A Randomized, Active-Controlled, Double-Blind, Phase 3 Study to Compare Efficacy and Safety of CT-P17 With Humira When Co-administered With Methotrexate in Patients With Moderate to Severe Active 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 CT-P17 with Humira when 
Co-administered with Methotrexate in Patients with Moderate to Severe 
Active Rheumatoid Arthritis 
 
Protocol Number CT-P17 3.1 
EudraCT Number: 
2018-001690-25 
Sponsor: 
 
 
 
 
Sponsor Contact: 
 
 
 
 
 
 
SAE Reporting and Data Centre: 
 
 
 
 
 
 
Version and Date of Protocol:  
Protocol Version 3.0, 06 Aug 2018  
 
CONFIDENTIAL 
 
All financial and nonfinancial support for this study will be provided by CELLTRION, Inc. The concepts and 
information contained in this document or generated during the study are considered proprietary and may not be 
disclosed in whole or in part without the expressed, written consent of CELLTRION, Inc. The study will be 
conducted according to the protocol and in compliance with the International Council for Harmonisation 
harmonised tripartite guideline E6(R2): Good Clinical Practice 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. 
CT-P17 
Protocol Number: CT-P17 3.1 
Protocol Version 3.0 
 
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 CT-P17 
with Humira 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 3.0, dated 06 Aug 2018, the International Council for 
Harmonisation harmonised tripartite 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. 
CT-P17 
Protocol Number: CT-P17 3.1 
Protocol Version 3.0 
 
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Table of Contents 
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-P17 ....................................................................................................................22 
1.3 
Pre-clinical Studies .................................................................................................23 
1.4 
Clinical Studies .......................................................................................................23 
1.5 
Study Rationale .......................................................................................................24 
1.5.1 
Choice of Study Population .....................................................................24 
1.6 
Benefit and Risk Assessment ..................................................................................25 
2 
Study Objectives...............................................................................................................26 
2.1 
Primary Objective ...................................................................................................26 
2.2 
Secondary Objectives..............................................................................................26 
3 
Investigational Plan ..........................................................................................................27 
3.1 
Study Design ...........................................................................................................27 
3.2 
Study Overview ......................................................................................................27 
4 
Patient Selection and Withdrawal Criteria .......................................................................30 
4.1 
Selection of Study Population .................................................................................30 
4.1.1 
Inclusion Criteria .....................................................................................30 
4.1.2 
Exclusion Criteria ....................................................................................32 
4.2 
Study Treatment Discontinuation and Study Termination  .....................................36 
4.2.1 
Recruitment of Additional Patients ..........................................................37 
4.3 
Premature Termination of the Study .......................................................................37 
5 
Study Treatment ...............................................................................................................38 
5.1 
Method of Assigning Patients to Treatment Groups ...............................................38 

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Protocol Version 3.0 
 
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5.2 
Treatments Administered ........................................................................................38 
5.2.1 
Co-administration of Methotrexate and Folic Acid .................................39 
5.2.2 
Premedication ..........................................................................................39 
5.2.3 
Training for Home Injection of Study Drug ............................................40 
5.2.4 
Other Supplies..........................................................................................40 
5.3 
Identity of Investigational Product..........................................................................41 
5.4 
Management of Clinical Supplies ...........................................................................42 
5.4.1 
Study Drug Packaging, Labelling, and Storage .......................................42 
5.4.2 
Study Drug Accountability ......................................................................43 
5.5 
Blinding...................................................................................................................44 
5.5.1 
Breaking the Blind ...................................................................................44 
5.6 
Treatment Compliance ............................................................................................45 
5.7 
Prior, Concomitant, and Subsequent Therapy .........................................................45 
5.8 
Prohibited Therapy ..................................................................................................46 
6 
Study Assessments and Procedures ..................................................................................47 
6.1 
Efficacy Assessments ..............................................................................................47 
6.1.1 
Joint Count Assessment ...........................................................................47 
6.1.2 
American College of Rheumatology Criteria and Individual 
Components .............................................................................................47 
6.1.3 
Disease Activity Score Using 28 Joint Counts ........................................48 
6.1.4 
Simplified Disease Activity Index and Clinical Disease Activity Index .48 
6.1.5 
Quality of Life .........................................................................................49 
6.1.6 
Joint Damage Progression .......................................................................49 
6.2 
Pharmacokinetic Assessments ................................................................................49 
6.3 
Pharmacodynamic Assessments..............................................................................49 
6.3.1 
Rheumatoid Factor and Anti-cyclic Citrullinated Peptide .......................50 
6.3.2 
C-Reactive Protein and Erythrocyte Sedimentation Rate ........................50 
6.4 
Biomarker Assessments (Optional).........................................................................50 
6.5 
Safety Assessments .................................................................................................50 
6.5.1 
Adverse Events ........................................................................................51 
6.5.1.1 
Definitions of Adverse Events .................................................................51 
6.5.1.1.1 
Adverse Events of Special Interest ..............................................52 
6.5.1.1.2 
Serious Adverse Events ................................................................53 

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Protocol Version 3.0 
 
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6.5.1.1.3 
Unlisted (Unexpected) Serious Adverse Events ..........................53 
6.5.1.2 
Eliciting and Documenting Adverse Events ............................................53 
6.5.1.3 
Reporting Adverse Events .......................................................................54 
6.5.1.4 
Patients’ Self-reporting of Adverse Events ..............................................55 
6.5.1.5 
Reporting Serious Adverse Events ..........................................................55 
6.5.1.6 
Suspected Unexpected Serious Adverse Reactions .................................57 
6.5.1.7 
Assessment of Severity ............................................................................58 
6.5.1.8 
Assessment of Causality ..........................................................................58 
6.5.1.9 
Follow-Up of Patients Reporting Adverse Events ...................................59 
6.5.2 
Other Safety Assessment .........................................................................59 
6.5.2.1 
Immunogenicity Testing ..........................................................................59 
6.5.2.2 
Injection Site Reaction .............................................................................60 
6.5.2.3 
Hypersensitivity/Allergic Reactions Monitoring .....................................60 
6.5.2.4 
Vital Signs and Weight, and Height .........................................................61 
6.5.2.5 
Electrocardiogram ....................................................................................61 
6.5.2.6 
Physical Examination ..............................................................................61 
6.5.2.7 
Tuberculosis Assessment .........................................................................62 
6.5.2.7.1 
Chest X-Ray .................................................................................63 
6.5.2.7.2 
Interferon- γ Release Assay .........................................................63 
6.5.2.8 
Hepatitis B and Hepatitis C and Human Immunodeficiency Virus .........64 
6.5.2.9 
Pregnancy.................................................................................................65 
6.5.2.10 Clinical Laboratory Analyses...................................................................65 
6.5.2.11 Patient’s Assessment of Local Site Pain ..................................................66 
6.6 
Sample Collections .................................................................................................66 
6.6.1 
Pharmacokinetic Blood Sampling ...........................................................67 
6.6.2 
Pharmacodynamic Blood Sampling.........................................................67 
6.6.3 
Biomarker Blood Sampling (Optional) ...................................................67 
6.6.4 
Immunogenicity Blood Sampling ............................................................67 
6.6.5 
Interferon-γ Release Assay Blood Sampling ...........................................68 
6.6.6 
Routine Safety Blood Sampling ..............................................................68 
6.7 
Labelling, Storage, and Transportation of Samples ................................................68 
6.7.1 
Sample Labelling .....................................................................................68 
6.7.2 
Sample Storage and Shipment .................................................................68 
7 
Statistical Analysis Plan ...................................................................................................70 
7.1 
Efficacy Analyses ....................................................................................................70 

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Protocol Version 3.0 
 
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7.1.1 
Primary Efficacy Analysis .......................................................................70 
7.1.1.1 
ACR20 .....................................................................................................70 
7.1.2 
Secondary Efficacy Analysis ...................................................................71 
7.1.2.1 
ACR20, ACR50, ACR70 and Individual Components ............................72 
7.1.2.1.1 
Health Assessment Questionnaire Disability Index .....................72 
7.1.2.2 
Hybrid ACR Response .............................................................................72 
7.1.2.3 
DAS28 .....................................................................................................73 
7.1.2.4 
EULAR Response Criteria.......................................................................74 
7.1.2.5 
Simplified Disease Activity Index and Clinical Disease Activity Index .74 
7.1.2.6 
Short-Form Health Survey .......................................................................75 
7.1.2.7 
Joint Damage Progression .......................................................................75 
7.2 
Pharmacokinetic Analyses ......................................................................................75 
7.3 
Pharmacodynamic Analyses ...................................................................................76 
7.4 
Biomarker Analyses ................................................................................................76 
7.5 
Safety Analyses .......................................................................................................76 
7.5.1 
Demographic and Baseline and Background Characteristics ..................77 
7.5.2 
Adverse Events ........................................................................................77 
7.5.3 
Immunogenicity .......................................................................................78 
7.5.4 
Clinical Laboratory Analyses, IGRA and Pregnancy ..............................78 
7.5.5 
Electrocardiograms, Physical examination, Vital Signs, and Weight ......78 
7.5.6 
Patient’s assessment of Local Site Pain ...................................................78 
7.5.7 
Prior and Concomitant Medications ........................................................78 
7.5.8 
Other Safety Analyses ..............................................................................78 
7.6 
Sample Size Calculation .........................................................................................79 
7.7 
Analysis Sets ...........................................................................................................79 
7.8 
Interim Analyses .....................................................................................................80 
7.9 
Data Quality Assurance...........................................................................................80 
8 
Investigator’s Obligations ................................................................................................81 
8.1 
Confidentiality ........................................................................................................81 
8.2 
Independent Ethics Committee or Institutional Review Board ..............................81 
8.3 
Patient Information and Consent ............................................................................82 
8.4 
Study Reporting Requirements ...............................................................................83 
8.5 
Financial Disclosure and Obligations .....................................................................83 

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CT-P17 
Protocol Number: CT-P17 3.1 
Protocol Version 3.0 
 
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8.6 
Investigator Documentation ....................................................................................84 
8.7 
Study Conduct .........................................................................................................84 
8.8 
Data Collection .......................................................................................................85 
8.8.1 
Electronic Case Report Forms and Source Documents ...........................85 
8.9 
Adherence to Protocol.............................................................................................86 
8.10 Adverse Events and Study Report Requirements ...................................................86 
8.11 Investigator’s Final Report .....................................................................................86 
8.12 Records Retention ...................................................................................................86 
8.13 Subject Identification Register ................................................................................87 
8.14 Publications .............................................................................................................87 
9 
Study Management ...........................................................................................................88 
9.1 
Sponsor ...................................................................................................................88 
9.2 
Vendor Contact........................................................................................................88 
9.3 
Analytical Facilities ................................................................................................89 
9.4 
Monitoring ..............................................................................................................90 
9.4.1 
Data Safety Monitoring Board .................................................................90 
9.4.2 
Monitoring of the Study ...........................................................................90 
9.4.3 
Inspection of Records ..............................................................................91 
9.5 
Management of Protocol Amendments and Deviations..........................................91 
9.5.1 
Modification of the Protocol ....................................................................91 
9.5.2 
Protocol Deviations..................................................................................91 
9.6 
Study Termination ...................................................................................................92 
9.7 
Final Report ............................................................................................................92 
10 Reference List...................................................................................................................94 
11 Appendices .......................................................................................................................98 
11.1 Schedule of Events ..................................................................................................98 
11.2 ACR Revised Criteria for Classification of Functional Status in RA ...................103 
11.3 VAS Patient’s Global Assessment of Disease Activity .........................................104 
11.4 VAS Physician Global Assessment of Disease Activity .......................................105 
11.5 VAS Patient’s Assessment of Pain ........................................................................106 

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Protocol Version 3.0 
 
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11.6 Health Assessment Questionnaire and Scoring of the Health Assessment 
Questionnaire ................................................................................................107 
11.7 General Health Status (Medical Outcomes Study Short-Form Health Survey) ...109 
11.8 DAS28................................................................................................................... 113 
 
List of Tables 
Table 6-1 
Eligibility based on Serologic Markers for Hepatitis B Infection .................. 64 
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 .......................................................................................... 99 
 
List of Figures 
Figure 1 
Study Design Overview .................................................................................. 29 

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CT-P17 
Protocol Number: CT-P17 3.1 
Protocol Version 3.0 
 
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Protocol Synopsis 
Protocol Number: CT-P17 3.1 
Title: A Randomized, Active-Controlled, Double-Blind, Phase 3 Study to Compare Efficacy and Safety of 
CT-P17 with Humira when Co-administered with Methotrexate in Patients with Moderate to Severe Active 
Rheumatoid Arthritis 
Study Phase: Phase 3 
Study Centers: Approximately 60 study centers in approximately 8 countries 
Test Drug, Dose and Regimen: CT-P17, 40 mg (100 mg/mL) by subcutaneous (SC) injection via pre-filled 
syringe (PFS) every other week (EOW), co-administered with methotrexate (MTX) between 12.5 to 
25 mg/week, or 10 mg/week if intolerant to a higher dose, oral or parenteral dose (dose and route must be 
maintained from beginning to end of the study) and folic acid (≥5 mg/week, oral dose) 
Reference Drug, Dose and Regimen: EU-approved Humira, 40 mg (100 mg/mL) by SC injection via PFS 
EOW, co-administered with MTX between 12.5 to 25 mg/week, or 10 mg/week if intolerant to a higher dose, 
oral or parenteral dose (dose and route must be maintained from beginning to end of the study) and folic acid 
(≥5 mg/week, oral dose) 
Objectives: 
Primary Objective 
• 
To demonstrate that CT-P17 is equivalent to Humira, in terms of efficacy as determined by clinical 
response according to the American College of Rheumatology (ACR) definition of a 20% 
improvement (ACR20) at Week 24. 
Secondary Objectives 
• 
To evaluate additional efficacy, pharmacokinetics (PK), pharmacodynamics (PD), and overall 
safety, including immunogenicity and biomarker. 
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 League Against 
Rheumatism (EULAR) classification criteria (Aletaha et al., 2010), despite previous treatment with MTX 
over at least 12 weeks, 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 who has active disease as defined by the presence of 6 or more swollen joints (of 66 assessed), 6 
or more tender joints (of 68 assessed) and either an erythrocyte sedimentation rate (ESR) >28 mm/hour 
or a serum C-reactive protein (CRP) concentration >1.0 mg/dL (>10 mg/L) at Screening. 
4. Patient who has been receiving oral or parenteral MTX at a dose of between 12.5 to 25 mg/week, or 
10 mg/week if intolerant to a higher dose, for at least 12 weeks and who has been on a stable dose and 
route of MTX for at least 4 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) 

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• 
Serum alanine aminotransferase ≤3.0 × ULN 
• 
Serum aspartate aminotransferase ≤3.0 × ULN 
• 
Serum total bilirubin ≤1.5 × ULN 
6. Patient has the following hematology laboratory test results at Screening: 
• 
Hemoglobin >8.0 g/dL (SI units: >80 g/L or 4.96 mmol/L) 
• 
Absolute neutrophil count ≥1.5 × 103 cells/µL (SI units: ≥1.5 × 109 cells/L) 
• 
Platelet count ≥75 × 103 cells/µL (SI units: ≥75 × 109 cells/L) 
7. 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. 
8. Patient and their partner of childbearing potential must agree to use a highly effective method of 
contraception throughout the study and for 6 months after the last dose of assigned treatment. Examples 
include the following: 
• 
Hormonal contraceptives (combined or progestogen-only) associated with inhibition of 
ovulation. 
• 
Intrauterine devices. 
• 
Sexual abstinence (not periodically, but for the entire period of risk). 
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. Male and female patients and their 
partners who have been surgically sterilized for less than 24 weeks prior to the date of informed consent 
must agree to use any medically acceptable methods of contraception. Menopausal females must have 
experienced their last period more than 1 year prior to the date of informed consent to be classified as 
not of childbearing potential. 
9. Patient must be able and willing to self-administer SC injections or designate a qualified person(s) to 
administer SC injection. 
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; biologic or targeted synthetic 
disease-modifying antirheumatic drugs (DMARDs) (e.g., tofacitinib, baricitinib) for the treatment of RA 
and/or a tumor necrosis factor (TNF) α inhibitor for any purposes. 
2. 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. 
3. 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), hepatitis C, or infection 
with human immunodeficiency virus (HIV). However, a patient with past hepatitis B virus is 
allowed if resolved. 
• 
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). A 
patient who has a past diagnosis with sufficient documentation of complete resolution of the 
infection can be enrolled in the study. 

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• 
Other serious infections within 24 weeks prior to the first administration of the study drug 
(Day 1) 
4. Patient who currently has, or has a history of, any of the following tuberculosis (TB): 
• 
Patient who has a history of TB or a current diagnosis of TB. A patient who has a previous 
diagnosis of active TB cannot be enrolled in the study even if there is sufficient documentation 
of complete resolution of active TB. 
• 
Patient who has had exposure to a person with active TB such as first-degree family members 
or co-workers. 
• 
Patient who has an indeterminate result for interferon-γ release assay (IGRA) or latent TB 
(defined as a positive result of IGRA with a negative examination of chest X-ray) at Screening. 
A patient who has a previous diagnosis of latent TB cannot be enrolled despite sufficient 
documentation of prophylaxis. If the result of the IGRA is indeterminate at Screening, 1 retest 
will be possible during the Screening period. If the repeated IGRA result is indeterminate again 
or positive, the patient will be excluded from the study. If the repeated IGRA result is negative, 
the patient can be enrolled in the study. 
5. Patient who has a medical condition including one or more of the following: 
• 
Classified as Class II or III obese by WHO classification (body mass index [BMI] ≥35 kg/m2) 
• 
Uncontrolled diabetes mellitus, even after insulin treatment 
• 
Uncontrolled hypertension (as defined by systolic blood pressure [BP] ≥160 mmHg or diastolic 
BP ≥100 mmHg) 
• 
Any other 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 
• 
Significant systemic RA involvement (e.g., Sjogren’s syndrome, vasculitis, pulmonary 
fibrosis), which would put the patient at risk if they are enrolled 
• 
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 
• 
New York Heart Association (NYHA) Class III or IV heart failure, severe uncontrolled cardiac 
disease (unstable angina or clinically significant electrocardiogram [ECG] abnormalities), 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 clinically significant respiratory disease, 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 conditions significantly affecting the nervous system (e.g., neuropathic conditions or 
nervous system damage) if it could interfere with the investigator’s assessment on disease 
activity scores including joint counts 
• 
Any other 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 
6. Patient who has received or plans to receive any of the following prohibited medications or treatment: 

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Protocol Number: CT-P17 3.1 
Protocol Version 3.0 
 
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• 
Intra-articular corticosteroids within 4 weeks prior to the first administration of the study drug 
(Day 1). 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 the primary endpoint assessment at  
Week 24. In addition, a patient is permitted to receive low-potency topical, otic, and ophthalmic 
glucocorticoid preparations provided 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 products 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 24 weeks after the first administration of the study drug (Day 1) 
7. 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) 
8. 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. 
9. Patient who currently abuses alcohol or drugs or has a history of alcohol or drug abuse within 2 years 
from Screening. 
10. Patient who, in the opinion of their general practitioner or 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, PD, overall safety including immunogenicity and biomarker of multiple single-dose (40 mg) of 
either CT-P17 or Humira administered by SC injection via PFS EOW in combination with MTX (between 
12.5 to 25 mg/week, or 10 mg/week if intolerant to a higher dose, oral or parenteral [intramuscular or SC] 
dose) and folic acid (≥5 mg/week, oral dose). The MTX dose and route must be maintained from beginning 
to end of the study. Approximately 564 male and female patients with moderate to severe active RA will be 
enrolled in a 1:1 ratio (approximately 282 patients per treatment group) into the CT-P17 or Humira treatment 
groups. 
The randomization to treatment assignment will be stratified by the following: 
• 
Country 
• 
Disease activity by Simplified Disease Activity Index (SDAI) at Screening; high (SDAI >26) vs. not 
high (SDAI ≤26) 
Patients will receive CT-P17 or Humira EOW up to Week 24. Prior to dosing at Week 26, patients in the 
Humira treatment group will be randomly assigned in a ratio of 1:1 to either continue Humira (Cohort 2) or 

CELLTRION, Inc. 
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Protocol Number: CT-P17 3.1 
Protocol Version 3.0 
 
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undergo transition to CT-P17 (Cohort 3) from Week 26. All patients who were initially randomly assigned to 
CT-P17 at Day 1 (Week 0) will continue their treatment with CT-P17 (Cohort 1) until the end of the study. 
Second randomization process will also be conducted in Cohort 1 at Week 26 to maintain the study blind. 
The second randomization to Cohorts 2 or 3 will be stratified by the following: 
• 
Disease activity by SDAI at Week 24; remission (SDAI ≤3.3) vs. non-remission (SDAI >3.3) 
The study design and patient assessment overview is presented in Figure S1. 
Figure S1 
Study Design Overview 
  
 
Abbreviations: C, CT-P17; EOS, end-of-study; EOW, every other week; H, Humira; N, number of patients; 
PK, pharmacokinetics; PD, pharmacodynamics; SC, subcutaneous. 
* Prior to dosing at Week 26, all patients will undergo a second randomization process. Patients who were initially 
randomized to Humira will be randomized again in a ratio of 1:1 to either continue Humira or undergo transition to 
CT-P17. Patients who are randomized to CT-P17 or Humira will receive assigned study drug EOW from Week 26 and 
thereafter up to Week 48. Only the study center visit is presented in this figure. 
1 The EOS assessments will be performed at Week 52 for all patients who completed or discontinued study treatment. 
The patients who early discontinued from the study treatment will also visit the study center until Week 52 by regular 
scheduled time interval for efficacy and safety assessments, even if they initiate RA medication changes (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. 
 

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After database lock for data up to Week 24 for all patients, the study will be unblinded for reporting purposes 
and efficacy, PK, PD, immunogenicity, and safety endpoints will be evaluated by the pre-defined unblinded 
Sponsor and Contract Research Operation (CRO) teams. The investigators, patients, and other Sponsor and 
CRO teams will remain blinded until the end of the study. 
 
Study Schedule: There will be 3 study periods in the study, which are the following: Screening Period, 
Treatment Period (I and II), and End-of-Study (EOS) visit. 
 
Screening Period (Day –42 [6 weeks] to Day –1):  
Screening will take place between Day –42 and Day –1 (6 weeks), prior to the first study drug 
administration.  
 
Treatment Period (Week 0 to Week 48):  
• 
Treatment Period I (from Week 0 to Week 24) 
• 
Treatment Period II (after Treatment Period I and prior to 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-P17 or Humira prior to treatment. The 
patient will receive either CT-P17 or Humira, as per first and second randomization, by SC injection EOW, 
co-administered with MTX between 12.5 to 25 mg/week, or 10 mg/week if intolerant to a higher dose, 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. 
 
All patients will return to the study center by regular scheduled time intervals for clinical assessments and 
blood samplings. 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. 
 
End-of-Study (Week 52) visit:  
An EOS visit will occur at Week 52 for all patients who completed or discontinued study treatment. The 
patients who early discontinued from the study treatment will also visit the study center until Week 52 by 
regular scheduled time interval for efficacy and safety assessments, even if they initiate RA medication 
changes (including those prohibited by the protocol). 
Efficacy Assessments: 
Primary Endpoint 
• 
Proportion of patients achieving clinical response (according to the ACR20 criteria) at Week 24. 
Secondary Endpoints 
The following secondary efficacy endpoints will be assessed up to Week 52: 
• 
ACR20 (except for Week 24), ACR50 and ACR70  
• 
Individual components of the ACR  
• 
Hybrid ACR response  
• 
DAS28 (CRP) and DAS28 (ESR)  
• 
Individual components of the DAS28 
• 
EULAR response 
• 
Simplified disease activity index (SDAI) and clinical disease activity index (CDAI)  
• 
36-item short form health survey (SF-36)  

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• 
Joint damage progression based on radiographic evaluations 
Pharmacokinetic Assessment: 
Secondary Endpoint 
The following PK endpoint will be assessed up to Week 52: 
• 
Ctrough 
 Trough concentration (concentration prior to the next study drug administration) 
Pharmacodynamic Assessments: 
Secondary Endpoints 
The following PD endpoints will be assessed up to Week 52: 
• 
CRP 
• 
ESR 
• 
Rheumatoid factor (RF) 
• 
Anti-cyclic citrullinated peptide (anti-CCP) 
Safety Assessments: 
Safety assessments will be performed on AEs (including serious AEs), AEs of special interest (AESI) 
(injection site reactions, hypersensitivity/allergic reactions, infections, and malignancies), 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, local site pain by 
visual analogue scale (VAS), signs and symptoms of TB, and prior and concomitant medications monitored 
throughout the study. Adverse events will be recorded according to the Common Terminology Criteria for 
Adverse Events (CTCAE) v5.0. 
Biomarker Assessments (Optional): 
For patients who sign a separate informed consent form for the biomarker assessment, a blood sample for 
evaluation of genotype (FcγRIIa, IIIa, and/or any necessary genotypes) will be collected prior to dosing on 
Week 0.  
Sample Size: 
A sample size of 450 patients (225 patients in each treatment group of CT-P17 and Humira) leads to 83% 
statistical power for the demonstration of similarity of ACR20 at Week 24 based on the expected ACR20 rate 
of 64% with an equivalence margin of –15% to 15% using a two one-sided 2.5% significance level of an 
equivalence test. The drop-out rate has been hypothesized at 20%; therefore, approximately 564 patients 
(282 patients in each treatment group of CT-P17 and Humira) will be randomized. 
Statistical Analysis: 
 
 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.  
Efficacy Analysis 
The proportion of patients achieving clinical response according to ACR20 criteria at Week 24 will be 
analyzed. The 95% confidence interval (CI) for the difference in proportion between the 2 treatment groups 
(CT-P17 and Humira) will be produced. Therapeutic equivalence of clinical response according to ACR20 
criteria will be concluded if the 95% CIs for the treatment difference is entirely within –15% to 15% at 
Week 24. A sensitivity analysis considering covariates will also be performed. 
The primary population of primary endpoint (ACR20 at Week 24) is intent-to-treat (ITT) population. All 
efficacy endpoints will be analyzed using the ITT and PP populations. 

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• 
ITT Population is defined as all patients enrolled and randomly assigned to receive a dose of either 
of the study drugs, regardless of whether or not any study drug dosing was completed. Patients will 
be assigned to treatment groups based on randomization. 
• 
PP Population is defined as all randomly assigned patients who have received all doses of study 
drug up to Week 22 (total 12 injections) and have an ACR assessment at Week 24. A major protocol 
deviation that may affect the interpretation of study results of primary efficacy endpoint will be 
excluded from PP population. Final determinations of the PP population will be made at the blinded 
data review meeting (DRM) held in accordance with International Council for Harmonization (ICH) 
harmonised tripartite guideline E9. Patients will be assigned to treatment groups based on 
randomization. 
Pharmacokinetic Analysis 
The PK population will consist of all patients who receive at least 1 dose (full) of either of the study drugs 
and have at least 1 post treatment PK concentration data. The PK population will be the primary population 
for the summary of PK data. If any patients are found to be non-compliant with respect to dosing, a decision 
will be made on a case-by-case basis at the blinded DRM prior to code breaking. 
Serum concentrations will be summarized using quantitative descriptive statistics (including geometric mean 
and coefficient of variation [CV%], as appropriate). Pharmacokinetic parameter will also be summarized 
using quantitative descriptive statistics (including geometric mean and CV%, as appropriate).  
Pharmacodynamic Analysis 
The PD population will consist of all patients who receive at least 1 dose (full) of either of study drugs and 
have at least 1 post treatment PD result. The PD population will be the primary population for the summary 
of PD data. The PD endpoints (CRP, ESR, RF, and anti-CCP) will be summarized using descriptive statistics 
(including geometric mean and CV%, as appropriate).  
Safety Analysis 
The safety population will consist of all patients who receive at least 1 dose (full or partial) of either of the 
study drugs. Patients will be assigned to treatment groups based on treatment actually received. The safety 
population will be the primary population for the summary of safety data. 
Adverse events will be recorded according to the CTCAE v5.0 and will be coded to system organ class and 
preferred term according to the Medical Dictionary for Regulatory Activities (MedDRA). Prior and 
concomitant medications will be coded using the WHO Drug Dictionary. 
Biomarker Analysis 
Analyses will be performed on genotypes (FcγRIIa, IIIa, and/or any necessary genotypes) in the ITT 
population. 
 
 

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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 
AE(s) 
adverse event(s) 
AESI(s) 
adverse event(s) of special interest 
AS 
BMI 
ankylosing spondylitis  
body mass index 
BP 
CDAI 
blood pressure 
clinical disease activity index 
CFR 
Code of Federal Regulations 
CI 
confidence interval 
CRO 
CRP 
Contract Research Organization 
C-reactive protein 
CSR 
clinical study report 
CTCAE 
Common Terminology Criteria for Adverse Events 
Ctrough 
trough concentration 
CV 
curriculum vitae 
CV% 
DAS28 
coefficient of variation 
Disease Activity Score 28 
DMARD(s) 
DRM 
disease-modifying antirheumatic drug(s) 
data review meeting 
DSMB 
data safety monitoring board 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EMA 
European Medicines Agency 
EOS 
end-of-study 
EOW 
every other week 
EPAR 
European Public Assessment Report 
ESR 
erythrocyte sedimentation rate 
EU 
European Union 
EULAR 
European League Against Rheumatism 
FDA 
US Food and Drug Administration 
GCP 
Good Clinical Practice 
HAQ 
Health Assessment Questionnaire 

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Abbreviation 
Definition 
HBcAb 
hepatitis B core antibody 
HBsAb 
hepatitis B surface antibody 
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 
IEC 
independent ethics committee 
IFU 
instructions for use 
IGRA 
interferon-γ release assays 
IM 
intramuscular 
IRB 
institutional review board 
ITT 
intent-to-treat 
IWRS 
interactive web response system 
MedDRA 
Medical Dictionary for Regulatory Activities 
MTX 
methotrexate 
NRI 
non-responder imputation 
NSAID(s) 
NYHA 
non-steroidal anti-inflammatory drug(s) 
New York Heart Association 
PD 
PFS 
pharmacodynamic(s) 
pre-filled syringe 
PK 
pharmacokinetic(s) 
PP 
per-protocol 
PT 
preferred term 
PVG 
pharmacovigilance 
RA 
RF 
rheumatoid arthritis 
rheumatoid factor 
SAE(s) 
serious adverse event(s) 
SAP 
statistical analysis plan 
SC 
subcutaneous 
SD 
SDAI 
SI 
standard deviation 
simplified disease activity index 
Système International d’Unités 
SJC 
SOC 
swollen joint count 
system organ class 
SOPs 
standard operating procedures 

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Abbreviation 
Definition 
SUSAR(s) 
suspected unexpected serious adverse reaction(s) 
TB 
tuberculosis 
TEAE(s) 
treatment-emergent adverse event(s) 
TJC 
TNF 
tender joint count 
tumor necrosis factor 
ULN 
upper limit of normal 
US 
United States 
VAS 
WHO 
visual analogue scale 
World Health Organizations 
 

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1 
Introduction 
1.1 Background 
Rheumatoid arthritis (RA) is the most common autoimmune inflammatory arthritis in adults, 
occurring in approximately 0.8% of the global population (Kim et al., 2007, Singh et al., 
2015). It is characterized by a progressive inflammatory synovitis of the joints, which may 
result in irreversible joint erosion within as early as 6 months of disease onset (van der 
Heijde et al., 2010). 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., 2016). 
Therefore, early identification and appropriate treatment should be the primary focus when 
managing patients with RA to reduce disease progression and loss of function. 
Standard antirheumatic therapy for RA usually consists of traditional/conventional 
disease-modifying antirheumatic drug (DMARD), low dose corticosteroids, non-steroidal 
anti-inflammatory drugs (NSAIDs), and analgesics (Furst et al., 2003). Methotrexate (MTX), 
a DMARD, has been shown to improve the signs and symptoms of RA and slow the 
progression of joint destruction in some patients; however, many patients fail to achieve an 
adequate or sustained response to MTX therapy or even when the patients respond to MTX 
therapy, patients experience less than 50% improvement (Weinblatt et al., 2003, Keystone et 
al., 2004, Kim et al., 2007).  
The proinflammatory cytokine tumor necrosis factor (TNF) α plays a critical role in the 
pathogenesis of RA and, as such, is a key target for directed biologic therapy (Furst et 
al., 2003). Among its diverse pathologic effects, TNFα induces the production of other 
proinflammatory cytokines; stimulates endothelial cells to express adhesion molecules that 
attract leukocytes into affected joints; increases the rate of synthesis of metalloproteinases by 
synovial macrophages, fibroblasts, osteoclasts, and chondrocytes; and inhibits the synthesis 
of proteoglycans in cartilage (Weinblatt et al., 2003). In recent years, TNF inhibitor biologic 
agents like adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab and 
non-TNF biologic agents like abatacept, rituximab, or tocilizumab have been developed for 
use in RA. Biological DMARDs, such as TNF inhibitors, are recommended when disease 
activity remains moderate or high despite DMARD monotherapy (Singh et al., 2016). 
Adalimumab, a novel biologic DMARD and the first fully humanized anti-TNF-α 
monoclonal antibody for RA treatment, has been shown to be effective in the treatment of 

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RA. Adalimumab is structurally and functionally analogous to naturally occurring human 
immunoglobulin G1 and demonstrates a high specificity and affinity for TNF. It does not 
bind other cytokines such as lymphotoxin (Keystone et al., 2004). Adalimumab also lyses 
surface TNF expressing cells in vitro in the presence of complement (Humira USPI 2017). It 
is superior to MTX alone in reducing disease activity, arresting structural damage, and 
decreasing disability over 2 years in patients with RA (Chen et al., 2009).  
1.2 CT-P17 
CT-P17, containing the active ingredient adalimumab, is a recombinant humanized 
monoclonal antibody that is being developed as a similar biological medicinal product to the 
reference product, Humira. The reference product was originally approved in the United 
States (US) in December of 2002 and in the European Union (EU) in September of 2003 
(FDA 2002, EMA EPAR for Humira 2017, Humira SmPC 2018). In the European Union, 
Humira is indicated for the following conditions: RA, juvenile idiopathic arthritis, axial 
spondyloarthritis (ankylosing spondylitis [AS], axial spondyloarthritis without radiographic 
evidence of AS), psoriatic arthritis, psoriasis, pediatric plaque psoriasis, hidradenitis 
suppurativa, Crohn’s disease, pediatric Crohn’s disease, ulcerative colitis, and uveitis; in the 
United States, Humira is indicated for the same conditions except axial spondyloarthritis 
without radiographic evidence of AS, pediatric uveitis and pediatric plaque psoriasis (Humira 
USPI 2017, Humira SmPC 2018). 
The reference product, Humira, is supplied as a sterile, preservative-free solution of 
adalimumab for subcutaneous (SC) administration (Humira USPI 2017). Humira is supplied 
in 2 strengths; 50 mg/mL (40 mg/0.8 mL) and 100 mg/mL (40 mg/0.4 mL). 
CT-P17 is manufactured using a Chinese Hamster Ovary cell line by fed-batch cell culture, 
followed by harvest, purification, formulation, and subsequent fill-finish operations. The 
primary amino acid sequences of adalimumab in CT-P17 are identical to that of Humira. Like 
Humira, CT-P17 will be supplied in a single syringe at a concentration of 100 mg/mL as a 
clear to opalescent, colorless to brown liquid for subcutaneous administration. The CT-P17 
drug product will have the same pharmaceutical form and strength as Humira and is intended 
to have a highly similar quality profile as Humira. 

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CELLTRION, Inc. plans to seek approval for all indications for which the innovator product 
has been approved by demonstrating similarity of CT-P17 with the reference product through 
an extensive array of quality, non-clinical, and clinical comparability assessments. 
1.3 Pre-clinical Studies 
Detailed information regarding the non-clinical pharmacology and toxicology of CT-P17 can 
be found in the investigator’s brochure (IB). 
1.4 Clinical Studies 
The efficacy and safety of adalimumab in RA was assessed in 4 multicenter, randomized, 
double-blind pivotal Phase 3 studies. 
The Safety Trial of Adalimumab in RA by Furst et al (2003) evaluated the safety and 
efficacy of adalimumab in 636 patients with RA, who were randomly assigned to receive 
adalimumab 40 mg SC every other week (EOW) or placebo while continuing standard 
antirheumatic therapy. The study demonstrated that addition of adalimumab 40 mg given SC 
EOW to concomitant standard antirheumatic therapy, including one or more traditional 
DMARDs, corticosteroids, NSAIDs, and/or analgesics, is well tolerated and provides 
significant improvements in signs and symptoms of RA. The results also indicated that 
adalimumab is a safe and effective therapeutic option in patients with active RA who have an 
inadequate response to standard antirheumatic therapy. 
A similar study by Weinblatt et al (2003), the ARMADA trial, showed that addition of 
adalimumab at a dose of 20 mg, 40 mg, or 80 mg administered subcutaneously EOW to long-
term MTX therapy in patients with active RA provided significant, rapid, and sustained 
improvement in disease activity over 24 weeks compared with MTX plus placebo. 
In the 52-week study of Keystone et al (2004), 619 patients with active RA who had an 
inadequate response to MTX were randomly assigned to receive adalimumab 40 mg 
subcutaneously EOW, adalimumab 20 mg subcutaneously every week, or placebo plus 
concomitant MTX. The study demonstrated that adalimumab was more effective than 
placebo at inhibiting the progression of structural joint damage, reducing the signs and 
symptoms, and improving physical function in patients with active RA who had 
demonstrated an incomplete response to MTX. 

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Likewise, the efficacy and safety of monotherapy with adalimumab in patients with RA for 
whom previous DMARD treatment has failed was assessed in 544 patients in the study of 
van de Putte et al (2004). The patients were randomized to monotherapy with adalimumab 
20 mg EOW, 20 mg weekly, 40 mg EOW, 40 mg weekly, or placebo and the study showed 
that after 26 weeks, patients treated with adalimumab (any dose) had significantly better 
response rates and achieved better improvements in mean Disability Index of the Health 
Assessment Questionnaire than those treated with placebo. In addition, the study also found 
no significant differences between adalimumab and placebo treated patients for serious 
AE(SAE)s, serious infections, or malignancies. 
1.5 Study Rationale 
CT-P17 is currently being developed by CELLTRION, Inc., and is intended to be developed 
as a biosimilar to Humira. For a biosimilar to be approved, it must be shown 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 CT-P17, EU-approved Humira, and US-licensed Humira will be 
compared to demonstrate PK equivalence in a Phase 1 study in healthy volunteers. An 
additional assessment of the similarity in efficacy, PK, safety, and immunogenicity will be 
carried out in this proposed comparative clinical trial (Study CT-P17 3.1) in patients with 
moderate to severe active rheumatoid arthritis. CELLTRION, Inc. considers that the 
proposed clinical development program will be sufficient to demonstrate PK equivalence of 
CT-P17 (Study CT-P17 1.1 PK similarity healthy volunteer study) and therapeutic 
equivalence and safety (Study CT-P17 3.1 comparative clinical similarity) to the reference 
product. In addition, the pilot study (Study CT-P17 1.2) will be conducted to evaluate safety 
to provide the first human data of CT-P17 in comparison to adalimumab.  
1.5.1 Choice of Study Population 
International regulations (WHO 2009, 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. 

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Consequently, RA has been selected as indication for the comparative clinical trial, due to the 
relatively high magnitude of the treatment effect and immunogenicity rates observed in the 
Humira clinical studies in this indication; thus, facilitating the detection of potential 
differences between CT-P17 and the Humira. 
The study population in the proposed Study CT-P17 3.1 was selected in order to be a 
representative of the original placebo controlled studies supporting the development of the 
reference product and to align with the indications approved for the reference product. 
1.6 Benefit and Risk Assessment 
The CT-P17 drug product will have the same pharmaceutical form and strength as the 
EU-approved Humira (40 mg/0.4 mL). The proposed dosing regimen is in line with the 
approved labeling for Humira (Humira USPI 2017, Humira SmPC 2018). 
The proposed safety monitoring is deemed to be sufficient to monitor potential risks of 
CT-P17 administration. In view of the structural, biological, and toxicological similarity to 
Humira, CT-P17 is expected to display a similar safety profile. Humira has been studied 
extensively and has been shown to be effective at reducing symptoms in patients with 
inflammatory conditions (EMA EPAR for Humira 2017, Humira USPI 2017). 
Based upon the clinical evidence (Section 1.4) as well as the proven safety profile of Humira, 
the benefits of the conduct of the proposed clinical study outweigh the associated risks. 

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2 
Study Objectives 
2.1 Primary Objective 
• To demonstrate that CT-P17 is equivalent to Humira, in terms of efficacy as 
determined by clinical response according to the ACR definition of a 20% 
improvement (ACR20) at Week 24. 
2.2 Secondary Objectives 
• To evaluate additional efficacy, PK, pharmacodynamics (PD), and overall safety, 
including immunogenicity and biomarker. 

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Investigational Plan 
3.1 Study Design 
This study is a randomized, active-controlled, double-blind, multicenter, Phase 3 study 
designed to evaluate efficacy, PK, PD, and overall safety including immunogenicity and 
biomarker of multiple single-dose (40 mg) of either CT-P17 or Humira administered by SC 
injection via pre-filled syringe (PFS) EOW in combination with MTX between 12.5 to 
25 mg/week, or 10 mg/week if intolerant to a higher dose, oral or parenteral (intramuscular 
[IM] or SC) dose (dose and route must be maintained from beginning to EOS) and folic acid 
(≥5 mg/week, oral dose). 
Approximately 564 male and female patients with moderate to severe active RA will be 
enrolled in a 1:1 ratio (approximately 282 patients per treatment group) into the CT-P17 or 
Humira 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. 
3.2 Study Overview 
The study will comprise 3 study periods including Screening Period, Treatment Period (I and 
II), and EOS visit. 
Screening Period (Day –42 to Day –1): 
Screening will take place between Days –42 and Day –1 (6 weeks), prior to the first study 
drug administration. 
Treatment Period (Week 0 to Week 48): 
• Treatment Period I (from Week 0 to Week 24) 
• Treatment Period II (after Treatment Period I and prior to EOS visit) 
On Day 1 (Week 0), patients who meet all the inclusion criteria and none of the exclusion 
criteria will be enrolled in the study and randomly assigned to receive either CT-P17 or 

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Humira prior to treatment. The patient will receive either CT-P17 or Humira, as per first and 
second randomization, by SC injection EOW, co-administered with MTX between 12.5 to 
25 mg/week, or 10 mg/week if intolerant to a higher dose, oral or parenteral dose (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 that will be performed at the 
time points specified in the schedule of events (Table 11-1). 
The study drug will be administered by the trained study center staff at Week 0, Week 2, and 
Week 4 or until the patient or caregiver is properly trained and confident to administer the 
study drug at home or the investigator considers patient self-injection or injection by 
caregiver is appropriate (see Section 5.2.3 for details). After Week 4, patients can self-inject 
the study drug at home also during their study center visits, under the investigator or 
designated study center staff’s supervision or it can be administered by the caregiver, if 
needed. 
All patients will return to the study center by regular scheduled time intervals for clinical 
assessments and blood samplings. 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).  
A self-reporting AE diary will be used to collect AEs experienced outside study center. 
Adverse events which occur during the patient’s stay in the study centers, will be evaluated 
and recorded by the investigator and will not be entered into self-reporting AE diary. In 
addition, self-injection diary will be used to record details about self-injection. Diaries will 
be distributed to patient and will be collected and checked for completeness and legibility by 
the study staff at the next site visit. If needed, the patient or caregiver will be re-trained on 
how to perform the injection of the study drug and complete the diary. 
End-of-Study (Week 52) visit:  
An EOS visit will occur at Week 52 for all patients who completed or discontinued study 
treatment. The patients who early discontinued from the study treatment will also visit the 
study center until Week 52 by regular scheduled time interval for efficacy and safety 
assessments, even if they initiate RA medication changes (including those prohibited by the 
protocol).  

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The study design and patient assessment overview is presented in Figure 1. 
Figure 1 
Study Design Overview 
 
Abbreviations: C, CT-P17; EOS, end-of-study; EOW, every other week; H, Humira; N, number of patients; PK, 
pharmacokinetics; PD, pharmacodynamics; SC, subcutaneous. 
* Prior to dosing at Week 26, all patients will undergo a second randomization process. Patients who are initially 
randomized to Humira will be randomized again in a ratio of 1:1 to either continue Humira or undergo transition to CT-P17. 
Patients who are randomized to CT-P17 or Humira will receive assigned study drug EOW from Week 26 and thereafter up 
to Week 48. Only the study center visit is presented in this figure. 
1 An EOS visit will occur at Week 52 for all patients who completed or discontinued study treatment. The patients who early 
discontinued from the study treatment will also visit the study center until Week 52 by regular scheduled time interval for 
efficacy and safety assessments, even if they initiate RA medication changes (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 Week 24 for all patients, the study will be unblinded for 
reporting purposes and efficacy, PK, PD, immunogenicity, and safety endpoints will be 
evaluated by the pre-defined unblinded Sponsor and Contract Research Organization (CRO) 
teams. The investigators, patients, and other Sponsor and CRO teams will remain blinded 
until the end of the study. 

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4 
Patient Selection and Withdrawal Criteria 
4.1 Selection of Study Population 
It is expected that approximately 564 patients will be enrolled at approximately 60 study 
centers in 8 countries. Male or female patients with moderate to severe active RA diagnosed 
according to the 2010 ACR/EULAR classification criteria (Aletaha et al., 2010), despite 
previous treatment with MTX over at least 12 weeks, will be considered for enrollment in the 
study if they meet all 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 who has active disease as defined by the presence of 6 or more swollen joints (of 
66 assessed), 6 or more tender joints (of 68 assessed) and either an erythrocyte 
sedimentation rate (ESR) >28 mm/hour or a serum C-reactive protein (CRP) 
concentration >1.0 mg/dL (>10 mg/L) at Screening. 
4. Patient who has been receiving oral or parenteral MTX at a dose of between 12.5 to 
25 mg/week, or 10 mg/week if intolerant to a higher dose, and who has been on a stable 
dose and route of MTX for at least 4 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 ≤3.0 × ULN 
• Serum aspartate aminotransferase ≤3.0 × ULN 

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• Serum total bilirubin ≤1.5 × ULN 
6. Patient has the following hematology laboratory test results at Screening: 
• Hemoglobin >8.0 g/dL (SI units: >80 g/L or 4.96 mmol/L) 
• Absolute neutrophil count ≥1.5 × 103 cells/µL (SI units: ≥1.5 × 109 cells/L) 
• Platelet count ≥75 × 103 cells/µL (SI units: ≥ 75 × 109 cells/L) 
7. 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 (ICF) with date 
prior to participation in the study. 
8. Patient and their partner of childbearing potential must agree to use a highly effective 
method of contraception throughout the study and for 6 months after the last dose of 
assigned treatment. Examples include the following: 
• Hormonal contraceptives (combined or progestogen-only) associated with 
inhibition of ovulation. 
• Intrauterine devices. 
• Sexual abstinence (not periodically, but for the entire period of risk). 
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. Male and female 
patients and their partners who have been surgically sterilized for less than 24 weeks 
prior to the date of informed consent must agree to use any medically acceptable methods 
of contraception. Menopausal females must have experienced their last period more than 
1 year prior to the date of informed consent to be classified as not of childbearing 
potential. 
9. Patient must be able and willing to self-administer SC injections or designate a qualified 
person(s) to administer SC injection. 

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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; biologic or 
targeted synthetic disease-modifying antirheumatic drugs (DMARDs) (e.g., tofacitinib, 
baricitinib) for the treatment of RA and/or tumor necrosis factor (TNF) α inhibitor for any 
purposes. 
2. 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. 
3. 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), hepatitis C, 
or infection with human immunodeficiency virus (HIV). However, a patient with 
past hepatitis B virus is allowed if resolved. 
• 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). 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) 
4. Patient who currently has, or has a history of, any of the following TB conditions: 
• Patient who has a history of TB or a current diagnosis of TB. A patient who has a 
previous diagnosis of active TB cannot be enrolled in the study even if there is 
sufficient documentation of complete resolution of active TB. 

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• Patient who has had exposure to a person with active TB such as first-degree 
family members or co-workers. 
• Patient who has an indeterminate result for interferon-γ release assay (IGRA) or 
latent TB (defined as a positive result of IGRA with a negative examination of 
chest X-ray) at Screening. A patient who has a previous diagnosis of latent TB 
cannot be enrolled despite sufficient documentation of prophylaxis. If the result 
of the IGRA is indeterminate at Screening, 1 retest will be possible during the 
Screening period. If the repeated IGRA result is indeterminate again or positive, 
the patient will be excluded from the study. If the repeated IGRA result is 
negative, the patient can be enrolled in the study. 
5. Patient who has a medical condition including one or more of the following: 
• Classified as Class II or III obese by WHO classification (body mass index 
[BMI] ≥35 kg/m2) 
• Uncontrolled diabetes mellitus, even after insulin treatment 
• Uncontrolled hypertension (as defined by systolic blood pressure [BP] 
≥160 mmHg or diastolic BP ≥100 mmHg) 
• Any other inflammatory or rheumatic diseases, including but not limited to 
psoriatic arthritis, AS, spondyloarthritis, systemic lupus erythematosus, Lyme 
disease or fibromyalgia, that may confound the evaluation of the effect of the 
study drug 
• Significant systemic RA involvement (e.g., Sjogren’s syndrome, vasculitis, 
pulmonary fibrosis) which would put the patient at risk if they are enrolled 
• 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 
• New York Heart Association (NYHA) Class III or IV heart failure, severe 
uncontrolled cardiac disease (unstable angina or clinically significant 
electrocardiogram [ECG] abnormalities), or myocardial infarction within 
24 weeks prior to the first administration of the study drug (Day 1) 

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• History of organ transplantation, including corneal graft/transplantation 
• Any clinically significant respiratory disease, 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 conditions significantly affecting the nervous system (e.g., neuropathic 
conditions or nervous system damage) if it could interfere with the investigator’s 
assessment on disease activity scores including joint counts 
• Any other 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 
6. 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 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 the primary endpoint assessment at Week 24. In addition, a patient is 
permitted to receive low-potency topical, otic, and ophthalmic glucocorticoid 
preparations provided the preparations are administered per the instructions on 
the product label. 

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• 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 products 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 24 weeks after the 
first administration of the study drug (Day 1) 
7. Severe physical incapacitation (severely limited in ability to perform routine self-care, 
has RA ACR global functional status Class IV [Hochberg et al., 1992; Appendix 11.2], or 
who cannot benefit from medication) 
8. 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. 
9. Patient who currently abuses alcohol or drugs or has a history of alcohol or drug abuse 
within 2 years from Screening. 
10. Patient who, in the opinion of their general practitioner or the investigator, should not 
participate in the study. 

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4.2 Study Treatment Discontinuation and Study Termination  
Patients are free to withdraw from the study at any time for any reason. The investigator may 
also discontinue the study treatment at any time in the interest of patient safety. The primary 
reasons for the discontinuation of the study treatment and study termination must be recorded 
in the patient’s medical record and in the electronic case report form (eCRF), with any 
comments (spontaneous or elicited) or complaints made by the patient. Reasons for study 
treatment discontinuation include the following: 
• Patient develops signs of disease progression in the judgement of the investigator. 
• Patient has any AE that would compromise his or her safety if he or she continues to 
participate in the study. 
• Patient has a significant protocol deviation(s). 
• Patient is pregnant. 
• Investigator’s decision. 
As it is vital to obtain follow-up data in patients who discontinued from study treatment for 
any reason, they will also visit the study center by regular scheduled time interval for 
efficacy and safety follow-up.  
Reasons for study termination include the following: 
• Patient withdraws consent or refuses to procedures/observations. 
• Patient is lost to follow-up. 
• Patient dies. 
• Study is terminated by the Sponsor. 
If necessary, the investigator may discuss with CELLTRION, Inc or its designee any patient’s 
reason for study termination or study treatment discontinuation. 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.  

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4.2.1 Recruitment of Additional Patients 
Patients who receive study drug and discontinue prior to study completion will not be 
replaced. Patients who are failed the Screening, for any reason, can be rescreened only once. 
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. 
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 institutional review board (IRB) or independent ethics committee (IEC) of 
any premature termination or suspension of the study, where applicable. 

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5 
Study Treatment 
5.1 Method of Assigning Patients to Treatment Groups 
An interactive web response system (IWRS) will be used for the randomization. Biostatistics 
will generate the randomization schedule for IWRS, which will link sequential patient 
randomization numbers to treatment codes. 
Patients will be randomly assigned at Day 1 (Week 0) to receive CT-P17 or Humira using a 
1:1 allocation ratio. The randomization to treatment assignment will be stratified by the 
following: 
• Country 
• Disease activity by SDAI at Screening; high (SDAI >26) vs. not high (SDAI ≤26) 
Patients will receive CT-P17 or Humira EOW up to Week 24. Prior to dosing at Week 26, 
patients in the Humira treatment group will be randomly assigned in a ratio of 1:1 to either 
continue Humira (Cohort 2) or undergo transition to CT-P17 (Cohort 3) from Week 26. All 
patients who were initially randomly assigned to CT-P17 at Day 1 (Week 0) will continue 
their treatment with CT-P17 (Cohort 1) until EOS. Second randomization will also be 
conducted in Cohort 1 at Week 26 to maintain the study blind. 
The second randomization to Cohorts 2 or 3 will be stratified by the following: 
• Disease activity by SDAI at Week 24; remission (SDAI ≤3.3) vs. non-remission 
(SDAI >3.3) 
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 
The patients will receive either CT-P17 or Humira, as per the first and second 
randomizations, 40 mg (100 mg/mL) by SC injection via PFS EOW. Patients will be dosed at 
specific time points as detailed in the schedule of events (Table 11-1). 

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For each new injection, a different injection site will be used (e.g., injection site should be 
rotated). Sites for injection may either be the front of the patient’s thighs or lower abdomen 
(except for the 5 cm around the patient’s navel) or the outer area of the upper arm (except for 
self-injection). The same injection sites can be used only if the other sites are unavailable due 
to safety reasons and, in that case, it is recommended that the new injection should be given 
at least 3 cm away from the most recent injection site. 
The study drug will be administered by the trained study center staff at Week 0, Week 2, and 
Week 4 or until the patient or caregiver is properly trained and confident to administer the 
study drug at home or the investigator considers patient self-injection or injection by 
caregiver is appropriate. Thereafter, the study drug can be administered by the patient or 
caregiver at home or by study staff at study center according to the regular study center visit 
schedule (Table 11-1) (see Section 5.2.3 for details). Patients can also self-inject the study 
drug during their study center visits, under the investigator or designated study center staff’s 
supervision or can be administered by the caregiver, if needed. 
5.2.1 Co-administration of Methotrexate and Folic Acid 
Methotrexate with folic acid is co-administered to minimize or prevent AEs related to MTX 
side effects. Therefore, all patients should have been receiving oral or parenteral (IM or SC) 
MTX at a dose of between 12.5 to 25 mg/week, or 10 mg/week if intolerant to a higher dose, 
for at least 12 weeks and have been on a stable dose and route of MTX for at least 4 weeks 
prior to the first administration of the study drug (Day 1). The same dose and route should be 
maintained throughout the study. 
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 Premedication 
Patient may also be pre-medicated 30 to 60 minutes prior to the study treatment 
administration for hypersensitivity/allergic reactions and any pre-medications (such as but 
not limited to antihistamine or paracetamol) can be given at the investigator’s discretion. 

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5.2.3 Training for Home Injection of Study Drug 
The investigator or designated study center staff will be trained about SC administration of 
study drug via PFS. The trained investigator or study center staff will be responsible for 
training each individual patient (or caregiver, if needed) about proper SC administration of 
study drug via PFS. Printed instruction for use (IFU) of PFS and instructions for 
self-injection of study drug will be provided to the patient that will serve as a guide while 
administering the study drug at home. 
Patients and caregivers will be instructed to contact the investigator promptly in the event of 
any signs and symptoms of injection site reactions, hypersensitivity/allergic reactions. 
To assess how well the patient or caregiver learned the SC injection of study drug via PFS 
and how well that information was retained, an actual patient/caregiver-injection of the study 
drug may be performed during a study center visit. During that visit, the investigator or study 
center staff will observe the patient or caregiver as they perform the injection without 
assistance or guidance provided from the investigator or study center staff. 
As discussed in Section 3.2, patients will return to the study center by regular scheduled time 
intervals for clinical assessments and blood samplings. If needed, the patient or caregiver will 
be re-trained during this time on how to perform the injection of the study drug. 
5.2.4 Other Supplies 
As discussed in Section 5.2.3, printed IFU of PFS and instructions for self-injection of study 
drug will be provided to the patient or caregiver that will serve as their guide while 
administering the study drug at home. 
The following will also be provided to the patient as a combined document form when the 
investigator considers the patient eligible for self-injection at home: 
• Patient self-injection paper diary to record treatment compliance (see Section 5.6 
for details) 
• Patient self-reporting of AE paper diary to record any AE including injection site 
reactions (see Section 6.5.1.4 for details). 

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• A sharps bin to store used syringes. The sharps bin with the used syringes will be 
returned to the study center for disposal. 
In addition, patient card which includes important safety risk and contact information for 
medical emergency will be provided. 
5.3 Identity of Investigational Product 
CT-P17 is a monoclonal antibody which is being developed by CELLTRION, Inc. as a 
potential biosimilar to Humira. 
The company code of the product is CT-P17. The International Non-proprietary Name of the 
commercially available reference material (Humira) is adalimumab and the Anatomical 
Therapeutic Chemical Classification System code is L04AB04. CT-P17 is a full-length IgG1 
kappa isotype antibody with a total molecular weight of 148 kDa. 
The reference product, Humira, is supplied as a sterile, preservative-free solution of 
adalimumab for SC administration. Humira is a clear and colorless solution, with a pH of 
approximately 5.2 (Humira USPI 2017, Humira SmPC 2018). 
Each 40 mg/0.4 mL pre-filled syringe or pre-filled pen delivers 0.4 mL (40 mg) of Humira 
drug product. Each 0.4 mL of Humira contains 40 mg adalimumab, 16.8 mg mannitol, 
0.4 mg polysorbate 80, and water for injection (Humira USPI 2017). 
CT-P17 will be supplied in a single-use, pre-filled syringe at concentration of 100 mg/mL (40 
mg/0.4mL) as clear to opalescent, colorless to brown liquid. 
Dosing instruction described in the Humira prescribing information are to be followed 
(Humira USPI 2017, Humira SmPC 2018). 
CELLTRION, Inc. will provide adequate supplies of CT-P17 and Humira for distribution to 
the study centers. 
The following drug supplies will be used in the study: 

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Product 
Supplied as: 
CT-P17 
Pre-filled syringes containing 100 mg/mL 
(40 mg/0.4 mL) of CT-P17 
EU-approved Humira 
Pre-filled syringes containing 100 mg/mL 
(40 mg/0.4 mL) of adalimumab 
5.4 Management of Clinical Supplies 
5.4.1 Study Drug Packaging, Labelling, and Storage 
The appropriate number of study drug syringes will be allocated to each patient via the IWRS 
system at each visit. 
A tear-off 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/study center number 
• Contents and quantity 
• Lot number 
• Randomization code/kit number 
• Investigator’s name 
• Storage instructions 
• Caution statement (for study use only) 
• CELLTRION, Inc.’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-P17 and Humira must be kept at a controlled refrigerated temperature 

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between 2°C and 8°C and it must not be frozen. As a reference, when needed (for example 
when travelling), a single CT-P17 or Humira PFS may be stored at room temperature up to a 
maximum of 25°C for a period of 14 days (Humira USPI 2017, Humira SmPC 2018). Once 
removed from the refrigerator for room temperature storage, the PFS must be used within 
14 days or prior to the expiry date, whichever comes earlier, even if it was returned to the 
refrigerator. If the study drug is stored at temperature up to a maximum of 25°C for over 14 
days at patient’s home, the patient should be instructed to not administer the study drug and 
contact the study center (in advance, if possible). The immediate containers must be kept in 
the outer carton until use in order to protect the study drug from light. The recommended 
storage conditions, and expiry date where required, are stated on the product label approved 
by each regulatory authority. 
The patient should be advised to always refer to the Instructions for Self-injection of Study 
Drug about proper storage of the study drug. 
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 
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 
CELLTRION, Inc. 
The investigator will retain and store all original containers until these containers are 
inventoried by CELLTRION, Inc. Unless otherwise instructed by CELLTRION, Inc., the 
investigator agrees at the end of the study to return all original containers, whether empty or 
containing study drug, to CELLTRION, Inc. 
Patients will return all the unused and empty syringes and containers. The used syringes can 
only be destroyed if it is written in local standard operating procedures (SOPs) and a specific 

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authorization is given by CELLTRION, Inc., which is required prior to a patient being 
randomly assigned to a treatment group. Permission will be granted by CELLTRION, Inc. on 
a study center-by-study center basis after reviewing the study center destruction policy. This 
authorization may also be granted to destroy used syringes immediately after administering 
to patients. The list of destroyed syringes 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 CELLTRION, Inc. 
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 treatment at the investigator’s discretion. 
 pharmacovigilance (PVG) will have access to the randomization code, if suspected 
unexpected serious adverse reactions (SUSARs), which are subject to expedited reporting, 
should be unblinded prior to submission to the regulatory authorities. 
The overall randomization code will be broken only for reporting purposes. This will occur 
after database lock for data up to Week 24 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 CELLTRION, Inc. and 
 blinded teams until 
all patients have completed the study and the database has been finalized for study 
termination. 

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5.6 Treatment Compliance 
Patient compliance will be determined by the study center staff by reviewing the 
self-injection diary regularly. As discussed in Section 5.2.3, after training about proper 
injection technique, the patient may self-inject the study drug or can be administered by the 
caregiver, if needed. 
When the patient is properly trained and confident to self-administer the study drug at home 
or the investigator considers patient self-injection appropriate, a patient self-injection paper 
diary will be provided to the patient to record the following: dates, time, site of injection, 
used PFS kit information, and injection completion. 
If the patient forgot to self-inject the study drug, the patient should inject the dose of study 
drug as soon as they remembered it and contact the investigator or designated staff to inform 
the delay in injection and reschedule the next study center visit. The next dosing schedule 
should be readjusted to every two weeks from the time of last study drug administration. 
Administration of co-administered treatments (MTX and folic acid) will be recorded 
throughout the study. 
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 study 
drug (Day 1) and the same dose must be maintained until the primary endpoint assessment at 
Week 24.  If there are any changes before Week 24, in terms of dose, need to be reported to 
and discussed with the medical monitors of CELLTRION, Inc. or its designee in advance. In 
addition, patients are permitted to receive low-potency topical, otic, and ophthalmic 
glucocorticoid preparations provided 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. 

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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 the exclusion 
criteria #6. 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 Prohibited Therapy 
The following medications, treatments, or procedures during the study period are prohibited: 
• Any biological agents indicated for RA treatment or TNF α inhibitor for any purposes 
• Conventional DMARDs or targeted synthetic DMARDs other than MTX 
• Intra-articular corticosteroids are not allowed until Week 24. After Week 24, an intra 
articular injection is allowed once to 1 joint during the study. The injected joint must 
be considered a non-responder joint during the response evaluation. 
• Alkylating agents 
• Herbal products 
• Live or live-attenuated vaccine 
• Any other investigational device or medical product  
• Any surgical procedure, including bone or joint surgery or synovectomy (including 
joint fusion or replacement) are not allowed until 24 weeks after the first 
administration of the study drug (Day 1) 

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6 
Study Assessments and Procedures 
Prior to performing any study procedures, all potential patients will sign an 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 Efficacy Assessments 
Efficacy will be assessed by the evaluation of the ACR criteria (individual components, 
ACR20, ACR50, and ACR70, and hybrid ACR response), DAS28 (DAS28 [ESR], DAS28 
[CRP], and individual components) score, EULAR response criteria, simplified disease 
activity index (SDAI), clinical disease activity index (CDAI), quality of life (SF-36), and 
joint damage progression at the time points specified in the schedule of events (Table 11-1). 
6.1.1 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 that has undergone 
any surgical procedure including joint surgery or synovectomy (including joint fusion or 
replacement) will not be included in the joint count. 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. 
6.1.2 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 

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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 visual 
analogue scale (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 (Section 6.3.2) 
• CRP (Section 6.3.2) 
6.1.3 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 VAS (Appendix 11.3) 
• ESR (Section 6.3.2) 
• CRP (Section 6.3.2) 
6.1.4 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: 

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• 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) (Section 6.3.2) 
6.1.5 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). 
6.1.6 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). 
6.2 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). 
Details of the PK endpoint and PK analysis are presented in Section 7.2. 
6.3 Pharmacodynamic Assessments 
Blood samples for PD assessments (rheumatoid factor [RF], anti-cyclic citrullinated peptide 
[anti-CCP], CRP, and ESR) will be collected prior to dosing at the time points specified in 
the schedule of events (Table 11-1). 

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Details of the PD endpoints and PD analyses are presented in Section 7.3. 
6.3.1 Rheumatoid Factor and Anti-cyclic Citrullinated Peptide 
Blood samples for RF and anti-CCP will be collected at the time points specified in the 
schedule of events (Table 11-1), at the same time as the clinical laboratory blood samples. 
The blood samples will be tested in the central laboratory. 
6.3.2 C-Reactive Protein and Erythrocyte Sedimentation Rate 
Blood samples for CRP (central laboratory) and ESR (local laboratory using kits supplied 
centrally) will be collected at the time points specified in the schedule of events (Table 11-1).  
Where CRP and ESR are required for efficacy, PD, and safety (clinical laboratory testing) 
assessments, the same sample can be used. 
A standard ESR kit using the Westergren method of assessment will be supplied to the study 
centers for use; normal level will be considered to be no more than 20 mm/hour for women 
and no more than 15 mm/hour for men. 
6.4 Biomarker Assessments (Optional) 
For patients who sign a separate ICF for the biomarker assessments, blood samples for 
evaluation of genotype (FcγRIIa, IIIa, and/or any necessary genotypes) will be collected prior 
to dosing on Day 1 (Week 0).  
Details of the biomarker analysis are presented in Section 7.4. 
6.5 Safety Assessments 
Safety assessments will be performed on AEs (including serious AEs), AEs of special interest 
(AESI) (injection site reactions, hypersensitivity/allergic reactions, infections, and 
malignancies), immunogenicity, hypersensitivity monitoring (via monitoring of vital signs, 
including 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, local site pain 
using 100 mm VAS, signs and symptoms of TB, and prior and concomitant medications 
monitored throughout the study. 

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At each visit, patients will be questioned about AEs and concomitant medications and will be 
monitored for the clinical signs and symptoms of TB. 
6.5.1 Adverse Events 
6.5.1.1 Definitions of Adverse Events 
The investigator is responsible for reporting all AEs that are observed or reported during the 
study, regardless of their relationship to study drug or their clinical significance. 
An AE is defined as any untoward medical occurrence in a patient enrolled into this study 
regardless of its causal relationship to study drug. Patients will be instructed to contact the 
investigator at any time after ICF was signed if any symptoms develop (see Section 6.5.1.4). 
Any new condition noted at Screening would be regarded as an AE, but not a 
treatment-emergent AE (TEAE). 
A 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 
• 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 by investigator’s 

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judgement and the disease aggravation reported in the previous visit will be deleted in the 
eCRF. 
Diagnostic or therapeutic non-invasive or invasive procedures, such as surgery, should not be 
reported as AEs. However, they will be recorded as treatment(s) of the AE(s), if medical 
condition for which the procedure was performed meets the definition of an AE. The event 
term of primary cause should be recorded and reported instead of the term of surgery, 
diagnostic procedure, or therapeutic procedure. For example, an acute appendicitis that 
begins during the AE reporting period should be reported as an AE and the resulting 
appendectomy should be recorded as treatment of the AE. 
6.5.1.1.1 
Adverse Events of Special Interest 
The following AESIs will be reported using the same process as for AEs: 
Injection site reactions 
Injection site reactions will be observed after study drug administration and assessed based 
on Common Terminology Criteria for Adverse Events (CTCAE) v5.0. All AEs related to 
injection site reaction including erythema, itching, hemorrhage, pain, and swelling will be 
reported. 
Hypersensitivity/allergic reactions 
All AEs related to hypersensitivity and allergic reactions occurring within 24 hours after the 
study drug administration will be reported. 
Infection 
All AEs related to infection including tuberculosis, sepsis, and other opportunistic infections 
will be reported. 
Malignancy 
All AEs related to malignancy including but not limited to the following: hepatosplenic T-cell 
lymphoma, leukemia, lymphoma, melanoma, and Merkel cell carcinoma. 

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6.5.1.1.2 
Serious Adverse Events 
An SAE is defined as any untoward medical occurrence that at any dose: 
• Results in death 
• Is immediately life threatening 
• 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. 
6.5.1.1.3 
Unlisted (Unexpected) Serious Adverse Events 
An unlisted or unexpected SAE is defined as an event of which the nature or severity is not 
consistent with the applicable product information (e.g., IB) for an unapproved 
investigational product or the label (e.g., package insert or summary of product 
characteristics/US product insert) for an approved product. Assessment of expectedness will 
be made with the use of the IB and the summary of product characteristics. 
6.5.1.2 Eliciting and Documenting Adverse Events 
Adverse events will be assessed from the date the patient signs the ICF until EOS visit. 
All AEs will be followed until resolution or improvement to baseline, death, confirmed by 
the investigator that no further improvement could be expected, no more collection of clinical 
or safety data, or final database closure. Adverse events of special interest (e.g., injection site 
reactions, hypersensitivity/allergic reactions, infections, and malignancies) will be closely 
monitored. 

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At every study visit, patients will be asked a standard non-leading 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 identified from review of other 
documents (e.g., patient diaries) that are relevant to patient safety will be documented on the 
AE page in the eCRF. 
6.5.1.3 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, 
reactions to concurrent medications, or progression of disease states must also be reported. 
Adverse events will be recorded according to the CTCAE v5.0. The Medical Dictionary for 
Regulatory Activities (MedDRA) will be used to code all AEs.  
Any medical condition that is present at the time that the patient is screened but does not 
deteriorate should not be reported as an AE. However, if it deteriorates at any time during the 
study, it should be recorded as an AE. 
The investigator’s assessment of an AE’s relationship to study drug is part of the 
documentation process, but it is not a factor in determining what is or is not reported in the 
study. If there is any doubt as to whether a clinical observation is an AE, the event will be 
reported. 
The severity and the relationship or association of the study drug in causing or contributing 
to the AE will be characterized as defined in Sections 6.5.1.7 and 6.5.1.8, respectively. 

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Adverse events (and SAEs) should be reported until the EOS visit regardless of the 
relationship to the study drug. After the EOS visit, serious adverse drug reactions will be 
reported to CELLTRION, Inc. or its designee. 
6.5.1.4 Patients’ Self-reporting of Adverse Events 
A diary will be distributed to all patients and patients and caregivers will be instructed on 
how to appropriately complete the diary according to the patient diary instructions. 
If there are any signs and symptoms from the time patients leave the study centers until the 
next visits, patients will record them in the patient diary and study center staff will review the 
diary at each visit throughout the study up to and including EOS visit. However, patients will 
be advised to contact the investigator if any severe symptoms develop; the investigator will 
determine whether the patient should be referred to the emergency room/hospital or to 
continue the next dose administration. If needed, the patient or caregiver will be re-trained on 
how to complete the diary. All AEs entered in the diary will be recorded on the AE page in 
the eCRF. 
6.5.1.5 Reporting Serious Adverse Events 
Any AE considered serious by the investigator or which meets SAE criteria 
(Section 6.5.1.1.2) must be reported to
 PVG within 24 hours from the time study center 
staff first learn about the event. The following contact information is to be used for SAE 
reporting: 
 
 
 
 
 
 
 
 
 
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 fax it to 
 
PVG 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 

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an SAE, a copy of the hospital discharge summary will be faxed to 
 PVG 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. All SAEs (regardless of 
relationship with the study drug) will be followed up until satisfactory resolution or until the 
principal investigator or sub-investigator deems the event to be chronic or not clinically 
significant or the patient to be stable. 
CELLTRION, Inc. or its designee is responsible for reporting relevant SAEs to the competent 
authority, other applicable regulatory authorities, and participating investigators, in 
accordance with European Clinical Trials Directive (Directive 2001/20/EC), International 
Council for Hamonisation (ICH) guidelines, and/or local regulatory requirements. 
CELLTRION, Inc. or its designee is responsible for reporting fatal or life-threatening 
SUSARs (expedited reports) to the regulatory agencies and competent authorities by 
telephone or fax within 7 calendar days after being notified of the event. CELLTRION, Inc. 
or its designee should report other relevant SAEs associated with the use of the study drug to 
the appropriate competent authorities (according to local guidelines), investigators, and 
central ethics committees by a written safety report within 15 calendar days of notification. 
Adverse events associated with hospitalization or prolongations of hospitalization are 
considered as 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 pre-existing condition not associated with the 
development of a new AE or worsening of the pre-existing 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) 

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• Protocol-specified admission during a study (e.g., for a procedure required by the 
study protocol) 
• Optional admission not associated with a precipitating clinical AE (e.g., for elective 
cosmetic surgery) 
• Hospitalization for observation without a medical AE 
• Pre-planned treatments or surgical procedures; these should be noted in the baseline 
documentation for the entire protocol and/or for the individual patient 
If a patient is hospitalized purely for convenience (e.g., for easier performance of study 
assessments), the hospitalization does not qualify as an SAE. If a patient is hospitalized 
solely due to disease progression without any other adverse events, the hospitalization does 
not qualify as an SAE. 
6.5.1.6 Suspected Unexpected Serious Adverse Reactions 
The sponsor will promptly evaluate all SUSARs against cumulative product experience to 
identify and expeditiously communicate possible new safety findings to investigators, 
IRBs/IECs, and applicable health authorities based on applicable legislation. 
To determine reporting requirements for single SAE cases, the sponsor will assess the 
expectedness of these events using the applicable reference documents (e.g., study drug 
investigator’s brochure). 
Reporting requirements will also be based on the investigator’s assessment of causality and 
seriousness, with allowance for upgrading by the sponsor as needed. 

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6.5.1.7 Assessment of Severity 
The severity of an AE refers to the extent to which an AE affects the patient’s daily activities. 
The severity of the AE will be graded based on the CTCAE v5.0, based on the following 
general guidelines (a semicolon indicates “or” within each description): 
Grade 1: 
Mild AE (minor; no specific medical intervention; asymptomatic laboratory 
findings only; radiographic findings only; marginal clinical relevance) 
Grade 2: 
Moderate AE (minimal intervention; local intervention; non-invasive 
intervention [packing, cautery]) 
Grade 3: 
Severe and undesirable AE (significant symptoms requiring hospitalization or 
invasive intervention; transfusion; elective interventional radiological 
procedure; therapeutic endoscopy or operation) 
Grade 4: 
Life-threatening or disabling AE (complicated by acute, life-threatening 
metabolic or cardiovascular complications such as circulatory failure, 
hemorrhage, or sepsis; life-threatening physiological consequences; need for 
intensive care or emergent invasive procedure; emergent interventional 
radiological procedure, therapeutic endoscopy, or operation) 
Grade 5: 
Death related to AE 
Changes in the severity of an AE should be documented to allow an assessment of the 
duration of the event at each level of severity to be performed. If an AE upgrades in severity 
or changes from a non-serious to a serious event, a new AE needs to be reported. If an AE 
downgrades in intensity, it should not be reported as a new AE. Adverse events characterized 
as intermittent do not require documentation of onset and duration of each episode. 
6.5.1.8 Assessment of Causality 
As discussed in Section 6.5.1.3, the investigator’s assessment of an AE’s relationship to 
study drug is part of the documentation process, but it is not a factor in determining what is 
or is not reported in the study. If there is any doubt as to whether a clinical observation is an 
AE, the event will be reported. 

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The relationship or association of CT-P17 or Humira in causing or contributing to the AE will 
be characterized using the following classification and criteria: 
Unrelated: 
This relationship suggests that there is no association between the study drug and 
the reported event. 
Possible: 
This relationship suggests that treatment with the study drug caused or 
contributed to the AE, e.g., the 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: 
This relationship suggests that a reasonable temporal sequence of the event 
with drug administration exists and, based upon the known pharmacological 
action of the drug, known or previously reported adverse reactions to the drug 
or class of drugs, or judgment based on the investigator’s clinical experience, 
the association of the event with the study drug seems likely. The event 
disappears or decreases on cessation or reduction of the dose of study drug. 
Definite: 
This relationship suggests that a definite causal relationship exists between drug 
administration and the AE, and other conditions (concurrent illness, 
progression/expression of disease state, or concurrent medication reaction) do 
not appear to explain the event. The event reappears or worsens if the study 
drug is re-administered. 
6.5.1.9 Follow-Up of Patients Reporting Adverse Events 
All AEs must be reported in detail on the appropriate page in the eCRF and followed to 
satisfactory resolution, until the investigator deems the event to be chronic or not clinically 
significant, or until the patient is stable.  
6.5.2 Other Safety Assessment 
6.5.2.1 Immunogenicity Testing 
Serum samples for immunogenicity testing will be collected prior to dosing of study drug at 
the time points specified in the schedule of events (Table 11-1). Additional immunogenicity 
will be assessed when immune-related AEs occur. Immune-related AEs are defined as the 
following: 

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• Hypersensitivity/allergic reactions due to study drug (within 24 hours after study drug 
administration) 
• Delayed hypersensitivity/allergic reactions due to study drug (after 24 hours after 
study drug administration) 
Blood sample for immunogenicity for patients with immune-related AEs will be obtained on 
onset date of immune-related AEs, if possible, or blood sample can be used if it was obtained 
at the same date of study drug administration. 
Sample analysis will be performed at the central laboratory. 
6.5.2.2 Injection Site Reaction 
Injection site reactions will be assessed 30 minutes (±10 minutes) after the end of the study 
drug administration, as specified in the schedule of events (Table 11-1).  
For injections that will be given at home, patients or caregivers should be advised to call the 
study center or get immediate medical help if they experience the symptoms of injection site 
reactions (Section 6.5.1.1.1). 
Details will be recorded in both the source documents and the eCRF. 
6.5.2.3 Hypersensitivity/Allergic Reactions Monitoring 
Hypersensitivity/allergic reactions will be assessed prior to the study drug administration and 
1 hour (±10 minutes) after the end of the study drug administration, as specified in the 
schedule of events (Table 11-1), by additional vital sign measurements including BP, heart 
and respiratory rates, and body temperature. If patients have signs and symptoms of 
hypersensitivity/allergic reactions at home (hives, difficulty breathing, or swelling of face, 
eyes, lips, or mouth or any symptoms of cardiac origin), patients or caregivers should be 
advised to call the study center or get immediate help. 
In addition, hypersensitivity will be monitored by routine continuous clinical monitoring 
including patient-reported signs and symptoms (see Section 6.5.1.4). In case of 
hypersensitivity, emergency medication and equipment, such as adrenaline, antihistamines, 
corticosteroids, and respiratory support including inhalational therapy, oxygen, and artificial 
ventilation must be available and any types of ECG can be performed. 

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For patients who experience or develop life-threatening treatment-related anaphylactic 
reactions, study drug must be stopped immediately and the patient withdrawn from the study. 
Details will be recorded in both the source documents and the eCRF. 
6.5.2.4 Vital Signs and Weight, and Height 
Vital signs and weight measurements will be performed at the time points specified in the 
schedule of events (Table 11-1). Vital signs (including BP, heart and respiratory rates, and 
body temperature; while sitting) and weight will be measured by the investigator or his or her 
designee after 5 minutes of rest. In addition, measurement of height will be documented at 
Screening. All measurements will be documented at each study center visit. Details will be 
recorded in both the source documents and the eCRF. 
Vital sign measurements will also be monitored prior to and after study drug injection as part 
of the hypersensitivity monitoring (Section 6.5.2.3). 
6.5.2.5 Electrocardiogram 
All scheduled 12-lead ECGs will be performed locally after the patient has rested quietly for 
at least 5 minutes in a supine position. A 12-lead ECG will be performed at the time points 
specified in the schedule of events (Table 11-1) and if the patient experienced cardiac 
symptoms during study drug administration. If following the ECG review by the investigator 
there are any ECG findings that would indicate cardiac insufficiency or QT prolongation, the 
patient will be referred to a cardiologist to confirm the abnormality. The investigator will 
then report the event in the source documents and the eCRF. Regardless of the 12-lead ECG 
result, further evaluation with a cardiologist can be done depending on the investigator’s 
discretion. In case of hypersensitivity, any type of ECG can be performed (Section 6.5.2.3). 
6.5.2.6 Physical Examination 
Physical examinations with particular attention to injection site reactions, 
hypersensitivity/allergic reactions, infections, and malignancy will be performed prior to 
study drug administration at the time points specified in the schedule of events (Table 11-1). 
Investigators should carefully evaluate patients for any indication of infections and injection 
site reactions and pursue further investigation and treatment indicated in accordance with the 
investigator’s medical judgment. 

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Physical examinations will be performed when patients visit the study center by regular 
scheduled time intervals for clinical assessments. 
Information about the physical examinations will be recorded by the investigator or designee 
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 in both the source documents and eCRF. 
6.5.2.7 Tuberculosis Assessment 
At Screening, a history of TB or a current diagnosis of TB will result in patient exclusion 
from the study. A patient who has a previous diagnosis of active TB cannot be enrolled in the 
study even if there is sufficient documentation of complete resolution of active TB. 
Patients with latent TB or who have had exposure to person with active TB such as first-
degree family members or co-workers will not be included in the study. 
A patient who has an indeterminate result for IGRA or latent TB at Screening will not be 
included in the study. Latent TB is defined as the presence of a positive IGRA 
(Section 6.5.2.7.2) with a negative examination of chest X-ray (Section 6.5.2.7.1). If the 
result of the IGRA is indeterminate at Screening, 1 retest will be possible during the 
Screening period. If the IGRA result is again indeterminate or positive, the patient should be 
excluded from the study. If the repeated IGRA result is negative, the patient can be enrolled 
in the study. A patient with confirmed latent TB during Screening cannot be enrolled. A 
patient who has a previous diagnosis of latent TB cannot be enrolled even if there is 
sufficient documentation of prophylaxis. 
Throughout the study, patients will be monitored for the clinical signs and symptoms of TB. 
Patients with active TB based on the chest X-ray result and/or the clinical signs and 
symptoms must be withdrawn from the study. 
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 

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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 
CELLTRION, Inc. 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 and at EOS visit 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.  
6.5.2.7.1 
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. 
6.5.2.7.2 
Interferon- γ Release Assay 
Given the seriousness of TB in this patient population, 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. 

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As described in the literature (Park et al., 2009), IGRA can be used as a method of 
identifying patients with a false negative response to latent TB infections or new TB 
infections in patients with RA. Specifically, these assays detect cell-mediated immune 
responses to TB infections by quantifying interferon-γ in the presence of specific 
antimicrobial agents. 
6.5.2.8 Hepatitis B and Hepatitis C and Human Immunodeficiency Virus 
At Screening, hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), 
and hepatitis B core antibody (HBcAb) (total or IgG) will be assessed in all patients as 
specified in Table 6-1. 
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: 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, aspartate aminotransferase, alanine aminotransferase, and total 
bilirubin will be performed at Week 26 and EOS visit. 
If the HBsAg test result is positive, the patient will be excluded from the study. If a patient 
has HBsAg negative, HBsAb negative or positive, and HBcAb positive, a hepatitis B virus 
(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, aspartate aminotransferase, alanine aminotransferase, 
and total bilirubin will be performed at Week 26 and the EOS visit. If the patient develops 
hepatitis B reactivation, the study drug must be stopped and the patient withdrawn from the 
study. 
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. 

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6.5.2.9 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. 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 
CELLTRION, Inc. and 
 Safety 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 
and be withdrawn from the study. The study center must complete the supplied pregnancy 
form (female patient or partner of a male patient) and return it to CELLTRION, Inc. and
 
Safety Department 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. 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 6.5.1.5). 
6.5.2.10 Clinical Laboratory Analyses 
Blood and urine samples for clinical laboratory assessments will be collected at the time 
points specified in the schedule of events (Table 11-1). Blood samples do not need to be 
performed in a fasting state unless required in the opinion of the investigator. 

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The following clinical laboratory analyses will be performed: 
Clinical chemistry 
total protein, serum bilirubin (total, direct), alanine aminotransferase, 
aspartate aminotransferase, alkaline phosphatase, 
γ-glutamyltransferase, blood urea nitrogen, creatinine, creatine 
kinase, creatine kinase-MB, albumin, sodium, potassium, calcium, 
chloride, inorganic phosphorus, glucose, lactate dehydrogenase, total 
cholesterol, triglyceride, and high-density lipoprotein cholesterol 
Hematology 
red blood cells, total and differential white blood cell count, absolute 
neutrophil count, lymphocyte count, platelet count, hemoglobin, 
mean corpuscular volume, mean corpuscular hemoglobin, mean 
corpuscular hemoglobin concentration, and hematocrit 
Urinalysis 
bilirubin, blood, glucose, ketones, leukocytes, nitrite, pH, protein, 
specific gravity, urobilinogen and microscopic examination. 
Creatinine clearance will be calculated using serum creatinine level only at screening for 
inclusion and recorded on eCRF. Clinical laboratory (clinical chemistry, hematology, and 
urinalysis) test samples will be analyzed at the central laboratory. Pharmacodynamic markers 
of CRP will also be analyzed with clinical laboratory analyses and CRP and ESR will be 
reported as safety parameter as well. 
6.5.2.11 Patient’s Assessment of Local Site Pain 
All patients will assess local site pain using 100 mm VAS immediately (within 15 minutes) 
after the administration of study drug at the time points specified in the schedule of events 
(Table 11-1). Patient assessment of pain is measured by the patient indicating the extent of 
their pain by marking one line (│) through the 100-mm line (Appendix 11.5). 
6.6 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. 

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6.6.1 Pharmacokinetic Blood Sampling 
Blood samples for PK assessments will be obtained accordance with the laboratory manual 
from each patient at the time points specified in the schedule of events (Table 11-1). All 
samples should be collected as close as possible to the scheduled time point.  
Samples should be stored and shipped as detailed in Section 6.7.2. 
6.6.2 Pharmacodynamic Blood Sampling 
Blood samples for PD (CRP, ESR, RF, and anti-CCP) will be obtained in accordance with the 
laboratory manual from each patient at the time points specified in the schedule of events 
(Table 11-1). All samples should be collected at the scheduled time point. 
Blood sample for CRP will be drawn at the same time as the collection of blood samples for 
clinical laboratory testing. Blood sample for ESR will be analyzed at the study center local 
laboratory using centrally distributed kits. 
Samples should be stored and shipped as detailed in Section 6.7.2. 
6.6.3 Biomarker Blood Sampling (Optional) 
For patients who sign a separate ICF for the biomarker assessments, blood samples for 
evaluation of genotype (FcγRIIa, IIIa, and/or any necessary genotypes) will be collected in 
accordance with the laboratory manual prior to dosing on Day 1 (Week 0) (Table 11-1). 
These samples will be used for research purposes to identify dynamic biomarkers that may be 
predictive of response to CT-P17 treatment (in terms of dose, efficacy, safety, and 
tolerability). 
Samples should be stored and shipped as detailed in Section 6.7.2. 
6.6.4 Immunogenicity Blood Sampling 
Blood samples for immunogenicity assessments will be obtained prior to study drug 
administration at the time points specified in the schedule of events (Table 11-1), or when 
immune-related AEs occur.  
Samples should be stored and shipped as detailed in Section 6.7.2. 

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6.6.5 Interferon-γ Release Assay Blood Sampling 
Blood samples for IGRA will be obtained at the time points specified in the schedule of 
events (Table 11-1). All samples should be collected at the scheduled time point. 
Samples should be stored and shipped as detailed in Section 6.7.2. 
6.6.6 Routine Safety Blood Sampling 
Blood samples for routine safety (clinical laboratory testing) will be collected for analysis 
throughout the study at the time points specified in the schedule of events (Table 11-1). 
An additional blood for hepatitis B and hepatitis C and HIV testing will also be required at 
Screening. A serum pregnancy test sample will be required at Screening and at the EOS visit 
for women of childbearing potential who have not been surgically sterilized. 
Samples should be stored and shipped as detailed in Section 6.7.2. 
6.7 Labelling, Storage, and Transportation of Samples 
6.7.1 Sample Labelling 
Each sample tube will be clearly labelled with the following information: study number, 
patient number, tube identification, and scheduled sampling time point. 
6.7.2 Sample Storage and Shipment 
During the study, blood samples will be collected for PK, PD, immunogenicity, safety, and/or 
biomarker 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, immunogenicity, and/or biomarkers should 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. If additional analysis for PK, immunogenicity, and/or 
biomarkers is not required, the sample will be stored at CELLTRION, Inc. or a designated 

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biobank for a further 5 years (from the date the sample is transferred to the biobank) unless a 
specific authorization is given by CELLTRION, Inc. to destroy the sample. Additional tests 
can be conducted at CELLTRION, Inc. 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. 

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7 
Statistical Analysis Plan 
The statistical analysis will be performed using 
 
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 final clinical 
study report (CSR). 
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 Efficacy Analyses 
7.1.1 Primary Efficacy Analysis 
The proportion of patients achieving clinical response (responder/non-responder) according 
to ACR20 criteria at Week 24 will be analyzed. The 95% CI for the difference in proportion 
between the 2 treatment groups (CT-P17 and Humira) will be produced. Therapeutic 
equivalence of clinical response according to ACR20 criteria will be concluded if the 95% 
CIs for the treatment difference are entirely within the limits of –15% to 15% at Week 24. 
The primary efficacy endpoint will be analyzed using the ITT and PP populations. The ITT 
population will be the primary population for the primary endpoint. The logistic regression 
model with treatment group as fixed effect using country and disease activity by SDAI at 
Screening (high, not high) as covariates will also be performed in the ITT and PP population. 
7.1.1.1 ACR20 
A patient is defined as a responder according to ACR20 criteria if the following are fulfilled: 
• A decrease of at least 20% in the number of tender joints (based on 68 joints) 
• A decrease of at least 20% in the number of swollen joints (based on 66 joints), and 

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• A 20% 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 will be summarized by treatment group. 
7.1.2  Secondary Efficacy Analysis 
All secondary efficacy endpoints will be analyzed using the ITT and PP populations. 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 (except for Week 24), ACR50, and ACR70 
• Individual components of the ACR 
• Hybrid ACR response 
• DAS28 (CRP) and DAS28 (ESR) 
• 
Individual components of the DAS28 
• EULAR response classification 
• SDAI and CDAI 
• SF-36 version 2 
• Joint damage progression based on radiographic evaluations 

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7.1.2.1 ACR20, ACR50, ACR70 and Individual Components 
The ACR20 (except for Week 24), ACR50, and ACR70 are calculated similarly to ACR20 
(Section 7.1.1.1); however, an improvement of 50% and 70% must be achieved for ACR50 
and ACR70, instead of 20%. 
The proportion of patients demonstrating 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. 
7.1.2.1.1 
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) 
• Walking (Questions 8, 9) 
• Hygiene (Questions 10, 11, 12) 
• Reach (Questions 13, 14) 
• Grip (Questions 15, 16, 17) 
• Activities (Questions 18, 19, 20) 
7.1.2.2 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 

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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. 
7.1.2.3 DAS28 
Disease activity score in 28 joints (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)  
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) 
• ESR = ESR measurement (mm/hour) 
• 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 (ESR and CRP) 
and components of the DAS28 (ESR and CRP) will be summarized by treatment group. 

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7.1.2.4 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 League Against Rheumatism. 
Reference: Fransen 2005. 
7.1.2.5 
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. 
 

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7.1.2.6 
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. 
7.1.2.7 
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 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. 
7.2 Pharmacokinetic Analyses 
Serum concentrations will be summarized using quantitative descriptive statistics (including 
geometric mean and coefficient of variation [CV%], as appropriate) by treatment group, 

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study visit, and time point. Pharmacokinetic parameter will also be summarized using 
quantitative descriptive statistics (including geometric mean and CV%, as appropriate). 
Pharmacokinetic parameters will be computed by non-compartmental methods using 
appropriate validated software such as Phoenix WinNonlin (Pharsight, St Louis, Missouri, 
USA) and, if applicable, SAS.  
The following PK parameter will be assessed up to Week 52: 
• Ctrough: Trough concentration (concentration prior to the next study drug 
administration) 
The PK population will be used for PK analysis. 
7.3 Pharmacodynamic Analyses 
The PD endpoints (CRP, ESR, RF, anti-CCP) will be summarized using descriptive statistics 
(including geometric mean and CV%, as appropriate) by treatment group and study visit. 
The PD population will be used for PD analyses. 
7.4 Biomarker Analyses 
Analyses will be performed on genotypes (FcγRIIa, IIIa, and/or any necessary genotypes) in 
the ITT population. Genotypes will be summarized using frequency tables. 
7.5 Safety Analyses 
Safety analyses will be performed on the safety population at the time points specified in the 
schedule of events (Table 11-1) by presenting data about the following: 
• AEs including SAEs 
• AESI (injection site reactions, hypersensitivity/allergic reactions, infection and 
malignancies) 
• Immunogenicity testing 
• Hypersensitivity/allergic reactions monitoring 

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• Vital sign measurements and weight 
• ECGs 
• Physical examination findings 
• Monitoring of TB signs and symptoms (see Section 6.5.2.7 for details) 
• Chest X-ray (see Section 6.5.2.7.1 for details) 
• IGRA (see Section 6.5.2.7.2 for details) 
• Hepatitis B and hepatitis C and HIV 
• Pregnancy testing 
• Clinical laboratory analyses 
• Patient’s assessment of local site pain 
• Previous and concomitant medications 
7.5.1 Demographic and Baseline and Background Characteristics 
Demographics (including gender, age, ethnicity, and race) and baseline and background 
characteristics (including RA history) will be presented in summary tables. Qualitative data 
(e.g., medical history) will be summarized in contingency tables, and quantitative data (e.g., 
age) will be summarized using quantitative descriptive statistics.  
7.5.2 Adverse Events 
Adverse events will be recorded according to the CTCAE v5.0 and will be coded to system 
organ class (SOC) and preferred term (PT) according to MedDRA. A TEAE is defined as 
described in Section 6.5.1.1. The following TEAE summaries will be reported by SOC, PT, 
and treatment group: 
• Number and percentage of patients reporting at least 1 TEAE 
• Number and percentage of patients reporting at least 1 treatment-emergent SAE 

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• Number and percentage of patients discontinuing the study drug due to a TEAE 
• Number and percentage of patients with TEAEs of special interest (injection site 
reactions, hypersensitivity/allergic reactions, infections, and malignancies) 
7.5.3 Immunogenicity 
All data will be listed and summarized by treatment group, where appropriate. 
7.5.4 Clinical Laboratory Analyses, IGRA and Pregnancy 
Clinical laboratory tests (hematology, clinical chemistry, urinalysis, CRP, and ESR), IGRA, 
and pregnancy testing will be summarized by treatment at each scheduled collection time. 
For continuous parameters, change from baseline will also be summarized for all scheduled 
collection times after the first administration of study drug. 
7.5.5 Electrocardiograms, Physical examination, Vital Signs, and Weight 
Electrocardiograms, physical examination, vital signs (systolic and diastolic BP, heart rate, 
respiratory rate, and body temperature) and weight will be summarized by treatment at each 
scheduled collection time. Change from baseline will also be summarized for all scheduled 
collection times after the first administration of study drug. 
7.5.6 Patient’s assessment of Local Site Pain 
Local site pain measurements by VAS will only be assessed immediately after the 
administration of study drug at each scheduled collection time and will be summarized by 
treatment group. 
7.5.7 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. 
7.5.8 Other Safety Analyses 
All other safety data will be listed and summarized by treatment group as appropriate. 

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7.6 Sample Size Calculation 
A sample size of 450 patients (225 patients in each treatment group of CT-P17 and Humira) 
leads to 83% statistical power for the demonstration of similarity of ACR20 at Week 24 
based on the expected ACR20 rate of 64% with an equivalence margin of –15% to 15% using 
a two one-sided 2.5% significance level of an equivalence test. The drop-out rate has been 
hypothesized at 20%; therefore, approximately 564 patients (282 patients in each treatment 
group of CT-P17 and Humira) will be randomized. nQuery Adviser (version 7.0) was used to 
determine these sample size calculations. 
7.7 Analysis Sets 
The following analysis sets will be used in the statistical analyses. 
Intent-to-treat (ITT) Population: The ITT population is defined as all patients enrolled and 
randomly assigned to receive a dose of either of the study drugs, regardless of whether or not 
any study drug dosing was completed. Patients will be assigned to treatment groups based on 
randomization. 
Per-Protocol (PP) Population: The PP population is defined as all randomly assigned 
patients who have received all doses of study drug up to Week 22 (total of 12 injections) and 
have an ACR assessment at Week 24. A major protocol deviation that may affect the 
interpretation of study results of primary efficacy endpoint will be excluded from PP 
population. Final determinations of the PP population will be made at the blinded data review 
meeting (DRM) held in accordance with ICH harmonised tripartite guideline E9. Patients 
will be assigned to treatment groups based on randomization. 
Pharmacokinetic Population: The PK population will consist of all patients who receive at 
least 1 dose (full) of either of the study drugs and have at least 1 post treatment PK 
concentration data. The PK population will be the primary population for the summary of PK 
data. If any patients are found to be non-compliant with respect to dosing, a decision will be 
made on a case-by-case basis at the blinded DRM prior to code breaking. 
Pharmacodynamic Population: The PD population will consist of all patients who receive 
at least 1 dose (full) of either of study drugs and have at least 1 post treatment PD result. The 
PD population will be the primary population for the summary of PD data. 

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Safety Population: The safety population will consist of all patients who receive at least 
1 dose (full or partial) of either of the study drugs. Patients will be assigned to treatment 
groups based on treatment actually received. The safety population will be the primary 
population for the summary of safety data. 
7.8 Interim Analyses 
No interim analyses are planned for this study. 
7.9 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 
CELLTRION, Inc. 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 
CELLTRION, Inc. 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 CELLTRION, Inc. 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 CELLTRION, Inc. or its designee if he or she has been contacted 
by a regulatory agency concerning an upcoming inspection. 

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8 
Investigator’s Obligations 
The following administrative items are meant to guide the investigator in the conduct of the 
study but may be changed based on industry and government SOPs, working practice 
documents, or guidelines. Changes will be reported to the IRB/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 IRB/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 or Institutional Review Board 
Regulations and the ICH guidelines require that approval be obtained from an IRB/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 IRB/IEC. Documentation of all IRB/IEC approvals 
and of the IRB/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 IRB/IEC approvals should be signed by the IRB/IEC chairman or designee and must 
identify the IRB/IEC name and address, the clinical protocol by title or protocol number or 
both, and the date approval or a favorable opinion was granted. 

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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 IRB/IEC. The 
investigator must promptly supply the sponsor or its designee, the IRB/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. 
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 IRB/IEC submission. Once reviewed, the consent will 
be submitted by the investigator to his or her IRB/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 

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• 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’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. 
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, IRB/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 6.5.1.5. In addition, 
the principal investigator or sub-investigator agrees to submit annual reports to his or her 
IRB/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 
 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
 is financially responsible for 
further treatment of the patient’s disease. 

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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: 
• IRB/IEC approval 
• Original investigator-signed investigator agreement page of the protocol 
• Form FDA 1572, fully executed, and all updates on a new fully executed Form 
FDA 1572 
• Curriculum vitae (CV) for the principal investigator and each sub-investigator listed 
on Form FDA 1572. 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. 
• Financial disclosure information to allow the sponsor to submit complete and 
accurate certification or disclosure statements required under 21 CFR 54. 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. 
• IRB/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, in accordance with 42 CFR 493 
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). 

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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 IRB/IEC. Documentation of 
all IRB/IEC approvals and of the IRB/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 IRB/IEC approvals will be signed by the IRB/IEC chairman or designee and must 
identify the IRB/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 IRB/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. 
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. 

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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 Adverse Events and Study Report Requirements 
By participating in this study, the investigator agrees to submit reports of SAEs to the 
sponsor and/or IRB/IEC according to the timeline and method outlined in Section 6.5.1.5. In 
addition, the investigator agrees to submit annual reports to the study center IRB/IEC as 
appropriate. 
8.11 Investigator’s Final Report 
Upon completion of the study, the investigator, where applicable, should inform the 
institution; the investigator/institution should provide the IRB/IEC with a summary of the 
study’s outcome and the sponsor and regulatory authority(ies) with any reports required. 
8.12 Records Retention 
All correspondence (e.g., with sponsor, IRB/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. 
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. 

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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. 
8.13 Subject Identification Register 
The Investigator agrees to complete a subject identification register, which will be used for 
the purpose of long-term follow-up, if needed. This form will be treated as confidential and 
will be filed by the investigator in the Study Center Master File. Otherwise, all reports and 
communications relating to the study will identify patients by assigned number only. 
8.14 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 
CELLTRION, Inc., 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. 

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9 
Study Management 
9.1 Sponsor 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
9.2 Vendor Contact 
 
 
 
 
 

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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: 
 
  
 
 
 
 
  
 
 
 
 
 
 
 

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9.4 Monitoring 
9.4.1 Data Safety Monitoring Board 
This study will be monitored by an independent data safety monitoring board (DSMB) 
consisting of a PK specialist, statistician, independent physician, and an independent chairing 
physician. The DSMB will review and evaluate accumulating safety data to ensure the safety 
of study patients. 
Additionally, study results when the CSR is available will be reviewed by the DSMB. 
Further details will be provided in the independent DSMB 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. 
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. 

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9.4.3 Inspection of Records 
Investigators and institutions involved in the study will permit study-related monitoring, 
audits, IRB/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. 
The investigator should promptly notify the sponsor and 
 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 
IRB/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 CELLTRION, Inc. or its designee, and prior review, 
documented approval, and favorable opinion of the amendment from the relevant IRB/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 IRB/IEC approval. As soon as possible after such an occurrence, the 
implemented deviation or change, the reasons for it, and any proposed protocol amendments 

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should be submitted to the IRB/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 IRB/IEC and agreed to by the 
investigator. A significant deviation occurs when there is non-adherence to the protocol by 
the patient or investigator that results in a significant and additional risk to the patient’s 
rights, safety, and well-being. Significant deviations can include non-adherence to inclusion 
or exclusion criteria, or non-adherence to regulations or ICH GCP guidelines, and will lead to 
the patient being withdrawn from the study (Section 4.2). 
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 IRB/IEC should be notified of all 
protocol deviations in a timely manner. 
9.6 Study Termination 
Although CELLTRION, Inc. has every intention of completing the study, CELLTRION, Inc. 
reserves the right to discontinue the study at any time for clinical or administrative reasons. 
The end of the study is defined as the date of final database is locked. 
9.7 Final Report 
Whether the study is completed or prematurely terminated, the sponsor will ensure that the 
CSRs are prepared and provided to the regulatory agency(ies) as required by the applicable 
regulatory requirement(s). The sponsor will also ensure that the CSRs in marketing 
applications meet the standards of the ICH harmonised tripartite guideline E3: Structure and 
content of CSRs. 
The sponsor plans to prepare 2 CSRs to report the following: 
• Data for each patient up to Week 24 
• All data after completion of the study 

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If additional CSRs are required for regulatory or academic purposes, CSRs will be generated 
after the first database lock and unblinding process. 

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10 Reference List 
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%2
0ACR20.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. 
Chen DY, Chou SJ, Hsieh, Chen YH, et al. Randomized, double-blind, placebo-controlled, 
comparative study of human anti-TNF antibody adalimumab in combination with 
methotrexate and methotrexate alone in Taiwanese patients with active rheumatoid arthritis. 
J Formos Med Assoc. 2009;108(4):310-9. 
DAS28. MW Word DAS28. Available from: https://www.das-
score.nl/das28/DAScalculators/DAS28frm%20v26-7-2012.doc 
Department of Health and Human Services (DHSS), Food and Drug Administration (FDA), 
Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and 
Research (CBER). Draft guidance. Considerations in demonstrating interchangeability with a 
reference product. Jan 2017 [cited 2017 Oct 02]. Available from: 
https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidanc
es/UCM537135.pdf 
Department of Health and Human Services (DHSS), Food and Drug Administration (FDA), 
Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and 
Research (CBER). 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 

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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/WC5
00099361.pdf 
European Medicines Agency (EMA). Humira. European public assessment report (EPAR): 
Summary for the public. EMEA/H/C/000481; 2017 [cited 2017 Oct 02]. Available from: 
http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-
_Summary_for_the_public/human/000481/WC500050865.pdf 
Food and Drug Administration (FDA), Center for Drug Evaluation and Research (CDER), 
Center for Biologics Evaluation and Research (CBER). Application number: 125057/0. 
Approval letter(s). Dec 2002. Available from: 
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/BLA_125057_S000_HUMIRA_
APPROV.PDF 
Fransen J, van Riel PLCM. The Disease Activity Score and the EULAR response criteria. 
Clin Exp Rheumatol. 2005;23(Suppl. 39):S93-9. Available from: 
http://www.clinexprheumatol.org/article.asp?a=2693 
Furst DE, Shciff MH, Fleischmann RM, et al. Adalimumab, a fully human anti–tumor 
necrosis factor-α monoclonal antibody, and concomitant standard antirheumatic therapy for 
the treatment of rheumatoid arthritis: results of STAR (Safety Trial of Adalimumab in 
Rheumatoid Arthritis). J Rheumatol. 2003;30:2563-71. 
Keystone EC, Kavanaugh AF, Sharp JT. Radiographic, clinical, and functional outcomes of 
treatment with adalimumab (a human anti–tumor necrosis factor monoclonal antibody) in 
patients with active rheumatoid arthritis receiving concomitant methotrexate therapy: a 
randomized, placebo-controlled, 52-week trial. Arthritis Rheum. 2004 May;50(5):1400-11. 
Kim HY, Lee SK, Song YW, et al. A randomized, double-blind, placebo-controlled, phase III 
study of the human anti-tumor necrosis factor antibody adalimumab administered as 
subcutaneous injections in Korean rheumatoid arthritis patients treated with methotrexate. 
APLAR J Rheumatol. 2007;10:9-16. 

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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. 
Humira Prescribing Information (PI). AbbVie Inc, IL, USA; Dec 2017. Available from: 
http://www.rxabbvie.com/pdf/humira.pdf 
Humira Summary of Product Characteristics (SmPC); AbbVie Limited, May 2018. Available 
from: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-
_Product_Information/human/000481/WC500050870.pdf 
Park JH, Seo GY, Lee JS, et al. Positive conversion of tuberculin skin test and performance 
of interferon release assay to detect hidden tuberculosis infection during anti-tumor necrosis 
factor agent trial. J Rheumatol. 2009;36:2158-63. 
Plant MJ, Saklatvala J, Borg AA, et al. Measurement and prediction of radiological 
progression in early rheumatoid arthritis. J Rheumatol. 1994;21:1808-13. 
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. 
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, Landewe R, Bijlsma J, et al. EULAR recommendations for the management of 
rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 
2016 update. Ann Rheum Dis. 2017;0:1-18. 
van de Putte LB, Atkins C, Malaise M, et al. Efficacy and safety of adalimumab as 
monotherapy in patients with rheumatoid arthritis for whom previous disease modifying 
antirheumatic drug treatment has failed. Ann Rheum Dis. 2004;63:508-16. 

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van der Heijde D, Breedveld FC, Kavanaugh A, et al. Disease activity, physical function, and 
radiographic progression after longterm therapy with adalimumab plus methotrexate: 5-year 
results of PREMIER. J Rheumatol. 2010;37:2237-46. 
Ward MM, Guthrie LC, Alba MI, et al. Rheumatoid arthritis response criteria and patient 
reported improvement in arthritis activity: is an ACR20 response meaningful to patients? 
Arthritis Rheumatol. 2014;66(9):2339-43. Available from: 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4146735/ 
Wason JMS and Jenkins M. Improving the power of clinical trials of rheumatoid arthritis by 
using data on continuous scales when analysing response rates: an application of the 
augmented binary method. Rheumatology (Oxford). 2016 Oct;55(10):1796-1802. Available 
from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5034221/ 
Weinblatt ME, Keystone EC, Daniel EF, et al. Adalimumab, a fully human anti–tumor 
necrosis factor α monoclonal antibody, for the treatment of rheumatoid arthritis in patients 
taking concomitant methotrexate: the ARMADA trial. Arthritis Rheum. 2003;48:35-45. 
Whittle SL, Hughes RA. Folate supplementation and methotrexate treatment in rheumatoid 
arthritis: a review. Rheumatology. 2004; 43(3):267-71. 
World Health Organizations (WHO). Expert Committee on Biological Standardization. 
Guidelines on evaluation of similar biotherapeutic products. 19-23 Oct 2009. Available from: 
http://www.who.int/biologicals/areas/biological_therapeutics/BIOTHERAPEUTICS_FOR_
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involving human patients. JAMA. 2013 Nov 27;310(20):2191-4. 

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11 Appendices 
11.1 Schedule of Events

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Table 11-1 
Schedule of Events 
 
Screening 
Treatment Period I 
Treatment Period II 
EOS 
1 
 
 
Dose 
1 
Dose 
2 
Dose 
3 
Dose 
5 
Dose 
7 
Dose 
9 
Dose 
11 
Dose 
13 
Dose 
14 
Dose 
15 
Dose 
17 
Dose 
19 
Dose 
21 
Dose 
23 
Dose 
25 
Study visit2 (Week) 
–6 
0 
2 
4 
8 
12 
16 
20 
24 
26 
28 
32 
36 
40 
44 
48 
52 
Study visit2 (Day) 
–42 to –1 
1 
15 
29 
57 
85 
113 
141 
169 
183 
197 
225 
253 
281 
309 
337 
365 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics, height, 
medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hepatitis-B/C and HIV-test3 
X 
 
 
 
 
 
 
 
 
(X) 
 
 
 
 
 
 
(X) 
Serum pregnancy test4 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Chest X-ray5 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
IGRA6 
X 
 
 
 
 
X7 
 
 
X7 
 
 
 
 
 
 
 
X 
Inclusion/ 
exclusion criteria 
X 
X7 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization 
 
X8 
 
 
 
 
 
 
 
X8 
 
 
 
 
 
 
 
Efficacy assessments7,9– Pre-dose 
Swollen joint count  
(66 joints/ 28 joints) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Tender joint count 
(68 joints/ 28 joints) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
VAS pain score 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
VAS global assessment of 
disease activity 
(patient/physician) scores 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Health assessment 
questionnaire 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
CRP10 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ESR (local)10 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
QoL (SF-36) assessment 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hand and foot x-ray11 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Safety and other assessments7 – Pre-dose 
Physical examination, vital 
signs, and weight 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Clinical laboratory tests12 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 

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Screening 
Treatment Period I 
Treatment Period II 
EOS 
1 
 
 
Dose 
1 
Dose 
2 
Dose 
3 
Dose 
5 
Dose 
7 
Dose 
9 
Dose 
11 
Dose 
13 
Dose 
14 
Dose 
15 
Dose 
17 
Dose 
19 
Dose 
21 
Dose 
23 
Dose 
25 
Study visit2 (Week) 
–6 
0 
2 
4 
8 
12 
16 
20 
24 
26 
28 
32 
36 
40 
44 
48 
52 
Study visit2 (Day) 
–42 to –1 
1 
15 
29 
57 
85 
113 
141 
169 
183 
197 
225 
253 
281 
309 
337 
365 
Urine pregnancy test4 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
12-lead ECG13 
X 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
Immunogenicity14 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pharmacokinetic blood 
sampling15 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Rheumatoid factor 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Anti-CCP 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Biomarker16 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study treatment17,18 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Hypersensitivity/ allergic 
reactions monitoring19 and 
injection site reaction20 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Local site pain by VAS21 
 
X 
X 
X 
X 
 
X 
 
X 
X 
 
X 
X 
 
X 
X 
 
Prior, concomitant 
medications22 
X 
TB clinical monitoring23 
X 
AEs24 
X 
Abbreviations: AE, adverse event(s); anti-CCP, anti-cyclic citrullinated peptide; CRP, C-reactive protein; ECG, electrocardiogram; eCRF, electronic case report forms; 
EOS, end-of-study; EOW, every other week, ESR, erythrocyte sedimentation rate; HIV, human immunodeficiency virus; IGRA, Interferon-Gamma Release Assays; ICF, 
informed consent form; IM, intramuscular; QoL, quality of life; SC, subcutaneous, TB, tuberculosis; VAS, visual analogue scale. 
Note: Only the study center visits are presented in this table. As the study drug will be administered EOW, the planned injections on Weeks 6, 10, 14, 18, 22, 30, 34, 38, 42 
and 46, which are not specified in this table can be self-administered or by caregiver at home. The patients who early discontinued from the study treatment will also visit 
the study center until Week 52 by regular scheduled time interval for efficacy and safety assessments, even if they initiate RA medication changes (including those 
prohibited by the protocol). However, any assessment(s) that could jeopardize the patients’ safety could be skipped, as per investigator judgement. 
1. 
An EOS visit will occur at Week 52 for all patients who completed or discontinued study treatment.   
2. 
A visit window of ±2 days is allowed, based on the previous dosing date, from Dose 2 up to the EOS visit. 

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3. 
At Screening, hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), and hepatitis B core antibody (HBcAb) (total or IgG) will be assessed in all 
patients. If the HBsAg test result is positive, the patient will be excluded from the study. If a patient is negative for HBsAg, negative or positive for HBsAb, and 
positive for HBcAb, an 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, aspartate aminotransferase, alanine aminotransferase, and total bilirubin will be performed at Week 26 and EOS visit. 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. 
4. 
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 treatment, urine pregnancy test is unnecessary after the discontinuation. 
5. 
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. 
6. 
The IGRA testing will be performed at the central laboratory. No further IGRA testing is required during the treatment period and at EOS visit 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. 
7. 
Procedures will be performed at the study center prior to the study drug administration. 
8. 
Patients will be randomly assigned to receive either CT-P17 or Humira prior to dosing on Day 1 (Week 0) (first randomization). Patients will be randomized again 
prior to dosing on Week 26 (second randomization). 
9. 
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.  
10. Both CRP and ESR rate are considered as efficacy, PD, and safety (clinical laboratory test) endpoints. CRP samples will be drawn and analyzed at the same time as the 
clinical laboratory blood samples and ESR samples will be analyzed at the local laboratory using kits supplied centrally. 
11. 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.  
12. Clinical laboratory (clinical chemistry, hematology and urinalysis) test samples will be analyzed at the central laboratory.  
Clinical chemistry 
total protein, serum bilirubin (total, direct), alanine aminotransferase, aspartate 
aminotransferase, alkaline phosphatase, γ-glutamyltransferase, blood urea nitrogen, 
creatinine, creatine kinase, creatine kinase-MB,  albumin, sodium, potassium, 
calcium, chloride, inorganic phosphorus, glucose, lactate dehydrogenase, total 
cholesterol, triglyceride, high-density lipoprotein cholesterol 
Hematology 
red blood cells, total and differential white blood cell count, absolute neutrophil 
count, lymphocyte count, platelet count, hemoglobin, mean corpuscular volume, 
mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and 
hematocrit 
Urinalysis 
bilirubin, blood, glucose, ketones, leukocytes, nitrite, pH, protein, specific gravity, 
urobilinogen and microscopic examination  
 
13. 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, an ECG could be performed at any time during the treatment period. Regardless of the 12-lead ECG result, further 

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evaluation with a cardiologist can be done depending on the investigator’s discretion. 
14. Samples will be drawn prior to dosing of study drug at the same time as the clinical laboratory tests where applicable. Analysis will be performed at the central 
laboratory. Additional immunogenicity will be assessed when immune-related AEs occur. 
15. Blood samples for PK analysis will be obtained only at pre-dose (just prior to study drug injection) 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 patient who early discontinued study treatment, PK samples will be obtained until 4 weeks after 
the last administration of study drug. 
16. Only for patients who sign a separate ICF for the biomarker assessment, a blood sample for evaluation of any necessary genotypes will be collected prior to dosing on 
Week 0. 
17. A single dose of CT-P17 (40 mg) or Humira (40 mg) will be administered by SC injection via PFS EOW. For each new injection, a different injection site will be used 
(e.g., injection site should be rotated). The same injection sites can be used only if the other sites are unavailable due to safety reasons and in that case, it is 
recommended that new injection should be given at least 3 cm away from the most recent injection site. The study drug will be administered by the trained study center 
staff at Week 0, Week 2, and Week 4 or until the patient or caregiver is properly trained and confident to administer the study drug at home or the investigator 
considers patient self-injection or injection by caregiver is appropriate. Thereafter, the study drug can be administered by the patient or caregiver at home or by study 
staff at study center according to the regular study center visit schedule (see Section 5.2.3 for details). Patients may also self-inject the study drug during their study 
center visits, under the investigator or designated study center staff’s supervision or can be administered by the caregiver, if needed. 
18. Methotrexate (12.5 to 25 mg/week, or 10 mg/week if intolerant to a higher dose, 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 treatment period.  
19. Additional vital signs including blood pressure, heart and respiratory rates, and body temperature will be monitored for possible hypersensitivity/allergic reactions 1 
hour (±10 minutes) after SC injection of study drug. For patient who early discontinued study treatment, monitoring of hypersensitivity/allergic reactions are 
unnecessary after the discontinuation. 
20. Injection site reaction will be assessed 30 minutes (±10 minutes) after SC injection of study drug. For injections that will be given at home, injection site reactions will 
be recorded by the patient or their caregiver in the patient self-reporting of AE diary. For patient who early discontinued study treatment, assessment of injection site 
reaction is unnecessary after the discontinuation. 
21. Local site pain using 100 mm VAS will be assessed immediately (within 15 minutes) after SC injection of study drug. For injections that will be given at home, local 
site pain will also be recorded by the patient or their caregiver in the patient self-reporting of AE diary. For patient who early discontinued study treatment, assessment 
of local site pain is unnecessary after the discontinuation. 
22. 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 the exclusion criteria #6.  
23. 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. 
24. Adverse events will be assessed from the date the ICF is signed until the EOS visit. After the EOS visit, serious adverse drug reactions will be reported to 
CELLTRION, Inc. or its designee. Adverse events of special interest (e.g., injection site reactions, hypersensitivity/allergic reactions, infections, and malignancies) 
should be closely monitored. 
* 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. 

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Protocol Number: CT-P17 3.1 
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Page 103 
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. 
 
 

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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 
 

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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 
 

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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 

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11.6 Health Assessment Questionnaire and Scoring of the Health 
Assessment Questionnaire 
 
 

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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.

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Protocol Version 3.0 
 
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Protocol Version 3.0 
 
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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 http://www.das-score.nl 
 
Left 
Right 
 
Swollen 
tender 
Swollen 
Tender 
Shoulder 
 
 
 
 
Elbow 
 
 
 
 
Wrist 
 
 
 
 
MCP 
1 
 
 
 
 
 
2 
 
 
 
 
 
3 
 
 
 
 
 
4 
 
 
 
 
 
5 
 
 
 
 
PIP 
1 
 
 
 
 
 
2 
 
 
 
 
 
3 
 
 
 
 
 
4 
 
 
 
 
 
5 
 
 
 
 
Knee 
 
 
 
 
Subtotal 
 
 
 
 
Total 
swollen 
 
Tender 
 
Abbreviations: MCP, metacarpophalangeal joints; PIP, proximal interphalangeal joints 
Reference: DAS28.