A Phase III, Open-label, Single-arm, Multiple-dose Study to Evaluate Usability of Subcutaneous Auto-injector of CT-P17 in Patients With Moderate to Severe Active Rheumatoid Arthritis
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Sponsor: Celltrion

CELLTRION, Inc. 
Clinical Study Protocol 
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CONFIDENTIAL 
 
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Title Page 
 
Protocol Title: A Phase III, Open-label, Single-arm, Multiple-dose Study to 
Evaluate Usability of Subcutaneous Auto-injector of CT-P17 in Patients with 
Moderate to Severe Active Rheumatoid Arthritis 
Protocol Number: CT-P17 3.2 
 
Sponsor Name and Legal Registered Address:  
CELLTRION, Inc.  
 
 
 
 
 
 
EudraCT Number: 2019-000660-25 
Approval Date: 11 November 2019 
Date and Version of Previous Protocol: Version 1.0, dated 30 January 2019 
 
 
 
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.  
 

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Clinical Study Protocol 
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Declaration of the Investigator 
I have read and understood all sections of the protocol entitled “A Phase III, Open-label, 
Single-arm, Multiple-dose Study to Evaluate Usability of Subcutaneous Auto-injector of CT-
P17 in Patients with Moderate to Severe Active Rheumatoid Arthritis” and the accompanying 
Investigator Brochure.  
I agree to supervise all aspects of the protocol and to conduct the clinical investigation in 
accordance with the protocol version 2.0, dated 11 November 2019, 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 Institutional Review 
Board/Independent Ethics Committee approval except to eliminate an immediate risk to 
patients. I agree to administer the study drug only to patients under my personal supervision 
or the supervision of a sub-Investigator.  
I will not supply the study drug to any person not authorized to receive it. Confidentiality will 
be protected. Patient identity will not be disclosed to third parties or appear in any clinical 
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 

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Clinical Study Protocol 
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CONFIDENTIAL 
 
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Table of Contents 
 
Protocol Approval ...................................................................................................................... 2 
Table of Contents ....................................................................................................................... 4 
Protocol Synopsis....................................................................................................................... 8 
1 
Introduction........................................................................................................................ 14 
1.1 
Study Rationale ............................................................................................................. 14 
1.1.1 
Choice of Study Population ....................................................................................... 14 
1.2 
Background.................................................................................................................... 14 
1.2.1 
Rheumatoid Arthritis ................................................................................................. 14 
1.2.2 
CT-P17 ....................................................................................................................... 15 
1.2.3 
Non-clinical Studies .................................................................................................. 16 
1.2.4 
Clinical Studies .......................................................................................................... 16 
1.3 
Benefit/Risk Assessment ............................................................................................... 16 
2 
Objectives and Endpoints .................................................................................................. 18 
3 
Study Design ...................................................................................................................... 18 
3.1 
Overall Study Design .................................................................................................... 18 
3.2 
Justification for Dose ..................................................................................................... 20 
3.3 
Study Duration............................................................................................................... 20 
4 
Study Population ................................................................................................................ 20 
4.1 
Inclusion Criteria ........................................................................................................... 21 
4.2 
Exclusion Criteria .......................................................................................................... 22 
4.3 
Study Drug Withdrawal/Discontinuation ...................................................................... 25 
4.3.1 
Recruitment of Additional Patients ........................................................................... 25 
4.4 
Premature Termination of the Study .............................................................................. 25 
5 
Study Treatment ................................................................................................................. 26 
5.1 
CT-P17 ........................................................................................................................... 26 
5.1.1 
Medical Devices ........................................................................................................ 26 
5.2 
Other Treatments Administered ..................................................................................... 26 
5.2.1 
Co-administration of Methotrexate and Folic Acid ................................................... 26 
5.2.2 
Premedication ............................................................................................................ 27 
5.3 
Study Drug Administration............................................................................................ 27 
5.3.1 
Training for Self-Injection of Study Drug ................................................................. 27 
5.4 
Other Supplies ............................................................................................................... 28 
5.5 
Management of Clinical Supplies ................................................................................. 28 

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5.5.1 
Study Drug Handling and Storage ............................................................................. 28 
5.5.2 
Study Drug Accountability ........................................................................................ 28 
5.6 
Treatment Compliance .................................................................................................. 29 
5.7 
Prior and Concomitant Medications and Therapy ......................................................... 29 
5.7.1 
Permitted Concomitant Medication and Therapies ................................................... 30 
5.7.2 
Prohibited Therapy .................................................................................................... 30 
5.7.3 
Rescue Medication .................................................................................................... 30 
5.8 
Dose Modification ......................................................................................................... 31 
6 
Study Procedures and Assessments ................................................................................... 31 
6.1 
Study Procedures ........................................................................................................... 31 
6.1.1 
Informed Consent and Enrollment ............................................................................ 31 
6.1.2 
Patient Identification Code ........................................................................................ 31 
6.1.3 
Patient Diaries ........................................................................................................... 31 
6.2 
Usability Assessments ................................................................................................... 32 
6.2.1 
PRE- and POST-SIAQ ............................................................................................... 32 
6.2.2 
Self-Injection Assessment Checklist ......................................................................... 33 
6.3 
Efficacy Assessments .................................................................................................... 33 
6.3.1 
Tender Joint Count (68) and Swollen Joint Count (66) ............................................. 33 
6.3.2 
Tender and Swollen Joints Count (28) ...................................................................... 33 
6.3.3 
Disease Activity Score Using 28 Joint Counts .......................................................... 33 
6.3.4 
Patient’s Global Assessment of Disease Activity Measured using VAS ................... 33 
6.3.5 
C-Reactive Protein and Erythrocyte Sedimentation Rate ......................................... 34 
6.4 
Safety Assessments ........................................................................................................ 34 
6.4.1 
Adverse Events .......................................................................................................... 34 
6.4.2 
Other Safety Assessments .......................................................................................... 40 
6.5 
Sample Collections ........................................................................................................ 46 
6.5.1 
Interferon-γ Release Assay Blood Sampling ............................................................. 46 
6.5.2 
Routine Safety Blood Sampling ................................................................................ 46 
6.6 
Labeling of Samples ...................................................................................................... 46 
7 
Statistical Analysis Plan ..................................................................................................... 46 
7.1 
Populations for Analyses ............................................................................................... 47 
7.2 
Usability Analysis .......................................................................................................... 47 
7.2.1 
Primary Usability Endpoint ....................................................................................... 47 
7.2.2 
PRE- and POST- SIAQ .............................................................................................. 47 
7.3 
Secondary Usability Endpoints ..................................................................................... 47 
7.3.1 
PRE- and POST- SIAQ .............................................................................................. 47 
7.3.2 
Observer Rating of Successful Self-Injection Using Self-Injection Assessment 
Checklist .................................................................................................................... 48 

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7.4 
Efficacy Analysis ........................................................................................................... 48 
7.4.1 
DAS28 (CRP) and DAS28 (ESR) ............................................................................. 48 
7.5 
Safety Analyses ............................................................................................................. 48 
7.5.1 
Demographic, Baseline, and Background Characteristics ........................................ 48 
7.5.2 
Adverse Events .......................................................................................................... 49 
7.5.3 
Clinical Laboratory Analyses, IGRA and Pregnancy ................................................ 49 
7.5.4 
Electrocardiogram, Physical Examination, and Vital Signs ...................................... 49 
7.5.5 
Prior and Concomitant Medications .......................................................................... 49 
7.5.6 
Other Safety Analyses ............................................................................................... 49 
7.6 
Interim Analyses ............................................................................................................ 49 
7.7 
Handling of Missing, Unused, and Spurious Data ........................................................ 49 
7.8 
Sample Size Determination ........................................................................................... 49 
8 
Supporting Documentation and Operational Considerations ............................................ 50 
8.1 
Regulatory, Ethical, and Study Oversight Considerations ............................................ 50 
8.1.1 
Regulatory and Ethical Considerations ..................................................................... 50 
8.1.2 
Financial Disclosure .................................................................................................. 50 
8.1.3 
Informed Consent Process ......................................................................................... 50 
8.1.4 
Data Protection .......................................................................................................... 51 
8.1.5 
Dissemination of Clinical Study Data ....................................................................... 51 
8.1.6 
Data Quality Assurance ............................................................................................. 52 
8.1.7 
Source Documents ..................................................................................................... 53 
8.1.8 
Study and Site Closure .............................................................................................. 53 
8.1.9 
Publication Policy ...................................................................................................... 53 
8.1.10 
Study Administration ................................................................................................. 54 
8.1.11 
Protocol Approval and Amendment and Protocol Deviations ................................... 54 
8.1.12 
Access to Source Data ............................................................................................... 55 
9 
Appendices ........................................................................................................................ 56 
9.1 
Appendix 1: Abbreviations ............................................................................................ 56 
9.2 
Appendix 2: Schedule of Activities (SoA) .................................................................... 58 
9.3 
Appendix 3: Self-Injection Checklist ............................................................................ 61 
9.4 
Appendix 4: Self-Injection Assessment Questionnaire ................................................. 62 
10 References.......................................................................................................................... 71 
 
List of Tables 
Table 1: Details of CT-P17 ....................................................................................................... 26 
Table 2: Clinical Laboratory Tests ........................................................................................... 43 

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Table 3: Eligibility Based on Serologic Markers for Hepatitis B Infection ............................. 44 
Table 4: Personnel and Organizations Responsible for Study Conduct................................... 54 
Table 5: Schedule of Activities ................................................................................................ 58 
List of Figures 
Figure 1: Study Design Overview............................................................................................ 20 
 
 
 

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Protocol Synopsis 
Protocol Number: CT-P17 3.2 
Title: A Phase III, Open-label, Single-arm, Multiple-dose Study to Evaluate Usability of Subcutaneous 
Auto-injector of CT-P17 in Patients with Moderate to Severe Active Rheumatoid Arthritis 
Study Phase: Phase III 
Study Centers: Approximately 5 study centers in approximately one country 
Test Investigational Drug, Dose and Regimen: CT-P17, 40 mg/0.4 mL (100 mg/mL) by subcutaneous (SC) 
injection via auto-injector (AI) every other week (EOW) from Week 0 to Week 24, co-administered with 
methotrexate (MTX) (12.5 to 25 mg/week, or 10 mg/week if intolerant to a higher dose, oral or intramuscular 
[IM], dose and route must be maintained from Screening to end-of-study [EOS]/early discontinuation [ED]) 
and folic acid (≥5 mg/week, oral). 
Objectives: 
Primary Objective 
 
To evaluate usability of CT-P17 AI assessed by patients at Week 4. 
Secondary Objectives 
 
To evaluate change in usability assessed by patients and observer over time up to Week 24.  
 
To evaluate overall safety and efficacy. 
Main selection criteria: Male or female patients 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, despite ongoing 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. Male or female patient between 18 to 70 years of age, inclusive. 
2. Patient must be able and willing to self-administer subcutaneous (SC) injections via auto-injector (AI).  
3. Patient with a diagnosis of rheumatoid arthritis (RA) according to the 2010 American College of 
Rheumatology (ACR)/ European League Against Rheumatism (EULAR) classification criteria for at 
least 24 weeks prior to the first administration of the study drug (Day 1). 
4. 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. 
5. Patient who has been receiving oral or intramuscular (IM) methotrexate (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). 
6. 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) (Système International d'Unités [SI] units: 
0.84 mL/second). 
 
Serum alanine aminotransferase 3.0  ULN. 
 
Serum aspartate aminotransferase 3.0  ULN. 
 
Serum total bilirubin 1.5  ULN. 
7. 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). 

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8. Patient (or legal guardian, if applicable) is informed of the full nature and purpose of the study, including 
possible risks and side-effects, has the ability to cooperate with the Investigator and is given ample time 
and opportunity to read and understand verbal and/or written instructions, and signs the written informed 
consent form (ICF) with date prior to participation in the study. 
9. 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 the study drug. 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 associated with the study 
drug). 
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. 
Exclusion Criteria: 
A patient meeting any of the following criteria will be excluded from the study: 
1. Patient who has previously received or plans to receive investigational or licensed product; biologic or 
targeted synthetic disease-modifying anti-rheumatic 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 has previous or current use of other SC self-injected drugs (e.g., insulin, MTX).     
4. Patient who currently has, or has a history of, any of the following infections: 
 
A known infection with hepatitis B (active or carrier of hepatitis B [HBV]), hepatitis C, or 
infection with human immunodeficiency virus (HIV). However, a patient with past HBV is 
allowed if resolved. Patient will be enrolled based on HBV infection eligibility criteria, 
specified in Section 6.4.2.8. 
 
Hospitalization for treatment of infection within 24 weeks prior to the first administration of the 
study drug (Day 1). 
 
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). 
 
Symptomatic or 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. 
5. Patient is ineligible according to the following tuberculosis (TB) screening criteria: 
 
Patient who has a history or a current diagnosis of active 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 completed TB 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. 

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6. Patient who has current signs or symptoms of liver or renal insufficiency or cardiac, vascular, 
pulmonary, gastrointestinal, endocrine, neurologic, hematologic, psychiatric, or metabolic disturbances 
that are severe, progressive, or uncontrolled. Including one or more of the following: 
 
Classified as Class II or III obese by World Health Organization classification (body mass index 
35 kg/m2). 
 
Uncontrolled diabetes mellitus, even after an appropriate 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., Sjögren’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 in situ 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. 
 
Hereditary or acquired immunodeficiency disorder, including immunoglobulin deficiency. 
 
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 (DAS) 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. 
7. Patient who has received or plans to receive any of the following prohibited medications or treatment: 
 
Intra-articular (IA) 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 drugs 
(NSAIDs), if they have received a stable dose for at least 4 weeks prior to the first 
administration of the study drug (Day 1). In addition, a patient is permitted to receive low-
potency topical, otic, and ophthalmic glucocorticoid preparations as 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 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). 
 
Traditional Chinese medicine within 4 weeks prior to the first administration of the study drug 
(Day 1). 

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 
A vaccination (live or live-attenuated) within 4 weeks prior to enrollment or Bacillus 
Calmette-Guérin (BCG) vaccination within 1 year prior to enrollment, or a live or attenuated 
vaccination planned during the course of the study. 
 
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).  
8. Severe physical incapacitation (severely limited in ability to perform routine self-care, has RA ACR 
global functional status Class IV, or who cannot benefit from medication). 
9. Female patient who is currently pregnant or breastfeeding or plans to become pregnant or breastfeed 
within 6 months after the last dose of study drug. 
10. Patient who has current drug or alcohol abuse or dependence, or a history of alcohol or drug abuse within 
2 years from the first administration of the study drug (Day 1). 
11. Patient who, in the opinion of their general practitioner or the Investigator, should not participate in the 
study. 
Study Design: 
This study is a Phase III, open-label, single-arm, multiple-dose study designed to evaluate usability, safety 
and efficacy of SC AI of CT-P17 (the study drug) in patients with moderate to severe active RA. The study 
drug will be administered EOW by SC injection via AI from Week 0 to Week 24 in combination with MTX 
(12.5 to 25 mg/week, or 10 mg/week if intolerant to a higher dose, oral or IM) and folic acid (5 mg/week, 
oral). The MTX dose and route must be maintained from Screening to EOS/ED visit. Approximately 60 male 
or female adult patients with moderate to severe active RA will be enrolled. 
The study design and patient assessment overview are presented in Figure S1. 
Figure S1: 
Study Design Overview 
 
Abbreviations: AI=auto-injector; EOS=end-of-study; ED=early discontinuation; N=number of patients; RA=rheumatoid 
arthritis; SC=subcutaneous. 
Note: The investigator or designated study center staff will instruct the patients on the proper administration of CT-P17 
via the AI prior to the first self-injection at Week 0. Thereafter, patients will self-inject the study drug at the study center 
during their scheduled visits under the Investigator or designated study center staff’s supervision. Patients will also self-
inject the study drug at home at Weeks 10, 14, 18 and 22 according to the treatment schedule. 
1 The EOS assessments need to be completed after 4 weeks from when the last dose (at Week 24) is received or prior to 
the start of new RA therapy, whichever comes earlier. The efficacy assessments will be performed only if the efficacy 
assessments were not performed at Week 24 as planned. 
2 The ED visit needs to be completed after 4 weeks from when the last dose is received or prior to the start of new RA 
therapy, whichever comes earlier, if a patient is discontinued from study prior to Week 24 treatment. 
Study Schedule: There will be 3 study periods in the study: Screening Period, Treatment Period, and Follow-
up Period. 
 
Screening Period (6 weeks):  
Screening will take place between Day -42 and Day -1 (6 weeks), prior to the first study drug administration.  
 
Treatment Period (24 weeks):  
Treatment Period will be from Week 0 to Week 24.  

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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. The patients will receive CT-P17 from Week 0 to Week 24 EOW by SC injection via 
AI, co-administered with MTX (12.5 to 25 mg/week, or 10 mg/week if intolerant to a higher dose, oral or IM, 
dose and route must be maintained from Screening to EOS/ED) and folic acid (5 mg/week, oral). Patients 
will comply with all appropriate visits and assessments. 
The investigator or designated study center staff will instruct the patients on the proper administration of CT-
P17 via the AI prior to the first self-injection on Day 1 (Week 0) visit. Thereafter, patients will self-inject the 
study drug at the study center during their scheduled visits under the Investigator or designated study center 
staff’s supervision. Patients will also self-inject the study drug at home at Weeks 10, 14, 18 and 22 according 
to the treatment schedule. 
All patients will return to the study center in regular scheduled time intervals for usability and clinical 
assessments and blood sampling. At each visit, the patients will be questioned about adverse events (AEs) 
and concomitant medications and will be monitored for the clinical signs and symptoms of tuberculosis (TB). 
 
Follow-up Period (4 weeks):  
An EOS visit will occur after 4 weeks from when the last dose of study drug is received (at Week 24) or prior 
to the start of new RA therapy, whichever comes earlier. The efficacy assessments will be performed only if 
the efficacy assessments were not performed at Week 24 as planned. 
An ED visit will occur after 4 weeks from when the last dose is received or prior to the start of new RA 
therapy, whichever comes earlier, if a patient is discontinued from study prior to Week 24 treatment.  
Usability Assessments: 
Primary Endpoint 
 
The usability as assessed by patients rating using PRE- and POST-Self-Injection Assessment 
Questionnaire (SIAQ) at Week 4. 
Secondary Endpoints 
 
The usability as assessed by patients rating using PRE- and POST-SIAQ at Weeks 0, 2 and 24. 
 
The observer rating of successful self-injection using self-injection assessment checklist at Weeks 0, 
2, 4 and 24. 
Efficacy Assessment: 
Secondary Endpoint 
 
Mean change from baseline in disease activity score (DAS)28 (C-reactive protein [CRP]) and 
DAS28 (erythrocyte sedimentation rate [ESR]) up to Week 24. 
Safety Assessments: 
Safety Endpoints 
Adverse events (including serious AEs [SAEs]), AEs of special interest (AESI) (injection site reactions, 
hypersensitivity/allergic reactions, anaphylactic reactions, infections, and malignancies), hypersensitivity 
monitoring (via monitoring of vital signs), vital signs measurements, ECGs, physical examination findings, 
interferon-γ release assay (IGRA), chest X-ray, pregnancy testing, clinical laboratory analyses, signs and 
symptoms of tuberculosis (TB), and prior and concomitant medications monitored throughout the study. 
Hepatitis B, hepatitis C, and HIV status will be tested for the patient’s eligibility determination. 
Sample Size: 
Approximately 60 male or female adult patients will be enrolled. In this usability study, a sample size 
justification based on a formal statistical hypothesis is not relevant, since a formal statistical inference will 
not be made.  
Statistical Analysis: 
The statistical analysis will be performed using SAS software Version 9.3 or later (SAS Institute, Inc., Cary, 
North Carolina). The statistical methods for this study will be described in a detailed statistical analysis plan 
(SAP), which will be finalized prior to database lock. The data documented in this study and the clinical 
parameters measured will be described using descriptive statistics (n, mean, median, standard deviation, 
minimum, and maximum) for quantitative variables and frequency counts and percentages for qualitative 
variables.  
For purposes of analysis, the following analysis populations are defined: 
 
Intent-to-treat (ITT) Population: The ITT Population includes all enrolled patients to receive a dose 
of study drug, regardless of whether or not any study drug dosing was completed.   

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 
Usability Population: The Usability Population includes all patients in the Safety Population who 
have evaluable usability measurements at Week 4 and who do not have major deviations that may 
affect the interpretation of study result. The major protocol deviations will be discussed during the 
data review meeting and the details of protocol deviations will be defined in the SAP. 
 
Safety Population: The Safety Population includes all patients who receive at least 1 dose (full or 
partial) of study drug. 
 
Usability Analysis 
The primary and secondary usability endpoints will be summarized using the ITT and Usability Population. 
The following parameters will be summarized: usability of AI assessed by patient using PRE- and POST-SIAQ 
and assessed by observer rating of successful self-injection using self-injection assessment checklist.  
 
Efficacy Analysis 
The efficacy endpoint will be summarized using the ITT Population. The following parameters will be 
summarized using descriptive statistics: actual value and change from baseline of DAS28 (CRP) and DAS28 
(ESR). 
 
Safety Analysis 
The safety analysis will be performed on the Safety Population. Adverse events will be recorded according to 
the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 and will be coded to system organ 
class (SOC) and preferred term (PT) according to the Medical Dictionary for Regulatory Activities 
(MedDRA). Prior and concomitant medications will be coded using the World Health Organization (WHO) 
Drug Dictionary. 
 
 
 

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1 Introduction 
1.1 Study Rationale 
CT-P17 is currently being developed by CELLTRION, Inc. (hereafter referred to as the 
Sponsor) and is intended to be developed as a biosimilar to Humira.  
The access to biologicals such as the original product, Humira, is limited in many countries 
because of the high costs of the treatment, owing to the complex development and 
manufacturing processes involved in its production. The availability of biosimilar products 
provides more affordable alternative treatments to patients with rheumatoid arthritis (RA).  
Subcutaneous (SC) injection of drugs offers patients the option to self-administer and likely 
to provide a better treatment experience for them1. Removing the need to attend a clinic or 
hospital for regular injections also brings economic benefits to both the patient and healthcare 
system1. Psychological and social barriers such as injection anxiety, lack of confidence in 
giving a self-injection, and potential embarrassment associated with self-injecting in public 
can become problematic in-patient groups that self-inject1. There is a need to assess the 
patients’ experience with self-injection and gauge their success in giving self-injections and 
likelihood of them adhering to self-injection regimen1. 
The purpose of this Phase III study is to evaluate the usability of CT-P17 auto-injector (AI) 
assessed by patients and observers following the recommendations of the guidance for 
industry, “Rheumatoid Arthritis: Developing Drug Products for Treatment”2. For products 
intended for self-administration by an RA patient, the device should be durable, and the 
dexterity and visual acuity required to use the device should be within the capacity of RA 
patients2. In addition, the safety and efficacy of CT-P17 will also be assessed. 
1.1.1 
Choice of Study Population 
International regulations3,4,5 suggest that proposed biosimilars should be tested in a 
population representative of approved therapeutic indications of the original product and 
sufficiently sensitive for detecting potential differences between the biosimilar and the 
original product. 
Consequently, RA has been selected as indication for the CT-P17 3.1 pivotal study (a 
randomized, active-controlled, double-blind study to compare efficacy and safety of CT-P17 
with European Union [EU] approved Humira when co-administered with methotrexate 
[MTX] in patients with moderate to severe active RA), due to the relatively high magnitude 
of the treatment effect and immunogenicity rates observed in the Humira clinical studies in 
this indication. 
This study is designed to take into consideration the characteristic of the RA population and 
their use environment in AI device use by assessing whether usability is within the capability 
of RA patients2. 
1.2 Background 
1.2.1 
Rheumatoid Arthritis 
Rheumatoid arthritis is the most common autoimmune inflammatory arthritis in adults, 
occurring in approximately 0.8% of the global population6,7. It is characterized by a 
progressive inflammatory synovitis of the joints, which may result in irreversible joint 
erosion from as early as 6 months of disease onset8. It has a significant negative impact on the 

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ability to perform daily activities and health related quality of life, and it increases mortality6. 
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 anti-rheumatic therapy for RA usually consists of traditional/conventional 
disease-modifying anti-rheumatic drug (DMARD), low dose corticosteroids, non-steroidal 
anti-inflammatory drugs (NSAIDs), and analgesics9. Methotrexate, 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% improvement6,10,11.  
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 therapy9. Among its 
diverse pathologic effects, TNF α 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 
cartilage10. 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 monotherapy7. 
Adalimumab, a novel biologic DMARD and the first fully human anti-TNF α monoclonal 
antibody for RA treatment, has been shown to be effective in the treatment of RA. 
Adalimumab is structurally and functionally analogous to naturally occurring human 
immunoglobulin (Ig) G1 and demonstrates a high specificity and affinity for TNF. It does not 
bind other cytokines such as lymphotoxin11. Adalimumab also lyses surface TNF expressing 
cells in vitro in the presence of complement12. It is superior to MTX alone in reducing disease 
activity, arresting structural damage, and decreasing disability over 2 years in patients with 
RA13. 
1.2.2 
CT-P17 
CT-P17, containing the active ingredient adalimumab, is a recombinant human monoclonal 
antibody that is being developed as a similar biological medicinal product to the original 
product, Humira. The original product was approved in the United States (US) in 
December 2002 and in the EU in September 200314,15,16. In the EU, Humira is indicated for 
the following conditions: RA, juvenile idiopathic arthritis (polyarticular juvenile idiopathic 
arthritis, enthesitis-related 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, uveitis and pediatric uveitis; in the US, Humira is indicated for the 
same conditions except axial spondyloarthritis without radiographic evidence of AS, and 
pediatric plaque psoriasis12,16. 
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 pre-filled syringe (PFS) and AI at a concentration of 
100 mg/mL as a clear to opalescent and colorless to brown solution for SC administration. 

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The CT-P17 will have the same pharmaceutical form and strength as Humira and is intended 
to have a highly similar quality profile as Humira. 
The Sponsor plans to seek approval for all indications for which the innovator product has 
been approved by demonstrating similarity of CT-P17 with the original product through an 
extensive array of quality, non-clinical, and clinical comparability assessments.  
A detailed description of the chemistry, pharmacology, efficacy, and safety of Humira and 
further details on CT-P17 are provided in the Investigator Brochure (IB). 
1.2.3 
Non-clinical Studies  
Detailed information regarding the non-clinical pharmacology and toxicology of CT-P17 can 
be found in the IB. 
1.2.4 
Clinical Studies  
The usability of adalimumab in RA was assessed in a Phase II multicenter, open-label, 
single-arm, sequential study. The TOUCH study which assessed tolerability and preference of 
an AI versus a PFS in patients with RA showed that the AI was generally well-tolerated 
without any new safety signals17. A total of 52 patients were enrolled and self-administered 
adalimumab at each of 3 monitored clinical visits. The first dose was self-administered via 
the PFS. The second and third doses were self-administered via the AI. The approved 
adalimumab dose of 40 mg every other week (EOW) was administered. The study 
demonstrated that patients preferred AI to the PFS, as they found it to be easier to use and 
more convenient, it had improved safety protection features, and required less time to inject.  
There are 4 clinical studies with CT-P17 that are planned or ongoing. Study CT-P17 1.1 is a 
planned randomized, double-blind, single-dose study to compare the pharmacokinetic (PK) 
and safety of CT-P17, US-licensed Humira and EU-approved Humira in healthy subjects. 
Study CT-P17 1.3 is a planned randomized, open-label, 2-arm, parallel group, single-dose 
study to compare the PK and safety of the AI and PFS in healthy subjects. One Phase III and 
one Phase I study are ongoing; Study CT-P17 3.1 (see Section 1.1.1) and Study CT-P17 1.2. 
Study CT-P17 1.2 is a randomized, double-blind, single-dose study to evaluate the safety and 
PK of CT-P17 and EU-approved Humira in healthy male subjects. Results up to Day 29 
showed that CT-P17 and EU-approved Humira were safe and well-tolerated in the healthy 
male subjects, and the PK result (maximum serum concentration [Cmax]) of CT-P17 obtained 
from this study was comparable to that of EU-approved Humira.  
1.3 Benefit/Risk Assessment 
The CT-P17 will have the same pharmaceutical form and strength as the Humira 
(40 mg/0.4 mL). The proposed dosing regimen is in line with the approved labeling for 
Humira12,16. 
The proposed safety monitoring, which includes monitoring the use of the AI, is deemed to 
be sufficient to monitor potential risks of CT-P17 SC administration by the AI. 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 conditions12,14. CT-P17 will be 
evaluated at the same 40 mg dosage, SC administration route, and EOW dosing schedule as 
approved for Humira, the original product. 

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Based upon the clinical evidence (Section 1.2.4) as well as the proven safety profile of 
Humira, the benefits of the conduct of this proposed clinical study outweigh the associated 
risks. 
More detailed information about the known and expected benefits and risks and reasonably 
expected adverse events (AEs) of adalimumab are found in the IB. 
2 Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
To evaluate usability of CT-P17 AI 
assessed by patients at Week 4. 
The usability as assessed by patients rating 
using PRE- and POST-Self-Injection 
Assessment Questionnaire (SIAQ) at Week 4. 
Secondary 
To evaluate change in usability assessed 
by patients and observer over time up to 
Week 24. 
 
 
The usability as assessed by patients rating 
using PRE- and POST-SIAQ at Weeks 0, 2 
and 24. 
The observer rating of successful 
self-injection using self-injection assessment 
checklist at Weeks 0, 2, 4 and 24. 
To evaluate overall efficacy. 
Mean change from baseline in disease 
activity score (DAS)28 (C-reactive protein 
[CRP]) and DAS28 (erythrocyte 
sedimentation rate [ESR]) up to Week 24. 
To evaluate overall safety.  
Adverse events (AEs) (including serious AEs 
[SAEs]), AEs of special interest (AESIs) 
(injection site reactions, 
hypersensitivity/allergic reactions, 
anaphylactic reactions, infections, and 
malignancies), hypersensitivity monitoring 
(via monitoring of vital signs), vital signs 
measurements, ECGs, physical examination 
findings, interferon-γ release assay (IGRA), 
chest X-ray, pregnancy testing, clinical 
laboratory analyses, signs and symptoms of 
tuberculosis (TB), and prior and concomitant 
medications monitored throughout the study. 
Hepatitis B, hepatitis C, and human 
immunodeficiency virus (HIV) status will be 
tested for the patient’s eligibility 
determination. 

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3 Study Design 
3.1 Overall Study Design 
This study is a Phase III, open-label, single-arm, multiple-dose study to evaluate usability, 
safety and efficacy of SC AI of CT-P17 (the study drug) in patients with moderate to severe 
active RA.   
The study drug will be administered EOW by SC injection via AI from Week 0 to Week 24 in 
combination with MTX (12.5 to 25 mg/week, or 10 mg/week if intolerant to a higher dose, 
oral or intramuscular [IM]) and folic acid (≥5 mg/week, oral). The patient must have been on 
a stable dose and route of MTX for at least 4 weeks prior to the first administration of the 
study drug on Day 1. The same dose and route should be maintained throughout the study.  
The study will include a Screening Period (6 weeks), a Treatment Period (24 weeks), and a 
Follow-up Period (4 weeks).  
Screening Period (6 weeks):  
Screening will take place between Day -42 and Day -1 (6 weeks), prior to the first study drug 
administration.  
Treatment Period (24 weeks):  
Treatment Period will be from Week 0 to Week 24.  
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. The patients will receive CT-P17 from Week 0 to Week 
24 EOW by SC injection via AI, co-administered with MTX (12.5 to 25 mg/week, or 10 
mg/week if intolerant to a higher dose, oral or IM; dose and route must be maintained from 
Screening to end-of-study [EOS]/early discontinuation [ED]) and folic acid (5 mg/week, 
oral). Patients will comply with all appropriate visits and assessments. 
The investigator or designated study center staff will instruct the patients on the proper 
administration of CT-P17 via the AI prior to the first self-injection on Day 1 (Week 0) visit. 
Thereafter, patients will self-inject the study drug at the study center during their scheduled 
visits under the Investigator or designated study center staff’s supervision. Patients will also 
self-inject the study drug at home at Weeks 10, 14, 18 and 22 according to the treatment 
schedule. 
All patients will return to the study center in regular scheduled time intervals for usability and 
clinical assessments and blood sampling. At each visit, the patients will be questioned about 
AEs and concomitant medications and will be monitored for the clinical signs and symptoms 
of tuberculosis (TB). 
Follow-up Period (4 weeks):  
An EOS visit will occur after 4 weeks from when the last dose of study drug is received (at 
Week 24) or prior to the start of new RA therapy, whichever comes earlier. The efficacy 
assessments will be performed only if the efficacy assessments were not performed at Week 
24 as planned. 
An ED visit will occur after 4 weeks from when the last dose is received or prior to the start 
of new RA therapy, whichever comes earlier, if a patient is discontinued from study prior to 
Week 24 treatment. 
The schedule of activities (SoA) is presented in Table 5. 

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The Sponsor will not be providing the study drug after the end of the study and the 
Investigator is responsible for ensuring that consideration for the post-study care of the 
patient has been given. 
The study design and patient assessment overview is presented in Figure 1. 
Figure 1: Study Design Overview 
 
Abbreviations: AI=auto-injector; EOS=end-of-study; ED=early discontinuation; N=number of patients; RA=rheumatoid 
arthritis; SC=subcutaneous. 
Note: The investigator or designated study center staff will instruct the patients on the proper administration of CT-P17 via 
the AI prior to the first self-injection at Week 0. Thereafter, patients will self-inject the study drug at the study center during 
their scheduled visits under the Investigator or designated study center staff’s supervision. Patients will also self-inject the 
study drug at home at Weeks 10, 14, 18 and 22 according to the treatment schedule. 
1 The EOS assessments need to be completed after 4 weeks from when the last dose (at Week 24) is received or prior to the 
start of new RA therapy, whichever comes earlier. The efficacy assessments will be performed only if the efficacy 
assessments were not performed at Week 24 as planned. 
2 The ED visit needs to be completed after 4 weeks from when the last dose is received or prior to the start of new RA 
therapy, whichever comes earlier, if a patient is discontinued from study prior to Week 24 treatment. 
3.2 Justification for Dose 
Humira is supplied in 2 strengths; 50 mg/mL (40 mg/0.8 mL) and 100 mg/mL (40 mg/0.4 
mL). The recommended dose of Humira for adult patients with RA is 40 mg of adalimumab 
administered EOW as a single-dose via SC injection. CT-P17 is being developed to have the 
same dosage form, route of administration and dosing regimen as the adalimumab (Humira) 
which is approved in the US and EU. The 40 mg/0.4 mL dose level will be used in this study 
as the recommended dose in RA treatment. 
The doses for MTX and folic acid used in this study are per label instructions for the drugs. 
3.3 Study Duration 
A patient is considered to have completed the study if he/she has completed all phases of the 
study including the last scheduled procedure shown in the SoA (Table 5). 
The end of the study is defined as the date of final database lock. An EOS visit will occur 4 
weeks after the last dose (at Week 24) is received or prior to the start of new RA therapy, 
whichever comes earlier. 
4 Study Population 
Male or female patients between 18 to 70 years of age, inclusive, with moderate to severe 
active RA diagnosed according to the 2010 American College of Rheumatology 
(ACR)/European League Against Rheumatism (EULAR) classification criteria18 despite 
previous treatment with MTX (12.5 to 25 mg/week, or 10 mg/week if intolerant to a higher 

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dose, oral or IM) 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.  
Approximately 60 patients are planned to be enrolled in the study. Only patients with a signed 
and dated informed consent form (ICF) in compliance with local regulations will be enrolled. 
Deviations from the inclusion and exclusion criteria could potentially jeopardize the scientific 
integrity of the study, regulatory acceptability, and, most importantly, patient safety. 
Therefore, strict adherence to the eligibility criteria as specified in the protocol is essential.  
4.1 Inclusion Criteria 
Each patient must meet all of the following criteria to be enrolled in this study: 
1. Male or female patient between 18 to 70 years of age, inclusive. 
2. Patient must be able and willing to self-administer subcutaneous (SC) injections via 
auto-injector (AI). 
3. Patient with a diagnosis of rheumatoid arthritis (RA) according to the 2010 American 
College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) 
classification criteria18 for at least 24 weeks prior to the first administration of the 
study drug (Day 1). 
4. 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. 
5. Patient who has been receiving oral or intramuscular (IM) methotrexate (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). 
6. Patient has adequate renal and hepatic function at Screening as defined by the 
following clinical chemistry results: 
o Serum creatinine 1.5  upper limit of normal (ULN) or an estimated 
creatinine clearance level >50 mL/minute (by Cockcroft-Gault formula19) 
(Système International d’Unités [SI] units: 0.84 mL/second). 
o Serum alanine aminotransferase ≤3.0 x ULN. 
o Serum aspartate aminotransferase ≤3.0 x ULN. 
o Serum total bilirubin ≤1.5 x ULN. 
7. Patient has the following hematology laboratory test results at Screening: 
o Hemoglobin >8.0 g/dL (SI units: >80 g/L or 4.96 mmol/L). 
o Absolute neutrophil count ≥1.5 x 103 cells/µL (SI units: ≥1.5 x 109 
cells/L). 
o Platelet count ≥75 x 103 cells/µL (SI units: ≥75 x 109 cells/L). 
8. Patient (or legal guardian, if applicable) is informed of the full nature and purpose of 
the study, including possible risks and side-effects, has the ability to cooperate with the 
Investigator and is given ample time and opportunity to read and understand verbal 
and/or written instructions, and signs the written informed consent form (ICF) with 
date prior to participation in the study. 
9. 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 
the study drug. Examples include the following: 

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o Hormonal contraceptives (combined or progestogen-only) associated with 
inhibition of ovulation 
o Intrauterine devices 
o Sexual abstinence (not periodically, but for the entire period of risk 
associated with the study drug) 
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.  
4.2 Exclusion Criteria 
A patient meeting any of the following criteria will be excluded from the study: 
1. Patient who has previously received or plans to receive investigational or licensed 
product; biologic or targeted synthetic disease-modifying anti-rheumatic 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 has previous or current use of other SC self-injected drugs (e.g., insulin, 
MTX). 
4. Patient who currently has, or has a history of, any of the following infections: 
o A known infection with hepatitis B (active or carrier of hepatitis B 
[HBV]), hepatitis C, or infection with human immunodeficiency virus 
(HIV). However, a patient with past HBV is allowed if resolved. Patient 
will be enrolled based on HBV infection eligibility criteria, specified in 
Section 6.4.2.8. 
o Hospitalization for treatment of infection within 24 weeks prior to the first 
administration of the study drug (Day 1). 
o 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). 
o Symptomatic or recurrent herpes zoster or other chronic or recurrent 
infection within 6 weeks prior to the first administration of the study drug 
(Day 1). 
o 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. 
5. Patient is ineligible according to the following tuberculosis (TB) screening criteria: 

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o Patient who has a history or a current diagnosis of active 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. 
o Patient who has had exposure to a person with active TB such as first-
degree family members or co-workers. 
o 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 completed TB 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. 
6. Patient who has current signs or symptoms of liver or renal insufficiency or cardiac, 
vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, psychiatric, 
or metabolic disturbances that are severe, progressive, or uncontrolled. Including one 
or more of the following: 
o Classified as Class II or III obese by World Health Organization 
classification (body mass index 35 kg/m2). 
o Uncontrolled diabetes mellitus, even after an appropriate treatment. 
o Uncontrolled hypertension (as defined by systolic blood pressure [BP] 
≥160 mmHg or diastolic BP ≥100 mmHg). 
o 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. 
o Significant systemic RA involvement (e.g., Sjögren’s syndrome, vasculitis, 
pulmonary fibrosis), which would put the patient at risk if they are 
enrolled. 
o 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 in situ of the uterine cervix in situ, cutaneous 
basal cell carcinoma, or cutaneous squamous cell carcinoma. 
o 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). 
o History of organ transplantation, including corneal graft/transplantation. 
o Hereditary or acquired immunodeficiency disorder, including 
immunoglobulin deficiency. 
o Any clinically significant respiratory disease, including but not limited to 
chronic obstructive pulmonary disease, asthma, or pleural effusion. 
o Previous diagnosis or symptoms suggestive of demyelinating disorders, 
including multiple sclerosis and Guillain-Barre syndrome. 

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o 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 (DAS) 
including joint counts. 
o 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. 
o History or evidence of any other clinically significant disorder, condition, 
or disease that, in the opinion of the Investigator, would pose a risk to 
patient safety or interfere with the study evaluation, procedures, or 
completion. 
7. Patient who has received or plans to receive any of the following prohibited 
medications or treatment: 
o Intra-articular (IA) 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 drugs (NSAIDs), if they have received a stable dose for at 
least 4 weeks prior to the first administration of the study drug (Day 1). In 
addition, a patient is permitted to receive low-potency topical, otic, and 
ophthalmic glucocorticoid preparations as per the instructions on the 
product label. 
o 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 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). 
o 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. 
o Alkylating agents within 1 year prior to the first administration of the 
study drug (Day 1). 
o Traditional Chinese medicine within 4 weeks prior to the first 
administration of the study drug (Day 1). 
o A vaccination (live or live-attenuated) within 4 weeks prior to enrollment 
or Bacillus Calmette-Guérin (BCG) vaccination within 1 year prior to 
enrollment, or a live or attenuated vaccination planned during the course of 
the study. 
o 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).  

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8. Severe physical incapacitation (severely limited in ability to perform routine self-care, 
has RA ACR global functional status Class IV20, or who cannot benefit from 
medication). 
9. Female patient who is currently pregnant or breastfeeding or plans to become pregnant 
or breastfeed within 6 months after the last dose of the study drug. 
10. Patient who has current drug or alcohol abuse or dependence, or a history of alcohol or 
drug abuse within 2 years from the first administration of the study drug (Day 1). 
11. Patient who, in the opinion of their general practitioner or the Investigator, should not 
participate in the study. 
4.3 Study Withdrawal/Study Drug Discontinuation 
Patients are free to withdraw from the study at any time for any reason. The Investigator may 
also discontinue the study drug at any time in the interest of patient safety. The primary 
reasons for the study withdrawal and the discontinuation of the study drug must be recorded 
in the patient’s source documents and the electronic case report form (eCRF), with any 
comments (spontaneous or elicited) or complaints made by the patient. Reasons for study 
drug discontinuation include the following: 
• 
Patient develops signs of disease progression in the judgment of the Investigator. 
• 
Patient withdraws consent or refuses having procedures/observations. 
• 
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 lost to follow-up. 
• 
Patient dies. 
• 
Study is terminated by the Sponsor. 
• 
Patient is pregnant. 
• 
Investigator’s decision. 
It is recommended that the Investigator contact the Sponsor or its designee if possible to 
discuss the particular situation before study withdrawal or study drug discontinuation. All 
patients who terminate from the study will retain their patient identification code (PIC). 
4.3.1 
Recruitment of Additional Patients  
Patients who receive study drug and discontinue prior to study completion will not be 
replaced. Patients who failed the Screening, for any reason, can be re-screened only once. 
4.4 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 CT-P17 
The study drug administered in this study is CT-P17. 
Details of CT-P17 are summarized in Table 1. 
Table 1: Details of CT-P17 
Study drug Name: 
CT-P17. 
Dosage Formulation: 
Clear to opalescent and colorless to brown solution of 
adalimumab for subcutaneous (SC) administration, with a 
pH of approximately 5.2. 
Unit Dose 
Strength(s)/Dosage Level(s): 
CT-P17 will be supplied as 40 mg/0.4 mL (100 mg/mL). 
Each 0.4 mL of CT-P17 contains 40 mg adalimumab, 
sodium acetate, glycine, and polysorbate 80 with no 
preservatives. 
Route of Administration: 
SC injection. 
Dosing Instructions: 
Every other week (EOW). 
Packaging and Labeling: 
 
CT-P17 is supplied as a sterile-use, auto-injector (AI) 
designed to deliver 0.4 mL (40 mg) of drug product. CT-
P17 will be provided in an individual container. Each 
container will be labeled as required per country 
requirement. 
Manufacturer: 
CELLTRION, Inc. 
Device: 
Auto-Injector (AI). 
5.1.1 
Medical Devices 
The study drug will be administered via an AI provided by the Sponsor. Instructions for use 
(IFU) and instructions for self-injection of the AI will be provided to each patient and will be 
included in the study manual provided to all sites.  
5.2 Other Treatments Administered 
5.2.1 
Co-administration of Methotrexate and Folic Acid 
All patients will receive MTX and folic acid concomitantly. Patients should have been 
receiving oral or IM 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. However, the dose of MTX may 
be reduced for reasons of documented intolerance to MTX (e.g., hepatic or hematologic 
toxicity or per local requirement). 
Patients are required to take folic acid (≥5 mg/week, oral dose) throughout the duration of the 
study to minimize or prevent AEs related to MTX side-effects21. 

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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 patient’s source 
documents and the eCRF.  
5.2.2 
Premedication 
Patient may also be pre-medicated 30 to 60 minutes prior to the study drug 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. 
5.3 Study Drug Administration 
Patients enrolled in the study will receive study drug and only authorized site staff may 
supply study drugs. The study drug will be self-injected at the study center under the 
Investigator or designee’s supervision.  
A fixed dose of the study drug (40 mg) will be administered EOW by SC injection via AI 
from Week 0 to Week 24 at the study center, under the Investigator or designee’s supervision. 
At Weeks 10, 14, 18 and 22, patients will self-inject at home according to the SoA (Table 5).  
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). 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.  
Where the study drug injection is scheduled for the same day as a clinic visit, the visit 
procedures for the study must be completed before study drug administration and the self-
injection must be performed under the supervision of the Investigator or designee. 
5.3.1 
Training for Self-Injection of Study Drug 
The Investigator or designee must have completed training on the self-injection technique 
before training patients. This training must be documented. Detailed training instructions will 
be provided in the study manual. After completing their own training, the investigator or 
designated study center staff will then instruct the patients on the proper administration of the 
study drug via the AI prior to self-injection on Day 1 (Week 0). Printed IFU and instructions 
for self-injection of the AI will be provided to each patient. Patients must self-inject at the 
study center during their visits under the Investigator or designee’s supervision to be assessed 
for their ability of self-administration. The training and performance of self-injection will be 
documented in the patient’s source documents. 
If the patient requests it, additional training can be provided during the visits to the study 
center. Patients will be instructed to contact the Investigator promptly in the event of any 
signs and symptoms of injection site reactions, hypersensitivity/allergic reactions and 
anaphylactic reactions when they self-inject at home. 
5.4 Other Supplies 
As discussed in Section 5.3.1, printed IFU and instructions for self-injection of the AI will be 
provided to the patients 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: 

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• 
Patient self-injection paper diary to record treatment compliance (see Sections 5.6 and 
6.1.3 for details). 
• 
Patient self-reporting of AE paper diary to record any AE including injection site 
reactions (see Sections 6.1.3 and 6.4.1.4 for details). 
• 
A sharps bin to store used AI. The sharps bin with the used AI will be returned to the 
study center for disposal. 
In addition, a patient card which includes important safety risk and contact information for 
medical emergency will be provided. 
5.5 Management of Clinical Supplies 
5.5.1 
Study Drug Handling and Storage 
The Investigator or designee must maintain a log to confirm appropriate temperature 
conditions have been maintained during transit for all study drugs received and any 
discrepancies are reported and resolved before use of the study drugs. All study drugs must be 
stored in a secure, environmentally controlled, and monitored (manual or automated) area in 
accordance with the labeled storage conditions with access limited to the Investigator and 
authorized site staff. The study drug must be dispensed only at the study center. 
The study drug must be kept at a controlled refrigerated temperature between 2°C (36°F) and 
8°C (46°F). The study drug must not be frozen: thawed (i.e., previously frozen) study drug 
must not be used. The study drug must be stored in the original carton until the time of 
administration to protect from light. 
A single study drug AI may be stored at room temperatures of up to a maximum of 25°C 
(77°F) for a period of up to 14 days. The AI must be protected from light and discarded if not 
used within the 14-day period. Used AI should be stored in a sharps bin and disposed of via 
standard procedures. 
5.5.2 
Study Drug Accountability 
The Investigator will maintain records that the study drug was received, including the date 
received, drug identity code, date of manufacture or expiration date, amount received, and 
disposition. In addition, records will be maintained that include the PIC, dispensation date, 
and amount dispensed.  
All remaining partially used and/or unused study drug will be returned to the Sponsor or its 
designee after study completion/termination or destroyed with the permission of the Sponsor 
in accordance with applicable laws and study center procedures. The used AI can only be 
destroyed locally if it is written in local standard operating procedures and a specific 
authorization is given by the Sponsor, which is required prior to study drug administration. 
Permission will be granted by the Sponsor on a study center-by-study center basis after 
reviewing the study center destruction policy. The list of destroyed AI 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 the Sponsor.   
This is an open-label, single-arm study and patients will not be randomized to treatment. 
Each eligible patient with a signed ICF, will be assigned a PIC by the Sponsor.   

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5.6 Treatment Compliance 
Patient compliance with the treatment regimen will be monitored by completion of a patient 
self-injection paper diary detailing the time and date of self-administration of the study drug 
at home at Weeks 10, 14, 18, and 22. All patients must record study drug administration 
details in their patient self-injection paper diary for the self-injections performed at home. 
The study drug container labels from all home injections should be returned and any unused 
study drug must be accounted for by the patient.  
Patients must be instructed to write the date of each injection on the study drug container and 
to bring all used and dated study drug container labels at each visit for the evaluation of 
compliance. 
Drug accountability details are provided in Section 5.5.2.  
If the patient forgets to self-inject the study drug, the patient should inject the dose of study 
drug as soon as they remember 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 2 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 and Concomitant Medications and Therapy 
Use of all prior and concomitant medications for the treatment of RA, from the diagnosis of 
disease until the EOS/ED visit, will be recorded in the patient’s source documents and the 
eCRF. Use of all medications for other purposes, taken from 42 days prior to the first 
administration of study drug until the EOS/ED visit, will be recorded in the patient’s source 
documents and the eCRF. However, in order to check eligibility, prior medications will be 
reviewed from date specified in exclusion criteria #7 (Section 4.2). This will include all 
prescription drugs, vitamins, minerals, and over-the-counter medications. Any changes in 
concomitant medications will also be recorded in the patient’s source documents and the 
eCRF.  
Any concomitant medication deemed necessary for the welfare of the patient during the study 
may be given at the discretion of the Investigator. Local standard of care practices and 
regulations for the indications being treated must be followed for any allowed concomitant 
medications. It is the responsibility of the Investigator to ensure that details regarding the 
medication are recorded in full in the patient’s source documents and the eCRF. 
The Sponsor Medical Monitor or its designee should be contacted if there are any questions 
regarding concomitant or prior medications. 
5.7.1 
Permitted Concomitant Medication and Therapies 
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 NSAIDs, if they 
have received a stable dose for at least 4 weeks prior to the first administration of the study 
drug (Day 1). In addition, the same dose must be maintained until the EOS/ED visit. If there 
are any changes needed in the dose during the study, they should be reported to and discussed 
with the Sponsor Medical Monitor or its designee in advance. In addition, patients are 
permitted to receive low-potency topical, otic, and ophthalmic glucocorticoid preparations 
provided as per the instructions on the product label. 

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Killed vaccinations are acceptable during the study.  
5.7.2 
Prohibited Therapy 
Concomitant medications, treatments and procedures not allowed during the study are: 
• 
Intra-articular corticosteroids are discouraged throughout the study; however, limited 
use of IA corticosteroids may be allowed as treatment for severe RA flares. No more 
than 1 injection to 1 joint should be injected throughout the study. The injected joint 
must be considered a non-responder joint during the response evaluation. 
• 
Any conventional DMARDs other than MTX (including but not limited to 
hydroxychloroquine, leflunomide, sulphasalazine, minocycline, ciclosporin, 
azathioprine) 
• 
Any other investigational device or medical product   
• 
Alkylating agents 
• 
Traditional Chinese medicine 
• 
Live or live-attenuated vaccines 
• 
Any surgical procedure, including bone or joint surgery or synovectomy (including 
joint fusion or replacement) 
• 
Any biologic agent (e.g., TNF inhibitors such as adalimumab, etanercept, infliximab, 
certolizumab pegol, golimumab or non-TNF inhibitors such as abatacept, rituximab, 
tocilizumab and belimumab or targeted synthetic DMARDs such as tofacitinib, 
baricitinib or any anti-rheumatic investigational compounds) 
• 
Narcotic analgesics (except tramadol) 
5.7.3 
Rescue Medication 
Rescue medication is any medication that is used to treat RA in addition to the study drug. 
The Sponsor will not supply any rescue medication. Acetaminophen/paracetamol and/or 
tramadol are allowed as rescue medication, but the medication should be stopped at least 24 
hours prior to each joint evaluation. However, other narcotic analgesics are not permitted for 
use. The date and time of rescue medication administration as well as the name and dosage 
regimen of the rescue medication must be recorded. 
The Investigator should contact the Medical Monitor if at any time, a patient needs rescue 
medication. If necessary, patient’s eligibility for continuation of the study drug administration 
will be determined. If the patient is no longer eligible to continue with the study drug, they 
should undergo the ED assessments listed in the SoA (Table 5). 
5.8 Dose Modification 
No dose adjustment of the study drug is allowed during the study. MTX dose may be reduced 
for reasons of documented intolerance to MTX (e.g., hepatic or hematologic toxicity or per 
local requirement). The folic acid dose can be increased to counteract the side-effects of 
MTX (which include nausea, mucositis and headache) as needed. Any dose modifications, 
and reasons, should be recorded in the patient’s source documents and the eCRF. 
6 Study Procedures and Assessments  
• 
Study procedures and their timing are summarized in the SoA (Table 5). 
• 
Adherence to the study design requirements, including those specified in the SoA 
(Table 5), is essential and required for study conduct. 

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• 
All Screening evaluations must be completed and reviewed to confirm that potential 
patients meet all eligibility criteria. The Investigator will maintain a screening log to 
record details of all patients screened and to confirm eligibility or record reasons for 
screening failure, as applicable. 
• 
Procedures conducted as part of the patient’s routine clinical management (e.g., blood 
count) and obtained before signing of ICF may be utilized for Screening or baseline 
purposes provided the procedure met the protocol-specified criteria and were 
performed within the time frame defined in the SoA (Table 5). 
• 
Repeat or unscheduled samples may be taken for safety reasons or for technical issues 
with the samples. 
6.1 Study Procedures 
6.1.1 
Informed Consent and Enrollment 
Any patient who provides informed consent (i.e., signs and dates the ICF and assent form, if 
applicable) is considered a study patient and enrolled in the study. 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 will also sign the ICF. 
6.1.2 
Patient Identification Code 
Each patient will be assigned a PIC produced by the Sponsor. 
All study documents (e.g., eCRFs, clinical documentation, sample containers, drug 
accountability logs, etc.) will be identified with the PIC. 
6.1.3 
Patient Diaries 
A patient self-injection paper diary will be provided to each patient on Day 1 (Week 0) to 
record study drug administration performed at home with the following information: 
• 
Study drug administration details such as: 
o Date 
o Time 
o Site of injection 
o Used AI kit information 
o 
Injection completion status  
In addition, patients will also be provided with a patient self-reporting of AE paper diary to 
record any AEs experienced outside of the study center, including injection site reactions, 
hypersensitivity/allergic reactions and anaphylactic reactions.  
Patients will be trained on use of the patient diaries. The patient diaries will remain with the 
patient for the duration of the study. The Investigator will review the patient diaries for 
completeness and request missing information periodically and in a timely manner. Untoward 
events recorded in the patient diaries will be reported as AEs according to the Investigator’s 
discretion and clinical judgment. 
The patient diaries will serve as source documents and remain at the study center at the end 
of the study. Entries in the patient diaries will be transferred into the appropriate collection 
device. Any entry in the eCRF that does not correspond with an entry in the patient diaries 
will be explained by the Investigator in the source documentation. 

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6.2 Usability Assessments 
Usability will be assessed by the evaluation of the patient rating using PRE- and POST- 
Self-Injection Assessment Questionnaire (SIAQ) and the observer rating of successful 
self-injection using self-injection assessment checklist at the time points specified in the SoA 
(Table 5). 
6.2.1 
PRE- and POST-SIAQ 
PRE- and POST-SIAQ will be assessed at the visits specified in SoA (Table 5). 
The primary outcome measure is the usability of the study drug as assessed by the patient 
rating on the PRE- and POST-SIAQ modules at Week 4. PRE- and POST-SIAQ will be 
completed by the patient prior to and after self-injection of the study drug SC via AI. Patients 
will complete PRE-SIAQ immediately before the administration of study drug and POST-
SIAQ within 20 to 40 minutes after the administration of study drug. This assessment should 
be recorded in the patient’s source documents and the eCRF. 
The SIAQ assesses the perceived advantages of self-injection and potential a barrier to 
self-injection, including psychological barriers, social barriers, and physical barriers, as well 
as satisfaction with self-injection and willingness to continue the treatment with self-
injection1. The PRE-SIAQ module is a 7-item questionnaire that investigates feelings about 
injections, self-confidence (regarding self-administration), and satisfaction with self-injection 
(each item graded on a 5-point scale). The POST-SIAQ module is a 27-item questionnaire 
that assesses feelings about injections, self-image, self-confidence (regarding 
self-administration), pain and skin reactions during or after the injection site reactions, ease 
of use of the self-injection device, and satisfaction with self-injection (each item graded on 
either a 5-point or 6-point scale). 
The SIAQ is included in Appendix 4. 
6.2.2 
Self-Injection Assessment Checklist 
Self-injection assessment checklist will be assessed at the visits specified in SoA (Table 5). 
The Investigator or designee will observe the patient’s ability to successfully follow the steps 
to self-administer the study drugs described in the IFU and complete the checklist within 
15 minutes after patient’s self-injection. 
Self-injection assessment checklist is included in Appendix 3. 
6.3 Efficacy Assessments 
Efficacy will be assessed by the evaluation of DAS28 (DAS28 [CRP], DAS28 [ESR], and 
individual components) at the time points specified in the SoA (Table 5). 
An independent joint count assessor will be assigned in each study center. If possible, it is 
recommended that the joint assessments should be performed independently by the same 
person, at each study center throughout the study. 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. If a patient received IA glucocorticoid injection during study participation, the 
injected joint must be considered a non-responder joint during the joint assessment. 

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6.3.1 
Tender Joint Count (68) and Swollen Joint Count (66) 
Sixty-eight joints will be assessed to determine the number of joints that are considered 
tender and 66 joints will be assessed for swelling at Screening visit by an independent joint 
assessor.   
6.3.2 
Tender and Swollen Joints Count (28) 
Tender joint counts (TJC) and swollen joint counts (SJC) (28) will be performed by the 
independent joint assessor at time points specified in the SoA (Table 5).   
6.3.3 
Disease Activity Score Using 28 Joint Counts 
The DAS28 (CRP)22 is a statistically derived index combining TJC and SJC (28) (Section 
6.3.2), CRP (Section 7.4.1), and patient’s global assessment of disease activity (PGA) 
measured using visual analogue scale (VAS) (Section 6.3.4). Similarly, DAS28 (ESR)23 score 
is a statistically derived index combining TJC and SJC (28) (Section 6.3.2), ESR (Section 
7.4.1), and PGA measured using VAS (Section 6.3.4).  
6.3.4 
Patient’s Global Assessment of Disease Activity Measured using 
VAS 
Patient’s global assessment of disease activity will be assessed by VAS at the visits specified 
in SoA (Table 5). Patients will rate their overall status with respect to RA signs and symptoms 
and functional capacity by marking one line (│) through the 100-mm line (0 mm equals very 
well, and 100 mm equals very poor disease activity) in the VAS scale. The length of the line 
is measured from the left (0 mm) and the value (in mm) recorded in the patient’s source 
documents and the eCRF. 
 
Very Well                                                                                                                       Very 
Poor  
6.3.5 
C-Reactive Protein and Erythrocyte Sedimentation Rate 
Blood samples for CRP and ESR will be analyzed locally at the time points specified in the 
SoA (Table 5). A standard ESR kit using the Westergren method of assessment will be 
supplied to the study centers for use. 
6.4 Safety Assessments 
Safety evaluations including AEs (including SAEs), AESI (injection site reactions, 
hypersensitivity/allergic reactions, anaphylactic reactions, infections, and malignancies), 
hypersensitivity monitoring (via monitoring of vital signs), vital signs measurements, ECGs, 
physical examination findings, IGRA, chest X-ray, pregnancy testing, clinical laboratory 
analyses, signs and symptoms of TB, and prior and concomitant medications will be 
monitored throughout the study according to the SoA (Table 5). Hepatitis B, hepatitis C, and 
HIV status will be tested for the patient’s eligibility determination. 

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6.4.1 
Adverse Events  
6.4.1.1 
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 is signed if any symptoms develop (see Section 6.4.1.4). 
Any new condition noted at Screening will 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 
judgment 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. 
6.4.1.1.1 
Adverse Events of Special Interests 
The following AESIs will be reported using the same process as for AEs; these events are to 
be considered serious only if they meet the definition of an SAE. 
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. 

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Hypersensitivity/allergic reactions 
All AEs related to hypersensitivity and allergic reactions occurring after the study drug 
administration will be reported. 
Anaphylactic reactions 
Anaphylaxis will be identified according to Sampson criteria24. Anaphylaxis is likely when 
any 1 of the 3 criteria are fulfilled. 
1. Acute onset of an illness (minutes to several hours) with involvement of the skin, 
mucosal tissue, or both (e.g., generalized hives, pruritus or flushing, swollen lips- 
tongue-uvula) and at least one of the following: 
a. Respiratory compromise (e.g., dyspnea, wheeze or bronchospasm, stridor, 
reduced peak expiratory flow, hypoxemia) 
b. Reduced BP or associated symptoms of end-organ dysfunction (e.g., hypotonia 
[collapse], syncope, incontinence) 
2. Two or more of the following that occur rapidly after exposure to a likely allergen for 
that patient (minutes to several hours):   
a. Involvement of the skin-mucosal tissue (e.g., generalized hives, itch-flush, 
swollen lips-tongue-uvula) 
b. Respiratory compromise (e.g., dyspnea, wheeze-bronchospasm, stridor, reduced 
peak expiratory flow, hypoxemia) 
c. Reduced BP or associated symptoms (e.g., hypotonia [collapse], syncope, 
incontinence) 
d. Persistent gastrointestinal symptoms (e.g., crampy abdominal pain, vomiting) 
3. Reduced BP after exposure to known allergen for that patient (minutes to several 
hours): 
Adults: Systolic BP of less than 90 mm Hg or greater than 30% decrease from that 
person’s baseline 
Infections 
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 will be reported. 
6.4.1.1.2 
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 

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dyscrasias or convulsions that do not result in inpatient hospitalization, or the development of 
drug dependency or drug abuse. 
6.4.1.1.3 
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 label. 
6.4.1.2 
Eliciting and Documenting Adverse Events 
Adverse events will be assessed from the date the patient signs the ICF until EOS/ED 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, anaphylactic reactions, infections, and 
malignancies) will be closely monitored. 
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 patient’s source documents and the eCRF. 
6.4.1.3 
Reporting Adverse Events 
All AEs reported or observed during the study will be recorded on the AE page in the 
patient’s source documents and 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 v.5.0. 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 
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Adverse events (and SAEs) should be reported until the EOS/ED visit regardless of the 
relationship to the study drug. After the EOS visit, serious adverse drug reactions will be 
reported to Sponsor or its designee. 
6.4.1.4 
Patients’ Self-reporting of Adverse Events 
A patient self-reporting AE diary will be provided to all patients who 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 self-reporting AE diary and study center 
staff will review the self-reporting AE diary at each visit throughout the study up to and 
including EOS/ED 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 will be re-trained on how to complete the self-reporting AE diary. All AEs 
entered in the self-reporting AE diary will be recorded on the AE page in the eCRF. 
6.4.1.5 
Reporting Serious Adverse Events 
Any AE considered serious by the Investigator or which meets SAE criteria 
(Section 6.4.1.1.2) must be reported to
 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 
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 Investigator or sub-Investigator. All SAEs (regardless of relationship with 
the study drug) will be followed up until satisfactory resolution or until the Investigator or 
sub-Investigator deems the event to be chronic or not clinically significant or the patient to be 
stable. 
The Sponsor or its designee is responsible for reporting relevant SAEs to the competent 
authority, other applicable regulatory authorities, and participating Investigators, in 
accordance with European Clinical Trials Directive (Directive 2001/20/EC), International 
Council for Harmonisation (ICH) guidelines, and/or local regulatory requirements. 
The Sponsor or its designee is responsible for reporting fatal or life-threatening suspected 
unexpected serious adverse reaction (SUSARs) (expedited reports) to the regulatory agencies 
and competent authorities by telephone or fax within 7 calendar days after being notified of 

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the event. The Sponsor or its designee should report other relevant SAEs associated with the 
use of the study drug to the appropriate competent authorities (according to local guidelines), 
Investigators, and IRBs/IECs 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) 
• 
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. 
6.4.1.6 
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 IB). 
Reporting requirements will also be based on the Investigator’s assessment of causality and 
seriousness, with allowance for upgrading by the Sponsor as needed. 
6.4.1.7 
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): 

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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. 
6.4.1.8 
Assessment of Causality 
As discussed in Section 6.4.1.3, 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. 
The relationship or association of CT-P17 in causing or contributing to the AE will be 
characterized using the following classification and criteria: 

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Unrelated: 
This relationship suggests that there is no association between the study drug and 
the reported event. 
Possible: 
This relationship suggests that treatment with the study drug caused or 
contributed to the AE, e.g., the 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. 
6.4.1.9 
Follow-up of Patients Reporting Adverse Events 
All AEs must be reported in detail on the appropriate page in the patient’s source documents 
and 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. 
6.4.2 
Other Safety Assessments 
6.4.2.1 
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 SoA (Table 5).  
For injections that will be self-injected at home, patients should be advised to call the study 
center or get immediate medical help if they experience the symptoms of injection site 
reactions (Section 6.4.1.1.1). 
Details will be recorded in both the patient’s source documents and the eCRF. 
6.4.2.2 
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 at the study center, as 
specified in the SoA (Table 5), by additional vital signs measurements including BP, heart and 
respiratory rates, and body temperature. If a patient has 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), the patient 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 6.4.1.4). In case of 
hypersensitivity, emergency medication and equipment, such as adrenaline, antihistamines, 
corticosteroids, and respiratory support including inhalational therapy, oxygen, artificial 

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ventilation and ECG equipment must be available at the study center. Any type of ECG can 
be performed. 
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 of the event will be recorded in both the patient’s source documents and the eCRF. 
6.4.2.3 
Vital Signs and Weight, and Height 
Vital signs measurements will be performed at the time points specified in the SoA (Table 5). 
Vital signs (including BP, heart and respiratory rates, and body temperature; while sitting) 
will be measured by the Investigator or designee after 5 minutes of rest. In addition, 
measurement of height and weight will be documented only at Screening. All measurements 
will be documented at each study center visit. Details will be recorded in both the patient’s 
source documents and the eCRF. 
Vital sign measurements will also be monitored prior to and after study drug administration 
as part of the hypersensitivity monitoring (Section 6.4.2.2). 
6.4.2.4 
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 SoA (Table 5) and if the patient experienced cardiac symptoms during study 
drug administration. If following the ECG review by the Investigator there are any significant 
ECG findings such as a new or worsening of 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 patient’s source documents and the eCRF. Regardless of the 12-lead 
ECG result, further evaluation with a cardiologist can be done based on the Investigator’s 
discretion. In case of hypersensitivity, any type of ECG can be performed (Section 6.4.2.2). 
6.4.2.5 
Physical Examination 
Physical examinations with particular attention to injection site reactions, 
hypersensitivity/allergic reactions, anaphylactic reactions, infections, and malignancy will be 
performed prior to study drug administration at the time points specified in the SoA (Table 5). 
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. 
Information about the physical examination will be recorded by the Investigator or designee 
in both the patient’s source documents and the eCRF. Any abnormalities will be recorded in 
the source documents. Significant findings and illnesses reported after the start of the study 
that meet the definition of an AE will be recorded as such in source documents. 
6.4.2.6 
Clinical Laboratory Analyses 
Patients’ blood and urine samples will be collected as specified in the SoA (Table 5). Blood 
sample does not need to be collected in a fasting state unless required in the opinion of the 
Investigator according to the laboratory manual. Clinical laboratory (clinical chemistry, 
hematology and urinalysis) test samples will be analyzed at the local laboratory. If a study 
center is not equipped to perform the specified tests, this will be discussed and arranged with 
the Sponsor or its designee. 

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All abnormal laboratory values will be evaluated for clinical significance by the Investigator. 
If the abnormality is considered as clinically significant (in the opinion of the Investigator) 
and meets the AE definition by the Investigator, then the results must be recorded as AE on e-
CRF.  
Unscheduled clinical laboratory tests will be performed at any time during the study to 
address any safety concerns. 
The clinical laboratory tests to be performed are listed in Table 2 below. 
Table 2: Clinical Laboratory Tests 
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 
 hematocrit 
Urinalysis 
 bilirubin 
 blood 
 glucose 
 ketones 
 leukocytes 
 nitrite 
 pH 
 protein 
 specific gravity 
 urobilinogen 
 microscopic examination 
 
Creatinine clearance will be calculated using serum creatinine level only at Screening for 
inclusion and recorded in the patient’s source documents and the eCRF. 
6.4.2.7 
Pregnancy  
Women of childbearing potential who have not been surgically sterilized will undergo 
pregnancy testing in the study center as specified in the SoA (Table 5). Only patients with a 
negative serum pregnancy test results can be enrolled into the study.  

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For women of childbearing potential who have not been surgically sterilized, a serum 
pregnancy test will be conducted at Screening and EOS/ED visit at the local laboratory.  A 
urine pregnancy test will be used to confirm patients are not pregnant prior to dosing 
according to SoA (Table 5) or more frequently if required by country-specific legislation. 
Urine pregnancy test will also be performed locally prior to the study drug administration. If 
a urine pregnancy test result is positive, a confirmatory serum pregnancy test will be 
performed. If a female patient becomes pregnant, the study drug must be discontinued 
immediately.  
In an event of unexpected pregnancy during study participation and for 6 months after the last 
dose of study drug, patients will be instructed to inform the Investigator. If a female patient 
becomes pregnant, the study drug must be discontinued immediately. If a female patient or 
the partner of a male patient becomes pregnant, the pregnancy must be reported to Sponsor 
and 
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 pregnancy form provided 
(female patient or partner of a male patient) and return it to Sponsor and
 Safety 
Department within 24 hours after receiving 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 6.4.1.5). 
6.4.2.8 
Hepatitis B, Hepatitis C and HIV Status 
At Screening, hepatitis B surface antigen (HbsAg), hepatitis B surface antibody (HbsAb), and 
hepatitis B core antibody (HbcAb) (total or immunoglobulin G [IgG]) will be assessed in all 
patients as specified in Table 3.  
Table 3: Eligibility Based on Serologic Markers for Hepatitis B Infection 
Test Results 
Eligibility 
HbsAg 
HbsAb 
HbcAb 
HBV DNA 
+ 
+/– 
+/– 
Not applicable 
Not eligible 
– 
+/– 
+ 
+ 
Not eligible 
– 
Eligible 
– 
+/– 
– 
Not applicable 
Eligible 
Abbreviations: HbcAb=hepatitis B core antibody; HbsAb=hepatitis B surface antibody; HbsAg=hepatitis B 
surface antigen; HBV=hepatitis B virus. 
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, a HBV 
deoxyribonucleic acid (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. 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 local laboratory. 

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6.4.2.9 
TB Signs and Symptoms 
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. 
A patient who has had exposure to someone with active TB such as first-degree family 
members or co-workers will not be included in the study.  
Additionally, 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 6.4.2.9.1) with a negative examination of chest X-ray (Section 6.4.2.9.2). 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. A patient who has a previous diagnosis of latent TB cannot be enrolled 
even if there is sufficient documentation of completed TB prophylaxis. 
Throughout the study, patients will be monitored for the clinical signs and symptoms of TB. 
Tuberculosis clinical monitoring, IGRA testing and chest X-ray will be performed according 
to the SoA (Table 5). 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 throughout 
the study.  
If the result of the IGRA is indeterminate during the study, 1 retest will be possible. If the 
repeated IGRA test result is again indeterminate, investigator will discuss and agree with 
Sponsor or its designee for next action taken. 
If the result of the IGRA is positive during the study, patients will be referred to the clinician 
immediately to investigate the presence of active TB based on medical history and any 
clinical signs and symptoms including chest X-ray result. Even in the absence of clinical 
suspicion for active TB, study drug administration will be temporarily stopped. It is 
recommended that study drug administration is resumed, in patients who have received at 
least 3 weeks of country-specific TB therapy and who intend to complete the entire course of 
TB therapy. However, study drug administration can be resumed simultaneously with the 
start of country-specific TB therapy after discussion with the Sponsor Medical Monitors or its 
designee in advance. 
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 patient is exposed to a person with active 
TB during the Treatment 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/ED 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. 
6.4.2.9.1 
Interferon- γ Release Assay 
The IGRA is the protocol-required method of Screening for TB. The IGRA testing will be 
performed at the local laboratory during the Screening Period, EOS and ED.  

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6.4.2.9.2 
Chest X-ray 
A chest X-ray (both lateral and posterior-anterior views) must be performed according to 
local health authority guidance during the Screening Period, EOS and ED. A chest X-ray 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. All chest X-rays should be available for 
review by the Investigator before the patient is enrolled into the study. 
The chest X-ray must be negative for active TB infection, fungal infections, or any other 
clinically significant abnormalities for a patient to be considered eligible for the study. All 
chest imaging must be read by a qualified radiologist/pulmonary physician who is 
specifically required to look for evidence of active TB or inactive TB.  
Radiographic findings suggestive of inactive TB or active TB may include but are not limited 
to: apical fibrosis, pleural thickening, pulmonary nodules, fibrotic scars, calcified 
granulomas, upper lobe infiltrates, cavitations and pleural effusions, calcified lung nodules, 
calcified hilar lymph nodes, and pericardial calcification.  
The 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 subsequent study drug administration. 
6.5 Sample Collections 
The total volume of blood collected for each assessment is discussed in each specific 
laboratory manual. The sample collection tube may be changed during the study and details 
will be provided in the laboratory manual.  
6.5.1 
Interferon-γ Release Assay Blood Sampling 
Blood samples for IGRA will be obtained at the time points specified in the SoA (Table 5). 
All samples should be collected at the scheduled time point. 
6.5.2 
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 SoA (Table 5). 
A blood sample for HBV and hepatitis C and HIV testing will be required at Screening. A 
serum pregnancy test sample will be required at Screening and at the EOS/ED visit for 
women of childbearing potential who have not been surgically sterilized. 
6.6 Labeling of Samples 
Each sample tube will be clearly labeled with the following information:  
• 
Study number 
• 
Patient identification number  
• 
Tube identification 
• 
Scheduled sampling time point. 
7 Statistical Analysis Plan 
The statistical analysis will be performed using 
 
. The statistical methods for this study will be described 
in a detailed statistical analysis plan (SAP), which will be finalized prior to database lock.  

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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. 
7.1 Populations for Analyses 
For purposes of analysis, the following analysis populations are defined: 
Intent-to-Treat (ITT) Population: The ITT Population includes all enrolled patients to 
receive a dose of study drug, regardless of whether or not any study drug dosing was 
completed.   
Usability Population: The Usability Population includes all patients in the Safety Population 
who have evaluable usability measurements at Week 4 and who do not have major deviations 
that may affect the interpretation of study result. The major protocol deviations will be 
discussed during the data review meeting and the details of protocol deviations will be 
defined in the SAP. 
Safety Population: The Safety Population includes all patients who receive at least 1 dose 
(full or partial) of study drug. 
7.2 Usability Analysis 
7.2.1 
Primary Usability Endpoint 
The primary usability endpoint is the patient rating using PRE- and POST- SIAQ at Week 4 
and will be summarized using the ITT and the Usability Population. 
7.2.2 
PRE- and POST- SIAQ  
Patient will complete each item of SIAQ on a 5-point or 6-point (semantic Likert-type scale). 
Item score will be transformed to obtain a score ranging from 0 to 10 for each item, based on 
the algorithm below:  
 
 
 
 
 
The domain score will be defined as the mean of the transformed item scores included in the 
domain. Domain scores will be calculated only if at least half of the domain items are 
completed. PRE- and POST-SIAQ will be summarized at Week 4 using the ITT and the 
Usability Population. 
7.3 Secondary Usability Endpoints 
The secondary usability endpoints are the patient rating using PRE- and POST-SIAQ and the 
observer rating of successful self-injection using self-injection assessment checklist at Weeks 
0, 2 and 24 and will be summarized using the ITT and the Usability Population.  
7.3.1 
PRE- and POST- SIAQ  
PRE- and POST- SIAQ will be summarized at Weeks 0, 2 and 24 using the ITT and the 
Usability Population. 

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7.3.2 Observer Rating of Successful Self-Injection Using Self-Injection 
Assessment Checklist 
The self-injection assessment will be summarized at Weeks 0, 2, 4 and 24 using the ITT and 
the Usability Population. It will be coded as successful if N7, N9, N10 and N11 of the 
self-injection assessment checklist are checked as Yes. In addition, the successful completion 
of all 14 instructions will be assessed from the self-injection assessment checklist (Appendix 
3). Successful self-injection will be summarized by scheduled time point as the number and 
proportion of successful injections and the number and proportion of patients who 
successfully completed all 4 instructions will be summarized.   
7.4 Efficacy Analysis 
The efficacy endpoint is the mean change from baseline in DAS28 (CRP) and DAS28 (ESR) 
up to Week 24 and will be summarized using the ITT Population. 
7.4.1 
DAS28 (CRP) and DAS28 (ESR)  
The following parameters will be summarized using descriptive statistics: actual value and 
change from baseline of DAS28 (CRP) and DAS28 (ESR) every 8 weeks up to Week 24 
using the ITT Population.  
DAS28 (CRP)=(0.56 ×√TJC28)+(0.28 × √SJC28)+(0.36 × ln[CRP+1])+(0.014 ×PGA)+0.96 
DAS28 (ESR)=(0.56 ×√TJC28)+(0.28 × √SJC28)+(0.70 × ln[ESR])+(0.014) ×PGA)   
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) 
PGA = patient’s global disease activity measured on 100 mm VAS  
The components of the DAS28 (CRP and ESR) will be summarized. 
7.5 Safety Analyses 
Safety analysis will be performed on the Safety Population at the time points specified in the 
SoA (Table 5) by presenting data on AEs (including SAEs), AESI (injection site reactions, 
hypersensitivity/allergic reactions, infections, and malignancies), hypersensitivity monitoring 
(via monitoring of vital signs), vital signs measurements, ECGs, physical examination 
findings, IGRA, chest X-ray, pregnancy testing, clinical laboratory analyses, signs and 
symptoms of TB, and prior and concomitant medications monitored throughout the study. 
Hepatitis B, hepatitis C, and HIV status will be tested for the patient’s eligibility 
determination.  
7.5.1 
Demographic, Baseline, and Background Characteristics 
Demographics (including gender, age ethnicity and race) and baseline and background 
characteristics will be presented in summary tables. Qualitative data (e.g., medical history) 
will be summarized in contingency tables, and quantitative data (e.g., age) will be 
summarized using quantitative descriptive statistics. 

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7.5.2 
Adverse Events 
Adverse events will be recorded according to the CTCAE v.5.0 and will be coded to system 
organ class (SOC) and preferred term (PT) according to MedDRA. A TEAE is defined as 
described in Section 6.4.1.1. The following TEAE summaries will be reported by SOC, PT: 
• 
Number and percentage of patients reporting at least 1 TEAE 
• 
Number and percentage of patients reporting at least 1 treatment-emergent SAE  
• 
Number and percentage of patients discontinuing the study drug due to a TEAE 
• 
Number and percentage of patients with TEAEs of special interest (injection site 
reactions, hypersensitivity/allergic reactions, infections, and malignancies) 
7.5.3 
Clinical Laboratory Analyses, IGRA and Pregnancy 
Clinical laboratory tests (hematology, clinical chemistry, urinalysis), IGRA, and pregnancy 
testing will be summarized 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. 
7.5.4 
Electrocardiogram, Physical Examination, and Vital Signs 
Individual data and standard summary statistics as well as changes from baseline for 12-lead 
ECG results, physical examination findings, and vital sign measurements will be presented by 
study visit. Change from baseline will also be summarized for all scheduled collection times 
after the first administration of study drug.  
7.5.5 
Prior and Concomitant Medications 
Prior and concomitant medications will be coded using the World Health Organization Drug 
Dictionary. All prior and concomitant medications data will be listed and summarized by 
treatment group as appropriate.  
7.5.6 
Other Safety Analyses 
All other safety data will be listed and summarized as appropriate. 
7.6 Interim Analyses 
Interim analyses are not planned in this study. 
7.7 Handling of Missing, Unused, and Spurious Data 
No imputation will be conducted for the primary and secondary usability analysis unless 
additional sensitivity with different imputation methods are requested by the Sponsor.  
7.8 Sample Size Determination 
Approximately 60 male or female adult patients will be enrolled. In this usability study, a 
sample size justification based on a formal statistical hypothesis is not relevant, since a 
formal statistical inference will not be made. 

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8 Supporting Documentation and Operational Considerations 
8.1 Regulatory, Ethical, and Study Oversight Considerations 
8.1.1 
Regulatory and Ethical Considerations 
This study will be conducted in accordance with the protocol and with: 
• 
Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences (CIOMS) International Ethical Guidelines. 
• 
Applicable ICH Good Clinical Practice (GCP) Guidelines. 
• 
Applicable laws and regulations. 
The protocol, protocol amendments, ICF, IB, and other relevant documents (e.g., 
advertisements) must be submitted to an IRB/ IEC by the Investigator and reviewed and 
approved by the IRB/IEC before the study is initiated. 
Any amendments to the protocol will require IEC/IRB approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study patients. 
The Investigator will be responsible for the following: 
• 
Providing written summaries of the status of the study to the IRB/IEC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/EC. 
• 
Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures. 
Overall conduct of the study at the site and adherence to requirements of ICH GCP 
guidelines, the IRB/IEC, European regulation 536/2014 for clinical studies (if applicable), 
and all other applicable local regulations. 
8.1.2 
Financial Disclosure 
Investigators and sub-Investigators will provide the Sponsor with sufficient, accurate 
financial information in accordance with local regulations to allow the Sponsor to submit 
complete and accurate financial certification or disclosure statements to the appropriate 
regulatory authorities. Investigators are responsible for providing information on financial 
interests during the course of the study and for 1 year after completion of the study. 
8.1.3 
Informed Consent Process 
The Investigator or his/her representative will explain the nature of the study to the patient or 
his/her legally authorized representative and answer all questions regarding the study. 
Patients must be informed that their participation is voluntary. Patients or their legal guardian 
will be required to sign and date a statement of informed consent that meets the requirements 
of local regulations, ICH guidelines, where applicable, and the IRB/IEC or study center. 
The medical record must include a statement that written informed consent was obtained 
before the patient was enrolled in the study and the date of the written consent was obtained. 
The authorized person obtaining the informed consent must also sign and date the ICF. 

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Patients must be re-consented to the most current version of the ICF(s) during their 
participation in the study. 
A copy of the ICF(s) must be provided to the patient or the patient’s legal guardian. 
Patients who are re-screened are required to sign and date a new ICF. 
If a protocol amendment is required, the ICF may need to be revised to reflect the changes to 
the protocol. If the ICF is revised, it must be reviewed and approved by the appropriate 
IEC/IRB and signed by all patients subsequently enrolled in the study as well as those 
currently enrolled in the study. 
8.1.4 
Data Protection 
Patients will be assigned a unique PIC by the Sponsor. Any patient records or datasets that are 
transferred to the Sponsor will contain the PIC; patient names or any information which 
would make the patient identifiable will not be transferred. 
The patient must be informed that his/her personal study-related data will be used by the 
Sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the patient. 
The patient must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the Sponsor, by 
appropriate IRB/IEC members, and by inspectors from regulatory authorities. 
8.1.5 
Dissemination of Clinical Study Data 
All information, including but not limited to information regarding the study drug, the 
Sponsor’s operation (e.g., patent application, formulas, manufacturing process, basic 
scientific data, prior clinical data, and formulation information) and any data generated as a 
result of this study, are considered confidential and are the sole property of the Sponsor. The 
Investigator agrees to maintain this information in confidence and use this information only 
to accomplish this study. The Investigator will not use this information for other purposes 
without the Sponsor’s prior written approval. 
The Investigator understands that the information developed in the clinical study will be used 
by the Sponsor in connection with the continued development of the study drug, and thus 
may be disclosed, as required, to other clinical Investigators or regulatory agencies. The 
Investigator is obligated to provide the Sponsor with all data obtained in the study. 
The results of the study will be reported in a clinical study report (CSR) generated by the 
Sponsor. 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 1 CSR to report: All data after completion of the study. 
Additional statistical analysis will be performed for regulatory submission usability data up to 
Week 4. Details on analysis will be pre-specified in the SAP.  
Any work created in connection with the performance of the study and data generated by the 
study shall be the property of the Sponsor as author and owner of copyright in such work. 
8.1.6 
Data Quality Assurance 
This study will be conducted according to the ICH E6(R2) risk and quality processes 
described in the applicable procedural documents. The quality management approach to be 

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implemented in this study will be documented and will comply with the current ICH GCP 
guidelines on quality and risk management. 
All patient data relating to the study will be recorded on the patients’ source document and 
the eCRFs unless transmitted to the Sponsor or designee electronically (e.g., laboratory data). 
The Investigator is responsible for verifying that data entries are accurate and correct by 
physically or electronically signing the eCRF. 
The Investigator must maintain accurate documentation (source data) that supports the 
information entered in the eCRF. 
The Investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source data documents. 
The Sponsor or designee is responsible for the data management of this study including 
quality checking of the data. 
Study monitors will perform ongoing source data verification to confirm that data entered 
into the eCRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of patients are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements. 
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. No records will be destroyed during the 
retention period without the written approval of the Sponsor. No records will be transferred to 
another location or party without written notification to the Sponsor. 
The specific procedures to be used for data entry and query resolution using the electronic 
data capture (EDC) system/eCRF will be provided to study centers in a training manual. In 
addition, site personnel will receive training on the EDC system/eCRF. 
8.1.7 
Source Documents 
Source documents are original documents, data, and records from which the patient’s eCRF 
data are obtained. These include but are not limited to hospital records, clinical and office 
charts, laboratory and pharmacy records, diaries, microfiches, radiographs, and 
correspondence.  
Source documents provide evidence for the existence of the patient and substantiate the 
integrity of the data collected. Source documents are filed at the Investigator’s site. 
Data entered in the eCRF that are transcribed from source documents must be consistent with 
the source documents or the discrepancies must be explained. The Investigator may need to 
request previous medical records or transfer records, depending on the study. Also, current 
medical records must be available. 
8.1.8 
Study and Site Closure 
The Sponsor designee reserves the right to close the study center or terminate the study at any 
time for any reason at the sole discretion of the Sponsor. Study centers will be closed upon 

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study completion. A study center is considered closed when all required documents and study 
supplies have been collected and a study center closure visit has been performed. 
The Investigator may initiate study center closure at any time, provided there is reasonable 
cause and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study center by the Sponsor or Investigator may include but 
are not limited to: 
• 
Failure of the Investigator to comply with the protocol, the requirements of the 
IRB/IEC or local health authorities, the Sponsor’s procedures, or GCP guidelines 
• 
Inadequate recruitment of patients by the Investigator 
• 
Discontinuation of further study drug development 
8.1.9 
Publication Policy 
The results of this study may be published or presented at scientific meetings.  
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 the standard operation process of the Sponsor, the publication to which it 
will be submitted, and other related issues. The Sponsor has final approval authority over all 
such issues.  
Data are the property of the Sponsor and cannot be published without prior authorization 
from the Sponsor, but data and publication thereof will not be unduly withheld. 
8.1.10 Study Administration 
A list of personnel and organizations responsible for the conduct of the study (details 
included in Table 4) will be provided by the Sponsor or its designee to the study center, as 
part of the Investigator Site File. 
Table 4: Organizations Responsible for Study Conduct 
Role 
Name /Address 
Sponsor 
CELLTRION, Inc.  
 
 
Contract Research Organization 
 
 
 
 
 
8.1.11 Protocol Approval and Amendment and Protocol Deviations 
8.1.11.1 Protocol and Protocol Amendments 
Before the start of the study, the study protocol and/or other relevant documents will be 
approved by the IEC/IRB/Competent Authorities, in accordance with local legal 
requirements. The Sponsor must ensure that all ethical and legal requirements have been met 
before the first patient is enrolled in the study. 

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This protocol is to be followed exactly. To alter the protocol, amendments must be written, 
receive approval from the appropriate personnel, and receive IRB/IEC/Competent Authority 
approval prior to implementation (if appropriate). Protocol amendments will be submitted to 
the appropriate authorities as required by the applicable regulatory requirements.     
Administrative changes (not affecting the patient benefit/risk ratio) may be made without the 
need for a formal amendment. All amendments will be distributed to all protocol recipients, 
with appropriate instructions. 
8.1.11.2  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 
must 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 (violation) occurs when there is non-adherence to the 
protocol by the patient or Investigator that may result in an additional risk to the patient or 
which may confound analysis of study results. Significant deviations can include enrollment 
of a patient with non-adherence to inclusion or exclusion criteria, or non-adherence to Food 
and Drug Administration (FDA) regulations or ICH E6(R2) guidelines and may lead to the 
patient being withdrawn from the study (see Section 4.3). 
Protocol deviations (and violations) will be documented by the clinical monitor throughout 
the course of monitoring visits. Investigators will be notified in writing by the monitor of 
deviations. The site must notify the IRB/IEC of all protocol deviations in a timely manner.  
8.1.12 Access to Source Data 
During the study, a monitor will make site visits to review protocol compliance, compare 
eCRF entries and individual patient’s medical records, assess drug accountability, and ensure 
that the study is being conducted according to pertinent regulatory requirements. Electronic 
case report form entries will be verified with source documentation. The review of medical 
records will be performed in a manner to ensure that patient confidentiality is maintained. 
Checking of the eCRF entries for completeness and clarity, and cross-checking with source 
documents, will be required to monitor the progress of the study. Moreover, regulatory 
authorities of certain countries, IRBs, IECs, and/or the Sponsor’s Clinical Quality Assurance 
Group may wish to carry out such source data checks and/or on-site audit inspections. Direct 
access to source data will be required for these inspections and audits; they will be carried out 
giving due consideration to data protection and medical confidentiality. The Investigator 
assures the Sponsor or designee of the necessary support at all times. 
 

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9 Appendices 
9.1 Appendix 1: Abbreviations  
ACR 
American College of Rheumatology 
AE 
adverse event 
AI 
auto-injector 
AESI 
adverse events of special interest 
BP 
blood pressure 
CRP 
C-reactive protein 
CSR 
clinical study report 
CTCAE 
Common Terminology Criteria for Adverse Events 
DAS 
disease activity score 
DMARD 
disease-modifying anti-rheumatic drug 
DNA 
deoxyribonucleic acid 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
ED 
early discontinuation 
EOS 
end-of-study 
EOW 
every other week 
ESR 
erythrocyte sedimentation rate 
EU 
European Union 
EULAR 
European League Against Rheumatism 
GCP 
Good Clinical Practice 
HbsAb 
hepatitis B surface antibody 
HbsAg 
hepatitis B surface antigen 
HbcAb 
hepatitis C core antibody 
HBV 
Hepatitis B virus 
HIV 
human immunodeficiency virus 
IA 
intra-articular 
IB 
Investigator Brochure 
ICF 
informed consent form 
ICH 
International Conference on Harmonisation 
IEC 
Independent Ethics Committee 
IFU 
instructions for use 
IGRA 
interferon-γ release assay 
IM 
intramuscular 
IRB 
Institutional Review Board 
ITT 
intent-to-treat 

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MedDRA 
Medical Dictionary for Regulatory Activities 
MTX 
methotrexate 
NSAID 
non-steroidal anti-inflammatory drugs 
PIC 
patient identification code 
PFS 
pre-filled syringe 
PGA 
Patient’s Global Assessment 
PK 
pharmacokinetic(s) 
PT 
preferred term 
RA 
rheumatoid arthritis 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SC 
subcutaneous 
SIAQ 
Self-Injection Assessment Questionnaire 
SJC 
swollen joint count 
SoA 
schedule of activities 
SOC 
system organ class 
TB 
tuberculosis 
TEAE 
treatment-emergent adverse event 
TJC 
tender joint count 
TNF  
tumor necrosis factor 
ULN 
upper limit of normal 
US 
United States  
VAS 
visual analogue scale 
 
 

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9.2 Appendix 2: Schedule of Activities (SoA) 
The schedule of activities (SoA), as outlined in Table 5, consists of a Screening Period, a Treatment Period and a Follow-up Period. 
Table 5: Schedule of Activities 
 
Screening 
Period 
Treatment Period 
Follow-up 
Period 
 
 
Dose 1 
Dose 2 
Dose 3 
Dose 4 
Dose 5 
Dose 7 
Dose 9 
Dose 11 
Dose 13 
EOS1 
ED2 
Study visit3 (Week) 
–6 
0 
2 
4 
6 
8 
12 
16 
20 
24 
28 
 
Study visit3 (Day) 
–42 to –1 
1 
15 
29 
43 
57 
85 
113 
141 
169 
197 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
Demographics, height, weight and medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
Hepatitis B/C and HIV test4 
X 
 
 
 
 
 
 
 
 
 
 
 
Serum pregnancy test5 
X 
 
 
 
 
 
 
 
 
 
X 
X 
Chest X-ray6 
X 
 
 
 
 
 
 
 
 
 
X 
X 
IGRA7 
X 
 
 
 
 
 
 
 
 
 
X 
X 
Inclusion/exclusion criteria 
X 
X8 
 
 
 
 
 
 
 
 
 
 
Usability assessments 
PRE- and POST-SIAQ9 
 
X 
X 
X 
 
 
 
 
 
X 
 
 
Self-injection assessment checklist by observer10 
 
X 
X 
X 
 
 
 
 
 
X 
 
 
Efficacy assessments11 – Pre-dose  
Swollen joint count (66 joints) 
X 
 
 
 
 
 
 
 
 
 
 
 
Tender joint count (68 joints) 
X 
 
 
 
 
 
 
 
 
 
 
 
Tender joint count and swollen joint count (28 joints) 
X 
X 
 
 
 
X 
 
X 
 
X 
(X) 
X 
CRP and ESR12 
X 
X 
 
 
 
X 
 
X 
 
X 
(X) 
X 
VAS global assessment of disease activity (patient) 
scores 
X 
X 
 
 
 
X 
 
X 
 
X 
(X) 
X 
Safety assessments11 – Pre-dose 
Physical examination, vital signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Clinical laboratory tests13 
X 
X 
 
X 
 
 
X 
 
 
X 
X 
X 
Urine pregnancy test5 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
12-lead ECG14 
X 
X 
 
 
 
 
 
 
 
 
X 
X 
Study drug administration15,16 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Hypersensitivity/ allergic reactions17 and injection site 
reaction18 monitoring 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Prior, concomitant medications19 
X 
TB clinical monitoring20 
X 
AE21 
X 

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Abbreviations: AE=adverse event(s); AI=auto-injector; CRP=C-reactive protein; ECG=electrocardiogram; eCRF=electronic case report forms; ED=early discontinuation; 
EOS=end-of-study; EOW=every other week; ESR=erythrocyte sedimentation rate; HIV=human immunodeficiency virus; ICF=informed consent form; igG=immunoglobulin G;  
IGRA=Interferon-Gamma Release Assays; IM=intramuscular; RA=rheumatoid arthritis; SC=subcutaneous; SIAQ=Self-Injection Assessment Questionnaire; 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 10, 14, 18 and 22 which are not 
specified in this table (Dose 6, 8, 10 and 12) will be self-administered at home.  
1. 
An EOS visit will occur 4 weeks after the last dose (at Week 24) is received or prior to the start of new RA therapy, whichever comes earlier. The efficacy assessments will be 
performed only if the efficacy assessments were not performed at Week 24 as planned. 
2. 
An ED visit will be completed 4 weeks after the last dose is received or prior to the start of new RA therapy, whichever comes earlier, if a patient is discontinued from study 
prior to Week 24 treatment.  
3. 
A visit window of ±2 days is allowed, based on the previous dosing date, from Week 2 (dose 2) up to the EOS visit. 
4. 
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. If hepatitis C or HIV test result is positive, the patient will be excluded from the study. Hepatitis and HIV analysis will be 
performed locally. 
5. 
For women of childbearing potential who have not been surgically sterilized, a serum pregnancy test will be conducted locally at Screening and EOS/ED visit. A urine 
pregnancy test will also be performed locally and 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. If a urine pregnancy test result is positive, a confirmatory serum pregnancy test will be performed.  
6. 
A chest X-ray (both lateral and posterior-anterior 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. 
7. 
The IGRA testing will be performed locally. A patient who has a previous diagnosis of latent TB cannot be enrolled even if there is sufficient documentation of completed TB 
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. 
8. 
Inclusion and exclusion criteria should be confirmed on Day 1 again. 
9. 
PRE- and POST-SIAQ will be completed by patient prior to and after self-injection of CT-P17 SC via AI. Patients will complete PRE-SIAQ immediately before the 
administration of study drug and POST-SIAQ within 20 to 40 minutes after the administration of study drug. 
10. The Investigator or designee will observe the patient’s self-injection and complete the checklist within 15 minutes after patient’s self-injection. 
11. Procedures will be performed at the study center prior to the study drug administration. Where possible, the same Investigator should perform all efficacy assessments for an 
individual patient. 
12. Both CRP and ESR samples will be drawn and analyzed locally at the same time as the clinical laboratory blood samples. 
13. Clinical laboratory (clinical chemistry, hematology and urinalysis) test samples will be analyzed locally. See Section 6.4.2.6 for details of the clinical laboratory tests. 
Creatinine clearance will be calculated using serum creatinine level only at Screening for inclusion and recorded on eCRF. 
14. 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 
cardiac origin, a 12-lead ECG could be performed at any time during the Treatment Period. Regardless of the 12-lead ECG result, further evaluation with a cardiologist can be 
done depending on the Investigator’s discretion. 
15. A fixed dose of CT-P17 (40 mg) will be administered EOW by SC injection via AI from Week 0 to Week 24. 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. Patients must self-inject the study drug during their study center visits under the 
Investigator or designated study center staff’s supervision at the indicated visits. Patients will self-inject the study drug at home at Weeks 10, 14, 18 and 22. 
16. Methotrexate (12.5 to 25 mg/week, or 10 mg/week if intolerant to a higher dose, oral or IM, dose and route must be maintained from Screening to EOS/ED visit) and folic 
acid (≥5 mg/week, oral) will be administered throughout the study.  

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17. Additional vital signs will be monitored for possible hypersensitivity/allergic reactions 1 hour (±10 minutes) after injection of study drug. In case of hypersensitivity, 
emergency medication and equipment, such as adrenaline, antihistamines, corticosteroids, and respiratory support including inhalational therapy, oxygen, artificial ventilation 
and ECG equipment must be available at the study center. Any type of ECG can be performed. 
18. 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 in the patient self-reporting of AE diary. 
19. Use of all prior and concomitant medications for the treatment of RA, from the diagnosis of disease until the EOS/ED visit, 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/ED 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 #7 (Section 4.2).  
20. 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 subsequent study drug administration. 
21. AEs will be assessed from the date the ICF is signed until the EOS/ED visit. After the EOS/ED visit, serious adverse drug reactions will be reported to the Sponsor or its 
designee. Adverse events of special interest (e.g., injection site reactions, hypersensitivity/allergic reactions, anaphylactic reactions, infections, and malignancies) should be 
closely monitored. 

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9.3 Appendix 3: Self-Injection Checklist 
No. 
Instructions for Use 
1 
Removed the auto-injector from the outer carton 
2 
Checked expiration date on the auto-injector label 
3 
Inspected the auto-injector for damage 
4 
Checked liquid for discoloration or particles 
5 
Washed hands with soap and water 
6 
Cleaned the injection site 
7 
Removed the cap from auto-injector 
8 
Held the auto-injector so that patient could see the window  
9 
Placed the auto-injector at 90° angle on the injection site 
10 
Pressed the auto-injector firmly against the skin to start the injection (1st 
loud click), and kept holding the auto-injector firmly against the skin until 
heard the 2nd loud click 
11 
After the 2nd loud click, continued to hold the auto-injector firmly against 
the skin and count slowly to five to ensure the injection was completed 
12 
Checked if the grey indicator fills the window completely 
13 
Removed auto-injector from injection site at 90° angle to skin 
14 
Disposed used auto-injector and the cap in a sharps container 
* The bolded steps are considered as critical steps for the usability assessment.  

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9.4 Appendix 4: Self-Injection Assessment Questionnaire  

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10 References 
 

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