A Multi-Center, Open-Label Study to Evaluate the Pharmacokinetics of Certolizumab Pegol in Adults With Active Rheumatoid Arthritis Using an Electrochemiluminescent Immuno-Assay
Phase: PHASE1
Conditions: Rheumatoid Arthritis
Sponsor: UCB Biopharma SRL

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 1 of 66 
A MULTI-CENTER, OPEN-LABEL STUDY TO EVALUATE THE 
PHARMACOKINETICS OF CERTOLIZUMAB PEGOL IN 
ADULTS WITH ACTIVE RHEUMATOID ARTHRITIS USING AN 
ELECTROCHEMILUMINESCENT IMMUNO-ASSAY 
PROTOCOL RA0138 AMENDMENT 2 
PHASE 1B 
 
SHORT TITLE: 
A study to evaluate the PK of certolizumab pegol in adults with active rheumatoid arthritis using 
an electrochemiluminescent immune-assay (ECLIA). 
Sponsor: 
UCB Biopharma SRL 
Allée de la Recherche 60 
1070 Brussels 
BELGIUM 
Regulatory agency identifying number(s): 
IND Number: 
009869 
Confidential Material 
Confidential 
This document is the property of UCB and may not – in full or in part – be passed on, 
reproduced, published, or otherwise used without the express permission of UCB. 
 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 2 of 66 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
Document history 
Document 
Date 
Type of amendment 
Amendment 2 
18 Mar 2021 
Nonsubstantial 
Amendment 1 
09 Dec 2020 
Nonsubstantial 
Original Protocol 
27 Mar 2020 
Not applicable 
Amendment 2 (18 Mar 2021) 
Overall rationale for the amendment 
The primary reasons for this nonsubstantial protocol amendment were to update the Screening 
Period duration from “7 days” to “up to 28 days,” to standardize the use of “inhibitor” vs 
“antagonist,” to update text describing rescreening procedures, to change Visit 3 from a “Home 
Visit” to a “Clinic Visit,” to clarify rescreening procedures, and to clarify the prohibited 
concomitant medications and permitted rescue medications.  
This amendment is considered to be nonsubstantial based on the criteria set forth in Article 10(a) 
of Directive 2001/20/EC of the European Parliament and the Council of the European Union. 
Section # and Name 
Description of Change 
Brief Rationale 
1.1 Synopsis 
1.2 Schema  
4.1 Overall design 
Changed the duration for the 
Screening Period from “7 days” to 
“up to 28 days.” 
The Screening Period was 
lengthened to 28 days to 
allow for sufficient time 
for laboratory samples to 
be processed ahead of a 
study participant’s first 
CZP dose. 
1.3 Schedule of Activities 
Visit 3 was changed from a “Home” 
visit to a “Clinic” visit. 
Due to logistical 
considerations with 
in-home nurse availability, 
this visit was changed 
from a home visit to a 
clinic visit. 
5.2 Exclusion criteria 
Modified the wording of Exclusion 
Criterion #10 to exclude the term 
“antagonist.” This change resulted 
in a global use of the term 
“inhibitor” to describe TNFα 
inhibitors. 
This change was made to 
avoid confusion in the 
understanding of 
TNFα inhibitors vs 
TNFα antagonists. 
5.2 Exclusion criteria 
Rescreening text for laboratory 
assessments was removed from 
Exclusion Criterion #13  
Updated to provide clarity 
and to be consistent with 
remainder of protocol and 
program. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 3 of 66 
Section # and Name 
Description of Change 
Brief Rationale 
5.4 Screen failures 
Clarifying text was added to 
describe the window in which tests 
that result in ALT, AST, or ALP up 
to 25% above the exclusion limit 
may be repeated for confirmation. 
Updated to provide clarity 
and to be consistent with 
remainder of protocol and 
program. 
6.5.2 Prohibited 
concomitant treatments 
(medications and 
therapies) 
The specific types of prohibited 
concomitant DMARDs were 
clarified. 
Updated to provide clarity 
and avoid confusion 
regarding which 
DMARDs are prohibited. 
6.5.3 Rescue medication 
The specific types of permitted 
rescue medications were clarified. 
Updated to provide clarity 
and avoid confusion 
regarding which rescue 
medications are permitted. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 4 of 66 
SERIOUS ADVERSE EVENT REPORTING 
 
Serious adverse event reporting (24h) 
Fax 
US and Canada: +1 800 880 6949 or +1 866 890 3175 
Email 
Global: DS_ICT@ucb.com (for interventional clinical studies) 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 5 of 66 
TABLE OF CONTENTS 
1 
PROTOCOL SUMMARY ................................................................................................. 9 
1.1 
Synopsis ......................................................................................................................... 9 
1.2 
Schema ......................................................................................................................... 12 
1.3 
Schedule of Activities .................................................................................................. 13 
2 
INTRODUCTION ........................................................................................................... 16 
2.1 
Study rationale ............................................................................................................. 16 
2.2 
Background .................................................................................................................. 16 
2.2.1 
Rheumatoid arthritis ............................................................................................ 16 
2.2.2 
Certolizumab pegol .............................................................................................. 16 
2.3 
Benefit/Risk assessment............................................................................................... 17 
3 
OBJECTIVES AND ENDPOINTS ................................................................................. 18 
4 
STUDY DESIGN ............................................................................................................. 18 
4.1 
Overall design .............................................................................................................. 18 
4.2 
Scientific rationale for study design ............................................................................ 19 
4.3 
Justification for dose .................................................................................................... 19 
4.4 
End of study definition................................................................................................. 19 
5 
STUDY POPULATION .................................................................................................. 20 
5.1 
Inclusion criteria .......................................................................................................... 20 
5.2 
Exclusion criteria ......................................................................................................... 21 
5.3 
Lifestyle restrictions..................................................................................................... 23 
5.3.1 
Meals and dietary restrictions .............................................................................. 23 
5.3.2 
Caffeine, alcohol, and tobacco ............................................................................. 23 
5.3.3 
Activity ................................................................................................................ 23 
5.4 
Screen failures .............................................................................................................. 23 
6 
STUDY TREATMENTS ................................................................................................. 23 
6.1 
Treatments administered .............................................................................................. 24 
6.2 
Preparation, handling, storage, and accountability requirements ................................ 24 
6.2.1 
Drug accountability ............................................................................................. 25 
6.3 
Measures to minimize bias: randomization and blinding ............................................ 25 
6.4 
Treatment compliance .................................................................................................. 25 
6.5 
Concomitant medication(s)/treatment(s) ..................................................................... 25 
6.5.1 
Permitted concomitant treatments (medications and therapies) .......................... 25 
6.5.2 
Prohibited concomitant treatments (medications and therapies) ......................... 26 
6.5.3 
Rescue medication ............................................................................................... 26 
6.6 
Dose modification ........................................................................................................ 26 
6.6.1 
Dose interruptions ................................................................................................ 26 
6.7 
Criteria for study hold or dosing stoppage ................................................................... 26 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 6 of 66 
6.8 
Treatment after the end of the study ............................................................................ 27 
7 
DISCONTINUATION OF STUDY MEDICATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ........................................................................ 27 
7.1 
Discontinuation of study medication ........................................................................... 27 
7.1.1 
Liver chemistry stopping criteria ......................................................................... 27 
7.2 
Participant Discontinuation/Withdrawal from the study ............................................. 28 
7.3 
Lost to follow-up.......................................................................................................... 29 
8 
STUDY ASSESSMENTS AND PROCEDURES ........................................................... 29 
8.1 
Efficacy assessments .................................................................................................... 30 
8.1.1 
Multi-dimensional Health Assessment Questionnaire (MDHAQ) and RAPID3 
scoring .................................................................................................................. 30 
8.2 
Safety assessments ....................................................................................................... 30 
8.2.1 
Physical examination ........................................................................................... 30 
8.2.2 
Vital signs ............................................................................................................ 30 
8.2.3 
Electrocardiograms .............................................................................................. 31 
8.2.4 
Clinical safety laboratory assessments ................................................................ 31 
8.2.5 
Tuberculosis assessment ...................................................................................... 31 
8.3 
Adverse events and serious adverse events ................................................................. 31 
8.3.1 
Time period and frequency for collecting AE and SAE information .................. 32 
8.3.2 
Method of detecting AEs and SAEs .................................................................... 32 
8.3.3 
Follow-up of AEs and SAEs ................................................................................ 32 
8.3.4 
Regulatory reporting requirements for SAEs ...................................................... 32 
8.3.5 
Pregnancy ............................................................................................................ 33 
8.3.6 
Adverse events of special interest ........................................................................ 33 
8.3.7 
Anticipated serious adverse events ...................................................................... 34 
8.4 
Safety signal detection ................................................................................................. 34 
8.5 
Treatment of overdose ................................................................................................. 34 
8.6 
Pharmacokinetics ......................................................................................................... 35 
8.7 
Genetics........................................................................................................................ 35 
8.8 
Pharmacodynamics ...................................................................................................... 35 
8.9 
Biomarkers ................................................................................................................... 35 
8.9.1 
Immunogenicity assessments ............................................................................... 35 
8.10 
Health economics or medical resource utilization and health economics ................... 35 
9 
STATISTICAL CONSIDERATIONS ............................................................................. 35 
9.1 
Definition of analysis sets ............................................................................................ 36 
9.2 
General statistical considerations ................................................................................. 36 
9.3 
Planned safety and other analyses................................................................................ 36 
9.3.1 
Other analyses ...................................................................................................... 36 
9.3.1.1 
Pharmacokinetic analyses .......................................................................... 36 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 7 of 66 
9.3.1.2 
Immunogenicity analyses .......................................................................... 37 
9.3.1.3 
RAPID3 analysis ....................................................................................... 37 
9.4 
Handling of protocol deviations................................................................................... 37 
9.5 
Handling of dropouts or missing data .......................................................................... 37 
9.6 
Planned interim analysis and data monitoring ............................................................. 37 
9.7 
Determination of sample size ....................................................................................... 37 
10 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS... 39 
10.1 
Appendix 1: Regulatory, ethical, and study oversight considerations ......................... 39 
10.1.1 
Regulatory and ethical considerations ................................................................. 39 
10.1.2 
Financial disclosure ............................................................................................. 39 
10.1.3 
Informed consent process .................................................................................... 40 
10.1.4 
Data protection ..................................................................................................... 40 
10.1.5 
Committees structure ........................................................................................... 41 
10.1.6 
Data quality assurance ......................................................................................... 41 
10.1.6.1 
Case Report form completion .................................................................... 41 
10.1.7 
Source documents ................................................................................................ 41 
10.1.8 
Study and Site Closure ......................................................................................... 42 
10.1.9 
Publication Policy ................................................................................................ 42 
10.2 
Appendix 2: Clinical Laboratory Tests ........................................................................ 43 
10.3 
Appendix 3: Adverse Events – Definitions and Procedures for Recording, Evaluating, 
Follow-up, and Reporting ............................................................................................ 45 
10.4 
Appendix 4: Contraceptive Guidance and Collection of Pregnancy Information ....... 50 
10.5 
Appendix 5: Genetics ................................................................................................... 53 
10.6 
Appendix 6: Liver Safety – Suggested Actions and Follow-up Assessments ............. 54 
Liver Chemistry Stopping Criteria and Follow-up assessments .......................................... 54 
10.7 
Appendix 7: Medical Device Adverse Events (AEs), Adverse Device Effects (ADEs), 
Serious Adverse Events (SAEs) and Device Deficiencies: Definition and Procedures 
for Recording, Evaluating, Follow-up, and Reporting ................................................ 57 
10.8 
Appendix 8: Rapid Alert Procedures ........................................................................... 58 
10.9 
Appendix 9: Country-specific Requirements............................................................... 59 
10.10 Appendix 10: Abbreviations and Trademarks ............................................................. 60 
10.11 Appendix 11: Protocol Amendment History ............................................................... 62 
10.12 Appendix 12: RAPID3 Assessment ............................................................................. 63 
How to calculate RAPID3 scores ........................................................................................ 63 
11 REFERENCES ................................................................................................................ 65 
SPONSOR DECLARATION .................................................................................................. 66 
 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 8 of 66 
LIST OF TABLES 
Table 8-1: 
Anticipated serious adverse event for RA population ..................................... 34 
 
LIST OF FIGURES 
Figure 7-1: 
Liver Chemistry Stopping Criteria and Increased Monitoring Algorithm ....... 28 
 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 9 of 66 
1 
PROTOCOL SUMMARY 
1.1 
Synopsis 
Protocol title: A multi-center, open-label study to evaluate the pharmacokinetics of 
certolizumab pegol in adults with active rheumatoid arthritis using an electrochemiluminescent 
immuno-assay 
Short Title: A study to evaluate the PK of certolizumab pegol in adults with active rheumatoid 
arthritis using an electrochemiluminescent immune-assay (ECLIA). 
Rationale: 
Certolizumab pegol (CZP) was approved in the United States (US) for adults with rheumatoid 
arthritis (RA) in May 2009. Certolizumab pegol pharmacokinetic (PK) and antidrug antibody 
(ADA) data in the adult RA population has thus far been generated with legacy bioanalytical 
methods which have more recently been superseded by new methods to comply with updated 
regulatory standards. As the safety and efficacy of CZP in adults with RA have been extensively 
studied and established, this Phase 1B study is focused on acquiring PK data in CZP-naive 
participants who receive CZP at the marketed dose within the study, and are prescribed CZP at 
the licensed dose (per US Prescribing Information) as part of the therapeutic management of 
their RA disease, using a PK or ADA electrochemiluminescent immuno-assay (ECLIA). This 
study is being undertaken in support of the polyarticular juvenile idiopathic arthritis (pJIA) 
Pediatric Research Equity Act (PREA) requirement for Cimzia. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 10 of 66 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
• To evaluate the PK of CZP (utilizing the 
ECLIA method) in adults with active RA 
• PK parameters (Cmin and AUC) following 
10 weeks of CZP dosing 
Secondary 
• To evaluate CZP exposure over a 
maximum of 24 weeks administration to 
adults with active RA 
• To evaluate the safety of CZP in adults 
with active RA 
• CZP plasma concentrations over the 
duration of study 
• Treatment-emergent SAEs and AEs 
leading to withdrawal from the time of the 
first CZP dose through the SFU Visit 
Other 
• To assess the occurrence of anti-CZP 
antibodies (utilizing the ECLIA method) 
over the duration of the study 
• ADA screening status (positive or 
negative screen), confirmatory status 
(positive or negative immunodepletion), 
and the titer for "positive 
immunodepletion" samples at each 
scheduled assessment after first CZP dose 
through SFU 
• To assess the efficacy of CZP 
• Change in Routine Assessment of Patient 
Index Data 3 (RAPID3) from Baseline to 
Week 12 
• To evaluate other safety parameters 
• TEAEs, vital signs, and laboratory 
assessments 
ADA=antidrug antibody; AE=adverse event; CZP=certolizumab pegol; ECLIA=electrochemiluminescent 
immuno-assay; PK=pharmacokinetic; RA=rheumatoid arthritis; RAPID3=Routine Assessment of Patient Index 
Data; SAE=serious adverse event; SFU=Safety Follow-up Visit; TEAE=treatment-emergent adverse event 
Overall Design 
This is a multi-center, open-label Phase 1B study to assess the PK, safety, and tolerability of 
CZP in adults with active RA. In this 24-week study, study participants (ie, male or female 
participants 18 to 69 years of age inclusive) who are naïve to CZP and are eligible to receive a 
biologic for RA will receive CZP in subcutaneous (sc) loading doses at Weeks 0, 2, and 4, 
followed by a treatment of 200mg every 2 weeks (Q2W), with the final dose taking place at 
Week 24. 
Number of Participants 
A total of 30 participants will be enrolled to receive CZP, such that a minimum of 25 evaluable 
participants are expected to complete Visit 13 (Week 12). 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 11 of 66 
Treatment Groups and Duration 
All study participants will receive CZP treatment. Study participants may be taking concomitant 
methotrexate (MTX); however, a minimum of 8 study participants must be enrolled who are not 
on concurrent administration of MTX. 
The duration of the study is approximately 38 weeks. The study consists of a Screening Period 
(up to 28 days), Baseline Visit, a Treatment Period (24 weeks), and a Safety Follow-up (SFU) 
Visit (70 days after the last study visit). 
 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 12 of 66 
1.2 
Schema 
 
ADA=antidrug antibody; BL=Baseline; CZP=certolizumab pegol; PK=pharmacokinetic; Q2W=every 2 weeks; W=week 
a CZP naïve at enrollment. 
 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 13 of 66 
1.3 
Schedule of Activities 
Procedure 
Screening Baseline 
Treatment Period 
SFU/ 
EDV 
V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
PK profile 
V13 
V14 
V15 
V16 
V9 
V10 
V11 
V12 
D-28/ 
W-4 
D0 
D7/ 
W1 
D14/ 
W2 
D28/ 
W4 
D42/ 
W6 
D56/ 
W8 
D70/ 
W10 
D72 
W10 
D75 
W10 
D77/ 
W11 
D80/ 
W11 
D84/ 
W12 
D126/ 
W18 
D168/ 
W24 
70 
days 
after 
last 
IMP 
Visit window a 
 
 
±1 day ±1 day 
±2 days 
±2 days 
±2 day 
±1 day ±6 hrs 
±6 hrs ±6 hrs ±6 hrs ±6 hrs 
±2 days 
±2 days 
±7 day 
Location b 
Clinic 
Clinic 
Clinic 
Home 
Home 
Clinic 
Home 
Home 
Home 
Home 
Home 
Home 
Clinic 
Home 
Clinic 
Clinic 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study participant 
card 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Verification of 
inclusion/exclusion 
criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demography 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
General 
medical/procedure 
history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical 
examination 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Body 
weight/height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital signs 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Pregnancy test c 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
X 
Laboratory 
assessments  
X 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
X 
12-lead ECG d 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
TB questionnaire 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 14 of 66 
Procedure 
Screening Baseline 
Treatment Period 
SFU/ 
EDV 
V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
PK profile 
V13 
V14 
V15 
V16 
V9 
V10 
V11 
V12 
D-28/ 
W-4 
D0 
D7/ 
W1 
D14/ 
W2 
D28/ 
W4 
D42/ 
W6 
D56/ 
W8 
D70/ 
W10 
D72 
W10 
D75 
W10 
D77/ 
W11 
D80/ 
W11 
D84/ 
W12 
D126/ 
W18 
D168/ 
W24 
70 
days 
after 
last 
IMP 
Visit window a 
 
 
±1 day ±1 day 
±2 days 
±2 days 
±2 day 
±1 day ±6 hrs 
±6 hrs ±6 hrs ±6 hrs ±6 hrs 
±2 days 
±2 days 
±7 day 
Location b 
Clinic 
Clinic 
Clinic 
Home 
Home 
Clinic 
Home 
Home 
Home 
Home 
Home 
Home 
Clinic 
Home 
Clinic 
Clinic 
TB screening 
(IGRA)  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Adverse event 
review 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Prior and 
Concomitant 
medication review 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
X 
 
X 
X 
IMP 
administration e  
 
X (site) 
 
X 
(nurse) 
X 
(nurse) 
X (site) 
X 
(nurse) 
X 
(nurse) 
 
 
 
 
X 
(site) 
X 
(nurse 
or self) 
X (site) 
 
IMP dispensing/ 
IXRS  
 
X 
  
 
 
X 
 
 
  
 
 
 
X 
 
 
 
IMP return 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
X 
 
CZP plasma 
concentration f, g 
  
X 
X  
X  
 
X 
 
X 
X 
X  
X  
X  
X 
X 
X  
 
Anti-CZP antibody 
sampling f 
 
X 
  
  
 
X 
 
 
 
  
 
 
X 
 
X 
X  
RAPID3 testing f 
 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
CZP=certolizumab pegol; D=day; ECG=electrocardiogram; EDV=Early Discontinuation Visit; hrs=hours; IGRA=Interferon-gamma release assay; IMP=investigational medicinal 
product; Q2W=every 2 weeks; PK=pharmacokinetic(s); RAPID3=Routine Assessment of Patient Index Data; SFU=Safety Follow-up; TB=tuberculosis; V=Visit; W=week 
a  Visit days may take place within a window relative to the Visit Day. 
b  Home Visits may occur at the clinic/site rather than at home per study participant preference. Assessments at Home Visits will be conducted by the Home Visit nurse. 
c  In WOCBP, at Screening, a serum pregnancy test will be performed; for subsequent visits, urine pregnancy tests will be performed according the to Schedule of Activities. 
d  All ECG recordings should be taken with the study participant resting in the supine position for at least 5 minutes before the recording. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 15 of 66 
e  Loading doses of 400mg CZP will be administered at Weeks 0, 2, and 4, followed by treatment with 200mg Q2W. Study participants will have the option to self-inject IMP at 
home on Weeks 14, 16, 20, and 22.  
f At Visits in which dosing will take place, all activities should take place prior to IMP administration (including PK collection). 
g PK profile samples to be collected at 2 (Visit 9), 5 (Visit 10), 7 (Visit 11) and 10 (Visit 12) days post-Week 10 IMP administration. 
 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 16 of 66 
2 
INTRODUCTION 
2.1 
Study rationale 
Certolizumab pegol (CZP) was approved for adults with rheumatoid arthritis (RA) in the United 
States (US) in May 2009. Certolizumab pegol pharmacokinetic (PK) and antidrug antibody 
(ADA) data in the adult RA population has thus far been generated with legacy bioanalytical 
methods which have more recently been superseded by new methods to comply with updated 
regulatory standards. Since the change in bioanalytical methods, no PK and ADA data have been 
generated for CZP in adults with RA. Further, there is no mathematical concordance between the 
previous and current (ECLIA) bioanalytical assays for CZP to enable bridging of PK data from 
one method to the other. 
The polyarticular juvenile idiopathic arthritis (pJIA) development program for CZP, to be based 
on ECLIA-generated PK data, is reliant on comparative CZP PK data from adults with RA. This 
study is being undertaken in order to generate this latter ECLIA-based adult PK data. As the 
safety and efficacy of CZP in adults with RA have been extensively established, this Phase 1B 
study is focused solely on acquiring ECLIA-based CZP PK data in CZP-naive participants who 
are eligible to receive a biologic for management of their RA disease. 
2.2 
Background 
2.2.1 
Rheumatoid arthritis 
Rheumatoid arthritis is a chronic, systemic, autoimmune disease with peripheral synovitis as its 
primary manifestation. Untreated, RA can lead to destruction, deformation, and dysfunction of 
affected joints which, in turn, may contribute to significant morbidity and increased mortality 
(Jacobsson et al, 2007). Moderate-to-severe RA is usually, if not always, treated with disease 
modifying antirheumatic drug (DMARDs), with methotrexate (MTX) being the agent most 
commonly used. For patients with an inadequate response to conventional DMARDs, biologic 
agents which inhibit tumor necrosis factor alpha (TNFα) (known as TNFα blockers), especially 
in combination with MTX, have been employed (Smolen et al, 2009). 
2.2.2 
Certolizumab pegol 
Certolizumab pegol (CZP) is a recombinant, humanized, monoclonal, antigen-binding prime 
antibody fragment (Fab′), with specificity for human TNFα, which is conjugated to polyethylene 
glycol (PEG). Certolizumab pegol has been studied for the treatment of inflammatory diseases, 
such as Crohn’s disease (CD; including pediatric CD), rheumatoid arthritis (RA), psoriatic 
arthritis, axial spondyloarthritis (including ankylosing spondylitis and nonradiographic axial 
spondyloarthritis), pJIA, and psoriasis. 
Certolizumab pegol was first approved for adults with Crohn's disease in the US in 2008 and for 
RA in 2009; it is available commercially in the US, EU, and approximately 64 other countries 
worldwide for the treatment of moderately to severely active RA in adults. Its safety and 
tolerability have been extensively studied and are detailed within the US Prescribing Information 
for health care professionals. 
Additional information on the nonclinical and clinical data for CZP is also available in the 
current version of the CZP Investigator’s Brochure. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 17 of 66 
2.3 
Benefit/Risk assessment 
Adult study participants, naive to CZP, will receive loading doses of 400mg CZP at Weeks 0, 2, 
and 4, followed by treatment with 200mg every 2 weeks (Q2W), with the final dose taking place 
at Week 24. This CZP dosing regimen has been approved for use in the US in adults with 
moderately to severely active RA. 
The risks of the present study are essentially those of experiencing an adverse event (AE) 
following administration of CZP and for progressive disability if the study participant does not 
respond to CZP. As a therapeutic class, currently available TNFα-inhibitors are known to be 
associated with serious infections, particularly reactivation of tuberculosis (TB) and 
opportunistic fungal infections. An association has also been reported with TNFα-inhibitor 
therapy and the development of malignancies including lymphoma and leukemia, Merkel Cell 
carcinoma, T-cell lymphoma, and melanoma, although it is not clear whether there is a causal 
relationship, as confounding factors exist (eg, the increased risk of lymphoma and leukemia 
associated with autoimmune diseases and immunosuppression). Other serious adverse events 
(SAEs) that have been reported in participants treated with currently available TNFα-inhibitors, 
including CZP, include moderate-to-severe congestive heart failure, hypersensitivity reactions 
including anaphylaxis, new-onset psoriasis, demyelinating disorders, blood dyscrasias including 
aplastic anemia, immunogenicity including sarcoidosis, lupus, lupus-like illness, and 
hepatobiliary events. The additional risks to participants due to participation in the study will be 
nominal (eg, possible complications associated with collection of blood samples and collection 
of participant data). 
For a full list of potential AEs please refer to the Cimzia US Prescribing Information. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 18 of 66 
3 
OBJECTIVES AND ENDPOINTS 
Objectives 
Endpoints 
Primary 
• To evaluate the PK of CZP (utilizing the 
ECLIA method) in adults with active RA 
• PK parameters (Cmin and AUC) following 
10 weeks of CZP dosing 
Secondary 
• To evaluate CZP exposure over a 
maximum of 24 weeks administration to 
adults with active RA 
• To evaluate the safety of CZP in adults 
with active RA 
• CZP plasma concentrations over the 
duration of study 
• Treatment-emergent SAEs and AEs 
leading to withdrawal from the time of the 
first CZP dose through the SFU Visit 
Other 
• To assess the occurrence of anti-CZP 
antibodies (utilizing the ECLIA method) 
over the duration of the study 
• ADA screening status (positive or 
negative screen), confirmatory status 
(positive or negative immunodepletion), 
and the titer for "positive 
immunodepletion" samples at each 
scheduled assessment after first CZP dose 
through SFU 
• To assess the efficacy of CZP 
• Change in Routine Assessment of Patient 
Index Data 3 (RAPID3) from Baseline to 
Week 12 
• To evaluate other safety parameters 
• TEAEs, vital signs, and laboratory 
assessments 
ADA=antidrug antibody; AE=adverse event; CZP=certolizumab pegol; ECLIA=electrochemiluminescent 
immuno-assay; PK=pharmacokinetic; RA=rheumatoid arthritis; RAPID3=Routine Assessment of Patient Index 
Data; SAE=serious adverse event; SFU=Safety Follow-up Visit; TEAE=treatment-emergent adverse event 
4 
STUDY DESIGN 
4.1 
Overall design 
This is a multi-center, open-label Phase 1B study to assess the PK, safety, and tolerability of 
CZP in adults with active RA. In this 24-week study, study participants who are naïve to CZP 
and have not previously failed to respond to treatment with ≥1 TNFα inhibitor will receive CZP 
in subcutaneous loading doses of 400 mg at Weeks 0, 2, and 4, followed by a treatment of 
200mg Q2W, with the final dose taking place at Week 24. 
A total of 30 study participants will be enrolled and will receive CZP. Study participants may be 
taking concomitant MTX; however, a minimum of 8 study participants must be enrolled who are 
not on concurrent administration of MTX. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 19 of 66 
The study consists of a Screening Period (up to 28 days), Baseline Visit, a Treatment Period 
(24 weeks), and a Safety Follow-Up (SFU) Visit (70 days after the last study visit). 
A schematic of the study design is presented in Section 1.2 and the Schedule of Activities for the 
study is presented in Section 1.3. 
4.2 
Scientific rationale for study design 
This study is being undertaken in support of the pJIA Pediatric Research Equity Act (PREA) 
requirement for Cimzia in pJIA. 
Through extensive interactions between the Food and Drug Administration and external experts, 
culminating in a collaborative workshop in October 2019 entitled “Accelerating Drug 
Development for polyarticular Juvenile Idiopathic Arthritis (pJIA)”, a therapeutic bridging 
approach from RA to pJIA has been derived for TNF-α inhibitors based on the relationship 
between RA and pJIA and the extensive knowledge of TNF-α inhibitors as therapeutic agents. 
This approach (based on "Pharmacokinetic (PK) matching") directs that the therapeutic effect of 
TNF-α inhibitors (such as CZP) in pJIA patients can be expected if the pediatric systemic 
exposure for the drug is within the therapeutic range for adult RA patients. 
Central to application of this approach is the existence of a reference systemic exposure (PK) 
range which is associated with therapeutic benefit of the drug in adult RA population. Although 
CZP has been approved in the US for RA in adults since May 2009, CZP PK and ADA data in 
the adult RA population have thus far been generated with legacy bioanalytical methods, which 
have more recently been superseded by new methods (namely, ECLIA) to comply with updated 
regulatory standards. Since the change in bioanalytical methods, no PK and ADA data have been 
generated for CZP in adults with RA. Further, there is no mathematical concordance between the 
previous and current (ECLIA) bioanalytical assays for CZP to enable bridging of PK data from 
one method to the other. 
The pJIA development program for CZP, to be based on ECLIA-generated PK data, is reliant on 
comparative CZP PK data from adults with RA. Thus, a supporting adult reference PK dataset 
for "PK matching" in the pJIA program will also need to be based on data generated with the 
ECLIA method. At present, such ECLIA-based PK data for CZP in the adult RA population are 
not available. Accordingly, this study is being undertaken in order to generate ECLIA-based 
CZP PK data for CZP in adults with RA. As the safety and efficacy of CZP in adults with RA 
have been extensively established, this Phase 1B study is focused solely on acquiring 
ECLIA-based CZP PK data in CZP-naive participants who are eligible to receive a biologic for 
management of their RA disease. 
4.3 
Justification for dose 
The commercially approved dosing regimen for adult patients with RA (loading doses of 400mg 
at Weeks 0, 2, and 4 then 200 mg Q2W) will be used for the duration of the study. This CZP 
dosing regimen has been approved for use in the US in adults with moderately to severely active 
RA. 
4.4 
End of study definition 
A participant is considered to have completed the study if he/she has completed all portions 
(Screening, Baseline Visit, Treatment Period [through Week 24], and SFU) of the study. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 20 of 66 
Following investigational medicinal product (IMP) administration at Week 24, participants may 
transition to treatment with commercial CZP in consultation with their health care professional. 
The SFU Visit will be conducted 70 days post last administration of IMP. 
The end of the study is defined as the date of the last visit of the last participant in the study. 
5 
STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, are not permitted. 
5.1 
Inclusion criteria 
Participants are eligible to be included in the study only if all of the following criteria apply: 
Age 
1. Participant must be 18 to 69 years of age inclusive, at the time of signing the informed 
consent. 
Type of participant and disease characteristics 
2. Participant must have a diagnosis of moderately-to-severely active RA. 
3. Participant must have had an inadequate response to, or intolerance to, at least 1 DMARD 
(nonbiologic or biologic). For example, the study participant had prior inadequate response to 
MTX (based on the Investigator’s clinical judgment). 
4. Participant has a negative interferon-gamma release assay (IGRA) at Screening. 
Weight 
5. Participant has a body mass index within the range 18.0kg/m2 to 35.0kg/m2 (inclusive). 
Sex 
6. Male or female 
− A female participant is eligible to participate if: 
◦ 
 she is not pregnant (see Appendix 4 [Section 10.4]), 
◦ 
not breastfeeding, 
◦ 
at least one of the following conditions applies: 
(1) Not a woman of childbearing potential (WOCBP) as defined in Appendix 4 
OR 
(2) A WOCBP who agrees to follow the contraceptive guidance in Appendix 4 during 
the Treatment Period and until the SFU Visit. 
Informed consent 
7. The participant is capable of giving signed informed consent as described in Appendix 1 
(Section 10.1) which includes compliance with the requirements and restrictions listed in the 
Informed Consent Form (ICF) and in this protocol. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 21 of 66 
5.2 
Exclusion criteria 
Participants are excluded from the study if any of the following criteria apply: 
Medical conditions 
1. Participant has any medical or psychiatric condition (including clinically significant 
laboratory abnormalities) that, in the opinion of the Investigator, could jeopardize or would 
compromise the study participant’s ability to participate in this study. 
2. Participant has a known hypersensitivity to any components of the study medication 
(including PEG) or comparative drugs (and/or an investigational device) as stated in this 
protocol. 
3. Participant with known concurrent viral hepatitis or known positivity for hepatitis B surface 
antigen or hepatitis C virus (HCV) antibody or known human immunodeficiency virus (HIV) 
infection. At Screening, a hepatitis panel result that indicates immunity due to hepatitis B 
vaccination is not considered an exclusion criterion. At Screening, a participant may not have 
any of the following: 
− Hepatitis B surface antigen, hepatitis B core antibody, hepatitis B virus deoxyribonucleic 
acid (DNA) assay: Positive to any of these. 
− HCV antibody: Positive. 
− HIV antigen or antibody: Positive to either test. 
4. Participant with a history of chronic or recurrent infections, or recent serious or 
life-threatening infection within the 6 months prior to the Baseline Visit (including 
hospitalization for any infection in the last 6 months or any current sign or symptom that may 
indicate an infection). 
5. Participant has known TB infection, is at high risk of acquiring TB infection, has latent TB 
infection, or has current or history of nontuberculous mycobacterial (NTMB) infection. 
− Known active TB disease 
− History of active TB involving any organ system unless adequately treated according to 
World Health Organization/Centers for Disease Control therapeutic guidance and proven 
to be fully recovered upon consult with a TB specialist 
− Latent tuberculosis infection (unless appropriate prophylaxis is initiated at least 4 weeks 
prior to IMP dosing and will be continued to completion of prophylaxis). Prophylaxis 
should be in accordance with applicable clinical guidelines and TB specialist judgment 
based on the origin of the infection. 
− High risk of acquiring TB infection. 
− Current NTMB infection or history of NTMB infection unless proven to be fully 
recovered 
Nontuberculous mycobacterial infection is defined as a group of lung infections caused by 
mycobacteria different from mycobacterium TB infections. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 22 of 66 
For further information relating to definitions of known active TB, past history of TB, latent 
TB infection, high risk of acquiring TB infection, and NTMB infection, refer to 
Section 8.2.5. 
6. Participant has active neoplastic disease or a history of neoplastic disease within 5 years of 
enrollment (except for basal or squamous cell carcinoma of the skin or carcinoma in situ 
which has been definitively treated with standard of care approaches). 
7. Participant has concomitant diagnosis of any other inflammatory condition (eg, psoriatic 
arthritis, sarcoidosis, or systemic lupus erythematosus). 
8. Participant has clinically significant electrocardiogram (ECG) abnormalities at Screening. 
Prior/Concomitant therapy 
9. Participant has previously been exposed to CZP. 
10. Participant is a primary failure to at least 1 TNFα inhibitor (a primary failure is defined as no 
clinical disease improvement within the first 12 weeks of treatment). Study participants who 
demonstrated clinical response within 12 weeks of treatment and subsequently lost response 
after 12 weeks of treatment are eligible. 
11. Participant has received a live vaccination within 6 weeks prior to Screening or intends to 
have a live vaccination during the course of the study or within 3 months following CZP 
treatment in the study. 
Prior/Concurrent clinical study experience 
12. Participant has received any investigational drug or experimental procedure within 90 days 
prior to the first dose of IMP. 
Diagnostic assessments 
13. Participant has a laboratory abnormality at Screening, including any of the following: 
− >3.0x upper limit of normal (ULN) of any of the following: alanine aminotransferase 
(ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP); or >ULN total 
bilirubin (>1.5xULN total bilirubin if the participant has a documented pre-study 
diagnosis of Gilbert’s syndrome). 
− white blood cell count <3.00x103/μL. 
− absolute neutrophil count (ANC) <1.5x103/μL. 
− lymphocyte count <500 cells/μL. 
− hemoglobin <8.5g/dL. 
− Any other laboratory abnormality, which, in the opinion of the Investigator, will prevent 
the study participant from completing the study or will interfere with the interpretation of 
the study results. 
 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 23 of 66 
5.3 
Lifestyle restrictions 
5.3.1 
Meals and dietary restrictions 
No meal or dietary restrictions are required during this study. 
5.3.2 
Caffeine, alcohol, and tobacco 
No caffeine, alcohol, and tobacco restrictions are required during this study; any restrictions (for 
the purposes of routine clinical management) are left to the judgment of the Investigator. 
5.3.3 
Activity 
No activity restrictions are required during this study. 
5.4 
Screen failures 
Screen failures are defined as participants who consent to participate in the clinical study but are 
not subsequently entered in the study. A minimal set of screen failure information is required to 
ensure transparent reporting of screen failure participants to meet the Consolidated Standards of 
Reporting Trials (CONSORT) publishing requirements and to respond to queries from regulatory 
authorities. Minimal information includes demography, screen failure details, eligibility criteria, 
and any SAE. 
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened.  
Tests that result in ALT, AST, or ALP up to 25% above the exclusion limit may be repeated only 
once for confirmation. This one-time repeat testing may be within the initial screening window 
or as part of a rescreening following a screen failure. Upon retesting, study participants whose 
results remain outside the exclusion limit are not to be enrolled. 
6 
STUDY TREATMENTS 
Study treatment is defined as any investigational treatment(s), marketed product(s), placebo, or 
medical device(s) intended to be administered to a study participant according to the study 
protocol. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 24 of 66 
6.1 
Treatments administered 
Certolizumab pegol is an engineered, humanized, monoclonal antibody Fab’ fragment with 
specificity for human TNFα, produced in an Escherichia coli expression system. The antibody 
fragment is subsequently purified and conjugated with high molecular weight PEG (40kDa). 
Intervention name 
CZP 
Type 
Biologic 
Dose formulation 
Pre-filled syringe (1mL) 
Unit dose strength(s) 
200mg/mL 
Dosage levels 
400mg loading dose for first 3 doses (at Weeks 0, 2, and 4), followed by 
200mg Q2W maintenance dose thereafter 
Route of 
administration 
sc injection 
Use 
Experimental 
Sourcing 
Provided by UCB Clinical Trial Supply or designee 
Packaging and labeling 
The study medication is packaged according to GMP guidelines and 
applicable laws or regulations; study medication is labeled in accordance with 
current ICH, GCP, and GMP and includes any locally required statements. 
Current/Former names 
CDP870, Cimzia, CZP 
CZP=certolizumab pegol; GCP=Good Clinical Practice; GMP=Good Manufacturing Practice; ICH=International 
Council for Harmonisation; Q2W=every 2 weeks; sc=subcutaneous 
6.2 
Preparation, handling, storage, and accountability requirements 
The Investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study treatment received and any discrepancies reported and 
resolved before use of the study treatment. 
Only participants enrolled in the study may receive study treatment and only authorized site staff 
and home health nurses may supply and administer study treatment prior to Week 12. After 
Week 12, study participants will have the choice to self-administer CZP or receive treatment at 
the clinic/study site. All study treatments must be stored in a secure, environmentally-controlled, 
and monitored (manual or automated) area in accordance with the labeled storage conditions 
with access limited to the Investigator and authorized site staff. 
The Investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study treatment accountability, reconciliation, and record maintenance 
(ie, receipt, reconciliation, and final disposition records). 
In case an out-of-range temperature is noted, it must be immediately reported as per instructions 
contained in the IMP Handling Manual. 
The Investigator (or designee) will instruct the participant to store the study medication 
following the instructions on the label. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 25 of 66 
Further guidance and information for the final disposition of unused study treatment are provided 
in the Study Reference Manual. 
6.2.1 
Drug accountability 
The Case Report Form (CRF) will be used to record study medication dispensing and return 
information on a by-participant basis and will serve as source documentation during the course 
of the study. Details of any study medication lost, damaged (due to breakage or wastage), not 
used, partially used, disposed of at the study site, or returned to the Sponsor or designee must 
also be recorded on the appropriate forms. All supplies and pharmacy documentation must be 
made available throughout the study for UCB (or designee) to review. 
The Investigator (or designee) is responsible for retaining all used, unused, and partially used 
containers of study medication until returned or destroyed. 
The Investigator may assign some of the Investigator’s duties for drug accountability at the study 
site to an appropriate pharmacist/designee. 
The Investigator must ensure that the study medication is used only in accordance with this 
protocol. 
Periodically, and/or after completion of the clinical phase of the study, all used (including empty 
containers)/partially used, unused, damaged, and/or expired study medication must be reconciled 
and either destroyed at the site according to local laws, regulations, and UCB Standard Operating 
Procedures or returned to UCB (or designee). Investigational medicinal product intended for the 
study cannot be used for any other purpose than that described in this protocol. 
6.3 
Measures to minimize bias: randomization and blinding 
This is an open-label study. 
6.4 
Treatment compliance 
At each visit after study medication is dispensed, participants must return all unused study 
medication and empty study medication containers. Drug accountability must be done in the 
participant’s presence in order to obtain explanations regarding discrepancies in compliance with 
the dosing regimen. Drug accountability must be recorded on the Drug Accountability Form. 
6.5 
Concomitant medication(s)/treatment(s) 
6.5.1 
Permitted concomitant treatments (medications and therapies) 
The following concomitant medications are permitted during the study: 
• Methotrexate, under the following conditions: 
− Participant must have been stable for at least 1 month before Screening. 
− The participant’s route of MTX administration and dose of MTX should not change until 
after Week 12 of the study. 
− The (minimum of) 8 participants who are not taking MTX upon study entry cannot begin 
MTX until after Week 12 of the Treatment Period. 
− Dose reductions are permitted at any point during the study for safety reasons. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 26 of 66 
Other medications not explicitly prohibited per Section 6.5.2 are also included as permitted 
concomitant treatments. 
6.5.2 
Prohibited concomitant treatments (medications and therapies) 
The following concomitant medications are prohibited during the study: 
• Conventional synthetic DMARDs (csDMARDs) other than MTX (see Section 6.5.1 for MTX 
parameters). 
• Targeted synthetic DMARDs (tsDMARDs), eg, the Janus kinase inhibitor, tofacitinib. 
• Biologic DMARDs (CZP study medication excepted). 
• Any experimental (biological or nonbiological) therapy (within or outside a clinical study). 
• Live and live attenuated vaccinations including, but not limited to, oral polio, chicken pox 
(varicella), measles-mumps-rubella, nasal influenza, and rotavirus. No data are available on 
the response to live vaccinations or the secondary transmission of infection by live vaccines 
in study participants receiving CZP. 
6.5.3 
Rescue medication 
The Sponsor will not supply rescue medications. Such medicines should be sourced/prescribed 
locally by the treating physician. The following rescue medications may be used: 
• Any RA rescue medications available, excluding biologic DMARDs (CZP study medication 
excepted), csDMARDs other than MTX (see Section 6.5.1), and tsDMARDs. Any 
participants who use a biologic DMARD (other than study medication), csDMARD other 
than MTX (as per Section 6.5.1), or tsDMARD should be immediately withdrawn from the 
study. 
The date and time of rescue medication administration as well as the name and dosage regimen 
of the rescue medication must be recorded. 
If the study participant requires administration of a biologic DMARD, csDMARD other than 
MTX (as per Section 6.5.1), or tsDMARD, they must be removed from the study (Section 7.2). 
6.6 
Dose modification 
No dose modifications of the IMP will be allowed in this study, outside the transition from the 
loading doses to the maintenance dose (Section 6.1). 
6.6.1 
Dose interruptions 
Dose interruptions may only take place due to safety concerns. Participants who have a dose 
interruption will be followed according to the Schedule of Activities (Section 1.3). 
6.7 
Criteria for study hold or dosing stoppage 
As this is a study of an approved therapeutic for an approved indication, there are no anticipated 
study hold or dosing stoppage criteria planned. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 27 of 66 
6.8 
Treatment after the end of the study 
Study participants may transition to treatment with commercially-available CZP in consultation 
with their health care professional following completion of the last administration of IMP. 
7 
DISCONTINUATION OF STUDY MEDICATION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1 
Discontinuation of study medication 
7.1.1 
Liver chemistry stopping criteria 
Discontinuation of study treatment for abnormal liver function should be considered by the 
Investigator when a participant meets one of the conditions outlined in Figure 7-1 or if the 
Investigator believes that it is in best interest of the participant. 
Study medication will be discontinued immediately and permanently for a participant if liver 
chemistry stopping criteria are met. 
 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 28 of 66 
Figure 7-1: Liver Chemistry Stopping Criteria and Increased Monitoring 
Algorithm 
 
 
Abbreviations: ALT=alanine transaminase; AST=aspartate aminotransferase; INR=international normalized ratio; 
SAE=serious adverse event; ULN=upper limit of normal 
Liver Safety: Suggested Actions and Follow-up Assessments can be found in Appendix 6 
(Section 10.6). 
7.2 
Participant Discontinuation/Withdrawal from the study 
Participants are free to withdraw from the study at any time, without prejudice to their continued 
care. 
A participant may withdraw from the study at any time at his/her own request, or may be 
withdrawn at any time at the discretion of the Investigator for safety, behavioral, compliance, or 
administrative reasons. 
If the participant withdraws consent for disclosure of future information, the Sponsor may retain 
and continue to use any data collected before such a withdrawal of consent. 
If a participant withdraws from the study, he/she may request destruction of any samples taken 
and not tested, and the Investigator must document this in the site study records. 
See the Schedule of Activities (Section 1.3) for data to be collected at the time of study 
discontinuation and follow-up and for any further evaluations that need to be completed. 
Continue Study Treatment 
Discontinue Study Treatment 
Plus 
Bilirubin≥2x
ULN (>35% 
direct) or plus
INR>1.5, if 
measured*
Possible  
Hy’s Law
ALT≥3xULN
ALT
≥8xULN
Plus
Symptoms of 
liver injury
or 
hypersensitivity
No
Yes
Yes
Yes
No
No
No
See algorithm 
for continued 
therapy with 
increased liver 
chemistry 
monitoring
Yes
ALT 
≥3xULN 
but 
<8xULN
Yes
Refer to the Liver Safety Required Actions and Follow-up Assessments section in 
Appendix 6. 
Report as an SAE if possible Hy’s Law case: AST/ALT ≥3xULN and Bilirubin 
≥2xULN (>35% direct) or INR >1.5, if measured* 
(Note: INR value not applicable to patients on anticoagulants) 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 29 of 66 
Participants should be withdrawn from the study if any of the following events occur: 
1. Participant develops an illness that would interfere with his/her continued participation. 
2. Participant is noncompliant with the study procedures or medications in the opinion of the 
Investigator. 
3. Participant takes prohibited concomitant medications as defined in this protocol. 
4. Participant may withdrawal at any time due to lack of efficacy. At study discontinuation, the 
participant may be offered other treatment options, at the Investigator’s discretion. 
5. Participant withdraws his/her consent. 
6. Participant has confirmation of a pregnancy during the study, as evidenced by a positive 
pregnancy test. 
7. The Sponsor or a regulatory agency requests withdrawal of the participant. 
Investigators should contact the Medical Monitor, whenever possible, to discuss the withdrawal 
of a participant in advance. 
7.3 
Lost to follow-up 
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. 
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit: 
• The site must attempt to contact the participant and reschedule the missed visit as soon as 
possible and counsel the participant on the importance of maintaining the assigned visit 
schedule and ascertain whether or not the participant wishes to and/or should continue in the 
study. 
• Before a participant is deemed lost to follow-up, the Investigator or designee must make 
every effort to regain contact with the participant (at least 1 phone call and 1 written message 
to the participant), and document his/her effort (date and summary of the phone call and copy 
of the written message in the source documents), to complete the final evaluation. All results 
of these evaluations and observations, together with a narrative description of the reason(s) 
for removing the participant, must be recorded in the source documents. The CRF must 
document the primary reason for withdrawal. 
Should the participant continue to be unreachable, he/she will be considered to have withdrawn 
from the study with a primary reason of lost to follow-up documented in the CRF. 
8 
STUDY ASSESSMENTS AND PROCEDURES 
Study procedures and their timing are summarized in the Schedule of Activities (Section 1.3). 
Protocol waivers or exemptions are not allowed. Immediate safety concerns should be discussed 
with the Sponsor immediately upon occurrence or awareness to determine if the participant 
should continue or discontinue study treatment. 
Adherence to the study design requirements, including those specified in the Schedule of 
Activities (Section 1.3), is essential and required for study conduct. All Screening evaluations 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 30 of 66 
must be completed and reviewed to confirm that potential participants meet all eligibility criteria. 
The Investigator will maintain a screening log to record details of all participants screened and to 
confirm eligibility or record reasons for screening failure, as applicable. 
Procedures conducted as part of the participant’s routine clinical management (eg, blood count) 
and obtained before signing of the ICF may be utilized for Screening or Baseline purposes 
provided the procedures met the protocol-specified criteria and were performed within the time 
frame defined in the Schedule of Activities (Section 1.3). 
The maximum amount of blood collected from each participant over the duration of the study, 
including any extra assessments that may be required, will not exceed 100mL. Repeat or 
unscheduled samples may be taken for safety reasons or for technical issues with the samples. 
8.1 
Efficacy assessments 
8.1.1 
Multi-dimensional Health Assessment Questionnaire (MDHAQ) and 
RAPID3 scoring 
The MDHAQ items that make up the Routine Assessment of Patient Index Data 3 RAPID3 
(Appendix 12 [Section 10.12]) will be assessed at Baseline and Week 12 as indicated in the 
Schedule of Activities (Section 1.3). The MDHAQ is derived from the HAQ, and the sections 
that will be utilized are the following: 
• MDHAQ-FN : Physical function listed in 10 activities; converted to a scale from 0 to 10 for 
the RAPID3 score 
• MDHAQ-PN : Pain assessed as 0.5 increments from 0 to 10 
• MDHAQ-PTGL : Patient's global status assessed as 0.5 increments from 0 to 10 
RAPID3 is calculated as the sum (0 to 30) of FN, PN, and PTGL. 
8.2 
Safety assessments 
Planned time points for all safety assessments are provided in the Schedule of Activities 
(Section 1.3). 
8.2.1 
Physical examination 
A complete physical examination will include, at a minimum, vital signs; general appearance; 
ear, nose, and throat; eyes, hair, and skin; and assessments of the Cardiovascular, Respiratory, 
Gastrointestinal Neurological, Musculoskeletal, and Hepatic systems. Height and weight will 
also be measured and recorded. 
Investigators should pay special attention to clinical signs related to previous serious illnesses. 
Clinically relevant findings or worsening of previous findings will be recorded as AEs. 
8.2.2 
Vital signs 
Oral temperature, pulse rate, respiratory rate, and blood pressure will be measured as described 
in the Schedule of Activities (Section 1.3). 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 31 of 66 
8.2.3 
Electrocardiograms 
Single 12-lead ECG will be obtained as outlined in the Schedule of Activities (see Section 1.3) 
using an ECG machine that automatically calculates heart rate and measures PR, QRS, QT, and 
QTc intervals. 
All ECG recordings should be taken with the study participant resting in the supine position for 
at least 5 minutes before the recording. 
8.2.4 
Clinical safety laboratory assessments 
See Appendix 2 (Section 10.2) for the list of clinical laboratory tests to be performed and to the 
Schedule of Activities (Section 1.3) for the timing and frequency. 
The Investigator must review the laboratory report, document this review, and record any 
clinically relevant changes occurring during the study in the AE section of the CRF. The 
laboratory reports must be filed with the source documents. Clinically significant abnormal 
laboratory findings are those which are not associated with the underlying disease, unless judged 
by the Investigator to be more severe than expected for the participant's condition. 
All laboratory tests with values considered to be clinically significantly abnormal during 
participation in the study should be repeated until the values return to normal or Baseline or are 
no longer considered clinically significant by the Investigator or Medical Monitor. 
If such values do not return to normal/baseline within a period of time judged reasonable by the 
Investigator, the etiology should be identified and the Sponsor notified. 
All protocol-required laboratory assessments, as defined in Appendix 2 (Section 10.2), must be 
conducted in accordance with the laboratory manual and the Schedule of Activities (Section 1.3). 
If laboratory values from non-protocol specified laboratory assessments performed at the 
institution’s local laboratory require a change in participant management or are considered 
clinically significant by the Investigator (eg, SAE or AE or dose modification), then the results 
must be recorded in the CRF. 
8.2.5 
Tuberculosis assessment 
The Investigator should consider all potential sites of infection when assessing for TB during the 
physical examination and other evaluations, and based on the study participant’s medical or 
social history. 
8.3 
Adverse events and serious adverse events 
The definitions of AEs and SAEs are provided in Appendix 3 (Section 10.3). 
AE will be reported by the participant (or, when appropriate, by a caregiver, surrogate, or the 
participant's legally authorized representative). 
The Investigator and any designees are responsible for detecting, documenting, and recording 
events that meet the definition of an AE or SAE and remain responsible for following up AEs 
that are serious, considered related to the study treatment or study procedures, or that caused the 
participant to discontinue the CZP (Section 7). 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 32 of 66 
8.3.1 
Time period and frequency for collecting AE and SAE information 
All AEs and SAEs will be collected from the signing of the ICF until the SFU visit as specified 
in the Schedule of Activities (Section 1.3). 
In order to ensure complete safety data collection, all AEs occurring during the study (ie, after 
the signing of the ICF), including any pretreatment and posttreatment periods required by the 
protocol, must be reported in the CRF even if no study medication was taken but specific study 
procedures were conducted. This includes all AEs not present prior to the initial visit and all AEs 
that recurred or worsened after the initial visit. 
All SAEs will be recorded and reported to the Sponsor or designee within 24 hours, as indicated 
in Appendix 3 (Section 10.3). The Investigator will submit any updated SAE data to the Sponsor 
within 24 hours of it being available. 
The Investigator is specifically requested to collect and report to UCB (or its representative) any 
SAEs (even if the Investigator is certain that they are in no way associated with the study 
medication), up to 70 days from the end of the study for each participant, and to also inform 
participants of the need to inform the Investigator of any SAE within this period. Serious AEs 
that the Investigator thinks may be associated with the study medication must be reported to 
UCB regardless of the time between the event and the end of the study. 
The method of recording, evaluating, and assessing causality of AE and SAE and the procedures 
for completing and transmitting SAE reports are provided in Appendix 3 (Section 10.3). 
8.3.2 
Method of detecting AEs and SAEs 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences. 
8.3.3 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the Investigator is required to proactively follow each 
participant at subsequent visits/contacts. All SAEs, and non-serious AEs of special interest (as 
defined in Section 8.3.6), will be followed until resolution, stabilization, the Investigator 
determines that it is no longer clinically significant, the event is otherwise explained, or the 
participant is lost to follow-up (as defined in Section 7.3). Further information on follow-up 
procedures is given in Appendix 3 (Section 10.3). 
8.3.4 
Regulatory reporting requirements for SAEs 
Prompt notification by the Investigator to the Sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a study 
treatment under clinical investigation are met. 
The Sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study treatment under clinical investigation. The 
Sponsor will comply with country-specific regulatory requirements relating to safety reporting to 
the regulatory authority, Institutional Review Boards (IRB)/Independent Ethics Committees 
(IEC), and Investigators. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 33 of 66 
Investigator safety reports must be prepared for suspected unexpected serious adverse reactions 
according to local regulatory requirements and Sponsor policy and forwarded to Investigators as 
necessary. 
An Investigator who receives an Investigator safety report describing an SAE or other specific 
safety information (eg, summary or listing of SAEs) from the Sponsor will review and then file it 
along with the Investigator’s Brochure and will notify the IRB/IEC, if appropriate according to 
local requirements. 
8.3.5 
Pregnancy 
Details of all pregnancies in female participants and, if indicated, female partners of male 
participants will be collected after the start of study treatment and until SFU Visit. 
If a pregnancy is reported, the Investigator must inform the Sponsor within 24 hours of learning 
of the pregnancy and should follow the procedures outlined in Appendix 4 (Section 10.4). 
The participant should be withdrawn from the study as soon as pregnancy is known (by positive 
pregnancy test), and the following should be completed: 
• The participant should immediately stop the intake of the study medication. 
• The participant should return for an Early Discontinuation Visit. 
• An SFU Visit should be scheduled 70 days after the participant has discontinued her study 
medication. 
• The participant should complete a Pregnancy Outcome Form per UCB Standard Operating 
Procedures. 
Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, ectopic pregnancy) are considered SAEs. 
8.3.6 
Adverse events of special interest 
An AE of special interest is any AE that a regulatory authority has mandated be reported on an 
expedited basis, regardless of the seriousness, expectedness, or relatedness of the AE to the 
administration of a UCB product/compound. For CZP, the following events require immediate 
reporting (within 24 hours regardless of seriousness) to UCB: 
• Hy’s Law 
− Potential Hy’s Law, defined as ≥3xULN ALT or AST with coexisting ≥2xULN total 
bilirubin in the absence of ≥2xULN ALP, with no alternative explanation for the 
biochemical abnormality (ie, without waiting for any additional etiologic investigations 
to have been concluded). Follow-up information should be reported if an alternative 
etiology is identified during investigation and monitoring of the participant. 
• Serious infections, including opportunistic infections. 
• Malignancies, including lymphoma. 
• Congestive heart failure. 
• Demyelinating-like disorders. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 34 of 66 
• Aplastic anemia, pancytopenia, thrombocytopenia, neutropenia, and leukopenia. 
• Serious bleeding events. 
• Lupus and lupus-like syndrome. 
• Serious skin reactions (eg, Stevens-Johnson syndrome, toxic epidermal necrosis, and 
erythema multiforme). 
8.3.7 
Anticipated serious adverse events 
The anticipated SAE in Table 8-1 is anticipated to occur in the population studied in this protocol 
at some frequency that is independent of drug exposure. 
• This list does not change the Investigator’s obligation to report all SAEs (including 
anticipated SAEs) as detailed in Section 8.3.4 and Appendix 3 (Section 10.3). 
Table 8-1: 
Anticipated serious adverse event for RA population 
Preferred term: 
Rheumatoid arthritis 
8.4 
Safety signal detection 
Selected data from this study will be reviewed periodically to detect as early as possible any 
safety concern(s) related to the study medication so that Investigators, clinical study participants, 
regulatory authorities, and IRBs/IECs will be informed appropriately and as early as possible. 
The Study Physician or medically qualified designee/equivalent will conduct an ongoing review 
of SAEs and perform ongoing SAE reconciliations in collaboration with the Patient Safety 
representative. 
As appropriate for the stage of development and accumulated experience with the study 
medication, medically qualified personnel at UCB may identify additional safety measures 
(eg, AEs, vital signs, laboratory or ECG results) for which data will be periodically reviewed 
during the course of the study. 
8.5 
Treatment of overdose 
Excessive dosing (beyond that prescribed in the protocol and including overdose) should be 
recorded in the Drug Accountability module of the CRF. Any SAE or nonserious AE associated 
with excessive dosing must be followed as any other SAE or nonserious AE. These events are 
only considered AEs or SAEs if there are associated clinical signs and symptoms or if the act of 
taking the excess medicine itself is an AE or SAE (eg, suicide attempt). 
UCB does not recommend specific treatment for an overdose. In the event of an overdose, the 
Investigator should: 
1. Contact the Medical Monitor immediately. 
2. Closely monitor the participant for any AE/SAE and laboratory abnormalities until CZP can 
no longer be detected systemically (at least 70 days). 
3. Obtain a plasma sample for PK analysis within 70 days from the date of the last dose of study 
treatment if requested by the Medical Monitor (determined on a case-by-case basis). 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 35 of 66 
4. Document the quantity of the excess dose as well as the duration of the overdose in the CRF. 
Decisions regarding dose interruptions or modifications will be made by the Investigator in 
consultation with the Medical Monitor based on the clinical evaluation of the participant. 
8.6 
Pharmacokinetics 
Pharmacokinetic samples will be tested using the ECLIA method. All PK assessments will be 
evaluated as described in the Schedule of Activities (Section 1.3). 
Whole blood samples of approximately 5 mL will be collected for measurement of plasma 
concentrations of CZP as specified in the Schedule of Activities (Section 1.3). A maximum of 
3 samples may be collected at additional time points during the study if warranted and agreed 
upon between the Investigator and the Sponsor. Instructions for the collection and handling of 
biological samples will be provided by the Sponsor. The actual date and time (24-hour clock 
time) of each sample will be recorded. 
Samples will be used to evaluate the PK of CZP. Samples collected for analyses of CZP 
(plasma/serum/whole blood) concentration may also be used to evaluate safety or efficacy 
aspects related to concerns arising during or after the study. 
Genetic analyses will not be performed on the plasma or whole blood samples. 
8.7 
Genetics 
Genetics will not be evaluated in this study. 
8.8 
Pharmacodynamics 
Pharmacodynamic parameters will not be evaluated in this study. 
8.9 
Biomarkers 
Biomarkers will not be evaluated in this study. 
8.9.1 
Immunogenicity assessments 
Immunogenicity samples will be tested using the ECLIA method. Antibodies to CZP will be 
evaluated in plasma samples collected from all participants according to the Schedule of 
Activities (Section 1.3). These samples will be tested by the Sponsor or Sponsor's designee. 
Plasma samples will be screened for antibodies binding to CZP and the titer of confirmed 
positive samples will be reported. Other analyses may be performed to further characterize the 
immunogenicity of CZP. 
8.10 
Health economics or medical resource utilization and health 
economics 
Health economics/medical resource utilization and health economics parameters are not 
evaluated in this study. 
9 
STATISTICAL CONSIDERATIONS 
A description of statistical methods follows and will be described in more detail in the Statistical 
Analysis Plan. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 36 of 66 
9.1 
Definition of analysis sets 
The following analysis sets will be used in the study: 
• All Study Participants (ASP) will include those study participants who are confirmed as 
having signed the ICF form to participate in the study. 
• The Safety Set (SS) will include all study participants enrolled who receive ≥1 injection of 
study medication. Safety variables will be summarized using the SS. 
• The Pharmacokinetic Set (PKS) is a subset of the SS, consisting of study participants who 
have provided plasma samples with measurable concentrations (with recorded sampling 
time) on at least 1 visit, and who have no important protocol deviations affecting the PK 
parameters. 
9.2 
General statistical considerations 
Statistical analysis and generation of tables, figures, and study participant data listings will be 
performed using statistical analysis system (SAS®, SAS Institute, Cary, NC, US) version 9.3 or 
higher using validated program code according to relevant standard operating procedures. 
For categorical parameters, the number and percentage of study participants in each category will 
be presented. The denominator for percentages will be based on the number of study participants 
appropriate for the purpose of the analysis. For continuous parameters, descriptive statistics will 
include number of study participants, arithmetic mean, standard deviation, median, minimum, 
and maximum (with 25th and 75th percentiles as optional). 
For CZP plasma concentration, the geometric mean and corresponding coefficient of variation 
will be presented. The geometric coefficient of variation (CV) is calculated as 
sqrt (exp(std ln^2)-1)*100, where std ln is the standard deviation of the log-transformed data. 
Baseline is defined as the last nonmissing measurement collected before the first injection. 
9.3 
Planned safety and other analyses 
Safety will be assessed using the SS. Pharmacokinetics and immunogenicity will be assessed 
using the PKS. 
All safety endpoints will be analyzed using descriptive statistics. Safety summaries will include 
presentations of AEs, laboratory values, and vital signs. 
Adverse events will be coded according to the Medical Dictionary for Regulatory Activities. 
Treatment-emergent AEs will be defined as events that have a start date on or following the first 
administration of study treatment in RA0138 through the final administration of study treatment 
+70 days. 
9.3.1 
Other analyses 
9.3.1.1 
Pharmacokinetic analyses 
Pharmacokinetic analysis will be performed on the PKS population. 
Concentration-time profiles will be summarized by visit, and descriptive statistics performed, 
including: n, geometric mean, CV%, maximum, minimum, arithmetic mean, and standard 
deviation. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 37 of 66 
A PK analysis will be performed to derive noncompartmental CZP PK parameters (Cmin and 
AUC) after their Week 10 dose. If needed, additional PK parameters may be derived based on 
the data. Further details of the analysis will be specified in the Statistical Analysis Plan. 
9.3.1.2 
Immunogenicity analyses 
The incidence of immunogenicity will be summarized by body weight group and visit, as 
specified. Individual plots of the CZP concentrations, clinical response, and safety will be 
expressed by ADA titer category. 
9.3.1.3 
RAPID3 analysis 
As this is a PK study, the RAPID3 assessment (utilizing the MDHAQ) is included to assist in 
clinical decision-making, and RAPID3 data will be listed (including change from Baseline) 
based on the SS population (Appendix 12 [Section 10.12]). 
9.4 
Handling of protocol deviations 
Important protocol deviations are deviations from the protocol which potentially could have a 
meaningful impact on study conduct or on the primary efficacy, key safety, or PK outcomes for 
an individual study participant. The criteria for identifying important protocol deviations and the 
classification of important protocol deviations will be defined within the Important Protocol 
Deviations Template. To the extent feasible, rules for identifying protocol deviations will be 
defined without review of the data and without consideration of the frequency of occurrence of 
such deviations. Whenever possible, criteria for identifying important protocol deviations will be 
implemented algorithmically to ensure consistency in the classification of important protocol 
deviations across all study participants. 
All important protocol deviations will be listed by study participant. 
9.5 
Handling of dropouts or missing data 
Missing or partial dates for safety evaluations will be imputed and full details of these algorithms 
will be presented in the Statistical Analysis Plan. 
As discussed in Section 9.2, Baseline is defined as the last nonmissing pretreatment 
measurement. Therefore, data from the Screening Visit (if available) will be used as Baseline 
values, if data are missing at Week 0. 
No further imputations of any other missing data are planned. 
9.6 
Planned interim analysis and data monitoring 
No interim analysis or data monitoring is planned. 
9.7 
Determination of sample size 
With no formal hypothesis testing, a sample size of 30 enrolled participants with 25 participants 
who completed Visit 13 is deemed to provide sufficient plasma CZP concentration data with the 
ECLIA analytical method to serve as a reference PK dataset for PK matching in the pJIA 
program. Further, a simulation and re-estimation method applied using a non-RA CZP 
population PK model indicated that a sample size of 25 participants who completed Visit 13 in a 
study with the PK sampling scheme as that presently planned can estimate absorption rate 
constant, clearance, and distribution volume with acceptable precision (relative standard 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 38 of 66 
deviation of <16%). Participants who withdraw from the study may be replaced at the discretion 
of the Investigator and Sponsor, depending on the circumstances. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 39 of 66 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1 
Appendix 1: Regulatory, ethical, and study oversight 
considerations 
10.1.1 
Regulatory and ethical considerations 
The study will be conducted under the auspices of an IRB/IEC, as defined in local regulations, 
International Council for Harmonisation (ICH)-Good Clinical Practice (GCP), and in accordance 
with the ethical principles that have their origin in the Declaration of Helsinki. 
The Investigator/UCB will ensure that an appropriately constituted IRB/IEC that complies with 
the requirements of the current ICH-GCP version or applicable country-specific regulations will 
be responsible for the initial and continuing review and approval of the clinical study. Prior to 
initiation of the study, the Investigator/UCB will forward copies of the protocol, ICF, 
Investigator’s Brochure, Investigator’s curriculum vitae (if applicable), advertisement (if 
applicable), and all other participant-related documents to be used for the study to the IRB/IEC 
for its review and approval. 
Before initiating a study, the Investigator will have written and dated full approval from the 
responsible IRB/IEC for the protocol. 
The Investigator will also promptly report to the IRB/IEC all changes in the study, all 
unanticipated problems involving risks to participants or others, and any protocol deviations, to 
eliminate immediate hazards to participants. 
The Investigator will not make any changes in the study or study conduct without IRB/IEC 
approval, except where necessary to eliminate apparent immediate hazards to the participants. 
For minor changes to a previously approved protocol during the period covered by the original 
approval, it may be possible for the Investigator to obtain an expedited review by the IRB/IEC as 
allowed. 
As part of the IRB/IEC requirements for continuing review of approved studies, the Investigator 
will be responsible for submitting periodic progress reports to the IRB/IEC (based on IRB/IEC 
requirements), at intervals appropriate to the degree of participant risk involved, but no less than 
once per year. The Investigator should provide a final report to the IRB/IEC following study 
completion. 
UCB (or its representative) will communicate safety information to the appropriate regulatory 
authorities and all active Investigators in accordance with applicable regulatory requirements. 
The appropriate IRB/IEC will also be informed by the Investigator or the Sponsor, as specified 
by the applicable regulatory requirements in each concerned country. Where applicable, 
Investigators are to provide the Sponsor (or its representative) with evidence of such IRB/IEC 
notification. 
10.1.2 
Financial disclosure 
Insurance coverage will be handled according to local requirements. 
Finance and insurance are addressed in the Investigator and/or contract research organization 
agreements, as applicable. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 40 of 66 
10.1.3 
Informed consent process 
A participant’s informed consent must be obtained and documented in accordance with local 
regulations, ICH-GCP requirements, and the ethical principles that have their origin in the 
principles of the Declaration of Helsinki. 
Prior to obtaining informed consent, information should be given in a language and at a level of 
complexity understandable to the participant, in both oral and written form, by the Investigator 
(or designee). Each participant will have the opportunity to discuss the study and its alternatives 
with the Investigator. 
Prior to participation in the study, the ICF should be signed and personally dated by the 
participant, or his/her legal representative, and by the person who conducted the informed 
consent discussion (Investigator or designee). The participant or his/her legal representative must 
receive a copy of the signed and dated ICF. As part of the consent process, each participant must 
consent to direct access to his/her medical records for study-related monitoring, auditing, 
IRB/IEC review, and regulatory inspection. 
If the ICF is amended during the study, the Investigator (or the Sponsor, if applicable) must 
follow all applicable regulatory requirements pertaining to the approval of the amended ICF by 
the IRB/IEC and use of the amended form. 
All studies conducted at centers in the US must include the use of a Health Insurance Portability 
and Accountability Act Authorization form. 
The participant may withdraw his/her consent to participate in the study at any time. A 
participant is considered as enrolled in the study when he/she has signed the ICF. A CRF must 
not be started, nor may any study-specific procedure be performed for a given participant, 
without having obtained his/her written consent to participate in the study. 
10.1.4 
Data protection 
UCB staff (or designee) will affirm and uphold the participant’s confidentiality. Throughout this 
study, all data forwarded to UCB (or designee) will be identified only by the participant number 
assigned at Screening. 
The Investigator agrees that representatives of UCB, its designee, representatives of the relevant 
IRB/IEC, or representatives of regulatory authorities will be allowed to review that portion of the 
participant’s primary medical records that directly concerns this study (including, but not limited 
to, laboratory test result reports, ECG reports, admission/discharge summaries for hospital 
admissions occurring during a participant’s study participation, and autopsy reports for deaths 
occurring during the study). 
The participant must be informed that his/her personal study-related data will be used by the 
Sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant. 
The participant must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the Sponsor, by 
appropriate IRB/IEC members, and by inspectors from regulatory authorities. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 41 of 66 
10.1.5 
Committees structure 
Not applicable. 
10.1.6 
Data quality assurance 
All participant data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the Sponsor or designee electronically (eg, laboratory data). The Investigator is 
responsible for verifying that data entries are accurate and correct by physically or electronically 
signing the CRF. 
The Investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF. 
The Investigator must permit study-related monitoring, audits, IRB/IEC review, and regulatory 
agency inspections and provide direct access to source data documents. 
The Sponsor or designee is responsible for the data management of this study including quality 
checking of the data. 
Study monitors will perform ongoing source data verification to confirm that data entered into 
the CRF by authorized site personnel are accurate, legible, contemporaneous, original, and 
attributable from source documents; that the safety and rights of participants are being protected; 
and that the study is being conducted in accordance with the currently approved protocol and any 
other study agreements, ICH GCP, and all applicable regulatory requirements. 
All essential documents must be retained by the Investigator for the minimum retention period 
mandatory under the applicable local laws and regulations. The Investigator will contact UCB 
for authorization prior to the destruction of any study records or in the event of accidental loss or 
destruction of any study records. The Investigator will also notify UCB should he/she relocate or 
move the study-related files to a location other than that specified in the Sponsor’s trial master 
file. 
10.1.6.1 
Case Report form completion 
The Investigator is responsible for prompt reporting of accurate, complete, and legible data in the 
electronic CRFs and in all required reports. 
Any change or correction to the CRF after saving must be accompanied by a reason for the 
change. 
Corrections made after the Investigator’s review and approval (by means of a 
password/electronic signature) will be reapproved by the Investigator. 
The Investigator should maintain a list of personnel authorized to enter data into the electronic 
CRF. 
Detailed instructions will be provided in the CRF Completion Guidelines. 
10.1.7 
Source documents 
All source documents must be accurate, clear, unambiguous, permanent, and capable of being 
audited. They should be made using some permanent form of recording (ink, typing, printing, 
optical disc). They should not be obscured by correction fluid or have temporary attachments 
(such as removable self-stick notes). 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 42 of 66 
Source documents are original records in which raw data are first recorded. These may include 
hospital/clinic/general practitioner records, charts, diaries, x-rays, laboratory results, printouts, 
pharmacy records, care records, ECG or other printouts, completed scales, quality of life 
questionnaires, or video, for example. Source documents should be kept in a secure, limited 
access area. 
Source documents that are computer generated and stored electronically must be printed for 
review by the monitor (eg, ECG reports). Once printed, these copies should be signed and dated 
by the Investigator and become a permanent part of the participant’s source documents. The 
Investigator will facilitate the process for enabling the monitor to compare the content of the 
printout and the data stored in the computer to ensure all data are consistent. 
Electronic data records, such as Holter monitor records or electroencephalogram records, must 
be saved and stored as instructed by UCB (or designee). 
10.1.8 
Study and Site Closure 
The Sponsor designee reserves the right to close the study site or terminate the study at any time 
for any reason at the sole discretion of the Sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies 
have been collected and a study-site closure visit has been performed. 
The Investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the Sponsor or Investigator may include, but are 
not limited to: 
• Failure of the Investigator to comply with the protocol, requirements of the IRB/IEC or local 
health authorities, Sponsor's procedures, or GCP guidelines 
• Inadequate recruitment of participants by the Investigator 
• Discontinuation of further study medication development 
10.1.9 
Publication Policy 
The results of this study may be published or presented at scientific meetings. If this is foreseen, 
the Investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission. 
This allows the Sponsor to protect proprietary information and to provide comments. 
The Sponsor will comply with the requirements for publication of study results. In accordance 
with standard editorial and ethical practice, the Sponsor will generally support publication of 
multicenter studies only in their entirety and not as individual site data. In this case, a 
coordinating Investigator will be designated by mutual agreement. 
Authorship will be determined by mutual agreement and in line with International Committee of 
Medical Journal Editors authorship requirements. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 43 of 66 
10.2 
Appendix 2: Clinical Laboratory Tests 
• The tests detailed in the table below will be performed by the central laboratory (PK and 
ADA samples) or by the local laboratory (safety samples). 
• Local laboratory results are only required in the event that the central laboratory results are 
not available in time for either study treatment administration and/or response evaluation. If a 
local sample is required, it is important that the sample for central analysis is obtained at the 
same time. Additionally, if the local laboratory results are used to make either a study 
treatment decision or response evaluation, the results must be entered into the CRF. 
• Protocol-specific requirements for inclusion or exclusion of participants are detailed in 
Section 5.1 and Section 5.2 of the protocol. 
• Additional tests may be performed at any time during the study as determined necessary by 
the Investigator or required by local regulations. 
Protocol-Required Safety Laboratory Assessments 
Laboratory 
Assessments 
Parameters 
Hematology 
Platelet Count 
RBC Indices: 
MCV 
MCH 
%Reticulocytes 
WBC Count with 
Differential: 
Neutrophils 
Lymphocytes 
Monocytes 
Eosinophils 
Basophils 
RBC Count 
Hemoglobin 
Hematocrit 
Clinical 
Chemistrya 
Blood Urea 
Nitrogen 
Potassium 
AST/ Serum glutamic-
oxaloacetic transaminase 
Total and direct 
bilirubin 
 
Creatinine 
Sodium 
ALT/ Serum glutamic-pyruvic 
transaminase 
Total protein 
 
Glucose 
(nonfasting) 
Calcium 
ALP 
 
Routine 
Urinalysis 
• 
pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, 
leukocyte esterase by dipstick 
Other Screening 
Tests 
• 
Serum or urine alcohol and drug screen (to include at minimum: 
amphetamines, barbiturates, cocaine, opiates, cannabinoids and 
benzodiazepines) 
• 
Serum or urine hCG pregnancy test (as needed for women of childbearing 
potential)b 
All study-required laboratory assessments will be performed by a central laboratory, 
with the exception of the urine pregnancy test. 
 
The results of each test must be entered into the CRF. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 44 of 66 
Laboratory 
Assessments 
Parameters 
ALP=alkaline phosphatase; ALT=alanine aminotransferase; AST=aspartate aminotransferase; eCRF=electronic 
Case Report form; hCG=human chorionic gonadotropin; HIV=human immunodeficiency virus; 
IEC=Independent Ethics Committee; INR=international normalized ratio; IRB=Institutional Review Board; 
LDH=lactate dehydrogenase; MCH=mean corpuscular hemoglobin; MCHC=mean corpuscular hemoglobin 
concentration; MCV=mean corpuscular volume; RBC=red blood cell; ULN=upper limit of normal; 
WBC=white blood cell 
a Details of liver chemistry stopping criteria and required actions and follow-up assessments after liver stopping 
or monitoring events are given in Section 7.1.1 and Appendix 6 (Section 10.6). All events of ALT 3 ×upper 
limit of normal (ULN) and bilirubin 2 × ULN (>35% direct bilirubin) or ALT 3 × ULN and international 
normalized ratio (INR) >1.5, if INR measured, may indicate severe liver injury (possible Hy’s Law) and must 
be reported as an SAE (excluding studies of hepatic impairment or cirrhosis). 
b Local urine testing will be standard for the protocol unless serum testing is required by local regulation or 
IRB/IEC. 
Investigators must document their review of each laboratory safety report. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 45 of 66 
10.3 
Appendix 3: Adverse Events – Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting 
Definition of AE 
AE Definition 
• 
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally 
associated with the use of study medication, whether or not considered related to the study 
medication. 
• 
NOTE: An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the 
use of study medication. 
 
Events Meeting the AE Definition 
• 
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or other 
safety assessments (eg, ECG, radiological scans, vital signs measurements), including those 
that worsen from baseline, considered clinically significant in the medical and scientific 
judgment of the Investigator (ie, not related to progression of underlying disease). 
• 
Exacerbation of a chronic or intermittent pre-existing condition including either an increase in 
frequency and/or intensity of the condition. 
• 
New conditions detected or diagnosed after study medication administration even though it 
may have been present before the start of the study. 
• 
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
• 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study medication or 
a concomitant medication. Overdose per se will not be reported as an AE/SAE unless it is an 
intentional overdose taken with possible suicidal/self-harming intent. Such overdoses should be 
reported regardless of sequelae. 
• 
The signs, symptoms, and/or clinical sequelae resulting from lack of efficacy will be reported 
as an AE or SAE if they fulfil the definition of an AE or SAE. Also, "lack of efficacy" or 
"failure of expected pharmacological action" also constitutes an AE or SAE. 
 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 46 of 66 
Events NOT Meeting the AE Definition 
• 
Any clinically significant abnormal laboratory findings or other abnormal safety assessments 
which are associated with the underlying disease, unless judged by the Investigator to be more 
severe than expected for the participant’s condition. 
• 
The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the study participant’s 
condition. 
• 
Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that leads to the 
procedure is the AE. 
• 
Situations in which an untoward medical occurrence did not occur (social and/or convenience 
admission to a hospital). 
• 
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or 
detected at the start of the study that do not worsen. 
Definition of SAE 
If an event is not an AE per definition above, then it cannot be an SAE even if serious conditions 
are met (eg, hospitalization for signs/symptoms of the disease under study, death due to 
progression of disease). 
A SAE is defined as any untoward medical occurrence that, at any dose: 
a. Results in death 
b. Is life-threatening 
The term 'life-threatening' in the definition of 'serious' refers to an event in which the participant was at 
risk of death at the time of the event. It does not refer to an event, which hypothetically might have 
caused death, if it were more severe. 
c. Requires inpatient hospitalization or prolongation of existing hospitalization 
In general, hospitalization signifies that the participant has been detained (usually involving at least an 
overnight stay) at the hospital or emergency ward for observation and/or treatment that would not have 
been appropriate in the physician’s office or outpatient setting. Complications that occur during 
hospitalization are AEs. If a complication prolongs hospitalization or fulfils any other serious criteria, 
the event is serious. When in doubt as to whether “hospitalization” occurred or was necessary, the AE 
should be considered serious. 
Hospitalization for elective treatment of a pre-existing condition that did not worsen from baseline is 
not considered an AE. 
d. Results in persistent disability/incapacity 
• 
The term disability means a substantial disruption of a person’s ability to conduct normal life 
functions. 
• 
This definition is not intended to include experiences of relatively minor medical significance 
such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, and accidental trauma 
(eg, sprained ankle) which may interfere with or prevent everyday life functions but do not 
constitute a substantial disruption. 
e. Is a congenital anomaly/birth defect 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 47 of 66 
f. Important medical events: 
• 
Medical or scientific judgment should be exercised in deciding whether SAE 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 participant or may 
require medical or surgical intervention to prevent one of the other outcomes listed in the 
above definition. These events should usually be considered serious. 
• 
Examples of such events include, but are not limited to, potential Hy’s law, 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, or 
development of drug dependency or drug abuse. 
Recording and Follow-up of AE and/or SAE 
AE and SAE Recording 
• 
When an AE/SAE occurs, it is the responsibility of the Investigator to review all 
documentation (eg, hospital progress notes, laboratory reports, and diagnostics reports) related 
to the event. 
• 
The Investigator will then record all relevant AE/SAE information in the CRF. 
• 
It is not acceptable for the Investigator to send photocopies of the participant’s medical records 
to UCB in lieu of completion of the AE/SAE CRF page. 
• 
There may be instances when copies of medical records for certain cases are requested by 
UCB. In this case, all participant identifiers, with the exception of the participant number, will 
be redacted on the copies of the medical records before submission to UCB. 
• 
The Investigator will attempt to establish a diagnosis of the event based on signs, symptoms, 
and/or other clinical information. Whenever possible, the diagnosis (not the individual 
signs/symptoms) will be documented as the AE/SAE. 
Assessment of Intensity 
The Investigator will make an assessment of intensity for each AE and SAE reported during the study 
and assign it to 1 of the following categories: 
• 
Mild: An event that is easily tolerated by the participant, causing minimal discomfort and not 
interfering with everyday activities. 
• 
Moderate: An event that causes sufficient discomfort and interferes with normal everyday 
activities. 
• 
Severe: An event that prevents normal everyday activities. An AE that is assessed as severe 
should not be confused with a SAE. Severe is a category utilized for rating the intensity of an 
event; and both AEs and SAEs can be assessed as severe. 
• 
An event is defined as ‘serious’ when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as severe (eg, a severe AE may be 
either serious or not serious, depending on whether these criteria are also met). 
The National Cancer Institute Common Terminology Criteria for Adverse Events should be used as a 
supportive standardization instrument to evaluate AEs and SAEs, but the final intensity grading by the 
Investigator must be mild, moderate, or severe. 
 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 48 of 66 
Assessment of Causality 
• 
The Investigator is obligated to assess the relationship between study medication and each 
occurrence of each AE/SAE. 
• 
A "reasonable possibility" of a relationship conveys that there are facts, evidence, and/or 
arguments to suggest a causal relationship, rather than a relationship cannot be ruled out. 
• 
The Investigator will use clinical judgment to determine the relationship. 
• 
Alternative causes, such as underlying disease(s), concomitant therapy, and other risk factors, 
as well as the temporal relationship of the event to study medication administration will be 
considered and investigated. 
• 
The Investigator will also consult the Investigator’s Brochure and/or Product Information, for 
marketed products, in his/her assessment. 
• 
For each AE/SAE, the Investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality. 
• 
There may be situations in which an SAE has occurred and the Investigator has minimal 
information to include in the initial report to UCB. However, it is very important that the 
Investigator always make an assessment of causality for every event before the initial 
transmission of the SAE data to UCB. 
• 
The Investigator may change his/her opinion of causality in light of follow-up information and 
send an SAE follow-up report with the updated causality assessment. 
• 
The causality assessment is one of the criteria used when determining regulatory reporting 
requirements. 
 
Follow-up of AEs and SAEs 
• 
The Investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by UCB to elucidate 
the nature and/or causality of the AE or SAE as fully as possible. This may include additional 
laboratory tests or investigations, histopathological examinations, or consultation with other 
health care professionals. 
• 
An AE should be followed until it has resolved, has a stable sequelae, the Investigator 
determines that it is no longer clinically significant, or the participant is lost to follow-up. This 
follow-up requirement applies to AEs, SAEs, and AEs of special interest. 
• 
If a participant dies during participation in the study or during a recognized follow-up period, 
the Investigator will provide UCB with a copy of any post-mortem findings including 
histopathology. 
• 
New or updated information will be recorded in the originally completed CRF. 
• 
The Investigator will submit any updated SAE data to UCB within 24 hours of receipt of the 
information. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 49 of 66 
Reporting of SAEs 
SAE Reporting to UCB via an Electronic Data Collection Tool 
• 
The primary mechanism for reporting an SAE to UCB will be the electronic data collection 
tool. 
• 
If the electronic system is unavailable for more than 24 hours, then the site will use the paper 
SAE data collection tool (see next section). 
• 
The site will enter the SAE data into the electronic system as soon as it becomes available. 
• 
After the study is completed at a given site, the electronic data collection tool will be taken off-
line to prevent the entry of new data or changes to existing data. 
• 
If a site receives a report of a new SAE from a study participant or receives updated data on a 
previously reported SAE after the electronic data collection tool has been taken off-line, then 
the site can report this information on a paper SAE form (see next section) or to the Medical 
Monitor or SAE coordinator by telephone. 
• 
Contacts for SAE reporting can be found in the section on SERIOUS ADVERSE EVENT 
REPORTING. 
 
SAE Reporting to UCB via Paper CRF 
• 
Facsimile transmission of the SAE paper CRF is the preferred method to transmit this 
information to the Medical Monitor or SAE coordinator. 
• 
In rare circumstances and in the absence of facsimile equipment, notification by telephone is 
acceptable with a copy of the SAE data collection tool sent by overnight mail or courier 
service. 
• 
Initial notification via telephone does not replace the need for the Investigator to complete and 
sign the SAE CRF pages within the designated reporting time frames. 
• 
Contacts for SAE reporting can be found in the section on SERIOUS ADVERSE EVENT 
REPORTING. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 50 of 66 
10.4 
Appendix 4: Contraceptive Guidance and Collection of 
Pregnancy Information 
Definitions 
A woman is considered fertile following menarche and until becoming post-menopausal unless 
permanently sterile (see below). 
Women in the following categories are not considered WOCBP: 
1. Premenarchal 
2. Premenopausal female with 1 of the following: 
− Documented hysterectomy 
− Documented bilateral salpingectomy 
− Documented bilateral oophorectomy 
Note:  Documentation can come from the site personnel’s review of the participant’s medical 
records, medical examination, or medical history interview. 
3. Postmenopausal female 
− A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal 
range may be used to confirm a postmenopausal state in women not using hormonal 
contraception or hormonal replacement therapy (HRT). However, in the absence of 
12 months of amenorrhea, a single FSH measurement is insufficient. 
− Females on HRT and whose menopausal status is in doubt will be required to use one of 
the non-estrogen hormonal effective contraception methods if they wish to continue their 
HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of 
postmenopausal status before study enrollment. 
Contraception Guidance 
Female participants 
Sexually active female participants of childbearing potential are eligible to participate if they 
agree to use an effective method of contraception consistently and correctly as described below: 
− hormonal contraceptives  (stable at least 2 months prior to Screening [Visit 1] if initiated 
prior to entering the study) 
− a combination of barrier and spermicide 
Study participants must agree to use an effective contraception during the study and for at least 
10 weeks after their final dose of IMP (or longer based on local approved label). 
In addition, 
− A vasectomized partner is an effective contraception method provided that the partner is 
the sole male sexual partner of the WOCBP and the absence of sperm has been 
confirmed. If not, an additional effective method of contraception should be used. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 51 of 66 
− Sexual abstinence is considered an effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study 
medication. The reliability of sexual abstinence needs to be evaluated in relation to the 
duration of the study and the preferred and usual lifestyle of the participant. 
Pregnancy testing 
• WOCBP should only be included after a confirmed menstrual period and a negative highly 
sensitive serum pregnancy test. For women who become WOCBP during the study, her first 
pregnancy test should be a serum pregnancy test. 
• Additional pregnancy testing should be performed during the Treatment Period and at the 
SFU (10 weeks after the last dose of study medication) and as required locally. 
• Pregnancy testing will be performed as outlined in the Schedule of Activities, to the 
sensitivity specified by the central laboratory. 
• Pregnancy testing will also be performed whenever pregnancy is suspected. 
Collection of pregnancy information 
Male participants with partners who become pregnant 
• The Investigator will attempt to collect pregnancy information on any male participant’s 
female partner who becomes pregnant while the male participant is in this study. This applies 
only to male participants who receive study medication. 
• After obtaining the necessary signed informed consent from the pregnant female partner 
directly, the Investigator will record pregnancy information on the appropriate form and 
submit it to the Sponsor within 24 hours of learning of the partner’s pregnancy. The female 
partner will also be followed to determine the outcome of the pregnancy. Information on the 
status of the mother and child will be forwarded to the Sponsor. Generally, the follow-up will 
be within 30 days after the delivery date. Any termination of the pregnancy will be reported 
regardless of fetal status (presence or absence of anomalies) or indication for the procedure. 
Female participants who become pregnant 
• Any female participant who becomes pregnant while participating in the study will 
discontinue study medication and be withdrawn from the study. 
The Investigator will collect pregnancy information on any female participant who becomes 
pregnant while participating in this study. Information will be recorded on the appropriate 
form and submitted to the Sponsor within 24 hours of learning of a participant's pregnancy. 
The participant will be followed to determine the outcome of the pregnancy. The Investigator 
will collect follow-up information on the participant and the neonate and the information will 
be forwarded to the Sponsor. Generally, the follow-up will be within 30 days after the 
delivery date. Any terminations of pregnancy will be reported, regardless of fetal status 
(presence or absence of anomalies) or indication for the procedure. 
• While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or 
elective termination of a pregnancy will be reported as an AE or SAE. A spontaneous 
abortion is always considered to be an SAE and will be reported as such. Any post-study 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 52 of 66 
pregnancy related SAE considered reasonably related to the study medication by the 
Investigator will be reported to the Sponsor as described in Section 8.3.5. While the 
Investigator is not obligated to actively seek this information in former study participants, he 
or she may learn of an SAE through spontaneous reporting. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 53 of 66 
10.5 
Appendix 5: Genetics 
Not applicable. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 54 of 66 
10.6 
Appendix 6: Liver Safety – Suggested Actions and Follow-up 
Assessments 
Participants with potential drug-induced liver injury must be assessed to determine if study 
medication must be discontinued (Section 7.1.1). In addition, all concomitant medications and 
herbal supplements that are not medically necessary should be discontinued. 
Investigators should attempt to obtain information on study participants in the case of study 
medication discontinuation to complete the final evaluation. 
Study participants with potential drug-induced liver injury should not be withdrawn from the 
study until investigation and monitoring are complete. All results of these evaluations and 
observations, as well as the reason(s) for study medication discontinuation and/or participant 
withdrawal (if applicable), must be recorded in the source documents. The CRF must document 
the primary reason for discontinuation of study medication. 
A specific monitoring plan must be agreed between the UCB Study Physician and the 
Investigator for study participants who have ALT >5xULN. The monitoring plan should include 
any necessary follow-up assessments (until resolution of the abnormal lab values). 
Liver chemistry stopping criteria are designed to assure participant safety and to evaluate liver 
event etiology. 
Liver Chemistry Stopping Criteria and Follow-up assessments 
Liver Chemistry Stopping Criteria 
ALT-absolute 
ALT 8xULN 
ALT Increase 
ALT 5xULN but <8xULN persists for 2 weeks 
ALT 3xULN but <5xULN persists for 4 weeks 
Bilirubina,b 
ALT 3xULN and bilirubin 2xULN (>35% direct bilirubin)  
INRb 
ALT 3xULN and international normalized ratio (INR) >1.5, if INR measured 
Cannot 
Monitor 
ALT 5xULN but <8xULN and cannot be monitored weekly for 2 weeks 
ALT 3xULN but <5xULN and cannot be monitored weekly for 4 weeks 
Symptomaticc 
ALT 3xULN associated with symptoms (new or worsening) believed to be related 
to liver injury or hypersensitivity 
Suggested Actions and Follow-up Assessments 
Actions 
Follow-up Assessments 
• 
Immediately discontinue study medication. 
• 
Report the event to UCB within 24 hours. 
• 
Complete the liver event case report form 
(CRF), and complete a serious adverse event 
(SAE) data collection tool if the event also met 
the criteria for an SAE.b 
• 
Perform liver chemistry follow-up assessments. 
• 
Viral hepatitis serology.d 
• 
Obtain INR and recheck with each liver 
chemistry assessment until the transaminase 
values show downward trend. 
• 
Only in those with underlying chronic 
hepatitis B at study entry (identified by 
positive hepatitis B surface antigen), 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 55 of 66 
Liver Chemistry Stopping Criteria 
• 
Monitor the participant until liver chemistry 
test abnormalities resolve, stabilize, or return to 
baseline (see MONITORING). 
• 
Do not restart/rechallenge participant with 
study medication unless allowed per protocol 
and UCB approval is granted. 
• 
If restart/rechallenge not allowed per protocol 
or not granted, permanently discontinue study 
medication and continue participant in the 
study for any protocol-specified follow-up 
assessments.Consider the need for a toxicology 
screening. 
 
MONITORING: 
For bilirubin or INR criteria 
• 
Repeat liver chemistry tests (include ALT, 
aspartate transaminase [AST], alkaline 
phosphatase, bilirubin) and perform liver event 
follow-up assessments within 24 hours. 
• 
Monitor participant twice weekly until liver 
chemistry test abnormalities resolve, stabilize, 
or return to baseline. 
• 
A specialist or hepatology consultation is 
recommended. 
For all other criteria 
• 
Repeat liver chemistry tests (include ALT, 
AST, alkaline phosphatase, bilirubin) and 
perform liver chemistry follow-up assessments 
within 24 to 72 hours. 
• 
Monitor participants weekly until liver 
chemistry abnormalities resolve, stabilize, or 
return to baseline. 
quantitative hepatitis B deoxyribonucleic 
acid (DNA), and hepatitis delta antibody.e 
• 
Obtain blood sample for pharmacokinetic 
(PK) analysis as soon as possible.f 
• 
Serum creatine phosphokinase (CPK) and 
lactate dehydrogenase (LDH). 
• 
Fractionate bilirubin, if total bilirubin 
2xULN. 
• 
Obtain complete blood count with 
differential to assess eosinophilia. 
• 
Record the appearance or worsening of 
clinical symptoms of liver injury (eg, 
fatigue, nausea, vomiting, right upper 
quadrant pain), or hypersensitivity, on the 
adverse event (AE) report form. 
• 
Record use of concomitant medications 
(including acetaminophen, herbal remedies, 
and other over-the-counter medications) on 
the concomitant medications CRF. 
• 
Record alcohol use on the liver event 
alcohol intake CRF. 
• 
Exclude pregnancy. 
For bilirubin or INR criteria: 
• 
Anti-nuclear antibody, anti-smooth muscle 
antibody, Type 1 anti-liver kidney 
microsomal antibodies, and quantitative 
total immunoglobulin G (IgG) or gamma 
globulins. 
• 
Serum acetaminophen adduct high 
performance liquid chromatography (HPLC) 
assay (quantifies potential acetaminophen 
contribution to liver injury in participants 
with definite or likely acetaminophen use in 
the preceding week; James, 2009). 
NOTE: Not required in China. 
• 
Liver imaging (ultrasound, magnetic 
resonance, or computerized tomography) 
and/or liver biopsy to evaluate liver disease; 
complete Liver Imaging and/or Liver 
Biopsy CRFs. 
a Serum bilirubin fractionation should be performed if testing is available. If serum bilirubin fractionation is not 
immediately available, discontinue study medication if ALT ≥3xULN and bilirubin ≥2xULN. Additionally, if 
serum bilirubin fractionation testing is unavailable, record the absence/presence of detectable urinary bilirubin 
on dipstick which is indicative of direct bilirubin elevations suggesting liver injury. 
b All events of ALT ≥3xULN and bilirubin ≥2xULN (>35% direct bilirubin) or ALT ≥3xULN and INR >1.5 may 
indicate severe liver injury (possible ‘Hy’s Law’) and must be reported as an SAE (excluding studies of 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 56 of 66 
hepatic impairment or cirrhosis). The INR measurement is not required and the stated threshold value will not 
apply to participants receiving anticoagulants. 
c New or worsening symptoms believed to be related to liver injury (such as fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, or jaundice) or hypersensitivity (such as fever, rash or eosinophilia). 
d Includes: Hepatitis A immunoglobulin M (IgM) antibody; HBsAg and HBcAb; hepatitis C RNA; cytomegalovirus 
IgM antibody; Epstein-Barr viral capsid antigen IgM antibody (or if unavailable, heterophile antibody or monospot 
testing); and hepatitis E IgM antibody. 
e If hepatitis delta antibody assay cannot be performed, it can be replaced with a polymerase chain reaction (PCR) of 
hepatitis D RNA virus (where needed; Le Gal, 2005). 
f Record the date/time of the PK blood sample draw and the date/time of the last dose of study medication prior to 
the PK blood sample draw on the CRF. If the date or time of the last dose is unclear, provide the participant’s best 
approximation. If the date/time of the last dose cannot be approximated OR a PK sample cannot be collected in the 
time period indicated above, do not obtain a PK sample. Instructions for sample handling and shipping are in the 
Study Reference Manual. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 57 of 66 
10.7 
Appendix 7: Medical Device Adverse Events (AEs), Adverse 
Device Effects (ADEs), Serious Adverse Events (SAEs) and 
Device Deficiencies: Definition and Procedures for Recording, 
Evaluating, Follow-up, and Reporting 
Not applicable. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 58 of 66 
10.8 
Appendix 8: Rapid Alert Procedures 
Not applicable. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 59 of 66 
10.9 
Appendix 9: Country-specific Requirements 
Not applicable. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 60 of 66 
10.10 
Appendix 10: Abbreviations and Trademarks 
ADA 
antidrug antibody 
AE 
adverse event 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
CONSORT 
Consolidated Standards of Reporting Trials 
CRF 
Case Report form 
csDMARD 
conventional synthetic disease modifying antirheumatic drug  
CV 
coefficient of variation 
CZP 
certolizumab pegol 
DMARD 
disease modifying antirheumatic drug 
DNA 
deoxyribonucleic acid 
ECG 
electrocardiogram 
ECLIA 
electrochemiluminescent immuno-assay 
FSH 
follicle stimulating hormone 
GCP 
Good Clinical Practice 
HCV 
hepatitis C virus 
HIV 
human immunodeficiency virus 
HRT 
hormonal replacement therapy 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonisation 
IEC 
Independent Ethics Committee 
IGRA 
Interferon-gamma release assay 
IMP 
investigational medicinal product 
IRB 
Institutional Review Board 
MDHAQ 
Multi-dimensional Health Assessment Questionnaire 
MTX 
methotrexate 
NTMB 
nontuberculous mycobacterial 
PDILI 
potential drug-induced liver injury 
PEG 
polyethylene glycol 
pJIA 
polyarticular juvenile idiopathic arthritis 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 61 of 66 
PK 
pharmacokinetic 
PKS 
Pharmacokinetic Set 
PREA 
Pediatric Research Equity Act 
Q2W 
every 2 weeks 
RA 
rheumatoid arthritis 
RAPID3 
Routine Assessment of Patient Index Data 3 
SAE 
serious adverse event 
SFU 
Safety Follow-up 
SS 
Safety Set 
TB 
tuberculosis 
TNF 
tumor necrosis factor 
tsDMARD 
targeted synthetic disease modifying antirheumatic drug  
ULN 
upper limit of normal 
US 
United States 
WOCBP 
woman of childbearing potential 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 62 of 66 
10.11 
Appendix 11: Protocol Amendment History 
The Protocol Amendment Summary of Changes Table for the current amendment is located 
directly before the Table of Contents. 
Amendment 1 (09 Dec 2020) 
Overall rationale for the amendment 
The primary reason for this nonsubstantial protocol amendment was to update the Schedule of 
Activities (Section 1.3) to include a safety laboratory assessment at Week 12 (Visit 13) that was 
omitted in error and to correct the study day associated with Visit 14. 
This amendment is considered to be nonsubstantial based on the criteria set forth in Article 10(a) 
of Directive 2001/20/EC of the European Parliament and the Council of the European Union. 
Section # and Name 
Description of Change 
Brief Rationale 
Global 
Minor administrative, formatting, 
and typographical changes have 
been made. 
Updated to provide clarity 
and to be consistent with 
remainder of protocol and 
program. 
1.3 Schedule of Activities 
Included a safety laboratory 
assessment at Week 12 (Visit 13). 
This was planned but 
omitted in the original 
protocol. 
1.3 Schedule of Activities 
Corrected the study day for Visit 14 
from Day 140 to Day 126. 
Updated to correct an 
error.  
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 63 of 66 
10.12 
Appendix 12: RAPID3 Assessment 
The RAPID3 includes a subset of core variables found in the Multi-dimensional HAQ 
(MDHAQ). The MDHAQ, shown here, includes an assessment of physical function (Section 1 of 
the RAPID3 assessment [below]), a patient global assessment for pain (Section 2 of the RAPID3 
assessment [below]), and a patient global assessment for global health (Section 3 of the RAPID3 
assessment [below]). RAPID3 scores are quickly tallied by adding subsets of the MDHAQ as 
follows: 
How to calculate RAPID3 scores 
1. Ask the patient to complete questions 1, 2, and 3 while in the waiting room prior to his/her 
visit. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 64 of 66 
2. For question 1, add up the scores in questions a to j only (questions k to m have been found 
to be informative, but are not scored formally). Use the formula in the box on the right to 
calculate the formal score (0 to 10). For example, a patient whose answers total 19 would 
score a 6.3. Enter this score as an evaluation of the patient’s functional status. 
3. For question 2, enter the raw score (0 to 10) in the box on the right as an evaluation of the 
patient’s pain tolerance. 
4. For question 3, enter the raw score (0 to 10) in the box on the right as an evaluation of the 
patient’s global estimate. 
5. Add the total score (0 to 30) from questions 1, 2, and 3 and enter them as the patient’s 
RAPID3 cumulative score. Use the final conversion table to simplify the patient’s weighed 
RAPID3 score. For example, a patient who scores 11 on the cumulative RAPID3 scale would 
score a weighed 3.7. A patient who scores between 0 and 1.0 is defined as near remission; 
1.3 and 2.0 as low severity; 2.3 and 4.0 as moderate severity; and 4.3 and 10.0 as high 
severity. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 65 of 66 
11 
REFERENCES 
Jacobsson LT, Turesson C, Nilsson JA, et al. Treatment with TNF blockers and mortality risk in 
patients with rheumatoid arthritis. Ann Rheum Dis. 2007;66(5):670-5. 
James LP, Letzig L, Simpson PM, et al. Pharmacokinetics of Acetaminophen-Adduct in Adults 
with Acetaminophen Overdose and Acute Liver Failure. Drug Metab Dispos. 2009;37:1779-84. 
Smolen J, Landewé RB, Mease P, et al. Efficacy and safety of certolizumab pegol plus 
methotrexate in active rheumatoid arthritis: the RAPID 2 study. A randomised controlled trial. 
Ann Rheum Dis. 2009;68(6):797-804. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
18 Mar 2021 
Clinical Study Protocol 
Certolizumab pegol 
RA0138 
 
 
 
Confidential 
Page 66 of 66 
SPONSOR DECLARATION 
I confirm that I have carefully read and understand this protocol and agree to conduct this 
clinical study as outlined in this protocol and according to current Good Clinical Practice. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

Approval Signatures
Name:
RA0138-protocol-amend-2
Version:
1. 0
Document Number:
CLIN-000171341
Title:
RA0138-protocol-amend-2
Approved Date:
19 Mar 2021
Document Approvals
Approval
Verdict: Approved
Name: 
Capacity: Subject Matter Expert
Date of Signature: 18-Mar-2021 19:36:56 GMT+0000
Approval
Verdict: Approved
Name: 
Capacity: Clinical
Date of Signature: 18-Mar-2021 21:47:55 GMT+0000
Approval
Verdict: Approved
Name: 
Capacity: Medical
Date of Signature: 19-Mar-2021 09:32:11 GMT+0000
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.