirubin will be performed at the Week 24 and EOS visits. Hepatitis B analysis will be performed at the central laboratory.  
6. 
If hepatitis C or HIV test result is positive, the patient will be excluded from the study. Hepatitis C and HIV analysis will be performed at the central laboratory.  
7. 
For women of childbearing potential who have not been surgically sterilized, a serum pregnancy test will be conducted at Screening and EOS visit by central laboratory and a urine 
pregnancy test will be used to confirm patients are not pregnant prior to dosing on each scheduled visit or more frequently if required by country-specific legislation. A urine pregnancy test 
will be performed locally. If a urine pregnancy test result is positive, a confirmatory serum pregnancy test will be performed at the central laboratory. For patient who early discontinued 
study drug, urine pregnancy test is unnecessary after the discontinuation. 

CELLTRION, Inc 
Confidential 
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 96 
8. 
A chest X-ray (both posterior-anterior and lateral views) is not required at Screening if a chest X-ray from within the 42 days prior to the first administration of the study drug (Day 1) is 
available. 
9. 
The IGRA testing will be performed at the central laboratory. No further IGRA testing is required during the study period for patients who have at least 1 positive result for IGRA test and 
have completed the prophylaxis at least for required duration by country specific legislation. 
10. Patients will be randomly assigned to receive either CT-P47 or RoActemra prior to dosing on Day 1 (Week 0) (first randomization). Patients will be randomized again prior to dosing on 
Week 24 (second randomization). 
11. Methotrexate (10 to 25 mg/week, oral or parenteral [IM or SC] dose, and dose and route must be maintained from beginning to EOS) and folic acid (≥5 mg/week, oral dose) will be 
administered throughout the study treatment, unless dose modification is required due to laboratory abnormalities as per Section 5.2.2.  
12. An independent joint count assessor will be assigned to each study center. If possible, it is recommended that the joint count assessments are performed independently by the same person, 
at each study center throughout the entire study period.  
13. Both CRP and ESR are considered as efficacy and safety (clinical laboratory test) endpoints.  
14. One image of each hand and each foot (both the right and left hands and feet, a total of 4 images) for analysis of efficacy will be obtained at the scheduled times. The baseline radiographs 
will be assessed within 42 days prior to the first administration of the study drug (Day 1). Joint damage progression as determined by radiography will be assessed using the modified total 
Sharp scoring system by the central independent reviewer.  
15. Blood samples for PK analysis will be collected at predose (prior to the beginning of study drug administration) for all PK sampling time points up to and including Week 48. For EOS 
visit, PK samples will be obtained anytime during the day. For patients who early discontinued the study drug, PK sampling will only be collected until the next scheduled visit and further 
PK sampling is unnecessary. 
16. Blood samples for immunogenicity analysis will be drawn prior to dosing of study drug at the same time as the clinical laboratory test where applicable. Analysis will be performed at the 
central laboratory. Additional immunogenicity will be assessed when immune-related AEs occur. For patients who early discontinued the study drug, immunogenicity sampling will only be 
collected until the next scheduled immunogenicity sampling visit and further immunogenicity sampling is unnecessary. 
17. Clinical laboratory (clinical chemistry, hematology and urinalysis) test samples will be analyzed at the central laboratory. Refer to Section 5.2.2 for guidelines for dosage modification and 
treatment interruption or discontinuation for laboratory abnormalities in liver enzymes (ALT and AST), absolute neutrophil count, or platelet counts. The laboratory results from previous 
visit will be used to determine if dose modification or discontinuation is needed. If the investigator confirms that the previous laboratory results of liver enzymes, ANC or platelet are within 
abnormal range, additional sample should be collected in advance (≤7 days prior to the next dose administration as unscheduled visit) to facilitate rapid clinical decision making.  
Clinical chemistry 
Total protein, serum bilirubin (total, direct), alanine aminotransferase (ALT), 
aspartate aminotransferase (AST), alkaline phosphatase, γ-glutamyltransferase, blood 
urea nitrogen, creatinine, albumin, sodium, potassium, calcium, chloride, inorganic 
phosphorus, glucose, magnesium, lactate dehydrogenase, total cholesterol, 
triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, 
Creatine kinase, Creatine kinase-MB, C-reactive protein, erythrocyte sedimentation 
rate, and uric acid 
Hematology 
Hematocrit, hemoglobin, red blood cells, total and differential white blood cell 
count, absolute neutrophil count (ANC), and platelet count 
Urinalysis 
Bilirubin, blood, color, glucose, ketones, leukocytes, nitrite, pH, protein, specific 
gravity, and urobilinogen  
 
18. All scheduled 12-lead ECGs will be performed locally after the patient has rested quietly for at least 5 minutes in supine position. If patients have signs and symptoms of hypersensitivity or 
other cardiac origin, a 12-lead ECG could be performed at any time during the study period by investigator’s discretion. Regardless of the 12-lead ECG result, further evaluation with a 
cardiologist can be done depending on the investigator’s discretion. 

CELLTRION, Inc 
Confidential 
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 97 
19. Additional vital signs including blood pressure, heart and respiratory rates, and body temperature will be monitored for hypersensitivity reactions before beginning of the study drug 
administration [within 15 minutes] and at 1 hour (±15 minutes) after the end of study drug infusion. In addition, any type of ECG will be performed for hypersensitivity monitoring 1 hour 
(±15 minutes) after the end of the study drug infusion. Emergency equipment, such as adrenaline, antihistamines, corticosteroids, and respiratory support including inhalational therapy, 
oxygen, and artificial ventilator will be available. For patient who early discontinued study drug, monitoring of hypersensitivity is unnecessary after the discontinuation. 
20. Use of all prior and concomitant medications for the treatment of RA, from the diagnosis of disease until the EOS visit (Week 52), will be recorded in both the source documents and the 
eCRF. Use of all medications for other purposes, taken from 42 days prior to the first administration of study drug will be recorded until EOS visit in both the source documents and the 
eCRF.  
21. Throughout the study, patients will be monitored for the clinical signs and symptoms of TB. The IGRA or chest X-ray can be performed at the investigator’s discretion based on the 
judgment on the signs and symptoms of TB monitoring. The investigator will confirm the absence of active TB prior to the subsequent dose administration. 
22. Adverse events will be assessed from the date the ICF is signed until the EOS visit.  
 
Note 1. The patients who early discontinued from the study drug will also visit the study center until Week 52 by regular scheduled time interval for efficacy and safety assessments (except for 
hypersensitivity monitoring and urine pregnancy), even if they change their RA medication (including those prohibited by the protocol). Blood samples for PK and immunogenicity 
analysis will only be collected until the next scheduled visit (from the last study drug administration) and further sampling is unnecessary. However, any assessment(s) that could 
jeopardize the patients’ safety could be skipped, as per investigator judgement. 
Note 2. If a study center is not equipped to perform the specified tests, this will be discussed and arranged with the sponsor or the sponsor’s designee. 
Note 3. Refer to Section 1.6.1.2 for COVID-19 mitigation plans. 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 98 
11.2 ACR Revised Criteria for Classification of Functional Status in 
RA 
Class I 
Completely able to perform usual activities of daily living 
(self-care, vocational, and avocational) 
Class II 
Able to perform usual self-care and vocational activities, but 
limited in avocational activities 
Class III 
Able to perform usual self-care, but limited in vocational and 
avocational activities 
Class IV 
Limited in ability to perform usual self-care, vocational, and 
avocational activities 
Note: Usual self-care activities include dressing, feeding, bathing, grooming, and toileting. 
Avocational (recreational and/or leisure) and vocational (work, school, homemaking) activities are 
patient-desired and age- and sex-specific. 
Reference: Hochberg et al., 1992. 
 
 
11.3 VAS Patient’s Global Assessment of Disease Activity 
Patient’s global assessment of disease activity is measured by the patient indicating the 
patient’s current disease activity by marking one line (│) through the 100-mm line (0 mm 
equals very well and 100 mm equals very poor disease activity). The length of the line is 
measured from the left (in mm) and the value (in mm) recorded in the patient’s eCRF. The 
converted score (in cm) for SDAI or CDAI will be calculated using 0.1 cm interval.  
 
Very well 
 
 
 
        Very poor 
 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 99 
11.4 VAS Physician Global Assessment of Disease Activity 
Physician’s global assessment of disease activity is measured by the physician indicating 
the patient’s current disease activity by marking one line (│) through the 100-mm line (0 
mm equals very well and 100 mm equals very poor disease activity). This is an evaluation 
based on the patient’s disease signs, functional capacity and physical examination, and 
should be independent of the patient’s global assessment of disease activity. The length of 
the line is measured from the left (in mm) and the value (in mm) recorded in the patient’s 
eCRF. The converted score (in cm) for SDAI or CDAI will be calculated using 0.1 cm 
interval. 
 
Very well 
 
 
 
        Very poor 
   
11.5 VAS Patient’s Assessment of Pain 
Patient assessment of pain is measured by the patient indicating the extent of their current 
pain by marking one line (│) through the 100-mm line (0 mm equals no pain and 100 mm 
equals most severe pain). The length of the line is measured from the left (in mm) and the 
value (in mm) recorded in the patient’s eCRF. 
 
No pain 
 
 
 
        Most severe pain 
 
 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 100 
11.6 Health Assessment Questionnaire and Scoring of the Health 
Assessment Questionnaire 
 
 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 101 
 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 102 
11.7 General Health Status (Medical Outcomes Study Short-Form 
Health Survey) 
Study centers are using the validated questionnaire for their country; this appendix is 
included for information only and is not to be used as the official questionnaire to collect 
patient data.

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 103 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 104 
 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 105 
 
11.8 DAS28 
The DAS28 score uses a calculation that requires the assessment of 28 joints for swelling 
and tenderness. The 28 joints are shoulders, elbows, wrists, metacarpophalangeal joints, 
proximal interphalangeal joints, and the knees.  
More information on DAS28 can be found at https://www.das-score.nl/en. 
 
Left 
Right 
 
Swollen 
Tender 
Swollen 
Tender 
Shoulder 
 
 
 
 
Elbow 
 
 
 
 
Wrist 
 
 
 
 
MCP 
1 
 
 
 
 
 
2 
 
 
 
 
 
3 
 
 
 
 
 
4 
 
 
 
 
 
5 
 
 
 
 
PIP 
1 
 
 
 
 

CELLTRION, Inc. 
Confidential  
CT-P47 3.1 
Protocol Version 1.1, including country specific A.0 
 
 
Page 106 
 
2 
 
 
 
 
 
3 
 
 
 
 
 
4 
 
 
 
 
 
5 
 
 
 
 
Knee 
 
 
 
 
Subtotal 
 
 
 
 
Total 
Swollen 
 
Tender 
 
Abbreviations: MCP, metacarpophalangeal joints; PIP, proximal interphalangeal joints 
Reference: DAS28.