Conditions: Rheumatoid Arthritis Plaque Psoriasis
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 359
Healthy volunteers: no

Brief summary:
An Open-label, Safety Extension Study (OLSES) evaluating the longer-term safety and durability of response of subjects who completed 48 weeks of evaluations in the confirmatory safety and efficacy studies, CHS 0214-02 or CHS-0214-04, evaluating CHS-0214 in patients with rheumatoid arthritis (RA) and plaque psoriasis (PsO), respectively.

Detailed description:

Arms:
arm 1: CHS-0214 50 mg weekly

Interventions: intervention 1: CHS-0214
Intervention descriptions: intervention 1: Open label

Protocol document:
Prot_000.pdf: 
 
Coherus BioSciences 
 
Clinical Study Protocol CHS-0214-05 
 
Confidential & Proprietary  
V 4.0 Amendment 3 
29 Feb 2016 
 
Study Title: 
An Open-Label Safety Extension Study (OLSES) 
Evaluating the Long-term Safety and Durability of 
Response of CHS-0214 (CHS-0214-05) 
 
 
Protocol Number: 
CHS-0214-05 
 
 
 
 
 
 
Protocol Date: 
19 March 2015 
 
 
Version 2.0 (Amendment 1): 
(UK Only) 
 
Version 3.0 (Amendment 2): 
 
Version 4.0 (Amendment 3): 
(Japan only)  
24 June 2015 
 
 
13 July 2015 
 
29 February 2016 
 
 
 
 
 
IND Number: 
115,675 
 
 
EudraCT Number: 
2015-000665-30 
 
 
Study Phase: 
Phase 3 
 
 
 
Sponsor Names: 
Coherus BioSciences, 
Inc. 
333 Twin Dolphin Drive 
Suite 600 
Redwood City, CA 
94065 
Tel: 650-649-3530 
Fax: 866-491-7350 
Daiichi Sankyo Co., Ltd. 
3-5-1 Nihonbashi-honcho 
Chuo-Ku  
Tokyo 103-
8426
 
Nihonbashi-honcho 
Tel: +81 3-6225-1111 
Fax: +81 3-6225-1900 
 
 
 
 
Coherus BioSciences, Inc.
Clinical Study Report CHS-0214-05
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Version 1.0, 01 October 2018
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Coherus BioSciences 
 
Clinical Study Protocol CHS-0214-05 
 
Confidential & Proprietary  
V 4.0 Amendment 3 
29 Feb 2016 
 
Medical Monitor: 
 
Axel Mescheder, M.D. 
Vice President ± Medical and Regulatory Affairs 
Europe 
Medpace Germany GmbH 
Theresienhoehe 30 
80339 Munich 
Germany 
Tel: +49 89 89 55 718 0 
Mobile: +49 173 682 3204 
Fax: +49 89 89 55 718 100 
E-mail: a.mescheder@medpace.com 
 
Medical Director: 
Barbara Finck, M.D. 
Chief Medical Officer 
Coherus BioSciences, Inc. 
333 Twin Dolphin Drive 
Suite 600 
Redwood City, CA 94065 
Tel: +1 650-649-3529 
Mobile: +1 415-713-6051 
E-mail: bfinck@coherus.com 
 
 
Medical Expert: 
Professor Tsutomu Takeuchi 
School of Medicine, Keio University 
Division of Rheumatology 
Department of Internal Medicine 
Shinanomachi 35, Shinjuku-ku 
Tokyo 160-8582 
Japan 
Tel: +81 3-3353-1211 
 
 
Coordinating Investigator 
Japan 
Professor Yoshiya Tanaka  
University of Occupational and Environmental Health 
Japan, Internal Medicine (I) 
1-1, Iseigaoka, Yahata-nishi-ku, Kitakyushu 
Fukuoka 807-8555 
Japan 
Tel: +81 93-603-1611 
 
 
 
Confidentiality Statement 
The information in this document is confidential and is not to be disclosed without the written consent of 
Sponsor except to the extent that disclosure would be required by law and for the purpose of evaluating and/or 
conducting a clinical study for Sponsor. You are allowed to disclose the contents of this document only to your 
Institutional Review Board and study personnel directly involved with conducting this protocol. Persons to whom 
the information is disclosed must be informed that the information is confidential and proprietary to Sponsor and 
that it may not be further disclosed to third parties. 
 
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Coherus BioSciences 
 
Clinical Study Protocol CHS-0214-05 
 
Confidential & Proprietary  
V 4.0 Amendment 3 
29 Feb 2016 
 
INVESTIGATOR 
SIGNATURE PAGE 
STUDY TITLE: An Open-Label Safety Extension Study (OLSES) Evaluating the 
Long-term Safety and Durability of Response of CHS-0214 (CHS-0214-05) 
 
By signing below I agree that: 
I have read this protocol and agree to conduct the study as outlined herein in 
accordance with International Conference on Harmonisation Good Clinical Practice, 
United States Food and Drug Administration regulations, Institutional Review Board 
regulations, and regional regulatory requirements. 
 
 
________________________                                      __________________________ 
Principal Investigator Signature 
 
 
  Date 
 
 
_________________________ 
Principal Investigator Name and Title (please print) 
 
Investigative Site Address 
_______________________ 
_______________________ 
_______________________ 
 
 
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Coherus BioSciences, Inc.
Clinical Study Report CHS-0214-05
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Coherus BioSciences, Inc.
Clinical Study Report CHS-0214-05
Confidential & Proprietary 
Version 1.0, 01 October 2018
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Coherus BioSciences 
 
Clinical Study Protocol CHS-0214-05 
 
Confidential & Proprietary  
6 
V 4.0 Amendment 3 
29 Feb 2016 
 
SYNOPSIS 
Study Title 
An Open-label, Safety Extension Study (OLSES) Evaluating the Long-term 
Safety and Durability of Response of CHS-0214 (CHS-0214-05) 
Sponsors 
Coherus BioSciences Inc., Daiichi Sankyo Co., Ltd.  
Study Objective 
Objectives:   
To evaluate the longer-term safety and durability of response of subjects who 
completed 48 weeks of evaluations in the confirmatory safety and efficacy 
studies, CHS-0214-02 or CHS-0214-04, evaluating CHS-0214 in rheumatoid 
arthritis (RA) and plaque psoriasis (PsO), respectively.  
Study Design 
This is an open-label safety extension study. Subjects completing the 48-week 
evaluation in the clinical studies CHS-0214-02 or CHS-0214-04 may be eligible 
to enroll into this study and receive open-label CHS-0214 50 mg as a 
subcutaneous (SC) injection every week (QW). Subjects will receive QW 
treatment of CHS-0214 for 48 weeks except in Japan,  where subjects with RA 
may receive CHS-0214 until marketing approval of CHS-0214. There will be a 
follow-up evaluation 28 days after last dose of study drug for any subject 
discontinuing treatment at any time during the study. Study drug will be supplied 
either as a prefilled syringe or a prefilled syringe in an auto-injector. Subjects 
will be evaluated at 1 month and 3 months following enrollment, and every 3 
months thereafter for safety, including immunogenicity, and durability of 
response. 
Study Centers 
Selected study centers that participated in CHS-0214-02 and/or CHS-0214-04  
Sample Size 
Approximately 400 subjects will be enrolled.  
Study Population 
Adult male and female subjects with:  
x 
RA who have completed 48 weeks of evaluations in CHS-0214-02 and, 
at Week 48, had at least a 20% improvement from Baseline (parent 
study) according to American College of Rheumatology criteria 
(ACR20)  
x 
Moderate to severe, chronic, stable PsO who have completed 48 weeks 
of evaluations in CHS-0214-04 and, at Week 48, had at least 50% 
improvement in Psoriasis Area and Severity Index (PASI-50) from 
Baseline (parent study). 
Main Inclusion Criteria 
Subjects must meet the following criteria to be enrolled in this study: 
1. Have completed 48 weeks of evaluations in CHS-0214-02 and, at Week 48, 
had at least an ACR20, or completed 48 weeks of evaluations in 
CHS-0214-04 and, at Week 48, had at least a PASI-50; 
2. Women who either: 
a) Are of childbearing potential with a negative urine pregnancy test at 
Week 0 Day 0 who agree to use 1 or more approved methods of birth 
control (hormonal contraception, intrauterine device, diaphragm plus 
spermicide, condom plus spermicide, or abstinence from heterosexual 
intercourse²abstinence from heterosexual intercourse will be 
acceptable only if it is the preferred and usual lifestyle of the subject 
regardless of study participation; abstinence should be practiced for the 
duration of the study Follow-up Visit 28 days after the last dose of 
study drug); 
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b) Have been postmenopausal for at least 2 years (with amenorrhea for at 
least 1 year) or have had a hysterectomy, bilateral 
salpingo-oophorectomy, or tubal ligation prior to signing the informed 
consent; and  
3. Able and willing to give written informed consent prior to performance of 
any study related procedures. 
Main Exclusion Criteria 
Subjects who meet the following criterion will be excluded from participation in 
this study: 
1. Men whose partners may become pregnant (do not agree to use 
contraception or who are not postmenopausal) or may breastfeed during the 
study (Japan only specific exclusion). 
Study Drug Dosage and 
Administration 
Subjects will receive open-label CHS-0214 50 mg in prefilled syringes or 
prefilled syringes in auto-injectors. Study drug will be self-injected or 
administered to the subject by a caregiver at home as a SC injection QW.  
Study Endpoints 
 
Safety:  
Safety will be assessed at 1 month and 3 months following enrollment and every 
3 months thereafter by: 
x 
Assessment of treatment-emergent AEs; 
x 
Determination of subject withdrawal information; 
x 
Assessment of injection site reactions;  
x 
Assessment of changes in safety laboratory parameters, including 
hematology, clinical chemistry, and pregnancy tests;  
x 
Assessment of changes in vital signs, physical examination, and 
electrocardiogram findings; 
x 
Monitoring for tuberculosis (TB) with regular QuantiFERON®-TB Gold 
test (every 12 months or more frequently for regions with high 
incidences of TB or to evaluate signs and symptoms that might be due 
to TB); and  
x 
Assessment of immunogenicity (anti-CHS-0214 antibodies) 
Retained samples: 
Serum samples will be collected at each visit and retained for potential analysis 
of serum concentration of CHS-0214, anti-drug antibodies, or other tests as 
necessary to evaluate AEs, loss of response, or compliance. Serum samples will 
not be used to assess population pharmacokinetics (PK), biomarkers, or genetics. 
Samples will be stored at Medpace Reference Laboratories, LLC (MRL) and 
may be transferred to Charles River Laboratories or other reference laboratory 
for analysis at the request of the Sponsor. All retained samples and remnants of 
samples will be destroyed 2 years after the completion of the study (database 
lock). 
Efficacy endpoints:  
 
Durability of response will be measured at each visit as follows: 
Primary endpoint: 
x 
For subjects with RA, maintenance of an ACR20 response or greater  
x 
For subjects with PsO, maintenance of PASI-50 response or greater  
Secondary endpoints: 
x 
For subjects with RA, Disease Activity Score using 28 tender and 
swollen joint counts, high sensitivity C-UHDFWLYHSURWHLQDQGVXEMHFW¶V
global assessment (DAS28-CRP [4]) to < 3.2 (low disease activity) 
assessed at all visits and < 2.6 (remission) assessed on all visits after 
DAS28-CRP (4) < 2.6 is achieved 
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Statistical Analysis 
Safety analyses will be performed in all subjects who receive at least 1 dose of 
CHS-0214 in this study (the Safety Population). Separate efficacy analyses will 
be performed in subjects who receive at least 1 dose of CHS-0214 and who have 
any efficacy measurements in 3 populations; all subjects with RA who complete 
the CHS 0214-02 study and meet the entry criteria for this study (the RA 
Population), all subjects with RA who complete the CHS 0214-02 study at 
Japanese sites and meet the entry criteria for this study (the Japanese RA 
Population-a subset of the RA population), and all subjects with PsO who 
complete the CHS 0214-04 study and meet the entry criteria for this study (the 
PsO Population).   
Continuous variables will be summarized using descriptive statistics (N, mean, 
standard deviation, median, minimum, and maximum, where appropriate). 
Discrete variables will be summarized using frequency counts and percentages. 
Study Duration 
Subjects may continue to participate in this study until 1 of the following occurs: 
x 
The subject has undergone follow-up evaluations 28 days after the last 
dose of study drug (the subject has completed the study); 
x 
The subject experiences a serious adverse event (SAE) or medically 
important AE (e.g., serious or opportunistic infection related to study 
drug) that would preclude further treatment with study drug; 
x 
The subject develops a malignancy while on study drug, except as 
below: 
o 
Please note, subjects who develop a malignancy while on study 
drug and receive localized and non-invasive treatment may 
stay in the study per the ,QYHVWLJDWRU¶VMXGJPHQW; 
x 
The subject requires medical treatment excluded by the protocol, or that 
could present a safety risk to the subject; 
x 
The subject is not willing to continue participation in the study 
(withdraws consent); 
x 
The subject is lost to follow up; 
x 
Lack of compliance with the provisions of the protocol; 
x 
The subject experiences an increase in disease activity that requires 
additional or different therapy; 
x 
The subject develops a positive response to the QuantiFERON®-TB 
Gold test at any time during the study, as defined by 2 consecutive 
positive tests (>2 IU/mL). During the study (every 12 months or more 
frequently for regions with a high incidence of TB, or to evaluate signs 
and symptoms that might be due to TB), if a patient has an 
indeterminate or low positive (0.35-2 IU/mL) or a positive (>2 IU/mL) 
QuantiFERON®-TB Gold test result, the QuantiFERON®-TB Gold test 
should be repeated. If the repeat test is indeterminate or low positive 
(0.35-2 IU/mL), the patient can continue in the study, providing 
symptoms and risk factors are all negative, i.e., the subject has not been 
exposed to TB, the chest x-ray is negative, and the Investigator does not 
believe the subject has latent TB. Only a conversion to positive 
(>2 IU/mL) on 2 consecutive tests would result in the subject not 
qualifying to continue in OLSES; 
x 
The subject becomes pregnant while on study medication (the subject 
will immediately be withdrawn from study drug and all procedures for 
the Follow-up Visit will be conducted 28 Days after the last dose of 
study drug); 
x 
In the opinion of the Investigator, it is in the best interest of the subject 
to discontinue study participation;  
x 
Subject has positive viral screen results; 
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x 
6XEMHFW¶V:HHNODERUDWRU\UHVXOWVIURP&+6-0214-02 or 
CHS 0214-04 are clinically significant; or 
x 
The Sponsor discontinues the study for any of the following reasons: 
o 
The Sponsor receives marketing approval in Japan;  
o 
Development of a previously unknown safety concern 
o 
The results of analyses indicate that either parent study 
(CHS-0214-02 or CHS-0214-04) did not meet its primary 
efficacy endpoints; 
o 
Other events that have not been anticipated by the Sponsor; 
o 
Any other reason (e.g., an unexpected SAE not previously 
observed with etanercept or another tumor necrosis factor 
inhibitor is observed in the study) 
 
Figure 1: Study Design 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ACR20 = 20% improvement according to American College of Rheumatology criteria; DAS28-CRP(4) = Disease Activity Score using 
28 tender and swollen joint counts, C-UHDFWLYHSURWHLQDQGVXEMHFW¶VJOREDODVVHVVPHQW(&* = electrocardiogram; ISR = injection site 
reaction; PASI-50 = 50% improvement in Psoriasis Area and Severity Index; PsO = plaque psoriasis; QW = every week; RA = rheumatoid 
arthritis; SC = subcutaneous; TEAE = treatment-emergent adverse event.  
 
 
 
CHS-0214-02 
RA  
Subjects 
CHS-0214-04 
PsO 
Subjects 
Open-label CHS-0214 
treatment starting at 
Week 0 Day 0 (within 
1 month of Week 48 of 
CHS-0214-02 or 
CHS-0214-04) 
CHS-0214-05 
50 mg SC QW 
Efficacy Primary Endpoints 
x 
For subjects with RA, maintenance of ACR20 response or greater 
x 
For subjects with PsO, maintenance of PASI-50 response or greater 
Efficacy Secondary Endpoints: 
x 
For subjects with RA, DAS28-CRP (4) < 3.2 (low disease activity) assessed at all visits and DAS28-CRP (4) < 2.6 
(remission) assessed on all visits after DAS28-CRP (4) < 2.6 is achieved 
Safety 
x 
TEAEs; withdrawals; ISRs; changes in laboratory safety parameters and vital sign, physical examination, and 
ECG findings; QuantiFERON®-TB Gold; immunogenicity 
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TABLE OF CONTENTS 
SYNOPSIS 6 
TABLE OF CONTENTS ..................................................................................................... 10 
LIST OF TABLES ................................................................................................................ 13 
LIST OF FIGURES .............................................................................................................. 13 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS ...................................... 14 
1 
INTRODUCTION ............................................................................................ 17 
1.1 
Overview ........................................................................................................... 17 
1.2 
Background....................................................................................................... 17 
1.3 
Development of CHS-0214 .............................................................................. 18 
2 
STUDY OBJECTIVES .................................................................................... 18 
3 
INVESTIGATIONAL PLAN .......................................................................... 19 
3.1 
Overall Study Design and Plan ....................................................................... 19 
3.2 
Rationale for Study Design/Dose Level .......................................................... 20 
3.3 
Selection of Study Population ......................................................................... 21 
3.3.1 
Inclusion Criteria ................................................................................................ 21 
3.3.2 
Exclusion Criteria............................................................................................... 21 
3.3.3 
Removal of Subjects from Therapy or Assessment ........................................... 21 
3.3.4 
Discontinuation of Study by Sponsor ................................................................ 23 
4 
TREATMENTS ................................................................................................ 24 
4.1 
Treatments Administered................................................................................ 24 
4.2 
Identity of Investigational Product ................................................................. 24 
4.3 
Labeling............................................................................................................. 24 
4.4 
Method of Assigning Subjects to Treatment Groups ................................... 24 
4.5 
Selection of Doses in the Study........................................................................ 24 
4.6 
Selection and Timing of Dosing for Each Subject ......................................... 25 
4.7 
Blinding ............................................................................................................. 25 
4.8 
Study Drug Dispensing .................................................................................... 25 
4.9 
Concomitant Medications................................................................................ 26 
4.9.1 
Rheumatoid Arthritis .......................................................................................... 26 
4.9.2 
Plaque Psoriasis .................................................................................................. 27 
4.10 
Treatment Compliance .................................................................................... 28 
5 
MEASUREMENTS AND EVALUATIONS ................................................. 30 
5.1 
Schedules of Procedures .................................................................................. 30 
5.2 
Study Schedule ................................................................................................. 35 
5.2.1 
Week 0 Day 0 ..................................................................................................... 35 
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5.2.2 
Week 4 Day 28 (± 3 Days), Week 12 Day 84 (± 7 Days) and Week 36 Day 252 
(± 7 Days) ........................................................................................................... 36 
5.2.3 
Week 24 Day 168 (± 7 Days) ............................................................................. 38 
5.2.4 
Week 48 Day 336 (± 7 days).............................................................................. 39 
5.2.5 
Quarterly Visits (± 7 days)²Subjects in Japan with RA Only, Beginning at 
Week 60 ............................................................................................................. 40 
5.2.6 
Follow-up Visit 28 Days (± 3 Days) Post Last Dose of Study Drug ................. 41 
5.3 
Informed Consent ............................................................................................ 42 
5.4 
Medical and Surgical History ......................................................................... 42 
6 
Efficacy Measurements .................................................................................... 43 
6.1 
Primary Efficacy Endpoints ............................................................................ 43 
6.1.1 
Rheumatoid Arthritis .......................................................................................... 43 
6.1.2 
Plaque Psoriasis .................................................................................................. 45 
6.2 
Secondary Efficacy Endpoints (Rheumatoid Arthritis) ............................... 45 
6.2.1 
DAS28-CRP(4) .................................................................................................. 46 
7 
Safety Measurements ....................................................................................... 47 
7.1 
Adverse Events ................................................................................................. 47 
7.1.1 
Unexpected Adverse Drug Reaction .................................................................. 48 
7.1.2 
Grading and Intensity of Adverse Events .......................................................... 48 
7.1.3 
Relationship to Study Drug ................................................................................ 48 
7.1.4 
Serious Adverse Event Reporting ...................................................................... 49 
7.1.5 
Adverse Event Outcome .................................................................................... 50 
7.1.6 
Serious Adverse Event Reporting ± Procedure for Investigators....................... 50 
7.1.7 
Serious Adverse Events Follow-up .................................................................... 51 
7.1.8 
Serious Adverse Event Reporting-Procedure for Sponsor ................................. 51 
7.2 
Physical Examination ...................................................................................... 52 
7.3 
Vital Signs ......................................................................................................... 52 
7.4 
Electrocardiogram ........................................................................................... 52 
7.5 
Pregnancy Reporting ....................................................................................... 53 
7.6 
Anti-Drug Antibody Assessment .................................................................... 53 
7.7 
Serum Retention Samples ............................................................................... 54 
7.8 
Sample Collection Procedures and Bioanalytical Methods.......................... 54 
8 
PLANNED ANALYSES .................................................................................. 55 
8.1 
Analysis Populations ........................................................................................ 55 
8.1.1 
Enrolled Subject Population ............................................................................... 55 
8.1.2 
Full Analysis Population .................................................................................... 55 
8.1.3 
Safety Population ............................................................................................... 55 
8.1.4 
Pharmacokinetic Population .............................................................................. 55 
8.1.5 
Per-Protocol Population ..................................................................................... 55 
8.1.6 
Rheumatoid Arthritis Population ....................................................................... 55 
8.1.7 
Japanese Rheumatoid Arthritis Population ........................................................ 55 
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8.1.8 
Plaque Psoriasis Population ............................................................................... 55 
8.2 
Statistical Methods ........................................................................................... 56 
8.2.1 
Demographic and Baseline Characteristics ........................................................ 56 
8.2.2 
Efficacy Analysis ............................................................................................... 56 
8.2.3 
Safety Analysis .................................................................................................. 56 
8.2.4 
Immunogenicity Analysis .................................................................................. 57 
8.2.5 
Pharmacokinetic Analysis .................................................................................. 57 
8.2.6 
Determination of Sample Size ........................................................................... 57 
9 
DATA SAFETY MONITORING BOARD .................................................... 58 
10 
DATA MANAGEMENT ................................................................................. 59 
10.1 
Data Handling .................................................................................................. 59 
10.2 
Computer Systems ........................................................................................... 59 
10.3 
Data Entry ........................................................................................................ 59 
10.4 
Medical Information Coding........................................................................... 59 
10.5 
Data Validation ................................................................................................ 59 
11 
STUDY ADMINISTRATION ......................................................................... 60 
11.1 
Regulatory and Ethical Considerations ......................................................... 60 
11.1.1 
Regulatory Authority Approval ......................................................................... 60 
11.1.2 
Ethics Approval .................................................................................................. 60 
11.1.3 
Subject Informed Consent .................................................................................. 61 
11.1.4 
Investigator Reporting Requirements ................................................................ 61 
11.2 
Study Monitoring ............................................................................................. 61 
11.3 
Quality Control ................................................................................................ 62 
11.4 
Study Initiation ................................................................................................. 62 
11.5 
Study Termination ........................................................................................... 63 
11.6 
Site Termination ............................................................................................... 63 
11.7 
Records Retention ............................................................................................ 63 
11.8 
Confidentiality of Information ........................................................................ 64 
11.9 
Publication Policy ............................................................................................. 64 
11.10 
Address List ...................................................................................................... 65 
11.10.1 
Sponsors ............................................................................................................. 65 
11.10.2 
Contract Research Organization ........................................................................ 65 
11.10.3 
Global Drug Safety ............................................................................................ 65 
11.10.4 
Central Laboratory ............................................................................................. 66 
11.10.5 
Bioanalytical Laboratory .................................................................................... 66 
12 
Bibliography ..................................................................................................... 67 
APPENDIX A: 
American College of Rheumatology/European League Against 
Rheumatism Criteria for Rheumatoid Arthritis ........................................... 70 
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APPENDIX B: 
American College of Rheumatology Revised Classification for 
Rheumatoid Arthritis ...................................................................................... 72 
APPENDIX C: 
Medication Restrictions ........................................................................ 73 
APPENDIX D: 
66/68 Swollen Joint Count/Tender Joint Count Assessment ............ 76 
APPENDIX E: 
6XEMHFW¶V3DLQ$VVHVVPHQW ................................................................... 78 
APPENDIX F: 
6XEMHFW¶V*OREDO$VVHVVPHQW ................................................................ 79 
APPENDIX G: 
3K\VLFLDQ¶V*OREDO$VVHVVPHQW ............................................................ 81 
APPENDIX H: 
3K\VLFLDQ¶V6WDWLF*OREDO$VVHVVPHQW ................................................. 82 
APPENDIX I: 
Clinical Laboratory Analytes............................................................... 83 
APPENDIX J: 
Psoriasis Area and Severity Index ....................................................... 85 
APPENDIX K: 
Health Assessment Questionnaire ± Disability Index ........................ 87 
APPENDIX L: 
Etanercept Prescribing Information ................................................... 93 
 
LIST OF TABLES 
Table 1: Schedule of Procedures for Subjects with Rheumatoid Arthritis ..................... 31 
Table 2: Schedule of Procedures for Subjects with Plaque Psoriasis .............................. 33 
 
LIST OF FIGURES 
Figure 1: Study Design ........................................................................................................... 9 
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LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
ACR 
  
American College of Rheumatology 
ACR20 
20% improvement according to American College of Rheumatology 
criteria 
ADA 
Anti-drug antibody 
AE 
  
Adverse event 
CFR 
  
Code of Federal Regulations  
CRA 
  
Clinical Research Associate 
CRP 
  
C-reactive protein 
DAS28-CRP(4) 
Disease Activity Score using 28 tender and swollen joint counts, 
C-UHDFWLYHSURWHLQDQGVXEMHFW¶V global assessment 
DMARD 
  
Disease-modifying anti-rheumatic drug 
DSMB 
  
Data Safety Monitoring Board 
EC 
  
Ethics Committee 
ECG 
  
Electrocardiogram  
ECL 
  
Electrochemiluminescent 
eCRF 
  
Electronic Case Report Form 
EDC 
  
Electronic data capture 
ELISA 
  
Enzyme-linked immunosorbent assay 
EU 
  
European Union 
EULAR 
  
European League Against Rheumatism 
FAP 
  
Full Analysis Population 
FDA 
  
United States Food and Drug Administration 
GCP 
  
Good Clinical Practice 
HAQ-DI 
  
Health Assessment Questionnaire±Disability Index 
HBcAb 
  
Hepatitis B core antibody 
HBsAg 
  
Hepatitis B surface antigen 
HBsAb 
  
Hepatitis B surface antibody 
HBV 
  
Hepatitis B virus 
HCV 
  
Hepatitis C virus 
HIV 
  
Human immunodeficiency virus 
hs-CRP 
  
high sensitivity C-reactive protein 
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ICF 
  
Informed consent form 
ICH 
  
International Conference on Harmonisation 
ID 
  
Identification number 
IMID 
  
Immune mediated inflammatory diseases 
IRB 
  
Institutional Review Board 
ISR 
  
Injection site reaction 
IVRS 
  
Interactive voice response system 
IWRS 
  
Interactive web response system 
/7Į 
  
Lymphotoxin-alpha 
JIA 
  
Juvenile idiopathic arthritis  
MedDRA 
  
Medical Dictionary for Regulatory Activities 
MRL 
  
Medpace Reference Laboratories, LLC 
MTX 
  
Methotrexate 
NAB 
  
Neutralizing anti-drug antibody 
NSAID 
  
Non-steroidal anti-inflammatory drug 
OLSES 
  
Open-label safety extension study 
p75 
  
75-kilodalton protein 
PASI 
  
Psoriasis Area and Severity Index 
PASI-50 
  
50% improvement in Psoriasis Area and Severity Index 
PGA 
  
3K\VLFLDQ¶V*OREDO$VVHVVPHQW 
PSGA 
  
3K\VLFLDQ¶V6WDWic Global Assessment 
PK 
  
Pharmacokinetic(s) 
PsA 
  
Psoriatic arthritis 
PsO 
  
Plaque psoriasis 
PUVA 
  
Psoralen plus ultraviolet A 
QW 
  
Every week 
RA 
  
Rheumatoid arthritis 
RF 
  
Rheumatoid factor 
SAE 
  
Serious adverse event 
SC 
  
Subcutaneous 
SGA 
  
6XEMHFW¶Vglobal assessment of disease activity 
SJC 
  
Swollen joint count 
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SUSAR 
  
Suspected unexpected serious adverse reaction 
TB 
  
Tuberculosis 
TEAE 
  
Treatment-emergent adverse event 
TJC 
  
Tender joint count 
TNF 
  
Tumor necrosis factor 
71)Į 
  
Tumor necrosis factor-alpha 
71)ȕ 
  
Tumor necrosis factor-beta 
TNFR 
  
Tumor necrosis factor receptor 
ULN 
  
Upper limit of normal 
US, USA 
  
United States 
UVA 
  
Ultraviolet A 
UVB 
  
Ultraviolet B 
VAS 
  
Visual analog scale 
WHO-DD 
  
World Health Organization Drug Dictionary 
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1 
INTRODUCTION  
1.1 
Overview 
Coherus BioSciences is developing CHS-0214 as a proposed biosimilar product to 
etanercept, Enbrel®, under a global development and regulatory strategy for 
rheumatoid arthritis (RA), plaque psoriasis (PsO), and other indications for which 
Enbrel is approved in various regulatory territories.  
1.2 
Background 
The purposes of this open-label safety extension study (OLSES) are to evaluate 
the longer-term safety and durability of response of subjects who completed 
48 weeks of evaluations in the confirmatory CHS-0214 safety and efficacy 
studies, CHS-0214-02 and CHS-0214-04 in RA and PsO, respectively. This study 
will only be offered in selected countries. 
Tumor necrosis factor (TNF) is a naturally occurring cytokine that plays an 
important role in the inflammatory processes of immune mediated inflammatory 
diseases (IMID) such as PsO, psoriatic arthritis (PsA), juvenile idiopathic arthritis 
-,$&URKQ¶VGLVHDVHXOFHUDWLYHFROLWLVDQG5$(OHYDWHGOHYHOVRI71)DUH
found in involved tissues and fluids of subjects with PsO and other IMIDs 
(Krueger, Krane, Carter, & Gottlieb, 1990), (Brotas, Cunha, Lago, Machado, & 
Carneiro, 2012), (Keystone & Ware, 2010). Two distinct tumor necrosis factor 
receptors (TNFRs), a 55-kilodalton protein and a 75-kilodalton protein (p75), 
exist naturally as monomeric molecules on cell surfaces and in soluble forms. 
Biological activity of TNF is dependent upon binding to either cell surface TNFR 
(Bluml, Scheinecker, Smolen, & Redlich, 2012). 
Etanercept (Enbrel®, Amgen Inc.), is a dimeric soluble form of the p75 TNFR that 
can bind TNF molecules. Etanercept inhibits binding of tumor necrosis 
factor-alpha 71)ĮDnd tumor necrosis factor-beta 71)ȕDOVRNQRZQDV
lymphotoxin-DOSKD/7ĮWRFHOOVXUIDFH71)5VUHQGHULQJ71)ELRORJLFDOO\
LQDFWLYH,QLQYLWURVWXGLHVODUJHFRPSOH[HVRIHWDQHUFHSWZLWK71)ĮZHUHQRW
detected, and cells expressing transmembrane TNF (that binds etanercept) are not 
lysed in the presence or absence of complement (Horiuchi, Mitoma, Harashima, 
Tsukamoto, & Shimoda, 2010). 
Enbrel was approved in the United States (US) in 1998 (Amgen, 2015), in the EU 
in 2000 (European Medicines Agency, 2014), and in Japan in 2005 (Pfizer, 2015). 
Enbrel is indicated in Japan for patients with RA and Juvenile RA and is indicated 
in Europe for patients with RA, JIA, PsA, axial spondyloarthritis, ankylosing 
spondylitis, non-radiographic axial spondyloarthritis, PsO, and pediatric PsO.  
Across clinical studies and postmarketing experience, the most serious adverse 
reactions related to Enbrel were infections, neurologic events, congestive heart 
failure, hematologic events, malignancies, and autoimmune reactions. The most 
common adverse reactions were infections, injection site reactions (ISRs), allergic 
reactions, development of autoantibodies, pruritus, and fever. Further details are 
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provided in the prescribing information for Enbrel (see Appendix L). Antibodies 
to the TNFR portion or other protein components of the Enbrel drug product were 
detected in sera of approximately 6% of adult subjects treated with Enbrel using 
an enzyme-linked immunosorbent assay (ELISA) (Amgen, 2015). These 
antibodies were all non-neutralizing. The clinical significance of this finding is 
unknown. 
Please refer to the CHS-0214 ,QYHVWLJDWRU¶V%URFKXUHfor information on adverse 
events (AEs) and anti-drug antibodies observed in clinical trials of CHS-0214.   
1.3 
Development of CHS-0214 
CHS-0214 has been evaluated in the following studies thus far. All 4 studies have 
met their primary endpoints. 
1. CHS-0214-01: A Randomized, Double-Blind, Single-Dose, Two-Period 
Crossover Study to Assess the Pharmacokinetic Similarity of CHS-0214 
DP and EU approved etanercept, Enbrel® (EU), in Healthy Male and 
Female Subjects-This study has been completed. 
2. CHS-0214-02: A Double-Blind, Randomized, Parallel-Group, Active-
Control Study to Compare the Efficacy and Safety of CHS-0214 Versus 
Enbrel® in Subjects With Rheumatoid Arthritis and Inadequate Response 
to Treatment With Methotrexate (RApsody). This study is ongoing  
3. CHS-0214-03: A Randomized, Double-Blind, Single-Dose, 2-Period 
Crossover Study to Assess the Pharmacokinetic Similarity of CHS-0214 
(European Union [EU]) and EU-Approved Etanercept (Enbrel® [EU]) and 
the Safety and Tolerability of CHS-0214 (EU) in Healthy Male and 
Female Subjects. This study has been completed. 
4. CHS-0214-04: A Double-Blind, Randomized, Parallel-Group, Active-
Control Study to Compare the Efficacy and Safety of CHS-0214 Versus 
Enbrel® in Subjects With Chronic Plaque Psoriasis (CHS-0214-04) 
RaPSOdy. This study is ongoing.  
See WKH,QYHVWLJDWRU¶V%URFKXUHIRUPRUHGHWDLOV 
2 
STUDY OBJECTIVES  
The purpose of this OLSES is to evaluate the longer-term safety and durability of 
response of subjects who completed 48 weeks of evaluations in the confirmatory 
CHS-0214 safety and efficacy studies, CHS-0214-02 and CHS-0214-04 in RA 
and PsO, respectively.  
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3 
INVESTIGATIONAL PLAN 
3.1 
Overall Study Design and Plan 
This multicenter, global OLSES is being conducted in the following subjects: 
x Adult subjects with RA who have completed 48 weeks of evaluations in 
Study CHS-0214-02 and, at Week 48, had at least a 20% improvement 
from Baseline according to American College of Rheumatology criteria 
(ACR20)  
x Adult subjects with moderate to severe, chronic, stable PsO who have 
completed 48 weeks of evaluations in Study CHS-0214-04 and, at 
Week 48, had at least a 50% improvement in Psoriasis Area and Severity 
Index (PASI-50) from Baseline (see Appendix J)  
x Study drug administration may continue uninterrupted for eligible subjects 
who decide to enroll into OLSES following participation in either 
Study CHS-0214-02 or Study CHS-0214-04.  
 Subjects will either enroll directly into OLSES on their Week 48 Visit 
of the parent study (either Study CHS-0214-02 or Study 
CHS-0214-04) or within 1 month of their Week 48 Visit of the parent 
study.  
 In both cases described above, data collected from procedures 
conducted at the Week 48 Visit of the parent study will also be 
considered Week 0 Day 0 data in OLSES. 
 If eligibility is not determined and consent is not obtained during the 
Week 48 Visit of the parent study, subjects will come back for an 
additional visit as soon as possible (within 1 month of the Week 48 
Visit) to complete the procedures/testing required for the OLSES study 
start, i.e., consent and viral laboratory and urine pregnancy (if 
applicable) tests. At that time, subjects will also be dispensed study 
drug supply as part of the OLSES study. 
Subjects will receive open-label CHS-0214 50 mg every week (QW) in prefilled 
syringes with passive needle guard or prefilled syringes in auto-injectors 
administered by self-injection or by a caregiver at home as a subcutaneous (SC) 
injection. Subjects will receive study drug for 48 weeks except in Japan, where 
subjects may receive study drug until marketing approval. Note that all subjects in 
Japan enrolled in OLSES are from the CHS-0214-02 parent study.  
Any subject discontinuing treatment at any time during the study will undergo 
follow-up evaluations 28 days after last dose of study drug.  
Safety will be assessed throughout the study by: 
x Assessment of treatment-emergent adverse events (TEAEs); 
x Determination of subject withdrawal information; 
x Assessment of ISRs;  
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x Assessment of changes in safety laboratory parameters, including 
hematology, clinical chemistry, and pregnancy tests;  
x Assessment of changes in vital sign, physical examination, and 
electrocardiogram (ECG) findings; 
x During the study (every 12 months or more frequently for regions with a 
high incidence of TB, or to evaluate signs and symptoms that might be due 
to TB), if a patient has an indeterminate or low positive (0.35-2 IU/mL) or 
a positive (>2 IU/mL) QuantiFERON®-TB Gold test result, the 
QuantiFERON®-TB Gold test should be repeated. If the repeat test is 
indeterminate or low positive (0.35-2 IU/mL), the patient can continue in 
the study, providing symptoms and risk factors are all negative, i.e., the 
subject has not been exposed to TB, the chest x-ray is negative, and the 
Investigator does not believe the subject has latent TB. Only a conversion 
to positive (>2 IU/mL) on 2 consecutive tests would result in the subject 
not qualifying to continue in OLSES;    
x Assessment of immunogenicity (anti-CHS-0214 antibodies). 
Durability of response will be measured at each visit as follows: 
x For subjects with RA, maintenance of an ACR20 response or greater  
x For subjects with PsO, maintenance of PASI-50 (see Appendix J) response 
or greater  
Serum samples will be collected at each visit and retained for potential analysis of 
serum concentration of CHS-0214, anti-drug antibodies (ADAs), or other tests as 
necessary to evaluate AEs, loss of response, or compliance. Serum samples will 
not be used to assess population pharmacokinetics (PK), biomarkers, or genetics. 
Samples will be stored at Medpace Reference Laboratories, LLC (MRL) and may 
be transferred to Charles River Laboratories or other reference laboratory for 
analysis at the request of the Sponsor. All retained samples and remnants of 
samples will be destroyed 2 years after the completion of the study (database 
lock). 
3.2 
Rationale for Study Design/Dose Level 
The rationale for the study design is to evaluate the longer-term safety and 
durability of response of subjects who completed 48 weeks of evaluations in the 
confirmatory safety and efficacy studies, CHS-0214-02 or CHS-0214-04, 
evaluating CHS-0214 in RA and PsO, respectively.  
The dose selected for this safety study is 50 mg QW. Studies comparing dosing at 
50 mg twice weekly to 50 mg QW in subjects with PsO have demonstrated that 
decreasing the dose after 12 weeks does not result in a loss of or diminishment of 
response or an exacerbation of disease for most subjects (Leonardi, et al., 2003) 
(Papp, et al., 2005). Also, in subjects with RA, the dosage form used is 50 mg 
QW, rather than 25 mg twice weekly, as this dosing has been determined to be 
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similar with respect to PK, efficacy (ACR20 responders at Week 8), and safety 
(Keystone, et al., 2004). 
3.3 
Selection of Study Population 
3.3.1 
Inclusion Criteria 
Subjects with RA or PsO must meet the following criteria to be enrolled in this 
study: 
1. Have completed 48 weeks of evaluations in CHS-0214-02 and, at 
Week 48, had at least an ACR20, or completed 48 weeks of evaluations in 
CHS-0214-04 and, at Week 48, had at least a PASI-50; 
2. Women who either: 
a) Are of childbearing potential with a negative urine pregnancy test at 
Week 0 Day 0 who agree to use 1 or more approved methods of birth 
control (hormonal contraception, intrauterine device, diaphragm plus 
spermicide, condom plus spermicide, or abstinence from heterosexual 
intercourse²abstinence from heterosexual intercourse will be 
acceptable only if it is the preferred and usual lifestyle of the subject 
regardless of study participation; abstinence should be practiced for 
the duration of the study [study duration includes the Follow-up Visit 
28 days after the last dose of study drug]); or  
b) Have been postmenopausal for at least 2 years (with amenorrhea for at 
least 1 year) or have had a hysterectomy, bilateral 
salpingo-oophorectomy, or tubal ligation prior to signing the informed 
consent; and  
3. Able and willing to give written informed consent prior to performance of 
any study related procedures. 
3.3.2 
Exclusion Criteria 
Subjects who meet the following criterion will be excluded from participation in 
this study: 
1. Men whose partners may become pregnant (do not agree to use 
contraception or who are not postmenopausal) or who may breastfeed 
during the study (Japan only specific exclusion). 
3.3.3 
Removal of Subjects from Therapy or Assessment 
Subjects will be advised that they are free to withdraw from the study at any time 
for any reason. Subjects who discontinue study drug at any time will be 
encouraged to return for the Follow-up Visit 28 days after the last dose of study 
drug for safety and immunogenicity evaluations. Subjects may be withdrawn from 
study therapy or assessment prematurely for any of the following reasons: 
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x The subject experiences a serious adverse event (SAE) or medically 
important AE (e.g., serious or opportunistic infection related to study 
drug) that would preclude further treatment with study drug; 
o The subject develops a malignancy while on study drug, except as 
below:Please note, subjects who develop a malignancy while on 
study drug and who receive localized and non-invasive treatment 
may stay in the study per the ,QYHVWLJDWRU¶VMXGJPHQW; 
x The subject requires medical treatment excluded by the protocol or that 
could present a safety risk to the subject; 
x The subject is not willing to continue participation in the study (withdraws 
consent); 
x The subject is lost to follow up; 
x Lack of compliance with the provisions of the protocol; 
x The subject experiences an increase in disease activity that requires 
additional or different therapy; 
x The subject develops a positive response to the QuantiFERON®-TB Gold 
test at any time during the study, as defined by 2 consecutive positive tests 
(>2 IU/mL). During the study (every 12 months or more frequently for 
regions with a high incidence of TB, or to evaluate signs and symptoms 
that might be due to TB), if a patient has an indeterminate or low positive 
(0.35-2 IU/mL) or a positive (>2 IU/mL) QuantiFERON®-TB Gold test 
result, the QuantiFERON®-TB Gold test should be repeated. If the repeat 
test is indeterminate or low positive (0.35-2 IU/mL), the patient can 
continue in the study, providing symptoms and risk factors are all 
negative, i.e., the subject has not been exposed to TB, the chest x-ray is 
negative, and the Investigator does not believe the subject has latent TB. 
Only a conversion to positive (>2 IU/mL) on 2 consecutive tests would 
result in the subject not qualifying to continue in OLSES;  
x The subject becomes pregnant while on study medication (the subject will 
immediately be withdrawn from study drug and all procedures for the 
Follow-up Visit will be conducted 28 days after the last dose of study 
drug); 
x In the opinion of the Investigator, it is in the best interest of the subject to 
discontinue study participation; 
x The subject has positive viral screen results; or 
x 7KHVXEMHFW¶V:HHNODERUDWRU\UHVXOWVRI&+6-0214-02 or 
CHS-0214-04 are clinically significant. 
If a subject withdraws prematurely from the study, study staff should make every 
effort to complete the full panel of assessments scheduled for the Follow-up Visit 
28 days after the last dose of study drug (see Section 5.2.5). 
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The subject will be considered to have completed the study after undergoing 
follow-up evaluations 28 days after the last dose of study drug.  
3.3.4 
Discontinuation of Study by Sponsor 
The Sponsor may suspend temporarily or  terminate the study for any of the 
following reasons: 
x The Sponsor receives marketing approval for CHS-0214 in Japan;  
x Development of a previously unknown safety concern; 
x The results of analyses indicate that either parent study (CHS-0214-02 or 
CHS-0214-04) did not meet its primary efficacy endpoints; 
x Other events that have not been anticipated by the Sponsor; or  
x Any other reason (e.g., an unexpected SAE not previously observed with 
etanercept or another TNF inhibitor is observed in the study). 
 
 
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4 
TREATMENTS 
4.1 
Treatments Administered 
CHS-0214 50 mg will be administered SC QW from Week 0 Day 0 through 
Week 48 except in Japan, where subjects may receive study drug until marketing 
approval. Note that all subjects in Japan enrolled in OLSES are from the CHS-
0214-02 parent study. 
4.2 
Identity of Investigational Product 
CHS-0214 50-mg prefilled syringes with passive needle guards or prefilled 
syringes in auto-injectors for SC injection (manufactured by Coherus 
BioSciences, Inc., Redwood City, CA 94065) will be supplied by the Sponsor. 
CHS-0214 should be refrigerated between 2°C and 8°C (36°F and 46°F) in the kit 
provided to protect from light.  
4.3 
Labeling 
Each study drug kit and syringe will be labeled according to country specific 
requirements. 
4.4 
Method of Assigning Subjects to Treatment Groups 
Once the subject has signed the informed consent form (ICF), site personnel will 
assign a subject identification number (ID). The subject ID will include the site 
number (3 digits) and a 3-digit subject number assigned sequentially starting with 
7KLVQXPEHUDQGWKHVXEMHFW¶VLQLWLDOVZLOOEHXWLOL]HGWRLGHQWLI\WKHVXEMHFW
throughout the study period. Once the subject ID has been assigned, the site will 
contact the Interactive Voice Response System/Interactive Web-based Response 
System (IVRS/IWRS) to register the subject. They will also be requested to input 
WKHVXEMHFW¶V,'IURPWKHSDUHQWVWXG\&+6-0214-02 or CHS-0214-04. 
Approximately 400 subjects will be assigned to receive CHS-0214 50 mg SC 
QW. 
4.5 
Selection of Doses in the Study 
The recommended dose of Enbrel for adult subjects with RA is 50 mg given QW 
or 25 mg given twice weekly as a SC injection. (In Japan, the recommended 
dosage is 25 mg or 50 mg weekly or 10 mg or 25 mg twice weekly.) In this study, 
CHS-0214 will be administered at a recommended dose of 50 mg SC QW. 
The recommended dosage of Enbrel for subjects with chronic moderate to severe 
PsO is 50 mg as a SC injection QW as a maintenance dose. In this study, 
CHS-0214 will be administered per the approved dosing regimen for chronic PsO 
at a dose of 50 mg QW. 
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4.6 
Selection and Timing of Dosing for Each Subject 
Study drug will consist of CHS-0214 50 mg and will be self-administered (or 
administered by a caregiver) SC QW for 48 weeks except in Japan, where 
subjects may receive study drug until marketing approval. Note that all subjects in 
Japan enrolled in OLSES are from CHS-0214-02 parent study 
Subjects and/or caregivers will be instructed to continue to administer the study 
drug on approximately the same day and time QW. However, if an injection is 
planned on the day of a study visit, this injection should be performed after the 
completion of all visit procedures, so that the blood sample collected represents a 
trough serum sample (see Section 4.10). Subjects who miss a dose of study drug, 
for whatever reason, should administer or receive the missed dose before the next 
ZHHN¶VGRVH 
4.7 
Blinding 
The study will be conducted in an open-label manner. All subjects will receive 
CHS-0214.   
4.8 
Study Drug Dispensing 
The study site will be supplied with a sufficient quantity of study drug to treat 
enrolled subjects. Open-label study drug will be shipped under appropriate 
storage conditions to site personnel according to the regulations of the study 
country. Each delivery must be acknowledged by the addressee by confirming 
receipt of the study drug shipment in IVRS/IWRS. Study drug will not be 
assigned to a subject until the site confirms receipt in the IVRS/IWRS system. 
Site personnel or the investigational storage manager will dispense study drug to 
each subject.  
Prior to dispensing study drug, study personnel or the investigational storage 
manager should visually inspect each syringe for foreign particulate matter and 
discoloration. The solution may be colorless to pale yellow and clear to slightly 
opalescent in appearance. There may be small white particles of protein in the 
solution. This is not unusual for proteinaceous solutions. The syringes should not 
be dispensed if discolored or cloudy or if foreign or dark particulate matter is 
present, but other unaffected syringes in the kit should be dispensed at the discretion 
of the Investigator.  
 
 
 
A dispensing log will be kept by site personnel or the investigational storage 
manager who will record the dates and quantity of the study drug kits dispensed to 
each subject at each visit. All used and unused syringes will be accounted for 
during the study XVLQJWKHVXEMHFW¶VH-Diary entries and/or the numbers of 
provided and returned syringes. Study monitors will review and reconcile study 
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drug receipts, dispensing logs, and records of any study drug destruction to study 
drug on-hand. 
The subject and/or caregiver will be instructed to place used syringes into the 
sharps container provided and return the sharps container to the clinic once it is 
full. A new sharps container will be provided to the subject and/or caregiver. The 
subject and/or caregiver will also be provided with cool packs should there be a 
need to bring unused study drug to the clinic for any reason (e.g., further training 
with self-injection or issues with study drug). At each study visit, sufficient 
syringes for dosing through the next study visit will be provided to the subject 
and/or caregiver. 
Used and unused syringes may be destroyed on site per each Institution's Standard 
Operating Procedure or policy once the site's monitor has reviewed and confirmed 
drug accountability. Site personnel or the investigational product storage manager 
may also return any unused syringes to the Sponsor or designee once the site's 
monitor has reviewed and confirmed accountability. 
4.9 
Concomitant Medications 
Any medications, both prescription and non-prescription, taken during this study 
will be recorded in the source documents and entered into the eCRFs.  
Required or allowed and prohibited concomitant medications are listed below. 
These lists are not intended to be all-inclusive; Investigators must review each 
VXEMHFW¶VFDVHLQGLYLGXDOO\DQGXVHWKHLUFOLQLFDOMXGJPHQW 
4.9.1 
Rheumatoid Arthritis 
For subjects with RA, the following concomitant medications are required or 
allowed during the study provided that the subject has been on a stable dose 
(unless otherwise noted) (see Appendix C): 
x A single non-steroidal anti-inflammatory drug (NSAID) at a dose not 
exceeding the maximum dose allowed per the prescribing instructions for 
that NSAID. NOTE: A topical NSAID used on a regular basis (at least 
daily) will be considered the subject's single NSAID permitted during the 
study. Topical NSAIDs taken on a regular basis should not be applied 
within 24 hours prior to each study visit. Occasional use of topical 
NSAIDs (less frequently than once per day) will not be considered as the 
VXEMHFW¶VVLQJOH16$,'DQGPD\EHXVHGLQFRQMXQFWLRQZLWKDQRWKHU
systemic NSAID (NOTE: a change in NSAID dose may be allowed for 
safety considerations only);   
x Oral corticosteroid (d 10 mg prednisone per day or equivalent 
corticosteroid) providing the dose of prednisone or equivalent 
corticosteroid will remain stable for the duration of the study (NOTE: a 
change in prednisone dose may be allowed for safety considerations only); 
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x Methotrexate (MTX) at stable dose (t 8 mg/week to d 25 mg/week, not to 
exceed local approved dose level) and at the dose the subject was 
receiving throughout the parent study (NOTE: a change in MTX dose may 
be allowed for safety considerations only). If the MTX dose was reduced 
below 8 mg/week in the parent study and remains stable, the subject may 
enter the OLSES study at that reduced dose; 
x Folic or folinic acid at the dose and schedule presFULEHGE\WKHVXEMHFW¶V
primary or personal physician to prevent MTX toxicity; 
x Steroid injections should be kept at a minimum. The injected joint should 
be noted as swollen and tender in all subsequent joint counts going 
forward;  
x Insulin for diabetes mellitus, replacement hormone therapy, and hormonal 
contraception; and  
x All medications required to adequately treat AEs or concurrent medical 
conditions at the discretion of the Investigator. 
For subjects with RA, the following concomitant medications are prohibited 
during the study (see Appendix C): 
x Any biologic medication for any indication (other than insulin or 
hormones), other than study drug (including but not limited to tocilizumab 
[RoACTEMRA, Actemra], certolizumab pegol [CIMZIA], adalimumab 
[HUMIRA], anakinra [Kineret], abatacept [ORENCIA], infliximab 
[Remicade], rituximab [MabtThera, Rituxan], golimumab [SIMPONI]); 
x Any kinase inhibitor for RA (e.g., tofacitinib citrate [XELJANZ]); 
x Non-biological disease-modifying anti-rheumatic drugs (DMARDS), other 
than MTX (Rheumatrex, Trexall) (e.g., hydroxychloroquine [Plaquenil], 
oral or injectable gold, D-penicillamine, sulfasalazine [Azulfidine], 
leflunomide [Arava], and iguratimod [Careram, Kolbet]).;   
x Parenteral steroids, intra-articular steroids (except as described above), or 
oral steroids > 10 mg prednisone per day or equivalent corticosteroid; 
x Cyclophosphamide, azathioprine (Imuran), or any other chemotherapies or 
immunosuppressants; or 
x Live vaccines. 
4.9.2 
Plaque Psoriasis 
For subjects with PsO, the following concomitant medications are allowed 
during the study (see Appendix C): 
x Mild (class 6-7 based on US classification system of topical steroids) 
topical corticosteroids on scalp, face, axillae, groin, and genitalia are 
allowed except within 24 hours prior to study visits;  
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x Mild/bland moisturizers/lubricants are allowed at any time except within 
24 hours prior to study visits; 
x Single NSAID use is not prohibited in this protocol; however, the dose 
should not exceed the maximum dose recommended for that NSAID; and  
x All medications required to adequately treat AEs or concurrent medical 
conditions at the discretion of the Investigator. 
For subjects with PsO, the following concomitant medications are prohibited 
during the study (see Appendix C): 
x All biologics (other than study drug, insulin and hormone replacement 
therapy) for any indication (including but not limited to tocilizumab 
[RoACTEMRA, Actemra], certolizumab pegol [CIMZIA], etanercept 
[Enbrel], adalimumab [HUMIRA], anakinra [Kineret], abatacept 
[ORENCIA], infliximab [Remicade], rituximab [Mathera, Rituxan], 
golimumab [Simponi ARIA], ustekinumab [STELARA]); 
x Any kinase inhibitor for any reason (e.g., tofacitinib citrate [XELJANZ]); 
x Any PDE4 inhibitor (e.g., apremilast [Otezla]); 
x Systemic psoriasis treatments such as oral retinoids, MTX, or 
cyclosporine; systemic glucocorticoids, vitamin A or D analog 
preparations; dithranole; psoralen plus ultraviolet A (PUVA); ultraviolet B 
(UVB) phototherapy;  
x Drugs that may cause new onset or exacerbation of psoriasis (including 
but not limited to; beta-blockers, lithium and anti-malarials) unless the 
subject has been on a stable dose for 6 months prior to enrollment in 
OLSES without exacerbation of psoriasis; 
x Use of topical corticosteroids (class 1-5); and 
x Live vaccines 
4.10 
Treatment Compliance 
Study drug will be dispensed in single-use prefilled syringes with passive needle 
guards or as a prefilled syringe in an auto-injector in a quantity required for the 
period of time until the next visit. Subjects and/or caregivers will be reminded 
how to transport and store the study drug, to place used study drug syringes in the 
provided sharps container, and to return all used study drug syringes when the 
sharps container is full. If the subject is required to return any unused study drug 
to the site, the unused study drug should be transported using the provided cold 
packs and insulated cooler. 
Subjects and/or caregivers will utilize an e-Diary to record information about the 
weekly injections through Week 48 and possible ISRs. The study staff will help 
the subject and/or caregiver re-register into the e-Diary system at the time of the 
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first visit. Subjects will access the e-Diary via a web-based system or telephone, if 
available in the region/country. 
Study staff and subjects will be notified if the subject and/or caregiver does not 
enter information into the e-Diary system within 24 hours of the expected 
date/time of a dose. Site staff should follow up with subjects to ensure subjects 
are receiving doses per protocol and provide retraining as necessary. At each 
post-dosing study visit through Week 48 and at the Follow-up Visit 28 days after 
the last dose of study drug for subjects who discontinue study drug prior to or at 
Week 48, study staff will review the e-Diary entries with the subject and/or 
caregiver and provide retraining as necessary. 
Compliance and possible ISRs to study drug during the first 48 weeks of receipt 
of study drug will be assessed by the Investigator and study staff based on study 
drug use recorded by the subject and/or caregiver in the e-Diary. Subjects and/or 
caregivers who have had any compliance issues will be re-educated by the 
Investigator or study staff on the importance of taking study drug weekly. 
Subjects and/or caregivers should be instructed to inject study drug on a regular 
weekly schedule and not to inject study drug on the day of a study visit until all 
visit procedures are complete so that a trough serum sample may be obtained 
prior to dosing.    
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5 
MEASUREMENTS AND EVALUATIONS 
5.1 
Schedules of Procedures 
The schedules of procedures performed at each clinic visit are presented in Error! 
eference source not found. for RA subjects and Error! Reference source not 
found. for PsO subjects. 
Note that all subjects in Japan enrolled in OLSES are from CHS-0214-02 parent 
study. 
All PsO subjects will receive CHS-0214 for a no longer than 48 weeks.  
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Table 1: Schedule of Procedures for Subjects with Rheumatoid Arthritis 
Day 
0 
28 
84 
168 
252 
336 
 
 
Week 
0* 
4 
12 
24 
36 
48 
Quarterly 
Visitsa 
28 Days Post 
Last Dose  
Window 
Dosing 
± 3 Days 
± 7 Days 
± 7 Days 
± 7 Days 
± 7 Days 
± 7 Days 
± 3 Days 
Study Procedures 
Informed consent 
Xb 
 
 
 
 
Xc 
 
 
Assign subject ID 
Xb 
 
 
 
 
 
 
 
Contact IVRS/IWRS 
Xb 
X 
X 
X 
X 
X 
X 
X 
Physical examinationd 
** 
X 
X 
X 
X 
X 
X 
Xe 
Vital signsf 
** 
X 
X 
X 
X 
X 
X 
X 
Concomitant medications 
** 
X 
X 
X 
X 
X 
X 
X 
ECG 
** 
 
 
 
 
X 
Xg 
Xh 
Hematologyi 
** 
 
 
X 
 
X 
Xj 
X 
Chemistryk 
** 
 
 
X 
 
X 
Xj 
X 
Urinalysisl 
** 
 
 
X 
 
X 
Xj 
X 
Viral Screening (HBsAg, HBcAb, 
HBsAbm, HCV, HIV)n 
Xb 
 
 
 
 
Xo 
Xg 
 
QuantiFERON®-TB Gold 
** 
 
 
 
 
X 
Xg 
 
66/68 SJC/TJC assessment 
** 
X 
X 
X 
X 
X 
X 
 
6XEMHFW¶VSDLQDVVHVVPHQW9$6 
** 
X 
X 
X 
X 
X 
X 
 
hs-CRP 
** 
X 
X 
X 
X 
X 
X 
 
HAQ-DI  
** 
X 
X 
X 
X 
X 
X 
 
SGA (VAS)p 
** 
X 
X 
X 
X 
X 
X 
 
PGA (VAS)p 
** 
X 
X 
X 
X 
X 
X 
 
Serum sample (trough retention 
sample)q 
** 
X 
X 
X 
X 
X 
Xj 
X 
Serum sample for ADA (pre-dose 
on dosing days)q 
** 
X 
X 
X 
X 
X 
Xj 
X 
Urine pregnancy testr 
**s 
X 
X 
X 
X 
X 
X 
X 
Assess AEs 
** 
X 
X 
X 
X 
X 
X 
X 
Injection site assessmentt 
** 
X 
X 
X 
X 
X 
X 
X 
e-Diary review and/or compliance 
evaluation 
** 
X 
X 
X 
X 
X 
 
 
Drug dispensing 
Xb 
X 
X 
X 
X 
Xu 
Xu 
 
 
ACR20 = at least a 20% improvement from Baseline according to American College of Rheumatology criteria; ADA = anti-drug antibody; 
AE = adverse event; ECG = electrocardiogram; HAQ-DI = Health Assessment Questionnaire-Disability Index; HBcAb = hepatitis B core antibody; 
HBsAg = hepatitis B surface antigen; HBsAb=Hepatitis B surface antibody; HCV = hepatitis C virus; HIV = human immunodeficiency virus; 
hs-CRP = high sensitivity C-reactive protein; ID = identification number; ISR = injection site reaction; IVRS = interactive voice response system; 
IWRS = interactive web response system; OLSES = open-label safety extension study; PGA = 3K\VLFLDQ¶V*OREDO$VVHVVPHQW4: = every week; 
RA = rheumatoid arthritis; SGA = VXEMHFW¶s global assessment of disease activity; SJC  = swollen joint count; TJC = tender joint count; 
VAS = visual analog scale.  
  *     The Week 0 Visit of OLSES is considered to correspond to the Week 48 Visit of CHS-0214-$QLQWHUYDORIPRQWKXQOHVVDQ interval 
>1 month is approved by the Sponsor per subject) between completion of CHS-0214-02 and start of OLSES is allowed. Subjects awaiting 
hs-CRP results to determine if they meet ACR20 criteria can enroll in OLSES after hs-CRP results are available and it is determined ACR20 
criteria are met. Therefore, for these subjects, the Day 0 Visit for OLSES will not coincide exactly with (but, for assessments, will be 
considered to correspond to) the Week 48 Visit of CHS-0214-02. 
  **    Same evaluations/procedures as for Week 48 of CHS-0214-02; these evaluations will serve as baseline evaluations for this study.  
 
a 
Begins with the Week 60 Visit for subjects in Japan who continue participation in OLSES beyond Week 48. 
b 
A subject who meets ACR20 criteria based on hs-CRP results not available at the Week 48 Visit of CHS-0214-02 will be asked to return to the 
clinic for a separate OLSES Week 0 Day 0 Visit in addition to the Week 48 Visit of CHS-0214-02, at which time informed consent will be 
obtained, subject ID will be assigned, blood samples for viral screening will be obtained, IVRS/IWRS will be contacted to register the subject 
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Table 1: Schedule of Procedures for Subjects with Rheumatoid Arthritis 
in the study, and study drug will be dispensed.   
c 
Subjects in Japan will consent on or before their OLSES Week 48 Visit to be able to continue participation in OLSES beyond Week 48. 
d 
Abbreviated physical examinations are conducted at the Week 48 Visit in the parent study (considered to correspond to the Week 0 Day 0 
Visit in this study) and all the subsequent visits. Abbreviated physical examinations will consist of respiratory, gastrointestinal, 
musculoskeletal, and cardiovascular system evaluations and evaluations of other physical conditions of note.  
e 
Weight will be recorded at the Follow-up Visit 28 days after the last dose of study drug. 
f 
Vital signs include blood pressure (NOTE: an arm or wrist cuff is acceptable); heart rate; respiratory rate; and oral, aural, or axillary 
temperature and are to be obtained after the subject has rested in a seated position for at least 5 minutes. 
g 
Repeat every 12 months for subjects in Japan who continue participation in OLSES beyond Week 48. 
h 
Perform ECG at the Follow-up Visit 28 days after the last dose of study drug for those subjects who discontinue study drug  
i 
Hematology parameters include hematocrit, hemoglobin, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and 
mean corpuscular volume, red blood cell count, white blood cell count with differential, reticulocyte count, and platelet count. 
j 
Perform every 6 months for subjects in Japan who continue participation in OLSES beyond Week 48. 
k 
Chemistry parameters include alkaline phosphatase; sodium; potassium; total protein; calcium; chloride; bicarbonate; glucose; creatine 
phosphokinase; lactate dehydrogenase; alanine aminotransferase; aspartate aminotransferase; albumin; total, direct and indirect bilirubin; 
blood urea nitrogen; creatinine; and uric acid. 
l 
Urinalysis parameters include pH, specific gravity, protein, glucose, leukocyte esterase, bilirubin, blood, nitrite, and ketones. A urine 
microscopic examination will be performed when there are any abnormalities on any of the following 3 dipstick results: leukocyte esterase, 
blood, or nitrite. 
m 
Japan only (see Section 5.2.1). 
n 
Perform HIV and hepatitis screen testing prior to subject enrolling in OLSES (the subject may be enrolled in OLSES prior to receipt of 
results); assess ongoing participation in OLSES upon receipt of results.  
o 
Perform for subjects in Japan who continue participation in OLSES beyond Week 48. 
p 
Perform PGA (VAS) prior to SGA (VAS). 
q 
Blood samples will be collected (pre-dose on dosing days) and serum retained at each visit through Week 48 and every 6 months for subjects 
in Japan who continue participation in OLSES beyond Week 48 for possible evaluation of CHS-0214 serum concentrations, ADA, or other 
tests as necessary to evaluate adverse effects or compliance. The exact date and time of each sample collection will be recorded. 
r 
Perform for female subjects who are of childbearing potential and not surgically sterile at the Week 0 Day 0 Visit, and at the Follow-up Visit 
28 days after the last dose of study drug; for these subjects using abstinence as birth control, perform at every visit.  
s 
A urine pregnancy test will be required on Week 0 Day 0 if Week 0 does not coincide with Week 48 of the parent study. 
t 
Record ISRs observed by site personnel as AEs. 
u 
Perform only for the subjects in Japan who consent to continue participation in OLSES beyond Week 48. If this visit LVWKHVXEMHFW¶VODVWYLVLW
do not dispense study drug. 
 
 
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Table 2: Schedule of Procedures for Subjects with Plaque Psoriasis 
Day 
0 
28 
84 
168 
252 
336 
28 Days Post 
Last Dose 
Week 
0* 
4 
12 
24 
36 
48 
4 Weeks Post 
Last Dose 
Window 
Dosing 
± 3 Days 
± 7 Days 
± 7 Days 
± 7 Days 
± 7 Days 
± 3 Days 
Study Procedures 
Informed consent 
X 
 
 
 
 
 
 
Assign subject ID 
X 
 
 
 
 
 
 
Contact IVRS/IWRS 
X 
X 
X 
X 
X 
X 
X 
Physical examinationa 
** 
X 
X 
X 
X 
X 
Xb 
Vital signsc 
** 
X 
X 
X 
X 
X 
X 
Concomitant medications 
** 
X 
X 
X 
X 
X 
X 
ECG 
** 
 
 
 
 
X 
Xd 
Hematologye 
** 
 
 
X 
 
X 
X 
Chemistryf 
** 
 
 
X 
 
X 
X 
Urinalysisg 
** 
 
 
X 
 
X 
X 
Viral Screening (HBsAg, HCV, HIV)h 
X 
 
 
 
 
 
 
QuantiFERON®-TB Gold 
** 
 
 
 
 
X 
 
PASI assessment for subjects with PsO 
** 
X 
X 
X 
X 
X 
 
SGA (VAS) 
** 
X 
X 
X 
X 
X 
 
PSGA  
** 
X 
X 
X 
X 
X 
 
Serum sample (trough retention sample)i 
** 
X 
X 
X 
X 
X 
X 
Serum sample for ADA (pre-dose on 
dosing days) 
** 
X 
X 
X 
X 
X 
X 
Urine pregnancy testj 
**k 
X 
X 
X 
X 
X 
X 
Assess AEs 
** 
X 
X 
X 
X 
X 
X 
Injection site assessmentl 
** 
X 
X 
X 
X 
X 
X 
e-Diary Review and/or Compliance 
Evaluation 
** 
X 
X 
X 
X 
X 
X 
Drug dispensing 
X 
X 
X 
X 
X 
 
 
 
ADA = anti-drug antibody; AE = adverse event; ECG = electrocardiogram; HBsAg = hepatitis B surface antigen; HCV = hepatitis C 
virus; HIV = human immunodeficiency virus; ID = identification number; ISR = injection site reaction; IVRS = interactive voice 
response system; IWRS = interactive web response system; OLSES = open-label safety extension study; PASI = Psoriasis Area and 
Severity Index; PSGA = 3K\VLFLDQ¶V6WDWLF*OREDO$VVHVVPHQWPsO = plaque psoriasis; QW = every week; SGA = VXEMHFW¶VJOREDO
assessment of disease activity; VAS = visual analog scale.  
  *    The Week 0 Visit of this study is considered to correspond to the Week 48 Visit of CHS-0214-$QLQWHUYDORIPRQWKXQOHVV
an interval >1 month is approved by the Sponsor per subject) between completion of the CHS-0214-04 and start of OLSES is 
allowed.  
  **    Same evaluations/procedures as for Week 48 of CHS-0214-04; these evaluations will serve as baseline evaluations for this study. 
a. 
Abbreviated physical examinations are conducted at the Week 48 Visit in the parent study (considered to correspond to the Week 
0 Day 0 Visit in this study) and all the subsequent visits. Abbreviated physical examinations will consist of respiratory, 
gastrointestinal, musculoskeletal, and cardiovascular system evaluations and evaluations of other physical conditions of note.  
b. 
Weight will be recorded at the Follow-up Visit 28 days after the last dose of study drug. 
c. 
Vital signs include blood pressure(NOTE: an arm or wrist cuff is acceptable); heart rate; respiratory rate; and oral, aural, or 
axillary temperature and are to be obtained after the subject has rested in a seated position for at least 5 minutes. 
d. 
Perform ECG 28 days after last dose of study drug for those subjects who discontinue study drug prior to Week 48. 
e. 
Hematology parameters include hematocrit, hemoglobin, mean corpuscular hemoglobin, mean corpuscular hemoglobin 
concentration, and mean corpuscular volume, red blood cell count, white blood cell count with differential, reticulocyte count, 
and platelet count. 
f. 
Chemistry parameters include alkaline phosphatase; sodium; potassium; total protein; calcium; chloride; bicarbonate; glucose; 
creatine phosphokinase; lactate dehydrogenase; alanine aminotransferase; aspartate aminotransferase; albumin; total, direct and 
indirect bilirubin; blood urea nitrogen; creatinine; and uric acid. 
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Table 2: Schedule of Procedures for Subjects with Plaque Psoriasis 
g. 
Urinalysis parameters include pH, specific gravity, protein, glucose, leukocyte esterase, bilirubin, blood, nitrite, and ketones. A 
urine microscopic examination will be performed when there are any abnormalities on any of the following 3 dipstick results: 
leukocyte esterase, blood, or nitrite. 
h. 
Perform HIV and hepatitis screen testing prior to subject enrolling in OLSES (the subject may be enrolled in OLSES prior to 
receipt of results); assess ongoing participation in OLSES upon receipt of results.  
i. 
Blood samples will be collected (pre-dose on dosing days) and serum retained at each visit for possible evaluation of CHS-0214 
serum concentrations, ADA, or other tests as necessary to evaluate adverse effects or compliance. The exact date and time of 
each sample collection will be recorded. 
j. 
Perform for female subjects who are of childbearing potential and not surgically sterile at the Week 0 Day 0 Visit and at the 
Follow-up Visit 28 days after the last dose of study drug; for these subjects using abstinence as birth control, perform at every 
visit.  
k. 
A urine pregnancy test will be required on Week 0 Day 0 if Week 0 does not coincide with Week 48 of the parent study. 
l. 
Record ISRs observed by site personnel as AEs. 
 
 
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5.2 
Study Schedule  
5.2.1 
Week 0 Day 0  
The Week 0 Day 0 Visit of this study is considered to correspond to the Week 48 
Visit of the parent study, CHS-0214-02 or CHS-0214-$QLQWHUYDORIPRQWK
(unless an interval >1 month is approved by the Sponsor for the subject) between 
completion of the parent study and start of OLSES is allowed. The following 
procedures will be performed: 
x Obtain written informed consent;  
x Assign subject ID in sequential order; 
x Collect blood samples for viral screening (hepatitis B surface antigen 
[HBsAg], hepatitis B core antibody [HBcAb], hepatitis B surface antibody 
[HBsAb; Japan only], hepatitis C virus, and human immunodeficiency 
virus)  
x If Week 0 does not coincide with Week 48 of the parent study, perform 
urine pregnancy test for female subjects who are of childbearing potential 
and not surgically sterile (see Appendix I); 
x In Japan  
o In accordance with current Japanese Society of Hepatology 
guidelines for the management of hepatitis B virus (HBV) 
infection (Drafting Committee for Hepatitis Management 
Guidelines and the Japan Society of Hepatology, 2014): 
 In an HBsAg negative subject, if HBsAb is positive and 
there is documented evidence of HBV vaccination, do not 
initiate nucleotide/nucleoside analogue therapy and 
continue the subject in the study. 
 If HBsAb is positive and there is no documented evidence 
of HBV vaccination, HBV DNA will be evaluated. 
 ,I+%9'1$LVORJFRSLHVSHUP/initiate 
nucleotide/nucleoside analogue therapy and continue the 
subject in the study. 
 If HBV DNA is <2.1 log copies/mL, the subject can 
continue in the study. 
o In all cases, monitor liver function tests per current protocol. 
x Contact the IVRS/IWRS to register the subject in the study; and 
x Dispense study drug (see Section 4.8). 
The Investigator should review CHS-0214-02 or CHS-0214-04 Week 48 (OLSES 
Week 0/Day 0) assessment results (including viral and QuantiFERON®-TB Gold 
WHVWUHVXOWVZKHQWKH\DUHDYDLODEOHWRHQVXUHWKHVXEMHFW¶VFRQWLQXDWLRQLQ
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OLSES is appropriate. The QuantiFERON®-TB Gold test can be repeated once 
using a fresh sample in a subject with an indeterminate result or low positivity 
(defined as QuantiFERON®-TB antigen minus Nil value = 0.35-2 IU/mL).  
If the repeat test is indeterminate or low positive (0.35-2 IU/mL), the patient can 
continue in the study, providing symptoms and risk factors are all negative, i.e., 
the subject has not been exposed to TB, the chest x-ray is negative, and the 
investigator does not believe the subject has latent TB. Only a conversion to 
positive (>2 IU/mL) on 2 consecutive tests would result in the subject being 
terminated from the study (Raychaudhuri, Nguyen, Raychaudhuri, & Gershwin, 
2009). Subjects with a history of adequately treated TB may have signs of 
obsolete pulmonary TB (consistent with scarring) on chest x-ray. These subjects 
may continue on OLSES provided that their QuantiFERON®-TB Gold test results 
is negative or low positive (< 2.0 IU/mL). A repeat chest x-ray may be obtained to 
ensure that there is no change in the obsolete lesions. In addition:  
x Subjects with RA are eligible for continuation into OLSES if they meet 
the ACR20 criteria at the Week 48 Visit of the parent study. If Week 48 
hs-CRP results are needed to determine whether or not ACR20 criteria are 
met and not yet available, enrollment into OLSES will be delayed until 
hs-CRP results are available and it is determined that ACR20 criteria are 
met. In this case, the subject will be asked to return to the clinic for a 
separate OLSES Week 0 Day 0 Visit. At this visit, informed consent will 
be obtained, subject ID will be assigned, blood samples for viral screening 
will be obtained, urine pregnancy testing will be performed for females 
who are of childbearing potential and not surgically sterile; IVRS/IWRS 
will be contacted to register the subject in the study; and study drug will 
be dispensed. Every effort should be made to maintain the QW dosing 
schedule. 
x For subjects with PsO, eligibility for continuation will be determined by 
calculation of Psoriasis Area and Severity Index (PASI). Subjects are 
required to have had at least a PASI-50 from Baseline at Week 48 in the 
parent study. 
5.2.2 
Week 4 Day 28 (± 3 Days), Week 12 Day 84 (± 7 Days) and Week 36 
Day 252 (± 7 Days) 
The following procedures will be performed: 
x Perform abbreviated physical examination (see Section7.2); 
x Obtain vital sign measurements, including blood pressure (NOTE: an arm 
or wrist cuff is acceptable), heart rate, respiratory rate, and body 
temperature (using oral, aural, or axillary thermometer), after the subject 
has rested in a seated position for at least 5 minutes (see Section 7.3);  
x Record concomitant medications (see Section 4.9); 
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x Collect pre-dose (trough) blood sample for retained serum (see 
Section 7.8);  
x Collect pre-dose blood sample for ADA testing (see Section 7.6); 
x Perform urine pregnancy test for female subjects who are of childbearing 
potential and not surgically sterile using who are using abstinence as birth 
control (see Appendix I); 
x Assess and record AEs (see Section 7.1); 
x Perform injection site assessment and record ISRs observed during the 
examination as AEs (see Section 7.1 and Section 7.2); 
x Review subjHFW¶VH-Diary for any issues with compliance or with injecting 
study drug;  
x Contact the IVRS/IWRS to assign study drug kits to be dispensed; 
x Dispense study drug (see Section 4.8); 
x At Week 36, remind subject to bring all used and unused study drug to 
their Week 48 Visit; 
x For subjects with RA: 
o 3HUIRUP3K\VLFLDQ¶V*OREDO$VVHVVPHQW3*$YLVXDODQDORJVFDOH
(VAS) (see Appendix GSULRUWRVXEMHFW¶VJOREDODVVHVVPHQWRI
disease activity (SGA) (VAS) (see Appendix F);  
o Perform SGA (VAS) (see Appendix F) after PGA (VAS) (see 
Appendix G); 
o Perform joint assessment (66/68 SJC/TJC assessment) (see 
Appendix D); 
o Obtain blood sample for hs-CRP (see Section 6.1.1.6 and 
Appendix I)  
o Administer HAQ-DI (see Appendix K); and 
o 3HUIRUPVXEMHFW¶VSDLQDVVHVVPHQW9$6VHHAppendix E).  
x For subjects with PsO: 
o Perform PASI assessment (see Appendix J);  
o 3HUIRUP3K\VLFLDQ¶V6WDWLF*OREDO$VVHVVPHQW36*$VHH
Appendix H) prior to SGA (VAS) (see Appendix F); and  
o Perform SGA (VAS) (see Appendix F) after PSGA (see 
Appendix H). 
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5.2.3 
Week 24 Day 168 (± 7 Days) 
The following procedures will be performed: 
x Perform abbreviated physical examination (see Section 7.2); 
x Obtain vital sign measurements, including blood pressure (NOTE: an arm 
or wrist cuff is acceptable), heart rate, respiratory rate, and body 
temperature (using oral, aural, or axillary thermometer), after the subject 
has rested in a seated position for at least 5 minutes (see Section 7.3);  
x Record concomitant medications (see Section 4.9); 
x Collect blood samples for chemistry and hematology assessments (see 
Appendix I); 
x Collect urine sample for urinalysis (see Appendix I); 
x Collect pre-dose (trough) blood sample for retained serum (see 
Section 7.8); 
x Collect pre-dose blood sample for ADA testing (see Section 7.6); 
x Perform urine pregnancy test for female subjects who are of childbearing 
potential and not surgically sterile who are using abstinence as birth 
control (see Appendix I); 
x Assess and record AEs (see Section 7.1); 
x Perform injection site assessment and record ISRs observed during the 
examination as AEs (see Section 7.1 and Section 7.2); 
x 5HYLHZVXEMHFW¶VH-Diary for any issues with compliance or with injecting 
study drug;  
x Contact the IVRS/IWRS to assign study drug kits to be dispensed;  
x Dispense study drug (see Section 4.8); 
x For subjects with RA: 
o Perform PGA (VAS) (see Appendix G) prior to SGA (VAS) (see 
Appendix F);  
o Perform SGA (VAS) (see Appendix F) after PGA (VAS) (see 
Appendix G); 
o Perform joint assessment (66/68 SJC/TJC assessment) (see 
Appendix D); 
o Obtain blood sample for hs-CRP (see Section 6.1.1.6 and 
Appendix I);  
o Administer HAQ-DI (see Appendix K); and 
o 3HUIRUPVXEMHFW¶VSDLQDVVHVVPHQW9$6VHHAppendix E). 
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x For subjects with PsO: 
o Perform PASI assessment (see Appendix J);  
o Perform PSGA (see Appendix H) prior to SGA (VAS) (see 
Appendix F); and  
o Perform SGA (VAS) (see Appendix F) after PSGA (see 
Appendix H). 
5.2.4 
Week 48 Day 336 (± 7 days) 
The following procedures will be performed: 
x Perform abbreviated physical examination (see Section 7.2); 
x Obtain vital sign measurements, including blood pressure (NOTE: an arm 
or wrist cuff is acceptable), heart rate, respiratory rate, and body 
temperature (using oral, aural, or axillary thermometer), after the subject 
has rested in a seated position for at least 5 minutes (see Section 7.3);  
x Record concomitant medications (see Section 4.9); 
x Perform resting 12-lead ECG (see Section 7.4);  
x Collect blood samples for chemistry and hematology assessments (see 
Appendix I); 
x Collect urine sample for urinalysis (see Appendix I); 
x Obtain blood sample for QuantiFERON®-TB Gold test to rule out active 
or latent TB (see Appendix I);  
x Collect pre-dose (trough) blood sample for retained serum (see 
Section 7.7); 
x Collect pre-dose blood sample for ADA testing (see Section 7.6); 
x Perform urine pregnancy test for female subjects who are of childbearing 
potential and not surgically sterile who are using abstinence as birth 
control (see Appendix I); 
x Assess and record AEs (see Section 7.1); 
x Perform injection site assessment and record ISRs observed during the 
examination as AEs (see Section 7.1 and Section 7.2);  
x 5HYLHZVXEMHFW¶VH-Diary for any issues with compliance or with injecting 
study drug; and 
x 
For subjects not continuing study participation beyond Week 48, contact the 
,956,:56WRUHJLVWHUVXEMHFW¶VFRPSOHWLRQRIWUHDWPHQW  
x For subjects with RA: 
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o Perform PGA (VAS) (see Appendix G) prior to SGA (VAS) (see 
Appendix F);  
o Perform SGA (VAS) (see Appendix F) after PGA (VAS) (see 
Appendix G); 
o Perform joint assessment (66/68 SJC/TJC assessment) (see 
Appendix D); 
o Obtain blood sample for hs-CRP (see Section 6.1.1.6 and 
Appendix I); 
o Administer HAQ-DI (see Appendix D);  
o 3HUIRUPVXEMHFW¶VSDLQDVVHVVPHQW9$6VHHAppendix E); 
x 
For subjects in Japan continuing study participation beyond Week 48:  
 Obtain written informed consent on or before the Week 48 
Visit; 
 Collect blood samples for viral screening (HBsAg, HBcAb, 
HBsAb, hepatitis C virus, and human immunodeficiency 
virus); 
 Contact the IVRS/IWRS for study drug kit assignment; and 
 Dispense study drug (see Section 4.8). 
x For subjects with PsO: 
o Perform PASI assessment (see Appendix J); 
o Perform PSGA (see Appendix H) prior to SGA (see Appendix F); 
and  
o Perform SGA (VAS) (see Appendix F) after PSGA (see 
Appendix H). 
Quarterly Visits (± 7 days)²Subjects in Japan with RA Only, Beginning at Week 
60The following procedures will be performed quarterly: 
x Perform abbreviated physical examination (see Section 7.2); 
x Obtain vital sign measurements, including blood pressure (NOTE: an arm 
or wrist cuff is acceptable), heart rate, respiratory rate, and body 
temperature (using oral, aural, or axillary thermometer), after the subject 
has rested in a seated position for at least 5 minutes (see Section 7.3);  
x Record concomitant medications (see Section 4.9); 
x Perform urine pregnancy test for female subjects who are of childbearing 
potential and not surgically sterile who are using abstinence as birth 
control (see Appendix I); 
x Assess and record AEs (see Section 7.1); 
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x Perform injection site assessment and record ISRs observed during the 
examination as AEs (see Section 7.1 and Section 7.2);  
x Perform PGA (VAS) (see Appendix G) prior to SGA (VAS) (see 
Appendix F);  
x Perform SGA (VAS) (see Appendix F) after PGA (VAS) (see 
Appendix G); 
x Obtain blood sample for hs-CRP (see Section 6.1.1.6 and Appendix I)  
x 
Perform joint assessment (66/68 SJC/TJC assessment) (see Appendix D); 
x 
Administer HAQ-DI (see Appendix D); 
x 
3HUIRUPVXEMHFW¶VSDLQDVVHVVPHQW9$6VHHAppendix E); and  
x Contact the IVRS/IWRS to assign study drug kits to be dispensed unless 
subject is discontinuing in the study; if so, contact the IVRS/IWRS to 
register subjecW¶VFRPSOHWLRQRIWUHDWPHQW. 
x Dispense study drug for subjects continuing in the study unless this is 
VXEMHFW¶VODVWYLVLW (see Section 4.8). 
The following procedures will be performed every 6 months: 
x Collect blood samples for chemistry and hematology assessments (see 
Appendix I); 
x Collect urine sample for urinalysis (see Appendix I); 
x Collect pre-dose (trough) blood sample for retained serum (see 
Section 7.7);  
x Collect pre-dose blood sample for ADA testing (see Section 7.6); and 
The following procedures will be performed annually beyond Week 48: 
x Perform resting 12-lead ECG (see Section 7.4); 
x Collect blood samples for viral screening (HBsAg, HBcAb, HBsAb, 
hepatitis C virus, and human immunodeficiency virus); and  
x Obtain blood sample for QuantiFERON®-TB Gold test to rule out active 
or latent TB (see Appendix I). 
5.2.5 
Follow-up Visit 28 Days (± 3 Days) Post Last Dose of Study Drug  
The following procedures will be performed: 
x &RQWDFWWKH,956,:56WRUHJLVWHUVXEMHFW¶VGLVFKDUJHIURPWhe study; 
x Perform abbreviated physical examination (see Section 7.2); 
x Measure weight (see Section 7.2); 
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x Obtain vital sign measurements, including blood pressure (NOTE: arm or 
wrist cuff is acceptable), heart rate, respiratory rate, and body temperature 
(using oral, aural, or axillary thermometer), after the subject has rested in a 
seated position for at least 5 minutes (see Section 7.3);  
x Record concomitant medications (see Section 4.9); 
x Perform resting 12-lead ECG at the Follow-up Visit 28 days after the last 
dose of study drug for subjects who discontinue study drug (see Section 
7.4); 
x Collect blood samples for chemistry and hematology assessments (see 
Appendix I); 
x Collect urine sample for urinalysis (see Appendix I); 
x Collect trough blood sample for retained serum (see Section 7.7); 
x Collect blood sample for ADA testing (see Section 7.6); 
x Perform urine pregnancy test for female subjects who are of childbearing 
potential and not surgically sterile (see Appendix I); 
x Assess and record AEs (see Section 7.1); 
x Perform injection site assessment and record ISRs observed during the 
examination as AEs (see Section 7.1 and Section 7.2); and 
 
5.3 
Informed Consent 
All subjects will be informed of the nature and purpose of the study prior to any 
study-related assessments or procedures and requested to review and to sign an 
Institutional Review Board/Ethics Committee (IRB/EC) approved consent form 
specific for either RA or PsO. Subjects in Japan with RA will consent on or 
before their Week 48 Visit to be able to continue participation in OLSES beyond 
Week 48. 
5.4 
Medical and Surgical History 
7KHVXEMHFW¶VPHGLFDODQGVXUJLFDOKLVWRU\ZLOOQRWEHFROOHFWHGLQ2/6(6EXWFDQ
be referenced from the parent study if required. 
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6 
EFFICACY MEASUREMENTS 
6.1 
Primary Efficacy Endpoints  
6.1.1 
Rheumatoid Arthritis 
In subjects with RA, durability of response (maintenance of an ACR20 response 
or greater at each assessment) will be measured at each visit based on the 
following assessments:  
x SJC; 
x TJC;  
x 6XEMHFW¶VSDLQDVVHVVPHQW9$6 
x SGA (VAS); 
x PGA (VAS);  
x HAQ-DI; and  
x hs-CRP. 
6.1.1.1 
66/68 Swollen Joint Count/Tender Joint Count Assessments 
All joint count assessors must demonstrate proficiency at performing joint counts. 
Every attempt should be made to use the same assessor for each subject 
throughout the study. Joints that were injected during the CHS-0214-02 study 
should be noted as swollen and tender during the OLSES (see Appendix D). The 
66/68 SJC/TJC will be assessed at Weeks 0 (as the Week 48 assessment of the 
parent study), 4, 12, 24, 36, and 48 and, for subjects in Japan who continue 
participation in OLSES beyond Week 48, at each quarterly visit thereafter. 
6.1.1.2 
6XEMHFW¶V3DLQ$VVHVVPHQW9LVXDO$QDORJ6FDOH 
The subject will rate the severity of pain at the time of visit using a horizontal 
10-cm VAS with the best anchor and lowest score on the left side and worst 
anchor and highest score on the right side (Felson, et al., 2011)7KHVXEMHFW¶VSDLQ 
VAS should be completed by the subject (see Appendix E) at Weeks 0 (as the 
Week 48 assessment of the parent study), 4, 12, 24, 36, and 48 and, for subjects in 
Japan who continue participation in OLSES beyond Week 48, at each quarterly 
visit thereafter. 
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6.1.1.3 
6XEMHFW¶V*OREDOAssessment (Visual Analog Scale) 
The subject will rate the actual state of disease activity by indicating the answer to 
WKHTXHVWLRQ³&RQVLGHULQJDOORIWKHZD\V\RXUDUWKULWLVKDVDIIHFWHG\RXKRZGR
\RXIHHO\RXUDUWKULWLVLVWRGD\"´RQDKRUL]RQWDO-cm VAS with the anchors 
³YHU\ZHOO´DQG³YHU\SRRU´VHHAppendix F) (Felson, et al., 2011). The SGA 
(VAS) will be conducted at Weeks 0 (as the Week 48 assessment of the parent 
study), 4, 12, 24, 36, and 48 and, for subjects in Japan who continue participation 
in OLSES beyond Week 48, at each quarterly visit thereafter. 
6.1.1.4 
3K\VLFLDQ¶V*OREDO$VVHVVPHQW9LVXDO$QDORJ6FDOH 
The clinician will assess the subject's disease activity at the time of the visit by 
indicating the answer WRWKHTXHVWLRQ³:KDWLV\RXUDVVHVVPHQWRIWKHVXEMHFW¶V
FXUUHQWGLVHDVHDFWLYLW\"´RQDKRUL]RQWDO-FP9$6ZLWKWKHDQFKRUV³QRQH´
DQG³H[WUHPHO\DFWLYH´VHHAppendix G) (Felson, et al., 2011). The PGA should 
be conducted prior to conducting the SGA at Weeks 0 (as the Week 48 
assessment of the parent study), 4, 12, 24, 36, and 48 and, for subjects in Japan 
who continue participation in OLSES beyond Week 48, at each quarterly visit 
thereafter. 
6.1.1.5 
HAQ-DI 
The HAQ-DI is a validated 20-LWHPDVVHVVPHQWRIDVXEMHFW¶VIXQFWLRQDODELOLWLHV
in 8 categories (Dressing and Grooming, Hygiene, Arising, Reach, Eating, Grip, 
Walking, Common Daily Activities) (see Appendix K). There are 4 response 
RSWLRQVUDQJLQJIURP³:LWKRXWDQ\'LIILFXOW\´WR³8QDEOHWR'R´VFRUHGWR
(Fries, Spitz, Kraines, & Holman, 1980) (Kawai, 1995). In subjects with RA, the 
HAQ-DI will be administered at Weeks 0 (as the Week 48 assessment of the 
parent study), 4, 12, 24, 36, and 48 and, for subjects in Japan who continue 
participation in OLSES beyond Week 48, at each quarterly visit thereafter.  
6.1.1.6 
High Sensitivity C-Reactive Protein 
Blood samples for measurement of hs-CRP will be collected at Weeks 0 (as the 
Week 48 assessment of the parent study), 4, 12, 24, 36, and 48 and, for subjects in 
Japan who continue participation in OLSES beyond Week 48, at each quarterly 
visit thereafter. In this study, hs-CRP is a marker of inflammation and is not being 
used as an assessment of cardiovascular risk. As such, the results of the hs-CRP 
test will not be shared with subjects. 
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6.1.2 
Plaque Psoriasis 
6.1.2.1 
Psoriasis Area and Severity Index Score 
All PASI score assessors must demonstrate proficiency at performing the PASI. 
Every attempt should be made to use the same assessor for each subject 
throughout the study.  
In subjects with PsO, durability of response (maintenance of a PASI-50 response 
or greater at each assessment) will be based on scoring the PsO lesions on a scale 
of 0 to 4 for 3 characteristics: erythema, infiltration, and desquamation, weighted 
by the area of involvement (Fredriksson & Pettersson, 1978) (Feldman & 
Krueger, 2005) (see Appendix J). The lesions are scored within 4 anatomical 
regions: head, upper extremities, trunk, and lower extremities including buttocks. 
Within each of these regions, the area of involvement is scored on a scale of 0-6. 
7KHFOLQLFLDQZLOODVVHVVWKHVXEMHFW¶V3V2lesions according to the PASI at 
Weeks 0 (as the Week 48 assessment of the parent study), 4, 12, 24, 36, and 48. 
6.1.2.2 
3K\VLFLDQ¶V6WDWLF*OREDO$VVHVVPHQW 
The PSGA of Psoriasis will be assessed on a scale of 0 to 5, with 0 indicating no 
psoriasis (clear of disease), 1 (almost clear), and 2 or higher indicating more 
severe disease (see Appendix H).  
7KHFOLQLFLDQ¶VDVVHVVPHQWVKRXOGEHPDGHDQGUHFRUGHGEHIRUHDWWDLQLQJWKH
VXEMHFW¶VDVVHVVPHQWWKH6*$DWDOOYLVLWV7KH36*$ZLOOEHSHUIRUPHGDW
Weeks 0 (as the Week 48 assessment of the parent study), 4, 12, 24, 36, and 48. 
6.1.2.3 
6XEMHFW¶V*OREDO$VVHVVPHQW 
The SGA of Psoriasis will be assessed on a scale ranging from 0 (good) to 5 
(severe) (Leonardi, et al., 2003) (see Appendix F). The SGA should be assessed at 
Weeks 0 (as the Week 48 assessment of the parent study), 4, 12, 24, 36, and 48. 
6.2 
Secondary Efficacy Endpoints (Rheumatoid Arthritis) 
The secondary efficacy variable for RA subjects will include DAS28-CRP(4) 
<3.2 at Weeks 0, 4, 12, 24, 36, and 48 and, for subjects in Japan who continue 
participation in OLSES beyond Week 48, at each quarterly visit thereafter 
(Fransen & van Riel, 2009) (van Gestel, Haagsma, & van Riel, 1998) (Wells, et 
al., 2009) and remission rate (defined as DAS28-CRP[4] < 2.6 on all visits after 
DAS28-CRP(4) < 2.6 is achieved) (Fransen & van Riel, 2009) (Fries, Spitz, 
Kraines, & Holman, 1980), DAS28-CRP(4). 
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6.2.1 
DAS28-CRP(4)  
The DAS28-CRP(4) is a composite score (ranging from 0-9.4) calculated using 
the results of the 28 joint subset of the 66/68 SJC/TJC, hs-CRP level (mg/L), and 
6XEMHFW¶V*OREDO$VVHVVPHQW-100 scale). The DAS28-CRP(4) is calculated 
using the following formula (DAS, 2013): 
0.56*sqrt(28TJC) + 0.28*sqrt(28SJC) + 0.36*ln(CRP+1) + 0.014* pt global 
VAS + 0.96. 
For DAS28-CRP(4), scores indicating high disease activity are > 5.1; low disease 
activity, < 3.2; and remission, < 2.6. 
 
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7 
SAFETY MEASUREMENTS 
Safety will be assessed by evaluating the incidence of and reason for 
discontinuations from study drug; TEAEs; ISRs; conversion of 
QuantiFERON®-TB Gold test to positive; changes in safety laboratory test, vital 
sign, 12-lead ECG, and physical examination findings; and immunogenicity 
(anti-CHS-0214 antibodies). 
A list of the analytes to be measured for the safety evaluation is found in 
Appendix I. Laboratory test results must be evaluated by the Investigator as to 
their clinical significance. Any laboratory value considered by the Investigator to 
be clinically significant should be considered an AE. 
7.1 
Adverse Events 
2QJRLQJ$(VIURPWKHVXEMHFW¶VLQYROYHPHQWLQ&+6-0214-02 or CHS-0214-04 
will continue to be followed in the OLSES. New AEs will be collected from the 
time the ICF is signed at the Week 0 Day 0 Visit through the Follow-up Visit 28 
days after the last dose of study drug. New TEAEs will be those starting with 
OLSES dosing (Week 0 Day 0). An AE is any unfavorable medical occurrence in 
a subject or clinical investigation subject administered a pharmaceutical product, 
which does not necessarily have to have a causal relationship with this treatment. 
An AE can therefore be any unfavorable and unintended sign, symptom, or 
disease temporally associated with the use of a medicinal (investigational) 
product, whether or not considered related to the medicinal (investigational) 
product. All AEs, including observed or suspected problems, complaints, or 
symptoms, are to be recorded on the appropriate eCRF. Documentation must be 
VXSSRUWHGE\DQHQWU\LQWKHVXEMHFW¶VVRXUFHGRFXPHQW(DFK$(LVWREH
evaluated for duration, severity, and causal relationship with the study drug or 
other factors. 
Whenever possible, a specific disease or syndrome rather than individual 
associated signs and symptoms should be identified by the Investigator and 
recorded on the eCRF. However, if an observed or reported sign or symptom is 
not considered a component of a specific disease or syndrome by the Investigator, 
it should be recorded as a separate AE on the eCRF. 
Any ongoing AE from the CHS-0214-02 study or the CHS-0214-04 study should 
continue to be followed as an AE in OLSES. 
Any clinically significant abnormal laboratory or other examination (e.g., ECG) 
findings that are detected at Week 48 of the CHS-0214-02 or CHS-0214-04 study 
or at any time during OLSES will be reported as an AE. The Investigator will 
exercise his or her medical and scientific judgment in deciding whether an 
abnormal laboratory finding or other abnormal assessment is clinically significant.  
The ISRs observed during examination of injection sites by study staff should be 
UHFRUGHGDV$(V7KH$(WHUP³,QMHFWLRQ6LWH5HDFWLRQ´ZLWKWKHJUDGHRI$(
consistent with the worst grade for any 1 of the characteristics of the ISR (pain, 
swelling, erythema, etc.) should be reported. 
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The ISRs reported by subjects will be recorded LQHDFKVXEMHFW¶VH-Diary for study 
drug received through Week 48 and will not be recorded as AEs unless also 
observed by study staff. 
7.1.1 
Unexpected Adverse Drug Reaction 
An unexpected adverse drug reaction is defined as an adverse reaction, the nature 
or severity of which is not consistent with the applicable product information 
(e.g., Investigator's Brochure for an unapproved investigational product or 
package insert/summary of product characteristics for an approved product). 
7.1.2 
Grading and Intensity of Adverse Events 
The Investigator will rate the intensity of each AE as mild, moderate, severe, or 
life threatening as outlined in the Guidance for Industry (FDA, 2007). 
Severity or Toxicity Grading: 
Grade 1: Mild ± An event that is usually transient in nature and generally does not 
interfere with activities. 
Grade 2: Moderate ± An event that is sufficiently discomforting to interfere with 
activities. 
Grade 3: Severe ± An event that is incapacitating, with inability to work or 
perform normal daily activity. 
Grade 4: Life Threatening ± An event that is potentially life threatening and 
generally requires emergency medical treatment or hospitalization. 
7.1.3 
Relationship to Study Drug 
The assessment of the relationship of an AE to the administration of study drug 
(yes, no) is a clinical decision based on all available information at the time of the 
completion of the eCRF. 
No (unrelated, not related, no relation): 
The time course between the administration of study drug and the occurrence or 
worsening of the AE rules out a causal relationship and another cause 
(concomitant drugs, therapies, complications, etc.) is suspected. 
Yes (related):  
The time course between administration of study drug and the occurrence or 
worsening of the AE is consistent with a causal relationship and no other cause 
can be identified (concomitant drugs, therapies, complications, etc.). 
The following factors should also be considered: 
x Temporal sequence from drug administration 
The event should occur after study drug is given. The length of time from 
drug exposure to event should be evaluated in the clinical context of the event. 
x Underlying, concomitant, intercurrent diseases 
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Each report should be evaluated in the context of the natural history and 
course of the disease being treated and any other disease the subject may have. 
x Concomitant medication 
Other drugs the subject is taking or the treatment the subject receives should 
be examined to determine whether any of them might be recognized to cause 
the event in question. 
x Known response pattern for this class of drug 
Clinical and/or preclinical data may indicate whether a particular response is 
likely to be a class effect. 
x Exposure to physical and/or mental stresses 
Exposure to stress might induce adverse changes in the recipient and provide a 
logical and better explanation for the event. 
x Pharmacology and PK of the test drug  
Known properties (absorption, distribution, metabolism, and excretion) of the 
test drug should be considered. 
Unexpected Adverse Event²An unexpected AE is an experience not previously 
reported or an AE that occurs with specificity, severity, or frequency that is not 
FRQVLVWHQWZLWKWKHFXUUHQW,QYHVWLJDWRU¶V%URFKXUH 
7.1.4 
Serious Adverse Event Reporting  
An SAE is any untoward medical occurrence that, at any dose: 
x Results in death; 
x Is life-threatening; 
NOTE: An AE or adverse reaction is FRQVLGHUHG³OLIH-WKUHDWHQLQJ´LILQ
the view of either the Investigator or Sponsor, its occurrence places the 
subject at immediate risk of death. It does not include an event that, had it 
occurred in a more severe form, might have caused death. 
x Requires hospitalization or prolongation of an existing hospitalization; 
NOTE: Any hospital admission with at least 1 overnight stay will be 
considered an inpatient hospitalization. An emergency room visit without 
hospital admission will not be recorded as an SAE under this criterion, nor 
will hospitalization for a procedure planned or scheduled before signing of 
the ICF. However, unexpected complications and/or prolongation of 
hospitalization that occur during elective surgery should be recorded as 
AEs and assessed for seriousness. 
Admission to the hospital for social or situational reasons (i.e., no place to 
stay, live too far away to come for hospital visits) will not be considered 
inpatient hospitalizations. 
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x Results in a disability/incapacity; 
x Is a congenital anomaly/birth defect; or 
x Is an important medical event.  
NOTE: Medical or scientific judgment should be exercised in deciding 
whether reporting is appropriate in other situations, such as important 
medical events that may not be immediately life-threatening or result in 
death or hospitalization but may jeopardize the subject or may require 
medical or surgical intervention to prevent 1 of the other outcomes listed 
in the above definition. These should also be considered serious. Examples 
of such events are invasive or malignant cancers, intensive treatment in an 
emergency room or at home for allergic bronchospasm, blood dyscrasias 
or convulsions that do not result in hospitalization, development of drug 
dependency, or drug abuse. 
7.1.5 
Adverse Event Outcome 
The Investigator will record the outcome of each AE as follows:  
x Resolved  
x Resolved with sequelae  
x Ongoing  
x Death 
x Unknown 
7.1.6 
Serious Adverse Event Reporting ± Procedure for Investigators 
All SAEs occurring from the Week 0 Day 0 Visit through 28 days following the 
last administration of study drug must be reported to Medpace Clinical Safety 
within 24 hours of the knowledge of the occurrence. All SAEs occurring after the 
28-day follow-up period, which the Investigator considers related to study drug, 
must also be reported to Medpace. 
To report the SAE, the Investigator will complete the SAE form electronically in 
the electronic data capture (EDC) system for the study. When the form is 
completed, Medpace Safety personnel will be notified electronically and will 
retrieve the form. If the event meets serious criteria and it is not possible to access 
the EDC system, an e-mail should be sent to the e-mail address listed below or a 
call made to the Medpace SAE hotline (phone number listed below), and fax or e-
mail the completed paper SAE form to Medpace (fax number/e-mail listed below) 
within 24 hours of awareness. When the EDC system becomes available, the SAE 
information must be entered within 24 hours of the system becoming available.  
The Investigator will be requested to supply detailed information regarding the 
event. The SAE must also be reported to the reviewing IRB/EC per IRB/EC 
requirements and a copy of that report must be retained at the investigative site 
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and filed in the Investigator Site File in accordance with the requirements of that 
institution. 
Safety Contact Information:  
Medpace Clinical Safety 
Medpace 
5375 Medpace Way 
Cincinnati, Ohio 45227 
USA 
Medpace SAE ± USA: 
Tel: +1-800-730-5779, ext. 2999 or +1-513-579-9911, ext. 2999 
Fax: +1-866-336-5320 or +1-513-579-0444 
e-mail: medpace-safetynotification@medpace.com  
Medpace SAE hotline ± Europe:  
Telephone: +49 89 89 55 718 44 
Fax: +49 89 89 55 718 104 
e-mail: EUsafetynotification@medpace.com 
Country specific toll-free numbers will be provided to the Investigators. 
7.1.7 
Serious Adverse Events Follow-up 
The Investigator must continue to follow the subject until the SAE has subsided 
or until the condition becomes chronic in nature, stabilizes (in the case of 
persistent impairment) or the subject dies. 
Within 24 hours of receipt of follow-up information, the Investigator must update 
the SAE form electronically in the EDC system for the study and submit any 
supporting documentation (e.g., subject discharge summary or autopsy reports) to 
Medpace Safety personnel via fax or e-mail. If it is not possible to access the EDC 
system, refer to the procedures outlined above (see Section 7.1.6) for initial 
reporting of SAEs.  
7.1.8 
Serious Adverse Event Reporting-Procedure for Sponsor 
The Sponsor will send copies of reports of SAEs and/or suspected unexpected 
serious adverse reactions (SUSARs) as required to regulatory authorities, 
Investigators/institutions, and IRBs/ECs in compliance with all reporting 
requirements according to local regulations and Good Clinical Practice (GCP). 
For all active Investigators located in Europe, the Sponsor or designee will be 
responsible for reporting SUSARs and any other applicable SAEs to regulatory 
authorities including the European Medicines Agency, Investigators, and central 
or local ECs, as applicable, in accordance with national regulations in the 
countries where the study is conducted. SUSARs will be submitted within 7 days 
for fatal and life-threatening events and within 15 days for other serious events, 
unless otherwise required by national regulations. 
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7.2 
Physical Examination 
An abbreviated physical examination will be performed at each visit and will 
consist of respiratory, gastrointestinal, musculoskeletal, and cardiovascular 
system evaluations and evaluations of other physical conditions of note. 
Study drug injection sites will be assessed at each study visit. An ISR observed 
during the examination of injection sites at each visit should be recorded on the 
,65ZRUNVKHHWDQGEHUHSRUWHGDVDQ$(ZLWKWKH$(WHUP³Injection Site 
Reaction´DQGWKHJUDGHRI$(FRQVLVWHQWZLWKWKHZRUVWJUDGHIRUDQ\of the 
characteristics of the ISR (pain, swelling, erythema, etc.).  
Weight (kg) will be measured at Week 0 Day 0 (considered to correspond to the 
Week 48 Visit of the parent study). Subjects should be weighed wearing indoor, 
daytime clothing with no shoes. Before being weighed, subjects should empty 
their bladders.  
In addition, weight will also be measured at the Follow-up Visit 28 days after the 
last dose of study drug for all subjects.  
7.3 
Vital Signs 
Vital signs, including blood pressure (arm or wrist cuff are acceptable), heart rate, 
respiratory rate, and body temperature (C°) (using an oral, aural, or axillary 
thermometer), will be measured at Weeks 0 (as the Week 48 assessment of the 
parent study), 4, 12, 24, 36, and 48 as well as at the Follow-up Visit 28 days after 
the last dose of study drug for all subjects. In addition, for subjects in Japan who 
continue participation in OLSES beyond Week 48, vital signs will be measured at 
each quarterly visit after Week 48. The following standardized processes will be 
used: 
x The subject should sit for 5 minutes with feet flat on the floor and his/her 
measurement arm supported so that the midpoint of the manometer cuff is 
at heart level; 
x A mercury sphygmomanometer or automatic blood pressure device with 
an appropriately sized cuff with the bladder centered over the brachial 
artery (NOTE: a wrist cuff centered over the radial artery is also 
acceptable) should be used; 
x Blood pressure and heart rate should then be measured and recorded. 
Blood pressure should be recorded to the nearest 2 mm Hg mark on the 
manometer or to the nearest whole number on an automatic device. 
7.4 
Electrocardiogram   
A resting 12-lead ECG will be performed after the subject has been in the supine 
position for at least 10 minutes. The ECG will include all 12 standard leads and 
will be recorded at a paper speed of 25 mm/sec. Standard ECG parameters will be 
measured, including RR, PR, QTc intervals, and QRS duration. All ECGs must be 
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evaluated by a qualified physician for the presence of abnormalities. ECGs will be 
performed at Week 0 Day 0 (considered to correspond to the Week 48 Visit of the 
parent study) and at Week 48 or for subjects terminating the study at the Follow-
up Visit 28 days after the last dose of study drug. In addition, for subjects in Japan 
who continue participation in OLSES beyond Week 48, ECGs will be performed 
every 12 months after Week 48. 
7.5 
Pregnancy Reporting 
If a subject becomes pregnant during the study or within 28 days of discontinuing 
study drug, the Investigator should report the pregnancy to Medpace Clinical 
Safety within 24 hours of being notified (see Section 7.1.6 for contact 
information). Medpace Clinical Safety will then forward the Exposure In Utero 
form to the Investigator for completion. 
A subject becoming pregnant while on study medication will immediately be 
withdrawn from the study drug and Follow-up Visit study procedures will be 
performed 28 days after the last dose of study drug. 
The subject should be followed by the Investigator until completion of the 
pregnancy. If the pregnancy ends for any reason before the anticipated date, the 
Investigator should notify the Sponsor. At the completion of the pregnancy, the 
Investigator will document the outcome of the pregnancy. If the outcome of the 
pregnancy meets the criteria for immediate classification as an SAE 
(i.e., postpartum complication, spontaneous abortion, stillbirth, neonatal death, or 
congenital anomaly), the Investigator should follow the procedures for reporting 
an SAE. 
7.6 
Anti-Drug Antibody Assessment  
Antibodies to CHS-0214 will be measured in the sera of subjects enrolled in this 
study at each study visit through Week 48 and at the Follow-up Visit 28 days after 
the last dose of study drug. In addition, for subjects in Japan who continue 
participation in OLSES beyond Week 48, ADA testing will be performed every 
6 months after Week 48. The immunogenicity testing will be performed using 
validated electrochemiluminescent (ECL) ADA assays. Presence of ADA based 
on this confirmatory assay will be assessed and compared with published data 
(Amgen, 2015). A cell-based neutralizing anti-drug antibody (NAB) assay is 
under development. NAB may be evaluated for samples testing positive in the 
confirmatory ADA assay and for subjects with loss of clinical response. 
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7.7 
Serum Retention Samples 
Serum samples will be collected from all subjects prior to dosing at each study 
visit through Week 48 and at the Follow-up Visit 28 days after the last dose of 
study drug. In addition, for subjects in Japan who continue participation in 
OLSES beyond Week 48, SRS samples will be collected every 6 months after 
Week 48. The exact date and time of each sample collection will be recorded. 
Serum samples may be used to evaluate an AE or loss of response to study drug, 
to confirm compliance to the dosing regimen, or for tests required by regulatory 
agencies. No population PK assessment is planned for these samples. These 
samples will not be used to assess biologic or genetic markers of disease. All of 
these samples will be stored at MRL and may be transferred to Charles River 
Laboratories or other reference laboratory for analysis at the request of the 
Sponsor. All retained samples and remnants of retained samples will be destroyed 
2 years after completion of the study (database lock).  
7.8 
Sample Collection Procedures and Bioanalytical Methods  
Instructions for sample collection and handling are included in the laboratory 
manual. All clinical laboratory evaluations (e.g., hematology, chemistry, 
urinalysis, QuantiFERON®-TB Gold test, hs-CRP) will be performed at a central 
clinical laboratory throughout the study. The ADA and PK evaluations will be 
performed at a central bioanalytical laboratory. In the event that immediate 
laboratory analyses are required to assess an AE, a local laboratory may be used; 
however, duplicate blood sample(s) should also be sent to the central laboratory. 
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8 
PLANNED ANALYSES 
8.1 
Analysis Populations 
8.1.1 
Enrolled Subject Population  
The Enrolled Subject Population will include all subjects enrolled from the parent 
CHS-0214-02 Study or CHS-0214-04 Study.  
8.1.2 
Full Analysis Population 
The Full Analysis Population (FAP) will include all enrolled subjects who receive 
1 or more doses of study drug in this study. The FAP is the efficacy analysis 
population. 
8.1.3 
Safety Population 
The Safety Population is defined the same as the FAP Population. The Safety 
Population is the safety analysis population. 
8.1.4 
Pharmacokinetic Population 
The PK Concentration Population will include any subjects with serum PK data 
measured because of AEs or loss of response or to fulfill a regulatory 
requirement.  
8.1.5 
Per-Protocol Population 
The Per-Protocol Population will include all subjects who complete the 48-week 
treatment period and have no protocol violations that may affect the interpretation 
of efficacy endpoints. These violations will be identified by the Sponsor prior to 
database lock. 
8.1.6 
Rheumatoid Arthritis Population 
The RA Population will include all subjects with RA who complete the 
CHS-0214-02 study, meet the entry criteria for this study, receive at least 1 dose 
of study drug of CHS-0214 and have any efficacy measurements. 
8.1.7 
Japanese Rheumatoid Arthritis Population  
The Japanese RA Population will include all subjects with RA who complete the 
CHS-0214-02 study at Japanese sites, meet the entry criteria for this study, 
receive at least 1 dose of study drug of CHS-0214 and have any efficacy 
measurements. 
8.1.8 
Plaque Psoriasis Population 
The PsO Population will include all subjects with PsO who complete the 
CHS-0214-04 study, meet the entry criteria for this study, receive at least 1 dose 
of study drug of CHS-0214 and have any efficacy measurements. 
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8.2 
Statistical Methods  
Continuous variables will be summarized using descriptive statistics (N, mean, 
standard deviation, median, minimum, and maximum, where appropriate). 
Discrete variables will be summarized using frequency counts and percentages. 
8.2.1 
Demographic and Baseline Characteristics 
Descriptive summaries of demographic and Baseline characteristics will be 
presented. A detailed description of subject disposition will also be provided. 
8.2.2 
Efficacy Analysis 
8.2.2.1 
 Rheumatoid Arthritis 
8.2.2.1.1 
 
Primary Endpoint 
Proportion of subjects with durability of response will be calculated in the RA 
Population, Per-Protocol RA Population, Japanese RA Population, and 
Per-Protocol Japanese RA Population.  
Durability of response is defined as the maintenance of the 20% improvement in 
the ACR score (ACR20) (or greater) at Week 4, Week 12 and every 3 months 
thereafter during the study. The baseline values to assess the ACR20 during this 
study will be the same baseline value used to assess the ACR20 during the parent 
study (i.e., the Week 0 assessment in the parent study). 
8.2.2.1.2 
 
Secondary Endpoints 
The secondary endpoints include DAS28-CRP (4) <3.2 (low disease activity) 
assessed at all visits and DAS28-CRP (4) <2.6 (remission) assessed on all visits 
after DAS28-CRP (4) <2.6 is achieved for rate calculations. 
8.2.2.2 
 Plaque Psoriasis 
8.2.2.2.1 
 
Primary Endpoint 
Proportion of subjects with durability of response will be calculated in the PsO 
Population and Per-Protocol PsO Population. Durability of response is defined as 
the maintenance of the 50% improvement in Psoriasis Area and Severity Index 
[PASI-50] (or greater) at Week 4, Week 12 and every 3 months thereafter during 
the study. The baseline values to assess the PASI-50 during this study will be the 
same baseline value used to assess the PASI-50 during the parent study (i.e., the 
Week 0 assessment in the parent study).  
8.2.3 
Safety Analysis 
Safety data will be summarized and listed. No inferential statistical analysis of the 
safety data is planned. All safety summaries and listings will be generated using 
the Safety Population.  
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All AEs will be coded and classified by system organ class and preferred term 
using the Medical Dictionary for Regulatory Activities (MedDRA). Data 
summaries will be based upon TEAEs. All TEAEs will be listed and summarized. 
A summary of all drug-related AEs will also be generated. If there are any SAEs 
or any AEs leading to the discontinuation of study drug, a separate data listing 
will be generated. Events recorded after enrollment (from the time of informed 
consent) but before treatment initiation will be listed separately. 
Clinical laboratory data will be summarized descriptively. The change from 
pre-dose to the end of the study will also be summarized. For selected laboratory 
assessments, the frequency of abnormal values may be tabulated, if appropriate. 
Prior and concomitant medications will be coded with the World Health 
Organization Drug Dictionary (WHO-DD) and listed. All concomitant medication 
taken after first dosing of study drug will be summarized. 
Vital signs and ECG data will be summarized and listed by visit. All other safety 
data will be listed. 
The safety profile of the subgroup of Japanese subjects with RA will be explored. 
8.2.4 
Immunogenicity Analysis 
The immunogenicity of CHS-0214 will be evaluated using a validated ECL assay 
for the presence of ADA. A cell-based assay may be used to assess whether the 
confirmed ADAs on ELISA are NABs. Immunogenicity data will be summarized 
and compared to the literature for immunogenicity of Enbrel. 
8.2.5 
Pharmacokinetic Analysis 
No overall population PK analysis is planned. Serum samples will be obtained at 
each study visit and may be used to evaluate an AE or loss of response to study 
drug, to confirm compliance to the dosing regimen, or used for tests required by 
regulatory agencies or to fulfill a regulatory requirement.  
 
8.2.6 
Determination of Sample Size 
No formal calculation of sample size is necessary as this is an extension study.  
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9 
DATA SAFETY MONITORING BOARD 
A Data Safety Monitoring Board (DSMB) will be convened to review 
accumulating data and monitor the safety of subjects over the course of the study.  
In addition to periodic reviews of the accumulating safety data (including 
unexpected AE data), the DSMB will review efficacy results. The Sponsor may 
discontinue the study should the results of the analysis indicate that either parent 
study (CHS-0214-02 or CHS-0214-04) did not meet its primary efficacy 
endpoints.- Additional information may be found in the DSMB charter. 
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10 
DATA MANAGEMENT 
10.1 
Data Handling 
Data will be recorded at the site on source documents and entered into eCRFs. 
The Clinical Research Associate (CRA) assigned to the site will verify data 
recorded in the eCRF system with source documents. All corrections or changes 
made to any study data must be appropriately tracked in an audit trail in the eCRF 
system. The eCRFs will be considered complete when all missing, incorrect, 
and/or inconsistent data have been accounted for.  
10.2 
Computer Systems 
Data will be processed using a validated computer system conforming to 
regulatory requirements. 
10.3 
Data Entry 
Data must be recorded using the eCRF system. All study site personnel must log 
into the system using their secure usernames and passwords in order to enter, 
review, or correct study data. These procedures must comply with 21 Code of 
Federal Regulations (CFR) Part 11 and local regulation. All passwords will be 
strictly confidential. 
10.4 
Medical Information Coding 
For medical information, the following thesauri will be used: 
x MedDRA for AEs and 
x WHO-DD for concomitant medications. 
10.5 
Data Validation 
Validation checks programmed within the eCRF system, as well as supplemental 
validation performed via review of the downloaded data, will be applied to the 
data in order to ensure accurate, consistent, and reliable data. Data identified as 
erroneous and data that are missing will be referred to the investigative site for 
resolution through data queries. 
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11 
STUDY ADMINISTRATION 
11.1 
Regulatory and Ethical Considerations 
11.1.1 
Regulatory Authority Approval 
This study will be conducted in accordance with GCP (an international ethical and 
scientific quality standard for designing, conducting, recording, and reporting 
studies that involve human subjects), the protocol, and any other applicable 
regulatory requirements. Such compliance provides public assurance that the 
rights, safety, and well-being of study subjects are protected, consistent with the 
principles that have their origin in the Declaration of Helsinki, and that the 
clinical study data are credible.  
11.1.2 
Ethics Approval 
It is the responsibility of the Investigator or the head of the medical institution to 
ensure that the appropriate IRB or EC has reviewed and approved this protocol 
prior to initiating the study.  
The IRB/EC must also review and aSSURYHWKHLQYHVWLJDWLYHVLWH¶V,&)VDQGRWKHU
written information provided to the subject.  
If the protocol or the ICFs are amended during the study, per local regulations, the 
Investigator or the head of the medical institution is responsible for ensuring that 
the IRB/EC has reviewed and approved these amended documents. In addition, 
IRB/EC approval of the amended documents must be obtained before 
implementation and before new subjects are consented to participate in the study 
using the amended version of an ICF. In Japan, the head of the medical institution 
must provide the Investigator and Sponsor with the dated IRB approval of the 
amended documents as soon as available; in the rest of the world, the Investigator 
is required to provide the Sponsor with the dated IRB/EC approval of the 
amended documents as soon as available. 
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11.1.3 
Subject Informed Consent 
Prior to study entry and, for subjects in Japan with RA (in order to continue 
participation in OLSES beyond Week 48), on or before their Week 48 Visit, the 
Investigator, or a qualified person designated by the Investigator, will explain the 
nature, purpose, benefits, and risks of participation or continued participation in 
WKHVWXG\WRHDFKVXEMHFWVXEMHFW¶VOHJDOO\DFFHSWDEOHUHSUHVHQWDWLYHRULPSDUWLDO
witness. Written informed consent must be obtained prior to the subject entering 
the study (before initiation of any study-related procedure and administration of 
the study medication) and prior to continuing participation in the study beyond 
Week 48 using an ICF specific for RA or for PsO as appropriate. Sufficient time 
will be allowed to discuss any questions raised by the subject. If the consenting 
process is conducted by an Investigator designee, then the subject is offered the 
opportunity to discuss any of his/her questions or concerns regarding informed 
consent with an Investigator. The Investigator or designated staff will document 
this process in the study records. An ICF must be signed by all subjects. The 
process of obtaining the informed consent will be in compliance with all federal 
regulations, International Conference on Harmonisation (ICH) requirements (ICH 
E6 4.8) and local laws. 
If an ICF is amended during the study, the Investigator must follow all applicable 
regulatory requirements pertaining to approval of the amended ICF by the 
IRB/EC. The investigative site must use the amended ICF for all new subjects and 
repeat the consent process with the amended ICF for any ongoing subjects if 
applicable. 
11.1.4 
Investigator Reporting Requirements 
In accordance with applicable regulatory requirements, the Investigator is solely 
obligated to inform the IRB/EC of progress of the study and notify the IRB/EC of 
study closure. The Investigator must also provide the Sponsor with copies of all 
IRB/EC correspondence that relate to study approvals, updates, or changes. The 
,QYHVWLJDWRUPXVWDOVRIRUZDUGDOO,5%(&UHQHZDOVWRWKH6SRQVRURU6SRQVRU¶V
representative. 
11.2 
Study Monitoring 
In accordance with applicable regulations, GCP, and the procedures of the 
Sponsor and its designees, the CRA will periodically contact the investigative 
site, including conducting on-site visits. 
During these contacts, the monitoring activities will include: 
x Checking and assessing the progress of the study; 
x Reviewing study data collected to date for completeness and accuracy; 
x &RQGXFWLQJVRXUFHGRFXPHQWYHULILFDWLRQVE\UHYLHZLQJHDFKVXEMHFW¶V
eCRF against source documents; and  
x Identifying any issues and addressing resolutions. 
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These activities will be done in order to verify that the: 
x Data are authentic, accurate, and complete; 
x Safety and rights of the subject are being protected; and 
x Study is conducted in accordance with the currently approved protocol 
(and any amendments), GCP, and all applicable regulatory requirements. 
In addition to contacts during the study, the CRA will contact the investigative 
site prior to the start of the study to discuss the protocol and data collection 
procedures with site personnel. 
A Data and Safety Monitoring Board will review safety data (e.g., AEs and SAEs, 
laboratory data, and ECG assessments) at regular time points while the clinical 
trial is ongoing. 
11.3 
Quality Control 
Medpace (in Japan, CMIC), as an agent for the Sponsor, will perform quality 
control and quality assurance checks. Before the enrollment of any subject in this 
study, Medpace (in Japan, CMIC) personnel will review and provide training as 
needed to the site Investigator and site personnel regarding the following: 
SURWRFRO,QYHVWLJDWRU¶V%URFKXUHH&5)VDQGSURFHGXUHVIRUWKHLUFRPSOHWLRQ
informed consent process, procedures for reporting SAEs, and subject enrollment 
and drug tracking requirements. Site visits will be performed by the Sponsor 
and/or Medpace (in Japan, CMIC) CRA periodically throughout the study. During 
these visits, information recorded on the eCRFs will be verified against source 
documents, and requests for clarification or correction may be made. The eCRFs 
will be reviewed by the CRA for safety information, legibility, completeness, 
accuracy, and logical consistency. Computer programs that identify data 
inconsistencies may be used to help monitor the clinical study. 
If necessary, requests for clarification or correction will be sent to Investigators 
via data queries. 
11.4 
Study Initiation 
Before the start of this study, the following documents must be on file with 
Sponsor or a Sponsor representative: 
x All regulatory documentation as required by local and national 
regulations, including United States Food and Drug Administration (FDA) 
Form 1572 and Financial Disclosure Forms (completed by the Investigator 
with the assistance of the Sponsor); 
x Current curricula vitae and medical licenses (or equivalent) of the 
Principal Investigator and all Sub-investigators; 
x IRB/EC membership list and/or Department of Health and Human 
Services number, where applicable; 
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x Written documentation of IRB/EC approval of protocol (identified by 
Sponsor protocol number or title and date of approval) and ICFs 
(identified by Sponsor protocol number or title and date of approval); 
x A copy of the IRB/EC-approved ICFs. ICFs must be reviewed and 
approved by Sponsor prior to submission to the IRB/EC; 
x Current laboratory certification of the laboratory performing the analysis 
as well as current normal laboratory ranges for all laboratory tests; 
x A signed Clinical Site Agreement. 
11.5 
Study Termination 
Upon completion of the study, the following activities, when applicable, must be 
conducted by the CRA and the Investigator: 
x Return of all electronic and any non-electronic study data (e.g., copies of 
ECG tracings) to Medpace, Inc. if requested by the Sponsor; 
x Data clarifications and/or resolutions; 
x Accounting, reconciliation, and final disposition of used and unused study 
drug; and 
x Review of site study records for completeness. 
In addition, the Sponsor reserves the right to temporarily suspend or prematurely 
terminate this study for any reason. 
If the study is suspended or terminated for safety reasons, the Sponsor will 
promptly inform the Investigator or head of the medical institution, and will also 
inform the regulatory authorities of the suspension or termination of the study and 
the reasons for the action. The Investigator or head of the medical institution is 
responsible for promptly informing the IRB/EC and providing the reasons for the 
suspension or termination of the study. 
11.6 
Site Termination 
The Sponsor has the right to terminate a study site at any time for various reasons. 
Study termination and follow-up will be performed in compliance with the 
conditions set forth in 21 CFR Parts 312.50 and 312.56 and local regulation. If the 
study is prematurely terminated, all study data must be returned if requested by 
the Sponsor. 
11.7 
Records Retention 
Records of subjects, source documents, monitoring visit logs, inventories of study 
product, regulatory documents, and other Sponsor correspondence pertaining to 
the study must be kept in the appropriate study files at the site. Source documents 
include all recordings and observations or notations of clinical activities and all 
reports and records necessary for the evaluation and reconstruction of the clinical 
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study. These records will be retained in a secure file for the period required by the 
institution or site policy but not less than 15 years. Prior to the transfer or 
destruction of these records, the Sponsor must be notified in writing and be given 
the opportunity to further store such records. 
11.8 
Confidentiality of Information 
6XEMHFWV¶QDPHVZLOOUHPDLQFRQILGHQWLDODQGZLOOQRWEHLQFOXGHGLQWKHGDWDEDVH
All study findings will be stored in electronic databases. The Investigators will 
maintain subject identification lists (subject and treatment numbers with the 
corresponding subject names) to enable records to be identified. 
11.9 
Publication Policy 
The Sponsor is responsible for the final clinical study report prepared according to 
the ICH guideline on structure and contents of clinical study reports. A final 
clinical study report will be prepared and include results for any subject who has 
signed an ICF, regardless of whether the study is completed or prematurely 
terminated. If appropriate, an abbreviated report may be prepared. The clinical 
study report will be in compliance with any applicable regulatory requirements 
and national laws and will be in English. 
All unpublished information given to the Investigators by the Sponsor shall not be 
published or disclosed to a third party without the prior written consent of the 
Sponsor. 
When the Sponsor or designee generates reports from the data collected in this 
study for presentation to regulatory authorities, drafts may be circulated to the 
Investigators for comments and suggestions. An endorsement of the final report 
will be sought from the Investigators when required by local regulatory agencies. 
No patent application(s) based on the results of the study may be made by the 
Investigators nor may assistance be given to any third party to make such an 
application without the written authorization of Sponsor. 
The Principal Investigator or anyone else working on the study may not submit 
any publications, papers, abstracts, or other written materials or oral presentations 
related to the study without written permission from the Sponsor.  
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11.10 
Address List 
11.10.1 
Sponsors 
Coherus BioSciences, Inc.  
 
 
Daiichi Sankyo Co., Ltd. 
333 Twin Dolphin Drive 
 
 
3-5-1 Nihonbashi-honcho 
Suite 600 
 
 
Chuo-Ku  
Redwood City, CA 94065 
 
 
Tokyo 103-8426 
USA 
 
 
Tel: +81 3-6225-1111  
Tel: +1 650-649-3530 
 
 
Fax: +81 3-6225-1900 
Fax: +1 866-491-7350  
 
 
 
 
11.10.2 
Contract Research Organization 
Medpace, Inc.  
5375 Medpace Way 
Cincinnati, OH 45227 
USA 
Tel: +1 513-579-9911 
Fax: +1 513-579-0444 
 
Japan Contract Research Organization: 
CMIC Co., Ltd. 
Hamamatsucho Bldg, 1-1-1 Shibaura, Minato-ku, 
Tokyo 105-0023 
Japan 
Tel: +81 3-6779-8111 
Fax: +81 3-5745-7075 
http://www.cmic-holdings.co.jp/corporate/group/cmic.shtml 
11.10.3 
Global Drug Safety 
Medpace Clinical Safety 
5375 Medpace Way 
Cincinnati, OH 45227 
USA 
Tel: +1 800-730-5779, ext. 2999 
Fax: +1 513-579-0444 
medpace-safetynotification@medpace.com  
 
Additional safety contact information is provided in Section 7.1.6. 
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11.10.4 
Central Laboratory 
Medpace Reference Laboratories 
5365 Medpace Way 
Cincinnati, OH 45227 
USA 
Tel: +1 513-366-3270 
Fax: +1 513-366-327 
 
Medpace Reference Laboratories 
85 Science Park Drive 
The Cavendish 
Singapore Science Park  
Singapore 118259 
Singapore 
 
Medpace Reference Laboratories BVBA  
Technologielaan 19 
3001 Heverlee (Belgium)  
Tel: +32 16 407775  
Fax: +32 16 407781 
 
11.10.5 
Bioanalytical Laboratory 
Charles River Laboratories Preclinical Services 
6995 Longley Lane  
Reno, NV 89511 
USA 
Tel: +1 775-682-2000 
 
 
 
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12 
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Schiff, M., Yu, E., Weinblatt, M., Moreland, L., Genovese, M., White, B., . . . Woolley, J. 
(2006). Long-term experience with etanercept in the treatment of rheumatoid arthritis 
in elderly and younger patients: patient-reported outcomes from multiple controlled 
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Kvien, T. (2010, May 5). EULAR recommendations for the management of rheumatoid 
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Weinblatt, M., Kremer, J., Bankhurst, A., Bulpitt, K., Fleischmann, R., Fox, R., . . . Burge, D. 
(1999). A trial of etanercept, a recombinant tumor necrosis factor receptor:Fc fusion 
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Validation of the 28-joint Disease Activity Score (DAS28) and European League 
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APPENDIX A: AMERICAN COLLEGE OF RHEUMATOLOGY/EUROPEAN 
LEAGUE AGAINST RHEUMATISM CRITERIA FOR 
RHEUMATOID ARTHRITIS 
The American College of Rheumatology (ACR)/European League Against Rheumatism 
(EULAR) criteria for RA (2010) are listed below. These criteria may also be accessed 
electronically at the following web address: 
http://www.rheumatology.org/practice/clinical/classification/ra/ra_2010.asp. 
 
Score 
Target population (Who should be tested?): Subjects who  
1. 
have at least 1 joint with definite clinical synovitis (swelling)* 
2. 
with the synovitis not better explained by another disease 
  
Classification criteria for RA (score-based algorithm: add score of categories A±D; 
DVFRUHRI 6/10 is needed for classification of a subject as having definite RA)Á 
  
A. Joint involvement § 
  
1 large joint¶ 
0 
2-10 large joints 
1 
1-3 small joints (with or without involvement of large joints)# 
2 
4-10 small joints (with or without involvement of large joints) 
3 
> 10 joints (at least 1 small joint)** 
5 
B. Serology (at least 1 test result is needed for classification) 
  
Negative RF and negative ACPA 
0 
Low-positive RF or low-positive ACPA 
2 
High-positive RF or high-positive ACPA 
3 
C. Acute-phase reactants (at least 1 test result is needed for classification)ÁÁ 
  
Normal CRP and normal ESR 
0 
Abnormal CRP or abnormal ESR 
1 
D. Duration of symptoms§§ 
  
< 6 weeks 
0 
 6 weeks 
1 
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'HVFULSWLRQRI5KHXPDWRLG$UWKULWLV3DUDPHWHUV 
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 6WXG\'D\DQG9LVLW:LQGRZV 
 +DQGOLQJRI0LVVLQJ'DWD 
 6HQVLWLYLW\$QDO\VHV6XEJURXSVDQG&RYDULDWHV 
 6DIHW\$QDO\VHV 
 ,QWHULP$QDO\VLV 
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6XPPDU\7DEOHV/LVWLQJVDQG)LJXUHV 
 *HQHUDO&RQYHQWLRQV 
 6XEMHFW'LVSRVLWLRQDQG7UHDWPHQW 
 3URWRFRO'HYLDWLRQV 
 6WXG\7UHDWPHQWDQG&RPSOLDQFH 
 'HPRJUDSKLFVDQG%DVHOLQH&KDUDFWHULVWLFV 
 3ULRUDQG&RQFRPLWDQW0HGLFDWLRQV 
 (IILFDF\3DUDPHWHUV 
 
5KHXPDWRLG$UWKULWLV3DUDPHWHUV 
 
3VRULDVLV3DUDPHWHUV 
 6DIHW\3DUDPHWHUV 
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7UHDWPHQWHPHUJHQW$GYHUVH(YHQWV 
 
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,PPXQRORJ\'DWD$QDO\VLVDQG$QWL'UXJ$QWLERGLHV 
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9LWDO6LJQV 
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 
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6XEMHFW5HSRUWHG,QMHFWLRQ6LWH5HDFWLRQV 
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3URWRFRODQG6$3$PHQGPHQWVDQG'HYLDWLRQVIURPWKH3URWRFRO 
 3URWRFRO$PHQGPHQWV 
 6$3$PHQGPHQWV 
 5HPRYDORIVXEJURXSDQDO\VLVE\$XWR,QMHFWRUXVDJHQHYHULQFRUSRUDWHGLQWULDO'HYLDWLRQV
IURPWKH3URWRFRO 
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$SSURYDO6KHHW 
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7DEOH%DVHOLQHDQG'LVSRVLWLRQ3DUDPHWHUV 
7DEOH(IILFDF\3DUDPHWHUV 
7DEOH6DIHW\3DUDPHWHUV 
7DEOH+$4',³DLGVRUGHYLFHVDQGKHOSIURPDQRWKHUSHUVRQ,WHPV 
7DEOH$QDO\VLV:LQGRZV 
7DEOH6FKHGXOHRI3URFHGXUHVIRU6XEMHFWVZLWK5KHXPDWRLG$UWKULWLV 
7DEOH/LYHU)XQFWLRQ3DUDPHWHU&7&$(*UDGHV 
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EH\RQG:HHNDQGUHFHLYHVWXG\GUXJXQWLOPDUNHWLQJDSSURYDOEHJLQQLQJDW:HHNZLWKTXDUWHUO\
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1.1 Objectives 
7KHREMHFWLYHRIWKLVVWXG\LVWRHYDOXDWHWKHORQJHUWHUPVDIHW\DQGGXUDELOLW\RIUHVSRQVHRIVXEMHFWVZKR
FRPSOHWHGZHHNVRIHYDOXDWLRQVLQWKHFRQILUPDWRU\VDIHW\DQGHIILFDF\VWXGLHV&+6RU
&+6HYDOXDWLQJ&+6LQ5$DQGSODTXH3V2UHVSHFWLYHO\ 
1.2 Study Design 
7KLVLVDQRSHQODEHOVDIHW\H[WHQVLRQVWXG\6XEMHFWVFRPSOHWLQJWKHZHHNHYDOXDWLRQLQWKHFOLQLFDO
VWXGLHV&+6RU&+6PD\EHHOLJLEOHWRHQUROOLQWRWKLVVWXG\DQGUHFHLYHRSHQODEHO
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VXSSOLHGLQDSUHILOOHGV\ULQJH6XEMHFWVZLOOEHHYDOXDWHGDWPRQWKDQGPRQWKVIROORZLQJHQUROOPHQW
DQGHYHU\PRQWKVWKHUHDIWHUIRUVDIHW\LQFOXGLQJLPPXQRJHQLFLW\DQGGXUDELOLW\RIUHVSRQVH 
7RTXDOLI\IRUWKHVWXG\VXEMHFWVIURPVWXG\&+6PXVWFRPSOHWHWKHVWXG\WKURXJK:HHN
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FULWHULD$&56XEMHFWVIURPVWXG\&+6PXVWFRPSOHWHWKHVWXG\WKURXJK:HHNDQGKDYH
DWOHDVWLPSURYHPHQWIURPEDVHOLQHLQ3VRULDVLV$UHDDQG6HYHULW\,QGH[3$6,
1.3  Method of Assigning Subjects to Treatment Groups 
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1.4 Blinding 
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1.5 Decision Rules 
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VXPPDUL]HHIILFDF\DQGVDIHW\SDUDPHWHUV
1.6 Sample Size 
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2.1 Populations Analyzed 
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a
Begins with the Week 60 Visit for subjects in Japan who continue participation in OLSES beyond Week 48. 
b
A subject who meets ACR20 criteria based on hs-CRP results not available at the Week 48 Visit of CHS-0214-02 will be asked to return to the 
clinic for a separate OLSES Week 0 Day 0 Visit in addition to the Week 48 Visit of CHS-0214-02, at which time informed consent will be 
obtained, subject ID will be assigned, blood samples for viral screening will be obtained, IVRS/IWRS will be contacted to register the subject 
in the study, and study drug will be dispensed.   
c
Subjects in Japan will consent on or before their OLSES Week 48 Visit to be able to continue participation in OLSES beyond Week 48. 
d
Abbreviated physical examinations are conducted at the Week 48 Visit in the parent study (considered to correspond to the Week 0 Day 0 
Visit in this study) and all the subsequent visits. Abbreviated physical examinations will consist of respiratory, gastrointestinal, 
musculoskeletal, and cardiovascular system evaluations and evaluations of other physical conditions of note.  
e
Weight will be recorded at the Follow-up Visit 28 days after the last dose of study drug. 
f
Vital signs include blood pressure (NOTE: an arm or wrist cuff is acceptable); heart rate; respiratory rate; and oral, aural, or axillary 
temperature and are to be obtained after the subject has rested in a seated position for at least 5 minutes. 
g
Repeat every 12 months for subjects in Japan who continue participation in OLSES beyond Week 48. 
h
Perform ECG at the Follow-up Visit 28 days after the last dose of study drug for those subjects who discontinue study drug  
i
Hematology parameters include hematocrit, hemoglobin, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and 
mean corpuscular volume, red blood cell count, white blood cell count with differential, reticulocyte count, and platelet count. 
j
Perform every 6 months for subjects in Japan who continue participation in OLSES beyond Week 48. 
k
Chemistry parameters include alkaline phosphatase; sodium; potassium; total protein; calcium; chloride; bicarbonate; glucose; creatine 
phosphokinase; lactate dehydrogenase; alanine aminotransferase; aspartate aminotransferase; albumin; total, direct and indirect bilirubin; 
blood urea nitrogen; creatinine; and uric acid. 
l
Urinalysis parameters include pH, specific gravity, protein, glucose, leukocyte esterase, bilirubin, blood, nitrite, and ketones. A urine 
microscopic examination will be performed when there are any abnormalities on any of the following 3 dipstick results: leukocyte esterase, 
blood, or nitrite. 
m
Japan only (see Section Error! Reference source not found.). 
n
Perform HIV and hepatitis screen testing prior to subject enrolling in OLSES (the subject may be enrolled in OLSES prior to receipt of results); 
assess ongoing participation in OLSES upon receipt of results.  
o
Perform for subjects in Japan who continue participation in OLSES beyond Week 48. 
p
Perform PGA (VAS) prior to SGA (VAS). 
q
Blood samples will be collected (pre-dose on dosing days) and serum retained at each visit through Week 48 and every 6 months for subjects 
in Japan who continue participation in OLSES beyond Week 48 for possible evaluation of CHS-0214 serum concentrations, ADA, or other tests 
as necessary to evaluate adverse effects or compliance. The exact date and time of each sample collection will be recorded. 
r
Perform for female subjects who are of childbearing potential and not surgically sterile at the Week 0 Day 0 Visit, and at the Follow-up Visit 
28 days after the last dose of study drug; for these subjects using abstinence as birth control, perform at every visit.  
s
A urine pregnancy test will be required on Week 0 Day 0 if Week 0 does not coincide with Week 48 of the parent study. 
t
Record ISRs observed by site personnel as AEs. 
u
Perform only for the subjects in Japan who consent to continue participation in OLSES beyond Week 48. If this visit is the subject’s last visit, 
do not dispense study drug. 
 
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v
Begins with the Week 60 Visit for subjects in Japan who continue participation in OLSES beyond Week 48. 
w
A subject who meets ACR20 criteria based on hs-CRP results not available at the Week 48 Visit of CHS-0214-02 will be asked to return to the 
clinic for a separate OLSES Week 0 Day 0 Visit in addition to the Week 48 Visit of CHS-0214-02, at which time informed consent will be 
obtained, subject ID will be assigned, blood samples for viral screening will be obtained, IVRS/IWRS will be contacted to register the subject 
in the study, and study drug will be dispensed.   
x
Subjects in Japan will consent on or before their OLSES Week 48 Visit to be able to continue participation in OLSES beyond Week 48. 
y
Abbreviated physical examinations are conducted at the Week 48 Visit in the parent study (considered to correspond to the Week 0 Day 0 
Visit in this study) and all the subsequent visits. Abbreviated physical examinations will consist of respiratory, gastrointestinal, 
musculoskeletal, and cardiovascular system evaluations and evaluations of other physical conditions of note.  
z
Weight will be recorded at the Follow-up Visit 28 days after the last dose of study drug. 
aa
Vital signs include blood pressure (NOTE: an arm or wrist cuff is acceptable); heart rate; respiratory rate; and oral, aural, or axillary 
temperature and are to be obtained after the subject has rested in a seated position for at least 5 minutes. 
bb
Repeat every 12 months for subjects in Japan who continue participation in OLSES beyond Week 48. 
cc
Perform ECG at the Follow-up Visit 28 days after the last dose of study drug for those subjects who discontinue study drug  
dd
Hematology parameters include hematocrit, hemoglobin, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and 
mean corpuscular volume, red blood cell count, white blood cell count with differential, reticulocyte count, and platelet count. 
ee
Perform every 6 months for subjects in Japan who continue participation in OLSES beyond Week 48. 
ff
Chemistry parameters include alkaline phosphatase; sodium; potassium; total protein; calcium; chloride; bicarbonate; glucose; creatine 
phosphokinase; lactate dehydrogenase; alanine aminotransferase; aspartate aminotransferase; albumin; total, direct and indirect bilirubin; 
blood urea nitrogen; creatinine; and uric acid. 
gg
Urinalysis parameters include pH, specific gravity, protein, glucose, leukocyte esterase, bilirubin, blood, nitrite, and ketones. A urine 
microscopic examination will be performed when there are any abnormalities on any of the following 3 dipstick results: leukocyte esterase, 
blood, or nitrite. 
hh
Japan only (see Section Error! Reference source not found.). 
ii
Perform HIV and hepatitis screen testing prior to subject enrolling in OLSES (the subject may be enrolled in OLSES prior to receipt of results); 
assess ongoing participation in OLSES upon receipt of results.  
jj
Perform for subjects in Japan who continue participation in OLSES beyond Week 48. 
kk
Perform PGA (VAS) prior to SGA (VAS). 
ll
Blood samples will be collected (pre-dose on dosing days) and serum retained at each visit through Week 48 and every 6 months for subjects 
in Japan who continue participation in OLSES beyond Week 48 for possible evaluation of CHS-0214 serum concentrations, ADA, or other tests 
as necessary to evaluate adverse effects or compliance. The exact date and time of each sample collection will be recorded. 
mm Perform for female subjects who are of childbearing potential and not surgically sterile at the Week 0 Day 0 Visit, and at the Follow-up Visit 
28 days after the last dose of study drug; for these subjects using abstinence as birth control, perform at every visit.  
nn
A urine pregnancy test will be required on Week 0 Day 0 if Week 0 does not coincide with Week 48 of the parent study. 
oo
Record ISRs observed by site personnel as AEs. 
pp
Perform only for the subjects in Japan who consent to continue participation in OLSES beyond Week 48. If this visit is the subject’s last visit, 
do not dispense study drug. 
 
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a.
Abbreviated physical examinations are conducted at the Week 48 Visit in the parent study (considered to correspond to the 
Week 0 Day 0 Visit in this study) and all the subsequent visits. Abbreviated physical examinations will consist of respiratory, 
gastrointestinal, musculoskeletal, and cardiovascular system evaluations and evaluations of other physical conditions of note.  
b.
Weight will be recorded at the Follow-up Visit 28 days after the last dose of study drug. 
c.
Vital signs include blood pressure(NOTE: an arm or wrist cuff is acceptable); heart rate; respiratory rate; and oral, aural, or 
axillary temperature and are to be obtained after the subject has rested in a seated position for at least 5 minutes. 
d.
Perform ECG 28 days after last dose of study drug for those subjects who discontinue study drug prior to Week 48. 
e.
Hematology parameters include hematocrit, hemoglobin, mean corpuscular hemoglobin, mean corpuscular hemoglobin 
concentration, and mean corpuscular volume, red blood cell count, white blood cell count with differential, reticulocyte count, 
and platelet count. 
f.
Chemistry parameters include alkaline phosphatase; sodium; potassium; total protein; calcium; chloride; bicarbonate; glucose; 
creatine phosphokinase; lactate dehydrogenase; alanine aminotransferase; aspartate aminotransferase; albumin; total, direct 
and indirect bilirubin; blood urea nitrogen; creatinine; and uric acid. 
g.
Urinalysis parameters include pH, specific gravity, protein, glucose, leukocyte esterase, bilirubin, blood, nitrite, and ketones. A 
urine microscopic examination will be performed when there are any abnormalities on any of the following 3 dipstick results: 
leukocyte esterase, blood, or nitrite. 
h.
Perform HIV and hepatitis screen testing prior to subject enrolling in OLSES (the subject may be enrolled in OLSES prior to 
receipt of results); assess ongoing participation in OLSES upon receipt of results.  
i.
Blood samples will be collected (pre-dose on dosing days) and serum retained at each visit for possible evaluation of CHS-0214 
serum concentrations, ADA, or other tests as necessary to evaluate adverse effects or compliance. The exact date and time of 
each sample collection will be recorded. 
j.
Perform for female subjects who are of childbearing potential and not surgically sterile at the Week 0 Day 0 Visit and at the 
Follow-up Visit 28 days after the last dose of study drug; for these subjects using abstinence as birth control, perform at every 
visit.  
k.
A urine pregnancy test will be required on Week 0 Day 0 if Week 0 does not coincide with Week 48 of the parent study. 
l.
Record ISRs observed by site personnel as AEs. 
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