Clinical trial NCT03357471
Conditions: Moderate and Severe Active Rheumatoid Arthritis Active Psoriatic Arthritis Active Ankylosing Spondylitis Moderately to Severely Active Crohn's Disease
Keywords: Certolizumab Pegol E-Device
Sponsor: UCB Biopharma S.P.R.L.
Start date: 2017-11-03; Completion date: 2018-07-02
Enrollment: 70 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of the study is to evaluate the ability of subjects who are already prescribed Certolizumab Pergol therapy and have been self injecting with prefilled syringes for at least the previous three months, to safely and effectively self-inject Certolizumab Pegol (CZP) using the e-Device and to evaluate the post-use structural integrity of used devices and cassettes via visual examination.

Detailed description:

Arms: arm 1: Subjects will self-inject Certolizumab Pegol 200 mg (1 x 200 mg injection) using the e-Device every 2 weeks. arm 2: Subjects will self-inject Certolizumab Pegol 400 mg (2 x 200 mg injection) using the e-Device every 4 weeks.
Interventions: intervention 1: e-Device
Intervention descriptions: intervention 1: * Active Substance: Certolizumab Pegol
* Pharmaceutical form: Solution for injection
* Route of administration: subcutaneous injection by e-Device

Protocol documents:
Prot_000.pdf: 
UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 1 of 82
PROTOCOL RA0098 AMENDMENT 2
A MULTICENTER, OPEN-LABEL STUDY TO EVALUATE THE 
SAFE AND EFFECTIVE USE OF AN ELECTRO-MECHANICAL 
INJECTION DEVICE (E-DEVICE) FOR THE SUBCUTANEOUS 
SELF-INJECTION OF CERTOLIZUMAB PEGOL SOLUTION BY 
SUBJECTS WITH MODERATE TO SEVERE ACTIVE 
RHEUMATOID ARTHRITIS, ACTIVE ANKYLOSING 
SPONDYLITIS, ACTIVE PSORIATIC ARTHRITIS, OR 
MODERATELY TO SEVERELY ACTIVE CROHN’S DISEASE
PHASE 3
IND Number: 011197
Sponsor:
UCB Biopharma SPRL
Allée de la Recherche 60
1070 Brussels
BELGIUM
Protocol/Amendment number
Date
Type of 
amendment
Final Protocol
28 Jun 2017
Not applicable
Protocol Amendment 1
26 Sep 2017
Nonsubstantial
Protocol Amendment 2
29 Sep 2017
Nonsubstantial
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.
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UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 2 of 82
STUDY CONTACT INFORMATION
Sponsor
UCB Biopharma SPRL
Allée de la Recherche 60
1070 Brussels
BELGIUM
Sponsor Study Physician
Name:
 MD
Address:
UCB BIOSCIENCES GmbH
Alfred-Nobel-Strasse 10
40789 Monheim am Rhein
GERMANY
Phone:
Clinical Project Manager
Name:
Address:
UCB Biosciences Inc.
8010 Arco Corporate Drive, Suite 100
Raleigh, NC 27617
USA
Phone:
Clinical Trial Biostatistician
Name:
Address:
UCB Biosciences Inc.
8010 Arco Corporate Drive, Suite 100
Raleigh, NC 27617
USA
Phone:
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UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 3 of 82
Clinical Monitoring Contract Research Organization
Name:
PAREXEL International (IRL) Limited
Address:
One Kilmainham Square 
Inchicore Road 
Kilmainham, Dublin 8
IRELAND
Phone:
+3531 473 9500
Fax:
+3531 477 3308
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UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 4 of 82
SERIOUS ADVERSE EVENT AND PRODUCT QUALITY COMPLAINTS
REPORTING
Serious Adverse Event Reporting (24h)
Email:
Global: DS_ICT@ucb.com
Fax:
US: +1 800 880 6949
+1 866 890 3175
Product Quality Complaints Reporting (24h)
Email:
Global: qactscomplaints@ucb.com
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29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 5 of 82
TABLE OF CONTENTS
LIST OF ABBREVIATIONS....................................................................................................9
1
SUMMARY.....................................................................................................................11
2
INTRODUCTION ...........................................................................................................12
3
STUDY OBJECTIVES....................................................................................................13
3.1 Primary objective.............................................................................................................13
3.2 Secondary objective.........................................................................................................13
3.3 Other objectives ...............................................................................................................13
3.4 Safety objective................................................................................................................13
4
STUDY VARIABLES.....................................................................................................13
4.1 Study outcome variables..................................................................................................13
4.1.1
Primary outcome variable....................................................................................13
4.1.2
Secondary outcome variables ..............................................................................14
4.1.3 
Other outcome variables ........................................................................................15
4.2 Safety variables................................................................................................................15
5
STUDY DESIGN.............................................................................................................15
5.1 Study description .............................................................................................................15
5.1.1
Study duration per subject ...................................................................................16
5.1.2
Planned number of subjects and sites ..................................................................16
5.1.3
Anticipated regions and countries .......................................................................17
5.2 Schedule of study assessments.........................................................................................17
5.3 Rationale for study design and selection of dose.............................................................21
6
SELECTION AND WITHDRAWAL OF SUBJECTS...................................................21
6.1 Inclusion criteria ..............................................................................................................21
6.2 Exclusion criteria .............................................................................................................22
6.3 Withdrawal criteria ..........................................................................................................23
7
IMP AND INVESTIGATIONAL DEVICE....................................................................24
7.1 Description of investigational device...............................................................................24
7.1.1
Instructions for use of investigational e-Device ..................................................25
7.2 Treatment to be administered...........................................................................................25
7.3 Packaging.........................................................................................................................26
7.4 Labeling ...........................................................................................................................26
7.5 Handling and storage requirements..................................................................................26
7.6 Drug and device accountability .......................................................................................26
7.7 Procedures for monitoring subject compliance................................................................27
7.8 Concomitant medications/treatments...............................................................................27
7.8.1
Permitted concomitant treatments (medications and therapies) ..........................27
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29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
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7.8.2
Prohibited concomitant treatments (medications and therapies).........................27
7.9 Blinding............................................................................................................................27
7.10 Randomization and numbering of subjects......................................................................27
8
STUDY PROCEDURES BY VISIT ...............................................................................27
8.1 Visit 1/ Screening and Study Treatment Period...............................................................27
8.2 Study procedures by visit for the Q2W group .................................................................28
8.2.1
Visit 2 (Week 2)...................................................................................................28
8.3 Study procedures by visit for the Q4W group .................................................................29
8.3.1
Visit 2 (Week 4)...................................................................................................29
8.4 Safety Follow-Up.............................................................................................................30
9
ASSESSMENT OF SELF-INJECTION..........................................................................30
9.1 Injection Site Pain (VAS) ................................................................................................30
9.2 Assessment of Self Injection (ASI)..................................................................................30
9.3 Self-Injection Preference Questionnaire..........................................................................31
9.4 Evaluation of post-use structural integrity of CZP-cassettes...........................................31
9.5 Evaluation of post-use structural and functional integrity of the e-Device .....................31
9.6 Evaluation of safe and effective self-injection.................................................................31
10
ASSESSMENT OF SAFETY..........................................................................................32
10.1 Adverse events (IMP) ......................................................................................................32
10.1.1
Definitions (IMP).................................................................................................32
10.1.1.1
Adverse event (IMP) .................................................................................32
10.1.1.2
Serious adverse event (IMP) .....................................................................32
10.1.1.3
Adverse events of special interest (IMP) ..................................................34
10.1.2
Procedures for reporting and recording adverse events (IMP)............................34
10.1.2.1
Description of adverse events (IMP).........................................................35
10.1.2.2
Rule for repetition of an adverse event (IMP)...........................................35
10.1.2.3
Additional procedures for reporting serious adverse events (IMP)...........35
10.1.3
Follow up of adverse events (IMP) .....................................................................36
10.2 Adverse events (investigational device) ..........................................................................36
10.2.1
Definitions (investigational device).....................................................................36
10.2.1.1
Adverse Events (investigational device) ...................................................36
10.2.1.2
Serious adverse event (investigational device)..........................................37
10.2.1.3
Device- or procedure-related.....................................................................37
10.2.2
Procedures for reporting and recording adverse events (investigational device), 
adverse device effects, and device deficiencies...................................................38
10.2.2.1
Adverse events ..........................................................................................38
10.2.3
Follow up of adverse events (investigational device)..........................................38
10.2.3.1
Device-related ...........................................................................................38
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Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 7 of 82
10.2.3.2
Rule for repetition of an adverse device effect and/or device deficiency .40
10.3 Pregnancy.........................................................................................................................40
10.4 Suspected transmission of an infectious agent.................................................................41
10.5 Overdose of investigational medicinal product ...............................................................41
10.6 Safety signal detection .....................................................................................................41
10.7 Laboratory measurements................................................................................................41
10.8 Other safety measurements..............................................................................................42
10.8.1
Vital signs ............................................................................................................42
10.8.2
Physical examination...........................................................................................42
11
STUDY MANAGEMENT AND ADMINISTRATION.................................................42
11.1 Adherence to protocol......................................................................................................42
11.2 Monitoring .......................................................................................................................42
11.2.1
Definition of source data .....................................................................................42
11.2.2
Source data verification .......................................................................................43
11.3 Data handling...................................................................................................................43
11.3.1
Case Report form completion..............................................................................43
11.3.2
Database entry and reconciliation........................................................................43
11.3.3
Subject Screening and Enrollment log/Subject Identification Code list..............44
11.4 Termination of the study..................................................................................................44
11.5 Archiving and data retention............................................................................................44
11.6 Audit and inspection ........................................................................................................44
11.7 Good Clinical Practice .....................................................................................................45
12
STATISTICS ...................................................................................................................45
12.1 Definition of analysis sets................................................................................................45
12.2 General statistical considerations.....................................................................................45
12.3 Planned analyses ..............................................................................................................46
12.3.1
Analysis of the primary outcome variable...........................................................46
12.3.2
Analyses of secondary outcome variables...........................................................46
12.3.3
Analyses of other outcome variables...................................................................47
12.4 Planned safety analyses....................................................................................................47
12.4.1
Safety analyses.....................................................................................................47
12.5 Handling of protocol deviations.......................................................................................48
12.6 Handling of dropouts or missing data..............................................................................48
12.7 Planned interim analysis and data monitoring.................................................................48
12.8 Determination of sample size...........................................................................................48
13
ETHICS AND REGULATORY REQUIREMENTS......................................................48
13.1 Informed consent .............................................................................................................48
13.2 Subject identification cards..............................................................................................49
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Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 8 of 82
13.3 Institutional Review Boards and Independent Ethics Committees..................................49
13.4 Subject privacy.................................................................................................................50
13.5 Protocol amendments.......................................................................................................50
14
FINANCE, INSURANCE, AND PUBLICATION.........................................................50
15
REFERENCES ................................................................................................................50
16
APPENDICES .................................................................................................................52
16.1 Injection Site Pain (VAS) ................................................................................................52
16.2 Assessment of Self Injection............................................................................................53
16.3 Self-Injection Preference Questionnaire..........................................................................66
16.4 Cochin Scale ....................................................................................................................68
16.5 Protocol Amendment 1 ....................................................................................................73
16.6 Protocol Amendment 2 ....................................................................................................79
17
DECLARATION AND SIGNATURE OF INVESTIGATOR .......................................81
18
SPONSOR DECLARATION ..........................................................................................82
LIST OF TABLES
Table 5‒1:
Schedule of study assessments for Q2W subjects ...........................................17
Table 5‒2:
Schedule of study assessments for Q4W subjects ...........................................19
Table 7‒1:
Treatments to be administered.........................................................................25
Table 10‒1:
Anticipated serious adverse events for study population.................................34
LIST OF FIGURES
Figure 7‒1:
CZP e-Device...................................................................................................24
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UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 9 of 82
LIST OF ABBREVIATIONS
ADE
adverse device effect
AE
adverse event
AS
ankylosing spondylitis
ASADE
anticipated serious adverse device effect
ASI
Assessment of Self Injection
BP
blood pressure
CD
Crohn’s disease
CDMS
clinical data management system
CI
confidence interval
CPM
Clinical Project Manager
CPMP
Committee for Proprietary Medicinal Products
CRO
contract research organization
CZP
certolizumab pegol
DMARD
disease-modifying antirheumatic drug
ECG
Electrocardiogram
eCRF
electronic Case Report form
EudraCT
European Union Drug Regulating Authorities Clinical Trials
FAS
Full Analysis Set
FDA
Food and Drug Administration
GCP
Good Clinical Practice
HCP
healthcare provider
ICH
International Council for Harmonisation
IEC
Independent Ethics Committee
IFU
Instructions for Use
IMP
investigational medicinal product
IRB
Institutional Review Board
IXRS
interactive response technology
LTB
latent tuberculosis
PFS
pre-filled syringe
PS
Patient Safety
PsA
psoriatic arthritis
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29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 10 of 82
Q2W
every 2 weeks
Q4W
every 4 weeks
RA
rheumatoid arthritis
RR
respiratory rate
SADE
serious adverse device effect
SAE
serious adverse event
sc
subcutaneous
SOP
Standard Operating Procedure
SS
Safety Set
TB
tuberculosis
TEAE
treatment-emergent adverse events
TNFα
tumor necrosis factor alpha
UADE
unanticipated adverse device effect
USADE
unanticipated serious adverse device effect
VAS
Visual Analog Scale
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Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
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1
SUMMARY
RA0098 is a multicenter, open-label, Phase 3 study of the e-Device in US subjects with 
rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), or Crohn’s 
disease (CD). 
The e-Device offers improved convenience with an enhanced, reusable electromechanical 
injector that provides full electronic management of the injection process including subject 
instructions and warnings via a graphical user interface, an electronic log of the injection history, 
and the speed of injection. The e-Device uses a disposable single-use certolizumab pegol 
(CZP)-cassette/dose dispensing cartridge (henceforth referred to as CZP-cassette) which houses a 
(market authorized) pre-filled syringe (PFS) containing CZP 200mg. The CZP-cassette is 
needle-safe (ie, automatic needle retraction to prevent needle-stick injury), and, once loaded into 
the e-Device, is electronically recognized (ie, expiry date, drug identity, and use status) by the 
e-Device. The e-Device and CZP-cassette together provide automatic needle insertion, dose 
delivery, needle retraction, and adjustable injection speed. They also provide a manual voluntary 
injection pause and resumption for additional control as well as an automatic stop (with needle 
retraction) should the e-Device lose contact with the skin during an injection to prevent needle 
stick injury and to minimize the loss of CZP. A production version of the e-Device will be 
utilized for this study.
The purpose of this study is to determine whether the e-Device can be used safely and effectively 
for self-injection by subjects with RA, AS, PsA, or CD after being trained on proper 
self-injection technique. All eligible subjects should be currently treated with commercial CZP. 
Eligible subjects with RA, PsA, or AS will perform CZP self-administration on a 2 week (Q2W)
or 4 week (Q4W) dosing schedule. Eligible subjects with CD will perform CZP 
self-administration on a Q4W dosing schedule. As the dosing schedule groups (Q2W vs Q4W)
are different regarding number of injections (1 CZP injection for Q2W vs 2 CZP injections per 
administration for Q4W) and study treatment period (2 weeks vs 4 weeks), these 2 subject 
populations will be evaluated separately.
The primary objective of the study is to evaluate the ability of subjects in the Q2W and Q4W 
groups to safely and effectively self-inject CZP using the e-Device.
The primary variable is the proportion (%) of subjects able to self-administer safe and effective 
injections using the e-Device at Visit 2. Safe and effective self-injection will be evaluated by the
healthcare provider (HCP) and is defined as:

Complete Dose Delivery: Subject self-injected the complete dose of CZP as confirmed by a 
visual inspection of the CZP-cassette(s) which shows the container PFS to be empty and

No adverse events (AE) related to the use of the e-Device (adverse device effects [ADE])
that would preclude continued use of the e-Device for self-injection 
During self-injection, if the skin sensor at the injection port loses contact with the skin, the 
e-Device will withdraw the needle and stop administration of CZP. If less than five minutes have 
elapsed since loss of contact with skin, the subject can reposition the e-Device on a new clean 
injection site and resume and complete the self-injection. If the subject is unable to complete the 
self-injection and deliver the entire dose of medication (ie, the device indicates incomplete 
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UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 12 of 82
administration and the CZP-cassette is not seen to be empty), the HCP evaluating the self-
injection will document the incomplete self-injection, note the reason why the complete dose was 
not administered, and using his/her best medical judgment, advise the subject regarding any 
further dosing.
For subjects on the Q4W dosing regimen who will self-inject twice (2×200mg CZP) at each 
visit, each injection will be evaluated for safety and effectiveness using the above criteria. The 
primary endpoint of safe and effective self-injection for subjects on the Q4W dosing regimen 
will be met only if both self-injections are determined to be safe and effective.
Approximately 80 subjects ≥18 years of age who are currently being treated with commercial 
CZP, are self-injecting with the PFS, and are on a stable dosing regimen for at least 3 months 
will be screened in order to have at least 60 subjects use the e-Device at Visit 1. The 60 subjects
using the e-Device at Visit 1 will be composed of a minimum of 15 subjects in each of the 
dosing groups (Q2W vs Q4W) with a minimum of 15 subjects with CD and a minimum of 10 
subjects with impaired hand function.
2
INTRODUCTION
Cimzia (certolizumab pegol [CZP]) is an anti-TNFα humanized PEGylated Fab’ fragment of a 
monoclonal antibody. Certolizumab pegol has demonstrated a high affinity for TNFα which has 
been shown to have a central role in the pathogenesis of RA, AS, PsA, and CD. Certolizumab 
pegol has received market authorization in the US for the treatment of moderate and severe 
active RA, active PsA, active AS, and moderately to severely active CD. Certolizumab pegol 
may be used as monotherapy or in combination with disease-modifying antirheumatic drugs 
(DMARDs). It is available for subcutaneous (sc) injection as a 200mg lyophilized powder for 
reconstitution (with 1 mL of sterile water for injection) in a single use vial or as 200mg/mL 
solution in a single-use 1mL PFS in the US.
The availability and convenience of the PFS device provide subjects with chronic diseases such 
as RA, AS, PsA, or CD with the option to manually self-inject their medication. 
The purpose of this study is to determine whether the e-Device can be used safely and effectively 
for self-injection by subjects with RA, AS, PsA, or CD after being trained on proper 
self-injection technique, described in the Instructions for Use (IFU) supplied with the e-Device. 
Eligible subjects with RA, PsA, or AS will perform CZP self-administration on a Q2W or Q4W
dosing schedule. Eligible subjects with CD will perform CZP self-administration on a Q4W 
dosing schedule. As the dosing schedule groups (Q2W vs Q4W) are different regarding number 
of injections (1 CZP injection for Q2W vs 2 CZP injections per administration for Q4W) and 
study treatment period (2 weeks vs 4 weeks), these 2 subject populations will be evaluated 
separately. For simplicity and where appropriate, the RA, AS, and PsA subjects on the Q2W 
dosing regimen will be called the Q2W group, and the RA, AS, PsA, and CD subjects on the 
Q4W dosing regimen will be called the Q4W group.
Impaired hand function is seen in patients with RA (Durmus et al, 2013), to a lesser extent in 
patients with PsA (Gottieb et al, 2008), and is uncommon in patients with AS (Tam et al, 2010) 
or CD (Lossos et al, 1995). Since prompt treatment can reduce inflammation and the level of 
functional impairment seen in patients with RA or PsA (Goossens et al, 2000), it is not possible 
to accurately predict the proportion of patients treated with CZP who will have impaired hand 
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UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 13 of 82
function or how easy or difficult it may be to recruit such patients. In a recently published 
simulated injection study, the author notes that the investigators had difficulties in recruiting 
patients with high (Cochin score ≥20) versus low (Cochin score <20) hand disability so much so 
that they decided to stop the recruitment process when only 12 out of 15 subjects with high hand 
disability were enrolled (Hundry et al, 2017). This suggests that recruiting patients with impaired 
hand function may be challenging. Given these considerations, this study will recruit a minimum 
of 10 patients with impaired hand function. Impaired hand function will be measured using the 
Cochin scale (Poiraudeau et al, 2000; Duruöz et al, 1996) and impaired hand function will be 
defined as patients who have a Cochin score ≥13.5 at baseline.
3
STUDY OBJECTIVES
3.1
Primary objective
The primary objective of the study is to evaluate the ability of subjects in the Q2W and Q4W 
groups to safely and effectively self-inject CZP using the e-Device at Visit 2.
3.2
Secondary objective
The secondary objectives are to evaluate the ability of subjects in the Q2W and Q4W groups to 
safely and effectively self-inject CZP using the e-Device at Visit 1 and the structural integrity of 
used cassettes via visual examination.
3.3
Other objectives
The other objectives are to evaluate:

The functional status of the e-Device following administration of the final study dose (ie, no 
visual signs of damage, device functions normally with training cassette)

Subject experience of self-injection as assessed by the Pain Visual Analog Scale (VAS) and 
Assessment of Self Injection (ASI).

Subject preference for e-Device vs PFS using a self-administered Self-Injection Preference 
Questionnaire
3.4
Safety objective
The safety objective is to evaluate the safety of CZP self-injection using the e-Device for CZP 
self-injection.
4
STUDY VARIABLES
4.1
Study outcome variables
4.1.1
Primary outcome variable
The primary outcome variable is the proportion (%) of subjects able to self-administer safe and 
effective injections using the e-Device at Visit 2. Safe and effective self-injection will be 
evaluated by the HCP and is defined as:

Complete Dose Delivery: Subject self-injected the complete dose of CZP as confirmed by a 
visual inspection of the CZP-cassette(s) which shows the PFS container to be empty and
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UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 14 of 82

No AEs related to use of the e-Device (ADEs) that would preclude continued use of the 
e-Device for self-injection
During self-injection, if the skin sensor at the injection port loses contact with the skin, the 
e-Device will withdraw the needle and stop administration of CZP. If less than five minutes have 
elapsed since loss of contact with skin, the subject can reposition the e-Device on a new clean 
injection site and resume and complete the self-injection. If the subject is unable to complete the 
self-injection and deliver the entire dose of medication (ie, the device indicates incomplete 
administration and the CZP-cassette is not seen to be empty), the HCP evaluating the self-
injection will document the incomplete self-injection, note the reason why the complete dose was 
not administered, and using his/her best medical judgment, advise the subject regarding any 
further dosing.
For subjects on the Q4W dosing regimen who will self-inject twice (2×200mg CZP) at each 
visit, each injection will be evaluated for safety and effectiveness using the above criteria. The 
primary endpoint of safe and effective self-injection for subjects on the Q4W dosing regimen 
will be met only if both self-injections are determined to be safe and effective.
4.1.2
Secondary outcome variables
The secondary outcome variables are:

The proportion (%) of subjects able to self-administer safe and effective injections using the 
e-Device at Visit 1. Safe and effective self-injection will be evaluated by the HCP and is 
defined as:

Complete Dose Delivery: Subject self-injected the complete dose of CZP as confirmed by 
a visual inspection of the CZP-cassette(s) which shows the PFS container to be empty
and

No AEs related to use of the e-Device (ADEs) that would preclude continued use of the 
e-Device for self-injection 
During self-injection, if the skin sensor at the injection port loses contact with the skin, the 
e-Device will withdraw the needle and stop administration of CZP. If less than five minutes 
have elapsed since loss of contact with skin, the subject can reposition the e-Device on a new 
clean injection site and resume and complete the self-injection. If the subject is unable to 
complete the self-injection and deliver the entire dose of medication (ie, the device indicates 
incomplete administration and the CZP-cassette is not seen to be empty), the HCP evaluating 
the self-injection will document the incomplete self-injection, note the reason why the
complete dose was not administered, and using his/her best medical judgment, advise the 
subject regarding any further dosing.
For subjects on the Q4W dosing regimen who will self-inject twice (2×200mg CZP) at each 
visit, each injection will be evaluated for safety and effectiveness using the above criteria. 
The primary endpoint of safe and effective self-injection for subjects on the Q4W dosing 
regimen will be met only if both self-injections are determined to be safe and effective.

Percentage of used CZP-cassettes identified as having structural integrity issues based on 
visual examination (ie, clear evidence of damage/compromised structural integrity, not 
superficial cosmetic imperfections)
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UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 15 of 82
4.1.3 
Other outcome variables
The other outcome variables are: 

Injection site pain due to self-injection (using a VAS; 100mm) by visit at all visits after self-
injection using the e-Device
Subjects on the Q4W dosing regimen who will self-inject twice (2×200mg CZP) at each visit
will complete the Pain VAS after the second injection at each of the 2 visits. For subjects on 
the Q4W dosing regimen, the Pain VAS will record the overall pain associated with both 
self-injections.

Responses to the preinjection ASI at Visit 1

Responses to the postinjection ASI by visit at all visits after self-injection using the e-Device 
Subjects on the Q4W dosing regimen who will self-inject twice (2×200mg CZP) at each visit 
will complete the postinjection ASI after the second injection at each of the 2 visits. For subjects 
on the Q4W dosing regimen, the postinjection ASI will collect the overall self-injection 
experience associated with both self-injections.

Responses to the Self-Injection Preference Questionnaire

In vitro functional evaluation of the e-Device following the final use per subject:

The percentage of e-Devices found to be functionally compromised (ie, visual signs of 
damage, device does not function normally with training cassette) 
4.2
Safety variables
The safety variables are:

Occurrence of AEs and ADEs

Vital signs 
5
STUDY DESIGN
5.1
Study description
In this Phase 3, open-label study of the e-Device, subjects diagnosed with RA, PsA, or AS 
(treated on Q2W dosing schedule, Q2W group), or RA, PsA, AS, or CD (treated on a Q4W
dosing schedule, Q4W group) will be recruited and evaluated. Subjects in the Q2W and Q4W
group should currently be treated with commercial CZP and be performing self-administration 
using the PFS. Hand function will be assessed at the screening visit by the Cochin Impaired 
Hand Function questionnaire. This study will recruit a minimum of 10 patients with impaired 
hand function. Impaired hand function will be measured using the Cochin scale (Poiraudeau et 
al, 2000; Duruöz et al, 1996) and impaired hand function will be defined as patients who have a 
Cochin score ≥13.5 at baseline.
Participating subjects must be at least 18 years of age and on a stable CZP dosing regimen for at 
least 3 months before Visit 1.
Visit 1 should be scheduled to coincide with the individual treatment schedule for each subject. 
The study will consist of 2 site visits and a follow-up telephone call. Following an initial 
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UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 16 of 82
eligibility check at Visit 1, all eligible subjects will enter the Study Treatment Period at that same 
visit. Subjects will self-inject using the e-Device immediately following training at Visit 1. 
For subjects in the Q2W group, subjects will self-inject CZP 200mg using the e-Device (ie, 
1×200mg injection). To meet the individual treatment schedule of the subjects, Visit 1 and
Visit 2 should be consistent with their scheduled CZP dose (ie, 2 weeks between their last dose
and Visit 1, and 2 weeks between Visit 1 and Visit 2).
For subjects in the Q4W group, subjects will self-inject CZP 400mg using the e-Device (ie, 
2×200mg injections). To meet the individual treatment schedule of the subjects, Visit 1 and 
Visit 2 should be consistent with their scheduled CZP dose (ie, 4 weeks between their last dose 
and Visit 1, and 4 weeks between Visit 1 and Visit 2).
For both groups, a follow-up telephone call will be conducted 1 week after the final study drug 
administration as a safety follow-up call. Follow-up requirements for adverse events (IMP and 
investigational device) and pregnancy are outlined in Section 10.1.3, Section 10.2.3, and 
Section 10.3, respectively. Subjects who have a positive pregnancy test and who have self-
administered at least 1 study dose of CZP who then discontinue CZP therapy will have a safety 
follow-up telephone call 70 days after the last study dose of CZP in addition to the 1-week 
Safety Follow-Up.
At both study visits, subjects may be provided with a brochure that summarizes an independent 
post-RA0098 market research study to be conducted by an independent external third party 
vendor. The market research study will evaluate the patient’s experience with the e-Device and 
the pre and postinjection questionnaire. If interested in the post-RA0098 market research study, 
the brochure will ask that patients contact the external third party vendor.
5.1.1
Study duration per subject
The study duration for each subject in the Q2W group on the Q2W dosing regimen is 3 weeks. 
The study duration for each subject in the Q4W group on the Q4W dosing regimen is 5 weeks.
Subjects will be required to perform a Safety Follow-Up by phone 1 week after their last study 
dose of CZP. Subjects who have a positive pregnancy test and who have self-administered at 
least 1 study dose of CZP who then discontinue CZP therapy will have a safety follow-up 
telephone call 70 days after the last study dose of CZP in addition to the 1-week Safety Follow-
Up.
The end of the study is defined as the date of the last telephone follow-up call for the last subject 
in the study.  
5.1.2
Planned number of subjects and sites
Approximately 80 subjects who are currently being treated with commercial CZP and are on a 
stable dosing regimen for at least 3 months will be screened in order to have at least 60 subjects 
use the e-Device at Visit 1 at approximately 45 sites. The 60 subjects using the e-Device at 
Visit 1 will be composed of a minimum of 15 subjects in each of the dosing groups (Q2W vs
Q4W) with a minimum of 15 subjects with CD and a minimum of 10 subjects with impaired 
hand function. Impaired hand function will be measured using the Cochin scale (Poiraudeau et 
al, 2000; Duruöz et al, 1996) and impaired hand function will be defined as patients who have a 
Cochin score ≥13.5 at baseline.
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UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 17 of 82
5.1.3
Anticipated regions and countries
The study is planned to be conducted in the US.
5.2
Schedule of study assessments
Table 5‒1:
Schedule of study assessments for Q2W subjects
Assessments
Visit 1
(Week 0)
Visit 2
(Week 2)
(±3 days)
Follow-Upa
(Week 3)
(±3 days)
Screening
Study Treatment 
Period
Written informed consent
X
Demographic data
X
Subject completes Cochin Impaired Hand 
Function questionnaire
X
Verification of inclusion/exclusion criteria
X
Withdrawal criteria
X
General medical/procedures history
X
Physical examination b
X
Vital signs c
X
X
Urine pregnancy test (βHCG)d
X
X
Contact IXRS
X
X
Recording of concomitant medication
X
X
Subject completes preinjection ASI
X
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self-administration 
X
Subject self-administers CZP using 
e-Device
X
X
HCP evaluates self-injection
X
X
Subject completes pain VAS 
(postinjection)e
X
X
Subject completes postinjection ASIf
X
X
Assessment of structural integrity for 
CZP-cassette
X
X
In vitro functional evaluation of e-Device
X
Subject completes Self-Injection Preference 
Questionnaire
X
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UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 18 of 82
Table 5‒1:
Schedule of study assessments for Q2W subjects
Assessments
Visit 1
(Week 0)
Visit 2
(Week 2)
(±3 days)
Follow-Upa
(Week 3)
(±3 days)
Screening
Study Treatment 
Period
Recording of AEs and ADEs
X
X
X
ADE=adverse device effect; AE=adverse event; AS=ankylosing spondylitis; ASI=Assessment of Self Injection; 
CZP=certolizumab pegol; HCP=healthcare provider; βHCG=beta human chorionic gonadotropin; IXRS= 
interactive response technology; Q2W=every 2 weeks; PsA=psoriatic arthritis; RA=rheumatoid arthritis; 
VAS=visual analog scale
Note: The visit window is ±3 days.
a Subjects will be required to perform a Safety Follow-Up by phone 1 week after their last study dose of CZP.
Subjects who are withdrawn from CZP treatment during the course of the study due to pregnancy will be 
required to perform a safety follow-up call 70 days following their final CZP administration in addition to the 
1-week Safety Follow-Up.
b Includes height and weight.
c Includes blood pressure, pulse, body temperature, and respiratory rate.
d For women of childbearing potential. A serum pregnancy test will be performed in the event of a positive 
urine result.
e Immediately postinjection (within 15 minutes).
f Within 30 minutes postinjection.
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UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 19 of 82
Table 5‒2:
Schedule of study assessments for Q4W subjects
Assessments
Visit 1
(Week 0)
Visit 2
(Week 4)
(±3 days)
Follow-Upa
(Week 5)
(±3 days)
Screening
Study Treatment 
Period
Written informed consent
X
Demographic data
X
Subject completes Cochin Impaired Hand 
Function questionnaire
X
Verification of inclusion/exclusion criteria
X
Withdrawal criteria
X
General medical/procedures history
X
Physical examination b
X
Vital signs c
X
X
Urine pregnancy test (βHCG)d
X
X
Contact IXRS
X
X
Recording of concomitant medication
X
X
Subject completes preinjection ASI
X
Training with e-Device prior to 
self-administration
X
Subject self-administers CZP using 
e-Device
X
X
HCP evaluates self-injection
X
X
Subject completes pain VAS 
(postinjection)e
X
X
Subject completes postinjection ASIf
X
X
Assessment of structural integrity for 
CZP-cassette
X
X
In vitro functional evaluation of e-Device
X
Subject completes Self-Injection Preference 
Questionnaire
X
Recording of AEs and ADEs
X
X
X
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UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 20 of 82
Table 5‒2:
Schedule of study assessments for Q4W subjects
Assessments
Visit 1
(Week 0)
Visit 2
(Week 4)
(±3 days)
Follow-Upa
(Week 5)
(±3 days)
Screening
Study Treatment 
Period
ADE=adverse device effect; AE=adverse event; ASI=Assessment of Self Injection; CD=Crohn’s disease; 
CZP=certolizumab pegol; HCP=healthcare practitioner; βHCG=beta human chorionic gonadotropin; IXRS= 
interactive response technology; Q4W=every 4 weeks; VAS=visual analog scale
Note: The visit window is ±3 days.
a Subjects will be required to perform a Safety Follow-Up by phone 1 week after their last study dose of CZP. 
Subjects who are withdrawn from CZP treatment during the course of the study due to pregnancy will be 
required to perform a safety follow-up call 70 days following their final CZP administration in addition to the 
1-week Safety Follow-Up.
b Includes height and weight.
c Includes blood pressure, pulse, body temperature, and respiratory rate.
d For women of childbearing potential. A serum pregnancy test will be performed in the event of a positive 
urine result.
e Immediately postinjection (within 15 minutes).
f Within 30 minutes postinjection.
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UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 21 of 82
5.3
Rationale for study design and selection of dose
UCB has developed a reusable e-Device for the self-administration of a sc dose of CZP. The 
e-Device provides subjects with another option to self-inject their medication. The e-Device 
offers improved convenience with an enhanced, reusable electromechanical injector that 
provides full electronic management of the injection process including subject instructions and 
warnings via a graphical user interface, and an electronic log of the injection history. A 
production version of the e-Device will be utilized for the purpose of this study.
Impaired hand function is seen in patients with RA (Durmus et al, 2013), to a lesser extent in 
patients with PsA (Gottieb et al, 2008), and is uncommon in patients with AS (Tam et al, 2010) 
or CD (Lossos et al, 1995). Since prompt treatment can reduce inflammation and the level of 
functional impairment seen in patients with RA or PsA (Goossens et al, 2000), it is not possible 
to accurately predict the proportion of patients treated with CZP who will have impaired hand 
function or how easy or difficult it may be to recruit such patients. In a recently published 
simulated injection study, the author notes that the investigators had difficulties in recruiting 
patients with high (Cochin score ≥20) versus low (Cochin score <20) hand disability so much so 
that they decided to stop the recruitment process when only 12 out of 15 subjects with high hand 
disability were enrolled (Hundry et al, 2017). This suggests that recruiting patients with impaired 
hand function may be challenging. Given these considerations, this study will recruit a minimum 
of 10 patients with impaired hand function. Impaired hand function will be measured using the 
Cochin scale (Poiraudeau et al, 2000; Duruöz et al, 1996) and impaired hand function will be 
defined as patients who have a Cochin score ≥13.5 at baseline.
The study will be open-label. All eligible subjects should be currently treated with commercial 
CZP, on a stable dosing regimen for the prior 3 months, and self-administering CZP using the 
PFS on a Q2W (RA, PsA, or AS) or Q4W (RA, PsA, AS, or CD) dosing regimen, as appropriate.
6
SELECTION AND WITHDRAWAL OF SUBJECTS
6.1
Inclusion criteria
To be eligible to participate in this study, all of the following criteria must be met:
1. An Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written 
Informed Consent form is signed and dated by the subject. 
2. Subject is considered reliable and capable of adhering to the protocol (eg, able to understand 
and complete questionnaires, able to use investigational device according to the Instructions 
for Use [IFU], visit schedule, or medication intake via self-administration) according to the 
judgment of the Investigator. 
3. Subject is male or female and must be at least 18 years old at Visit 1.
4. Subject must have been diagnosed at least 6 months prior to Visit 1 with documented 
moderate to severe active RA, active PsA, active AS (in US), or moderately to severely 
active CD (in US).
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UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 22 of 82
5. A minimum of 10 subjects will have impaired hand function. Impaired hand function will be 
measured using the Cochin scale (Duruöz et al, 1996; Poiraudeau et al, 2000) and impaired 
hand function will be defined as patients who have a Cochin score ≥13.5 at baseline.
6. Subjects must have been prescribed CZP and must have been self-injecting CZP using the 
PFS for at least 3 months prior to Visit 1. Subjects with RA, PsA, or AS must have been on a 
stable Q2W or Q4W CZP dosing regimen for at least 3 months prior to Screening. Subjects 
with CD must have been on a stable Q4W CZP dosing regimen for at least 3 months prior to 
Visit 1.
7. Subjects must have been screened according to the applicable national tuberculosis (TB)
screening guidelines (to be documented) or provide a documented TB screening activity (TB 
questionnaire, IGRA test, or chest x-ray) within the past 12 months prior to Visit 1.
8. Female subjects of childbearing potential should have a negative pregnancy test at Visit 1 
and should be using a medically accepted method of contraception during the entire duration 
of the study. Medically accepted methods of contraception are: hormonal contraception for at 
least 2 cycles prior to screening, intrauterine device, implant device, diaphragm with 
spermicide, bilateral tubal ligation, monogamous relationship with vasectomized partner (for 
at least 2 months prior to screening), or using condoms with spermicide gel. Abstinence is 
not an acceptable method of contraception for the study. Female subjects who are 
postmenopausal for at least 2 years or have undergone a complete hysterectomy, bilateral 
tubal ligation, and/or bilateral oophorectomy, or have a congenital sterility are considered not 
of childbearing potential.
6.2
Exclusion criteria
Subjects are not permitted to enroll in the study if any of the following criteria is met:
1. Subject is <18 years of age at Visit 1.
2. Subject has participated in another study of an investigational medicinal product (IMP) or an 
investigational device) within the previous 3 months or is currently participating in another 
study of an IMP or an investigational device. 
3. Subject has a history of chronic alcohol or drug abuse within the previous 6 months.
4. Female subjects who are breastfeeding, pregnant, or plan to become pregnant during the 
study or <6 months of the last study CZP dose.
5. Subject has a history of significant cardiovascular, respiratory, gastrointestinal, hepatic, 
endocrine, renal, dermatological, neurological, psychiatric, hematological, or bleeding 
disorders.
6. Subjects with known TB infection and at high risk of acquiring TB infection. Subjects with 
latent TB (LTB) who have not completed the prophylactic treatment regimen for LTB 
3 months prior to enrollment. 
a.
Known TB infection whether present or past is defined as:
i)
Active TB infection or clinical signs and symptoms suspicious for TB (pulmonary or 
extra pulmonary)
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UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 23 of 82
ii) History of active TB infection involving any organ system or findings in other organ 
systems consistent with TB infection
iii) Any evidence by radiography or other imaging modalities consistent with previously 
active TB infection that is not reported in the subject’s medical history.
b. High risk of acquiring TB infection is defined as:
i)
Known exposure to another person with active TB infection within the 3 months prior 
to Screening
ii) Time spent in a healthcare delivery setting or institution where individuals infected 
with TB are housed and where the risk of transmission of infection is high.
c. Latent TB infection (unless appropriate prophylaxis is completed 3 months prior to study 
enrollment. Subjects must have completed the full course of LTB prophylaxis treatment).
7. Subject has an active chronic/latent infection including but not limited to TB (untreated latent 
or active), hepatitis virus (HV), hepatitis C virus (HCV), or human immunodeficiency virus 
(HIV). 
8. Subject has a current malignancy or a history of malignancy. Subjects with less than 
3 completely excised basal cell carcinomas or with cervical carcinoma in situ successfully 
treated surgically more than 5 years prior to Screening may be included.
9. Subject is in a situation or has any condition which in the opinion of the Investigator or 
Sponsor, may interfere with the optimal participation in the study or produce a significant 
risk to the subject. 
10. Subject has had major surgery (including joint surgery) within 8 weeks prior to Visit 1, or 
has a scheduled surgery during the study.
6.3
Withdrawal criteria
Subjects are free to withdraw from the study at any time, without prejudice to their continued 
care. Subjects should be withdrawn from the study if any of the following events occur:
1. Subject develops an illness that would interfere with his/her continued participation.
2. Subject is noncompliant with the study procedures or medications in the opinion of the 
Investigator.
3. Subject withdraws his/her consent.
4. There is confirmation of a pregnancy during the study, as evidenced by a positive pregnancy 
test.
5. The Sponsor or a regulatory agency requests withdrawal of the subject.
6. Subject undergoes surgery related to an exacerbation of their disease. 
7. The Investigator is of the opinion that the subject’s continued participation in the study is not 
in the best interest of the subject.
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UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 24 of 82
8. Subject experiences a severe or serious injection site reaction (eg, bleeding, bruising, or pain) 
or a serious adverse event (SAE) that would, in the opinion of the Investigator, preclude the 
subject’s further participation in the study.
Investigators should attempt to obtain information on subjects in the case of withdrawal or 
discontinuation. For subjects considered as lost to follow up, the Investigator should make an 
effort (at least 1 phone call and 1 written message to the subject), 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 subject, must be recorded in the source 
documents. The electronic Case Report form (eCRF) must document the primary reason for 
withdrawal or discontinuation.
Investigators should contact the Medical Monitor in advance, whenever possible, to discuss the 
withdrawal of a subject.
7
IMP AND INVESTIGATIONAL DEVICE
In this study, the term investigational medicinal product (IMP) means the CZP drug substance. 
The term investigational device means the CZP-cassette and e-Device.
7.1
Description of investigational device
The reusable e-Device (auto-injector and CZP-cassette) is shown in Figure 7‒1.
Each single-use cassette contains 1 PFS with needle. The needle is covered by a needle cap until 
the CZP-cassette has been successfully inserted into the e-Device and the cap removed.
Figure 7‒1: CZP e-Device
Auto-injector
Cassette
The e-Device plus e-Device cassettes (containing CZP 200mg) will be supplied by UCB. 
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UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 25 of 82
7.1.1
Instructions for use of investigational e-Device
At Visit 1, prior to the first self-administration with the e-Device, subjects will be trained on 
proper self-injection technique and will receive and have the opportunity to review e-Device 
instruction materials that will be included with the e-Device kit. After the final self-injection and 
completion of the visual inspection and in vitro functional testing, site staff will print a hardcopy 
of the e-Device injection log. This log must be retained in the study file prior to disposing of the 
device. The injection log data may be used in the evaluation of device malfunctions or 
deficiencies. Details on how the injection log can be downloaded and printed can be found in the
IFU.
There is no recommended injection speed for self-injection using the e-Device. The e-Device 
offers the subject 4 injection speeds: “fastest” (8 seconds), “fast” (11 seconds), “slow” 
(14 seconds), or “slowest” (17 seconds). The e-Device will come set at the default “fast” 
(11 seconds) injection speed. As subjects enrolled in this study will be experienced in CZP 
self-injection using the PFS, they may have a preference for a fast or slow injection based on 
their experience with PFS self-injection. Subjects will be asked to select 1 of the 4 injection 
speeds; if they express no preference, then the default injection speed should be used. In either 
case, the injection speed used should be recorded for each self-injection with the e-Device. 
7.2
Treatment to be administered
The treatments are summarized in Table 7‒1.
Table 7‒1:
Treatments to be administered 
Delivery system
Reusable e-Device with single-use cassette
Manufacturer
UCB
Content
Loaded with a single-use cassette that houses a PFS 
containing 200mg/mL, 1mL of CZP liquid formulation in 
10mM sodium acetate, 125mM sodium chloride pH 4.7
CZP=certolizumab pegol; PFS=pre-filled syringe
Each dose will be administered as sc injections in either the right or left lateral abdominal wall or 
the right or left thigh. Treatment of the injection site with an anesthetic cream prior to dosing is 
not permitted.  
Each injection should be administered at a separate injection site, and rotation between the 
injection sites should be observed. 
At Visit 1 and Visit 2, Q2W group subjects will self-inject CZP 200mg (1×200mg injection) 
using the e-Device. At Visit 1 and Visit 2, Q4W group subjects will self-inject CZP 400mg 
(2×200mg injections) using the e-Device. 
Before injection, the CZP-cassette should be brought to room temperature by removing from the 
refrigerator and placing on a table at room temperature for 30 to 45 minutes. Subjects will be
observed onsite for 30 minutes after self-injection with CZP using the e-Device for any AEs. 
Subjects will be asked to contact the designated site personnel in case any AEs occur outside of 
the site visits.
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UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 26 of 82
7.3
Packaging
The site will receive uniquely numbered e-Devices and CZP-cassettes for use in this study. The 
CZP-cassettes will be provided in the intended final packaging. 
7.4
Labeling
Clinical drug and investigational device supplies will be labeled in accordance with the current 
International Council for Harmonisation (ICH) guidelines on Good Clinical Practice (GCP) and 
Good Manufacturing Practice and will include any locally required statements. If necessary, 
labels will be translated into the local language.
7.5
Handling and storage requirements
Certolizumab pegol (CZP-cassettes) must be securely stored at 2ºC to 8ºC, ie, in a refrigerator 
that is either in a locked room or in the pharmacy. Appropriate storage conditions must be 
ensured by controlled fridge temperature either using automated temperature monitoring and 
recording system or by using a minimum/maximum thermometer and completing a daily  
temperature log in accordance with local requirements. In case out of range temperature is noted, 
the Sponsor or designee must be notified so that the Sponsor or designee can determine whether 
the product should be used or not.
Each investigational e-Device must be individually stored (per subject) in a secured, limited 
access area at room temperature. The Investigator or hospital Pharmacist is responsible for the 
appropriate storage and accountability of the investigational device/CZP (CZP-cassettes) at the 
site, and documentation of appropriate storage and accountability.
7.6
Drug and device accountability
The Investigator will receive numbered treatments that will be assigned to eligible subjects by an 
interactive response technology (IXRS) at Visit 1. All drug administrations will be observed by 
the Investigator or his/her appropriately trained designee.
UCB, or its representatives, will supply a Drug Accountability form, to be kept up to date with 
record of all IMP administrations, ie, injections by means of the e-Device. This form will serve 
as source documentation during the course of the study. In addition, a Device Accountability 
form will be used to record investigational device used on a by-subject basis and will serve as 
source documentation during the course of the study. Details of any loss (e-Device auto-injectors 
or e-Device cassettes) due to breakage or wastage, not used, destructed 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 
IMP 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 IMP and investigational device (including e-Device auto-injectors and e-Device cassettes) 
intended for the study cannot be used for any other purpose than that described in this protocol.
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UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 27 of 82
7.7
Procedures for monitoring subject compliance
As all CZP self-administrations will be scheduled, performed at the site, and observed by the 
Investigator or his/her designee, monitoring subject compliance is not applicable.
7.8
Concomitant medications/treatments
7.8.1
Permitted concomitant treatments (medications and therapies)
Subjects are permitted to continue on their prescribed medical therapy for the disease in 
accordance with the instructions of their treating physician. Concomitant medications/treatments, 
including over-the-counter products and supplements, must be recorded in the subject’s notes 
(source documentation) and provided on the eCRF. This record should include the name of the 
drug, the dose, the route, and date(s) of administration, and the indication for use.
7.8.2
Prohibited concomitant treatments (medications and therapies)
Use of topical analgesics at the injection site are prohibited concomitant medications in this 
study. 
7.9
Blinding
This is an open-label study.
7.10
Randomization and numbering of subjects
There will be no randomization in this study. A subject number assigned by an IXRS at Visit 1
will serve as the subject identifier throughout the study. 
8
STUDY PROCEDURES BY VISIT
As the dosing schedule groups (Q2W vs Q4W) are different regarding number of injections       
(1 CZP injection for Q2W vs 2 CZP injections per administration for Q4W) and study treatment 
period (2 weeks vs 4 weeks), the schedule of assessments for the 2 subject populations differs.
8.1
Visit 1/ Screening and Study Treatment Period
Prior to any study activities, all subjects will be asked to read and sign an Informed Consent form
that has been approved by an IRB/IEC and which complies with regulatory requirements. 
Subjects will be given adequate time to consider any information concerning the study, described 
to them by the Investigator or designee. As part of the informed consent procedure, subjects will 
be given the opportunity to ask the Investigator any questions regarding potential risks and 
benefits of participation in the study.
The following procedures will be performed:

Recording of demographic data

Verification of eligibility criteria

General medical and procedures history

Physical examination, including height and weight

Measurement of vital signs (BP, pulse, body temperature, respiratory rate [RR])
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UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 28 of 82

Urine pregnancy test (female subjects of childbearing potential)

Contact IXRS

Subject completes Cochin Impaired Hand Function questionnaire 

Recording of concomitant medication

Recording of AEs and ADEs
Once all entry criteria have been verified, the following procedures will be performed:

Preinjection ASI

Training on use of e-Device

Self-administration of CZP using e-Device

HCP evaluates self-injection
During self-injection, if the skin sensor at the injection port loses contact with the skin, the 
e-Device will withdraw the needle and stop administration of CZP. If less than five minutes 
have elapsed since loss of contact with skin, the subject can reposition the e-Device on a new 
clean injection site and resume and complete the self-injection. If the subject is unable to 
complete the self-injection and deliver the entire dose of medication (ie, the device indicates 
incomplete administration and the CZP-cassette is not seen to be empty), the HCP evaluating 
the self-injection will document the incomplete self-injection, note the reason why the 
complete dose was not administered, and using his/her best medical judgment, advise the 
subject regarding any further dosing.

Assessment of structural integrity of CZP-cassette

Pain VAS (immediately postinjection [within 15 minutes])

Postinjection ASI (within 30 minutes postinjection)

Recording of AEs and ADEs
8.2
Study procedures by visit for the Q2W group
8.2.1
Visit 2 (Week 2)
The following procedures will be performed:

Review withdrawal criteria

Measurement of vital signs (BP, pulse, body temperature, RR)

Urine pregnancy test (female subjects of childbearing potential)

Contact IXRS

Recording of concomitant medication

Self-administration of CZP using e-Device

HCP evaluates self-injection
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UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 29 of 82
During self-injection, if the skin sensor at the injection port loses contact with the skin, the 
e-Device will withdraw the needle and stop administration of CZP. If less than five minutes 
have elapsed since loss of contact with skin, the subject can reposition the e-Device on a new 
clean injection site and resume and complete the self-injection. If the subject is unable to 
complete the self-injection and deliver the entire dose of medication (ie, the device indicates 
incomplete administration and the CZP-cassette is not seen to be empty), the HCP evaluating 
the self-injection will document the incomplete self-injection, note the reason why the 
complete dose was not administered, and using his/her best medical judgment, advise the 
subject regarding any further dosing.

Assessment of structural integrity of CZP-cassette

In vitro functional evaluation of e-Device

Pain VAS (immediately postinjection [within 15 minutes])

Postinjection ASI (within 30 minutes postinjection)

Self-Injection Preference Questionnaire

Recording of AEs and ADEs
8.3
Study procedures by visit for the Q4W group
8.3.1
Visit 2 (Week 4)
The following procedures will be performed:

Review withdrawal criteria

Measurement of vital signs (BP, pulse, body temperature, RR)

Urine pregnancy test (female subjects of childbearing potential)

Contact IXRS

Recording of concomitant medication

Self-administration of CZP using e-Device

HCP evaluates self-injection
During self-injection, if the skin sensor at the injection port loses contact with the skin, the 
e-Device will withdraw the needle and stop administration of CZP. If less than five minutes 
have elapsed since loss of contact with skin, the subject can reposition the e-Device on a new 
clean injection site and resume and complete the self-injection. If the subject is unable to 
complete the self-injection and deliver the entire dose of medication (ie, the device indicates 
incomplete administration and the CZP-cassette is not seen to be empty), the HCP evaluating 
the self-injection will document the incomplete self-injection, note the reason why the 
complete dose was not administered, and using his/her best medical judgment, advise the 
subject regarding any further dosing.

Assessment of structural integrity of CZP-cassette

In vitro functional evaluation of e-Device
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UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 30 of 82

Pain VAS (immediately postinjection [within 15 minutes])

Postinjection ASI (within 30 minutes postinjection) 

Self-Injection Preference Questionnaire

Recording of AEs and ADEs
8.4
Safety Follow-Up 
A Safety Follow-Up by telephone will be conducted 1 week after the subject’s final site visit
using the e-Device. Any AEs or ADEs will be recorded.
Subjects who are withdrawn from CZP treatment during the course of the study due to pregnancy
will be required to perform a safety follow-up telephone call 70 days following their final CZP 
administration in addition to the 1-week Safety Follow-Up.
9
ASSESSMENT OF SELF-INJECTION
9.1
Injection Site Pain (VAS)
A VAS will be used to assess overall injection pain due to self-injection postinjection at every
visit during the Study Treatment Period. Subjects will be required to indicate their injection pain 
by placing a mark on a 100mm line from 0 (no pain) to 100 (worst possible pain). The VAS will 
be assessed immediately postinjection (within 15 minutes). The subject will complete the VAS 
prior to completion of the postinjection ASI.
Subjects on the Q4W dosing regimen who will self-inject twice (2×200mg CZP) at each visit
will complete the Pain VAS after the second injection at each of the 2 visits. For subjects on the 
Q4W dosing regimen, the Pain VAS will record the overall pain associated with both 
self-injections.
9.2
Assessment of Self Injection (ASI)
The preinjection ASI is composed of 6 items grouped into 2 domains. The postinjection ASI is 
composed of 44 items grouped into 6 domains. The domains are feeling about injections, self-
image, self-confidence, pain and skin reactions during and after injections, ease of use of the 
self-injection device, and satisfaction with self-injection.
The preinjection ASI will be completed preinjection at Visit 1, and the postinjection will be 
completed within 30 minutes postinjection at each visit during the Study Treatment Period. The 
ASI has been developed from the Self-Injection Assessment Questionnaire and modified to 
reflect the improved features of the e-Device and is being piloted in this study. It will be 
validated using a separate psychometric analysis plan.
Subjects on the Q4W dosing regimen who will self-inject twice (2×200mg CZP) at each visit
will complete the postinjection ASI after the second injection at each of the 2 visits. For subjects
on the Q4W dosing regimen, the postinjection ASI will collect the overall self-injection 
associated with both self-injections.
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UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 31 of 82
9.3
Self-Injection Preference Questionnaire
The 9-item Self-Injection Preference Questionnaire was developed, based on patient input, to 
assess the self-injection experience and patient preference between the e-Device and PFS. The 
Self-Injection Preference Questionnaire will be completed by the subject at Visit 2 after the VAS 
and postinjection ASI have been completed.
9.4
Evaluation of post-use structural integrity of CZP-cassettes
The used CZP-cassettes will be inspected to determine if the entire dose was delivered based on 
whether the PFS housed in the CZP-cassette is empty or not (as per primary endpoint). During 
self-injection, if the skin sensor at the injection port loses contact with the skin, the e-Device will 
withdraw the needle and stop administration of CZP. If less than five minutes have elapsed since 
loss of contact with skin, the subject can reposition the e-Device on a new clean injection site 
and resume and complete the self-injection. If the subject is unable to complete the self-injection 
and deliver the entire dose of medication (ie, the device indicates incomplete administration and 
the CZP-cassette is not seen to be empty), the HCP evaluating the self-injection will document 
the incomplete self-injection, note the reason why the complete dose was not administered, and 
using his/her best medical judgment, advise the subject regarding any further dosing. The visual 
inspection of the used CZP-cassette will also check for structural integrity and damage (ie, clear 
evidence of damage/compromised structural integrity—not superficial, cosmetic imperfections). 
All evaluations will be performed by appropriately trained site staff.
9.5
Evaluation of post-use structural and functional integrity of the 
e-Device
Following the subject’s final self-administration using the e-Device, the e-Device will be 
visually inspected for structural integrity and damage (ie, clear evidence of 
damage/compromised structural integrity—not superficial, cosmetic imperfections). The 
e-Device will also be evaluated for functional integrity (ie, proper functioning) using a training 
cassette as specified in the in vitro e-Device functional testing directions. All evaluations will be 
performed by appropriately trained site staff.
9.6
Evaluation of safe and effective self-injection
Safe and effective self-injection will be evaluated by the HCP. Subject self-injection of the 
complete dose of CZP will be confirmed by a visual inspection of the CZP-cassette(s) which 
shows the PFS container to be empty. During self-injection, if the skin sensor at the injection 
port loses contact with the skin, the e-Device will withdraw the needle and stop administration of 
CZP. If less than five minutes have elapsed since loss of contact with skin, the subject can 
reposition the e-Device on a new clean injection site and resume and complete the self-injection. 
If the subject is unable to complete the self-injection and deliver the entire dose of medication 
(ie, the device indicates incomplete administration and the CZP-cassette is not seen to be empty), 
the HCP evaluating the self-injection will document the incomplete self-injection, note the 
reason why the complete dose was not administered, and using his/her best medical judgment, 
advise the subject regarding any further dosing. The self-injection will be considered safe if there 
are no AEs related to use of the e-Device (ADEs) that would preclude continued use of the 
e-Device for self-injection.
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UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 32 of 82
For subjects on the Q4W dosing regimen who will self-inject twice (2×200mg CZP) at each 
visit, each injection will be evaluated for safety and effectiveness using the above criteria. The 
primary endpoint of safe and effective self-injection for subjects on the Q4W dosing regimen 
will be met only if both self-injections are determined to be safe and effective.
10
ASSESSMENT OF SAFETY
In this study, safety reporting requirements apply to the IMP and to all constituents of the 
investigational device (including the e-Device auto-injector, and the CZP-cassette) per 
21 CFR 312.32, 21 CFR 812.150, and 21 CFR 812.3. Subjects in the study are experienced at 
self-injection and will be aware of their usual injection experience and events typically seen 
during the normal course of an injection. Effects that are considered usual by the subject and the 
HCP (eg, minor pain, bruising, or bleeding) during the course of self-injection are not to be 
classified as AEs. 
10.1
Adverse events (IMP)
10.1.1
Definitions (IMP)
10.1.1.1
Adverse event (IMP)
An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation 
subject administered a pharmaceutical product that does not necessarily have a causal 
relationship with this treatment. An AE can therefore be any unfavorable and unintended sign 
(including an abnormal laboratory finding), symptom, or disease temporally associated with the 
use of a medicinal (investigational) product, whether or not related to the medicinal 
(investigational) product.
In order to ensure complete safety data collection, all AEs occurring during the study (ie, after 
the signing of the Informed Consent form), including any pretreatment and posttreatment periods 
required by the protocol, must be reported in the eCRF even if no IMP 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.
Signs or symptoms of the condition/disease for which the IMP is being studied should be 
recorded as AEs only if their nature changes considerably or their frequency or intensity 
increases in a clinically significant manner as compared to the clinical profile known to the 
Investigator from the subject’s history or the Baseline Period.
10.1.1.2
Serious adverse event (IMP)
Once it is determined that a subject experienced an AE, the seriousness of the AE must be 
determined. An SAE must meet 1 or more of the following criteria:

Death

Life-threatening
(Life-threatening does not include a reaction that might have caused death had it occurred in 
a more severe form.)

Significant or persistent disability/incapacity
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UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 33 of 82

Congenital anomaly/birth defect (including that occurring in a fetus)

Important medical event that, based upon appropriate medical judgment, may jeopardize the 
patient or subject and may require medical or surgical intervention to prevent 1 of the other 
outcomes listed in the definition of serious
(Important medical events may include, but are not limited to potential Hy’s Law [see 
Section 10.1.1.3], allergic bronchospasm requiring intensive treatment in an emergency room 
or at home, blood dyscrasias that do not result in inpatient hospitalization, or the 
development of drug dependency or drug abuse.)

Initial inpatient hospitalization or prolongation of hospitalization
(A patient admitted to a hospital, even if he/she is released on the same day, meets the 
criteria for the initial inpatient hospitalization. An emergency room visit that results in 
admission to the hospital would also qualify for the initial inpatient hospitalization criteria. 
However, emergency room visits that do not result in admission to the hospital would not 
qualify for this criteria and, instead, should be evaluated for 1 of the other criteria in the 
definition of serious [eg, life-threatening adverse experience, important medical event].
Hospitalizations for reasons not associated with the occurrence of an AE [eg, preplanned 
surgery or elective surgery for a pre-existing condition that has not worsened or manifested 
in an unusual or uncharacteristic manner] do not qualify for reporting. For example, if a 
subject has a condition recorded on his/her medical history and later has a preplanned surgery 
for this condition, it is not appropriate to record the surgery or hospitalization as an SAE, 
since there is no AE upon which to assess the serious criteria. Please note that, if the 
pre-existing condition has worsened or manifested in an unusual or uncharacteristic manner, 
this would then qualify as an AE and, if necessary, the seriousness of the event would need to 
be determined.)
10.1.1.2.1
Anticipated serious adverse events (IMP)
The following Anticipated SAEs are 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 10.1.1.2.
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UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 34 of 82
Table 10‒1: Anticipated serious adverse events for study population
Population
Anticipated SAE
Rheumatoid arthritis
Rheumatoid arthritis
Crohn's disease 
Crohn’s disease 
Perianal abscess
Abdominal pain
Psoriatic arthritis
Psoriatic arthritis
Ankylosing spondylitis
Ankylosing spondylitis
SAE=serious adverse event
10.1.1.3
Adverse events of special interest (IMP)
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 the present study, the AEs of special interest 
are as follows:

Serious infections, including opportunistic infections

Malignancies, including lymphoma

Congestive heart failure

Demyelinating-like disorders

Aplastic anemia, pancytopenia, thrombocytopenia, neutropenia, and leucopenia

Serious bleeding events

Lupus and lupus-like syndrome

Serious skin reactions (ie, Stevens Johnson Syndrome, toxic epidermal necrosis, and 
erythema multiforme)
Potential Hy’s Law, defined as ≥3x upper limit of normal (ULN) alanine aminotransferase 
(ALT) or aspartate aminotransferase (AST) with coexisting ≥2xULN total bilirubin in the 
absence of ≥2xULN alkaline phosphatase (ALP), with no alternative explanation for the 
biochemical abnormality, must ALWAYS be reported to UCB as an AE of special interest (ie, 
without waiting for any additional etiologic investigations to have been concluded). Follow-up 
information should then be reported if an alternative etiology is identified during investigation 
and monitoring of the subject.
10.1.2
Procedures for reporting and recording adverse events (IMP)
The subject will be given the opportunity to report AEs spontaneously. A general prompt will 
also be given at each study visit to detect AEs. For example:
“Did you notice anything unusual about your health (since your last visit)?”
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UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 35 of 82
In addition, the Investigator should review any self-assessment procedures employed in the 
study.
10.1.2.1
Description of adverse events (IMP)
When recording an AE, the Investigator should use the overall diagnosis or syndrome using 
standard medical terminology, rather than recording individual symptoms or signs. The eCRF
and source documents should be consistent. Any discrepancies between the subject’s own words 
on his/her own records (eg, diary card) and the corresponding medical terminology should be 
clarified in the source documentation.
Details for completion of the Adverse Event eCRF (including judgment of relationship to IMP) 
are described in the eCRF Completion Guidelines.
10.1.2.2
Rule for repetition of an adverse event (IMP)
An increase in the intensity of an AE should lead to the repetition of the AE being reported with:

The outcome date of the first AE that is not related to the natural course of the disease being 
the same as the start date of the repeated AE, and the outcome of “worsening”

The AE verbatim term being the same for the first and repeated AE, so that the repeated AE 
can be easily identified as the worsening of the first one
10.1.2.3
Additional procedures for reporting serious adverse events (IMP)
If an SAE is reported, UCB must be informed within 24 hours of receipt of this information by 
the site (see contact information for SAE reporting listed in the Serious Adverse Event Reporting 
section at the front of the protocol). The Investigator must forward to UCB (or its representative) 
a duly completed “Investigator SAE Report Form for Development Drug” (SAE report form) 
provided by UCB, even if the data are incomplete, or if it is obvious that more data will be 
needed in order to draw any conclusions. Information recorded on this form will be entered into 
the global safety database.
An Investigator SAE report form will be provided to the Investigator. The Investigator SAE 
Report form must be completed in English. 
It is important for the Investigator, when completing the SAE report form, to include the 
assessment as to a causal relationship between the SAE and the IMP administration. This insight 
from the Investigator is very important for UCB to consider in assessing the safety of the IMP 
and in determining whether the SAE requires reporting to the regulatory authorities in an 
expedited manner.
Additional information (eg, autopsy or laboratory reports) received by the Investigator must be 
provided within 24 hours. All documents in the local language must be accompanied by a 
translation in English, or the relevant information included in the same document must be 
summarized in the Investigator SAE report form.
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 IMP), up to 
completion of the follow-up visit for each subject, and to also inform participating subjects of the 
need to inform the Investigator of any SAE within this period. Serious AEs that the Investigator 
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UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 36 of 82
thinks may be associated with the IMP must be reported to UCB regardless of the time between 
the event and the end of the study.
Upon receipt of the SAE report form, UCB will perform an assessment of expectedness of the 
reported SAE. The assessment of the expectedness of the SAE is based on the Investigator’s 
Brochure.
10.1.3
Follow up of adverse events (IMP)
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 subject is lost to follow up. This 
follow-up requirement applies to AEs, SAEs, and AEs of special interest. 
If an AE is ongoing at the end of the study for a subject, follow up should be provided until 
resolution/stable level of sequelae is achieved, or until the Investigator no longer deems that it is 
clinically significant, or until the subject is lost to follow up. If no follow up is provided, the 
Investigator must provide a justification. 
Information on SAEs obtained after clinical database lock will be captured through the Patient 
Safety (PS) database without limitation of time.
10.2
Adverse events (investigational device) 
10.2.1
Definitions (investigational device)
10.2.1.1
Adverse Events (investigational device)
An AE for an investigational device is any untoward medical occurrence, unintended disease or 
injury, or untoward clinical sign (including abnormal laboratory findings) in subjects enrolled in 
the study, including any pre- and posttreatment periods (as required by the protocol). This 
includes the following:

Events considered unrelated or related to the investigational medical device 

Events related to the procedures involved (even if no investigational device was used).
For users or other persons (eg, caregivers), AEs for a device are restricted to only events related 
to the investigational medical device.
In order to ensure complete safety data collection, all AEs occurring during the study (ie, after 
the signing of the Informed Consent form), including any pretreatment and posttreatment periods 
required by the protocol, must be reported in the eCRF even if no investigational device was 
used 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.
Signs or symptoms of the condition/disease for which the Investigational Device is being studied 
should be recorded as AEs only if their nature changes considerably or their frequency or 
intensity increases in a clinically significant manner as compared to the clinical profile known to 
the Investigator from the subject’s history or the Baseline Period.
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UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
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Page 37 of 82
10.2.1.2
Serious adverse event (investigational device)
Once it is determined that a subject experienced an AE for an investigational device, the 
seriousness of the AE must be determined. An SAE must meet 1 or more of the following 
criteria:

Death

Serious deterioration in the health of the subject that results in at least 1 of the following:

Life-threatening illness or injury

Permanent impairment of a body structure or body function

Inpatient or prolonged hospitalization

Medical or surgical intervention to prevent life-threatening illness or injury or permanent 
impairment to a body structure or body function

Fetal distress, fetal death, or a congenital abnormality or birth defect
Planned hospitalization for a pre-existing condition, or a procedure required by the protocol, 
without serious deterioration in health, is not considered a serious adverse event.
10.2.1.3
Device- or procedure-related
10.2.1.3.1
Adverse device effect (investigational device)
An adverse device effect (ADE) is an AE related to the use of an investigational device. An ADE 
must meet 1 or more of the following criteria:

Adverse event resulting from insufficiencies or inadequacies in the instructions for use, the 
deployment, the implantation, the installation, the operation, or any malfunction of the 
investigational medical device.

Adverse event that is a result of a use error or intentional misuse.
10.2.1.3.1.1 Unanticipated adverse device effect (investigational device)
An unanticipated adverse device effect (UADE) is any ADE that meets 1 or more of the 
following criteria:

Serious adverse effect on health or safety or any life-threatening problem or death caused by, 
or associated with a device, if that effect, problem, or death was not previously identified in 
nature, severity, or degree of incidence in the application

Any other unanticipated serious problem associated with a device that relates to the rights, 
safety, or welfare of subjects.
10.2.1.3.2
Serious adverse device effect (investigational device)
A serious adverse device effect (SADE) is an ADE that has resulted in any of the consequences 
characteristic of a SAE, as described in Section 10.2.1.2. Serious adverse device effects are 
classified as anticipated (anticipated serious adverse device effect; ASADE) and unanticipated 
(USADE) (definitions provided below).
An ASADE is a SADE which by its nature, incidence, severity, or outcome has been identified.
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29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 38 of 82
An USADE is a SADE which by its nature, incidence, severity, or outcome has not been 
identified.
10.2.1.3.3
Device deficiency (investigational device)
A device deficiency is an inadequacy of a medical device with respect to its identity, quality, 
durability, reliability, safety, or performance. Device deficiencies include malfunctions, use 
errors, and inadequate labeling.
10.2.2
Procedures for reporting and recording adverse events 
(investigational device), adverse device effects, and device 
deficiencies
The subject will be given the opportunity to report AEs, ADEs, and device deficiencies 
spontaneously. A general prompt will also be given at each study visit to detect AEs, ADEs, and 
device deficiencies. Below is an example prompt:
“Did you notice anything unusual about the device?”
10.2.2.1
Adverse events
Details for completion of the Adverse Event eCRF (including judgment of relationship to 
Investigational Device or Study procedure) are described in the eCRF Completion Guidelines.
10.2.2.1.1
Serious adverse events
See Section 10.1.1.2 for details.
10.2.3
Follow up of adverse events (investigational device)
See Section 10.1.3.
10.2.3.1
Device-related
10.2.3.1.1
Reporting of adverse device effects 
An Investigator Adverse Device Effect and Device Deficiency Form will be provided to the 
Investigator. The Investigator Adverse Device Effect and Device Deficiency Form must be 
completed in English.
An Investigator shall submit to UCB a report of any adverse device effect and device deficiency 
occurring during the study within 24 hours after the Investigator first learns of the event using 
the Adverse Device Effect and Device Deficiency Form. 
10.2.3.1.1.1 Reporting of unanticipated adverse device effects by the Investigator
An Investigator shall submit a report of any unanticipated adverse device effect occurring during 
an investigation to:

UCB within 24h, UCB will conduct an evaluation of the reported unanticipated adverse 
device effect and report the results of such evaluation to FDA and to all reviewing IRB’s and 
participating Investigators within 10 working days after UCB first receives notice of the 
effect.

The site IRB and reviewing IRB as soon as possible, but in no event later than 10 working 
days after the Investigator first learns of the effect.
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Clinical Study Protocol
Certolizumab pegol
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Confidential
Page 39 of 82
10.2.3.1.2
Reporting of serious adverse device effects
10.2.3.1.2.1 Reporting of serious adverse device effect including device 
deficiencies with risk of SAE
If an SADE or a device deficiency that could have led to a serious adverse event, if:

Either suitable action had not been taken or

Intervention had not been made or

Circumstances had been less fortunate
is reported, UCB must be informed within 24 hours of receipt of this information by the site (see 
contact information for SAE reporting listed in the Serious Adverse Event Reporting section at 
the front of the protocol). The Investigator must forward to UCB (or its representative) a duly 
completed “SAE Report Form for Investigational Medical Device” (SAE report form) provided 
by UCB, even if the data are incomplete, or if it is obvious that more data will be needed in order 
to draw any conclusions.
A SAE report form will be provided to the Investigator. The Investigator SAE Report form must 
be completed in English. 
It is important for the Investigator, when completing the SAE report form, to include the 
assessment as to a causal relationship between the SAE and the investigational device and/or 
study procedure.
Additional information (eg, autopsy or laboratory reports) received by the Investigator must be 
provided within 24 hours. All documents in the local language must be accompanied by a 
translation in English, or the relevant information included in the same document must be 
summarized in the Investigator SAE report form.
The Investigator is specifically requested to collect and report to UCB (or its representative) any 
SADEs or device deficiency with risk of SAE (even if the Investigator is certain that they are in 
no way associated with the Investigational device), up to completion of the follow-up visit for 
each subject, and to also inform participating subjects of the need to inform the Investigator of 
any SAE within this period. Serious AEs that the Investigator thinks may be associated with the 
investigational device must be reported to UCB regardless of the time between the event and the 
end of the study.
10.2.3.1.3
Reporting of device deficiencies
If a device deficiency related to the identity, quality, durability, reliability, safety, or performance 
of the investigational device is reported (even if the investigational device was not used), UCB 
must be informed within 1 business day of receipt of this information by the site. The 
Investigator must forward to UCB (or its representative) a duly completed Investigator Adverse 
Device Effect and Device Deficiency Form provided by UCB, even if the data are incomplete or 
if it is obvious that more data will be needed in order to draw any conclusions. 
An Investigator Adverse Device Effect and Device Deficiency Form will be provided to the 
Investigator. The Investigator Adverse Device Effect and Device Deficiency Form must be 
completed in English.
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UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 40 of 82
It is important for the Investigator, when completing the Investigator Adverse Device Effect and 
Device Deficiency Form, to include an assessment and documentation of whether the device 
deficiency could have led to a serious adverse event if any of the following occurred:

Suitable action had not been taken or

Intervention had not been made or

Circumstances had been less fortunate
All defective devices must be returned to UCB.
10.2.3.2
Rule for repetition of an adverse device effect and/or device 
deficiency
See Section 10.1.2.2 for details.
10.3
Pregnancy
If an Investigator is notified that a subject has become pregnant before or after the first dose IMP 
via e-Device, the Investigator must immediately notify UCB’s Patient Safety (PS) department by 
providing the completed Pregnancy Report and Outcome form (for contact details see Serious 
Adverse Event reporting information at the beginning of this protocol). The subject should be 
withdrawn from the study as soon as pregnancy is known (by positive pregnancy test), and the 
following should be completed:

The subject should immediately stop the intake of the IMP.

A safety follow-up call should be scheduled for 70 days after the last administration of CZP 
study dose (via e-Device). 
The Investigator must inform the subject of information currently known about potential risks 
and about available treatment alternatives.
The pregnancy will be documented on the Pregnancy Report and Outcome form provided to the 
Investigator. The progression of the pregnancy and the eventual birth (if applicable) must be 
followed up using the Pregnancy Report and Outcome form in which the Investigator has to 
report on the health of the mother and of the child. Every reasonable attempt should be made to
follow the health of the child for 30 days after birth for any significant medical issues. In certain 
circumstances, UCB may request that follow up is continued for a period longer than 30 days. If 
the subject is lost to follow up and/or refuses to give information, written documentation of 
attempts to contact the subject needs to be provided by the Investigator and filed at the site. 
UCB’s PS department is the primary contact for any questions related to the data collection for 
the pregnancy, eventual birth, and follow up.
In cases where the partner of a male subject enrolled in a clinical study becomes pregnant, the 
Investigator or designee is asked to contact the subject to request consent of the partner via the 
Partner Pregnancy Consent form that has been approved by the responsible IRB/IEC and should 
be available in the Investigator site file. In case of questions about the consent process, the 
Investigator may contact the UCB/contract research organization (CRO) contract monitor for the 
study. The Investigator will complete the Pregnancy Report and Outcome form and send it to 
UCB’s PS department (for contact details see Serious Adverse Event reporting information at the 
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UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 41 of 82
beginning of this protocol) only after the partner has agreed that additional information can be 
captured and has provided the signed Partner Pregnancy Consent form. UCB’s PS department is 
also the primary contact for any questions related to the data collection for the partner pregnancy, 
eventual birth, and follow up.
A pregnancy becomes a serious adverse event (SAE) in the following circumstances: 
miscarriage, abortion (elective or spontaneous), unintended pregnancy after hormonal 
contraceptive failure (if the hormonal contraceptive was correctly used), ectopic pregnancy, fetal 
demise, or any congenital anomaly/birth defect of the baby. Those SAEs must be additionally 
reported using the Investigator SAE Report form.
10.4 Suspected transmission of an infectious agent 
For the purposes of reporting, any suspected transmission of an infectious agent via a medicinal 
product should be considered as an SAE; such cases must be reported immediately, recorded in 
the AE module of the eCRF, and followed as any other SAE. Any organism, virus, or infectious 
particle (eg, prion protein transmitting transmissible spongiform encephalopathy), pathogenic or 
nonpathogenic, is considered an infectious agent.
There is no evidence that there is a risk of transmission of an infectious agent with the 
investigational device.
10.5
Overdose of investigational medicinal product
Excessive dosing (beyond that prescribed in the protocol and including overdose) should be 
recorded in the eCRF. 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).
There is no evidence that there is a risk of overdose with the IMP with the investigational device.
10.6
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 IMP or investigational device so that Investigators, clinical study 
subjects, 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 PS representative.
As appropriate for the stage of development and accumulated experience with the IMP and 
investigational device, medically qualified personnel at UCB may identify additional safety 
measures (eg, AEs, vital signs, laboratory or electrocardiogram [ECG] results) for which data 
will be periodically reviewed during the course of the study.
10.7
Laboratory measurements
For women of childbearing potential, a urine pregnancy test will be performed at Visit 1 and 
Visit 2. A serum pregnancy test will be performed in the event of a positive urine result.
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Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 42 of 82
10.8
Other safety measurements
10.8.1
Vital signs
Vital signs will include systolic and diastolic BP, pulse, RR, and body temperature. Subjects
should be supine for 5 minutes before and during the collection of BP and pulse measurements.
Vital signs will be measured at Visit 1 and Visit 2.
10.8.2
Physical examination
The physical examination will include general appearance; ear, nose, and throat; eyes, hair, and 
skin; respiratory; cardiovascular; gastrointestinal; musculoskeletal; hepatic; neurological 
(including limb reflexes); and mental status. Height and weight will also be measured. The 
physical examination will be performed at Visit 1. Any clinically significant changes since the 
physical examination at Visit 1 will be recorded as AEs. 
11
STUDY MANAGEMENT AND ADMINISTRATION 
11.1
Adherence to protocol
The Investigator should not deviate from the protocol. However, the Investigator should take any 
measure necessary in deviation from or not defined by the protocol in order to protect clinical 
study subjects from any immediate hazard to their health and safety. In this case, this action 
should be taken immediately, without prior notification of the regulatory authority, IRB/IEC, or 
Sponsor.
After implementation of such measure, the Investigator must notify the Clinical Project Manager
of the Sponsor within 24 hours and follow any local regulatory requirements.
11.2
Monitoring
UCB (or designee) will monitor the study to meet the Sponsor’s monitoring Standard Operating 
Procedures (SOPs), ICH-GCP guideline, and applicable regulatory requirements, and to ensure 
that study initiation, conduct, and closure are adequate. Monitoring of the study may be 
delegated by UCB to a CRO or a contract monitor.
The Investigator and his/her staff are expected to cooperate with UCB (or designee) and to be 
available during the monitoring visits to answer questions sufficiently and to provide any 
missing information. The Investigator(s)/institution(s) will permit direct access to source 
data/documents for study-related monitoring, audits, IRB/IEC review, and regulatory 
inspection(s).
The Investigator will allow UCB (or designee) to periodically review all eCRFs and 
corresponding source documents (eg, hospital and laboratory records for each study participant). 
Monitoring visits will provide UCB (or designee) with the opportunity to evaluate the progress 
of the study, verify the accuracy and completeness of eCRFs, ensure that all protocol 
requirements, applicable authorities regulations, and Investigator’s obligations are being 
fulfilled, and resolve any inconsistencies in the study records.
11.2.1
Definition of source data 
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, 
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Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 43 of 82
optical disc). They should not be obscured by correction fluid or have temporary attachments 
(such as removable self-stick notes). Photocopies and/or printouts of eCRFs are not considered 
acceptable source documents. 
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, or quality of life 
questionnaires, 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 subject’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).
11.2.2
Source data verification
Source data verification ensures accuracy and credibility of the data obtained. During monitoring 
visits, reported data are reviewed with regard to being accurate, complete, and verifiable from 
source documents (eg, subject files, recordings from automated instruments, tracings [ECG], 
x-ray films, laboratory notes). All data reported on the eCRF should be supported by source 
documents, unless otherwise specified in Section 11.2.1.
11.3
Data handling
11.3.1
Case Report form completion
The Investigator is responsible for prompt reporting of accurate, complete, and legible data in the 
eCRFs and in all required reports.
Any change or correction to the eCRF 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 eCRF.
Detailed instructions will be provided in the CRF Completion Guidelines.
11.3.2
Database entry and reconciliation
Case Report forms/external electronic data will be entered/loaded into a validated electronic 
database using a clinical data management system (CDMS). Computerized data cleaning checks 
will be used in addition to manual review to check for discrepancies and to ensure consistency of 
the data. The data are entered into the eCRFs once and are subsequently verified.
An electronic audit trail system will be maintained within the CDMS to track all data changes in 
the database once the data have been saved initially into the system or electronically loaded. 
Regular backups of the electronic data will be performed.
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29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 44 of 82
11.3.3
Subject Screening and Enrollment log/Subject Identification Code list
The subject’s screening and enrollment will be recorded in the Subject Screening and Enrollment 
log.
The Investigator will keep a Subject Identification Code list. This list remains with the 
Investigator and is used for unambiguous identification of each subject.
The subject’s consent and enrollment in the study must be recorded in the subject’s medical 
record. These data should identify the study and document the dates of the subject’s 
participation.
11.4
Termination of the study
UCB reserves the right to temporarily suspend or prematurely discontinue this study either at a 
single site, multiple sites, or at all sites at any time for reasons including, but not limited to, 
safety or ethical issues, inaccurate or incomplete data recording, noncompliance, or 
unsatisfactory enrollment with respect to quality or quantity.
If the study is prematurely terminated or suspended, UCB (or its representative) will inform the 
Investigators/institutions and the regulatory authority(ies) of the termination or suspension and 
the reason(s) for the termination or suspension, in accordance with applicable regulatory 
requirement(s). The IRB/IEC should also be informed and provided with reason(s) for the 
termination or suspension by the Sponsor or by the Investigator/institution, as specified by the 
applicable regulatory requirement(s). In addition, arrangements will be made for the return of all 
unused IMP and investigational devices, and other material in accordance with UCB procedures 
for the study.
11.5
Archiving and data retention
The Investigator will maintain adequate records for the study, including CRFs, medical records, 
laboratory results, Informed Consent documents, drug dispensing and disposition records, safety 
reports, information regarding participants who discontinued, and other pertinent data.
All essential documents are to be retained by the Investigator until at least 2 years after the last 
approval of a marketing application in an ICH region and until there are no pending or 
contemplated marketing applications in an ICH region, or at least 2 years have elapsed since the 
formal discontinuation of clinical development of the IMP. These documents should be retained 
for a longer period, however, if required by the applicable regulatory requirement(s) or by an 
agreement with UCB (CPMP/ICH/135/95, 2002 [Section 4.9.5]). 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.
11.6
Audit and inspection
The Investigator will permit study-related audits mandated by UCB, after reasonable notice, and 
inspections by domestic or foreign regulatory authorities.
The main purposes of an audit or inspection are to confirm that the rights and well-being of the 
subjects enrolled have been protected, that enrolled subjects (ie, signing consent and undergoing 
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UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 45 of 82
study procedures) are appropriate for the study, and that all data relevant for the evaluation of the 
IMP have been processed and reported in compliance with the planned arrangements, the 
protocol, investigational site, and IRB/IEC SOPs, ICH GCP, and applicable regulatory 
requirements.
The Investigator will provide direct access to all study documents, source records, and source 
data. If an inspection by a regulatory authority is announced, the Investigator will immediately 
inform UCB (or designee).
11.7
Good Clinical Practice
Noncompliance with the protocol, ICH-GCP, or local regulatory requirements by the 
Investigator, institution, institution staff, or designees of the Sponsor will lead to prompt action 
by UCB to secure compliance. Continued noncompliance may result in the termination of the 
site’s involvement in the study.
12
STATISTICS
A description of statistical methods follows and will be described in more detail in the Statistical 
Analysis Plan.
12.1
Definition of analysis sets
The Safety Set (SS) will consist of all subjects of the study who have received at least 1 dose of 
CZP during the study (e-Device). 
Safety variables will be analyzed using the Safety Set (SS).
The Full Analysis Set (FAS) will consist of all subjects in the SS who received at least 1 dose of 
CZP using the e-Device in the study. All outcome variables will be analyzed using the FAS. 
12.2
General statistical considerations
This is an estimation study design with no formal statistical hypothesis testing. The study will 
estimate the true population proportion and/or mean. Each endpoint will be summarized by 
dosing regimen (Q2W or Q4W) and by indication.  
Summary statistics for continuous variables will include: 

Number of available observations

Mean, standard deviation, minimum, median, and maximum
For categorical variables, the number and proportion of subjects, along with the 90% confidence 
interval (CI) based on the Exact Binomial method, will be presented.
The Baseline value is defined as the last nonmissing measurement prior to self-injection at 
Visit 1. Results from the Cochin Impaired Hand Function questionnaire at Visit 1 will be 
summarized.
No imputation of missing data will be performed.
All data recorded in the eCRF and questionnaires will be listed.
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29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 46 of 82
12.3
Planned analyses
All statistical analyses will be descriptive in nature. No inferential statistical analyses are 
planned. 
12.3.1
Analysis of the primary outcome variable
The primary outcome variable is the proportion (%) of all subjects able to self-administer safe 
and effective injections using the e-Device at Visit 2. Safe and effective self-injection will be 
evaluated by the HCP and is defined as:

Complete Dose Delivery: Subject self-injected the complete dose of CZP as confirmed by a 
visual inspection of the CZP-cassette(s) which shows the container PFS to be empty and

No AEs related to use of the e-Device (ADEs) that would preclude continued use of the 
e-Device for self-injection
For subjects on the Q4W dosing regimen who will self-inject twice (2×200mg CZP) at each 
visit, each injection will be evaluated for safety and effectiveness using the above criteria. The 
primary endpoint of safe and effective self-injection for subjects on the Q4W dosing regimen 
will be met only if both self-injections are determined to be safe and effective.
The number and proportion of subjects with safe and effective self-injections will be tabulated 
for the FAS overall, by dosing group, and by indication. A subgroup analysis will be performed 
for subjects in the FAS with impaired hand function. The 90% CIs for the proportion based on 
the Exact Binomial method will be reported as well. 
12.3.2
Analyses of secondary outcome variables
The secondary outcome variables include:

The proportion (%) of subjects able to self-administer safe and effective injections using the 
e-Device at Visit 1. Safe and effective self-injection will be evaluated by the HCP and is 
defined as:

Complete Dose Delivery: Subject self-injected the complete dose of CZP as confirmed by 
a visual inspection of the CZP-cassette(s) which shows the PFS container to be empty
and

No AEs related to use of the e-Device (ADEs) that would preclude continued use of the 
e-Device for self-injection.
For subjects on the Q4W dosing regimen who will self-inject twice (2×200mg CZP) at each 
visit, each injection will be evaluated for safety and effectiveness using the above criteria. The 
primary endpoint of safe and effective self-injection for subjects on the Q4W dosing regimen 
will be met only if both self-injections are determined to be safe and effective.

Percentage of used CZP-cassettes identified as having structural integrity issues based on 
visual examination (ie, clear evidence of damage/compromised structural integrity, not 
superficial cosmetic imperfections)
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UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 47 of 82
The secondary outcome variables will be summarized using descriptive statistics. All summary 
statistics will be presented for the FAS overall, by dosing group, and by indication. A subgroup 
analysis will performed for subjects in the FAS with impaired hand function.
12.3.3
Analyses of other outcome variables
Other outcome variables are:

Injection site pain due to self-injection (using a Visual Analog Scale [VAS]; 100mm) by visit 
at all visits after self-injection using the e-Device

Responses to the preinjection ASI at Visit 1

Responses to the postinjection ASI by visit at all visits after self-injection using the e-Device 

In vitro functional evaluation of the e-Device following the final use per subject:

The percentage of e-Devices found to be functionally compromised
The other outcome variables will be summarized using descriptive statistics. All other 
exploratory variables will be summarized for the FAS overall, by dosing group, and by 
indication.
12.4
Planned safety analyses
12.4.1
Safety analyses
Safety endpoints include AEs and changes from baseline in vital signs. Analyses of the safety 
data will be done on the SS. 
All summaries of continuous safety variables will be presented at scheduled time points. No 
statistical testing will be conducted on the safety parameters. All AE data will be listed. Only 
treatment-emergent adverse events (TEAEs) will be included in the summary tables. 
Treatment-emergent AEs are defined as AEs starting after the time of first injection in the study 
up to 70 days after the last self-administration of study medication. All AEs will be coded and 
classified by system organ class, high level term, and preferred term according to the latest 
version of the Medical Dictionary for Regulatory Activities (MedDRA®).
In this study, safety reporting requirements apply to all constituents of the IP (including CZP, the 
e-Device auto-injector, and the CZP-cassette) per 21 CFR 320. Adverse events related to use of 
the e-Device (ADEs) (including the CZP-cassette) will be summarized separately. Adverse 
events will be summarized by the frequency and percent of subjects having one or more of the 
events in question. Planned summaries include overall AEs, AEs by intensity, AEs by 
relationship to study drug, SAEs, AEs leading to withdrawal, AEs leading to death, ADEs, 
SADEs, and AEs of special interest. 
Physical examination findings will be recorded in the eCRF only at Screening. Clinically 
relevant changes in subsequent physical examinations will be recorded as AEs.
Physical examination findings at Screening will be listed. 
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UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 48 of 82
12.5
Handling of protocol deviations
Important protocol deviations are deviations from the protocol which potentially could have a
meaningful impact on the primary objective of the study. The criteria for identifying important
protocol deviations and the classification of important protocol deviations will be defined within
the project Data Cleaning Plan. To the extent feasible the 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 subjects.
12.6
Handling of dropouts or missing data
There will be no special procedures for handling missing data. All imputation of missing or 
partial dates for safety assessments will be detailed in the Statistical Analysis Plan.
12.7
Planned interim analysis and data monitoring
No interim analysis is planned.
There will be no Data Monitoring Committee established for this study.
12.8
Determination of sample size
This study will not be powered with respect to any endpoint and sample size is based on practical 
considerations. The number of subjects and their diagnosed conditions are summarized below.
Approximately 80 subjects who are currently being treated with commercial CZP and are on a 
stable dosing regimen for at least 3 months will be screened in order to have at least 60 subjects 
use the e-Device at Visit 1. The 60 subjects using the e-Device at Visit 1 will be composed of a 
minimum of 15 subjects in each of the dosing groups (Q2W vs Q4W) with a minimum of 15 
subjects with CD and a minimum of 10 subjects with impaired hand function. Impaired hand 
function will be measured using the Cochin scale (Poiraudeau et al, 2000; Duruöz et al, 1996) 
and impaired hand function will be defined as patients who have a Cochin score ≥13.5 at 
baseline.
13
ETHICS AND REGULATORY REQUIREMENTS
13.1
Informed consent
Subject’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 subject in both oral and written form by the Investigator (or 
designee). Each subject will have the opportunity to discuss the study and its alternatives with 
the Investigator.
Prior to participation in the study, the Informed Consent form should be signed and personally 
dated by the subject and by the person who conducted the informed consent discussion 
(Investigator or designee). The subject must receive a copy of the signed and dated Informed 
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UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 49 of 82
Consent form. As part of the consent process, each subject must consent to direct access to 
his/her medical records for study-related monitoring, auditing, IRB/IEC review, and regulatory 
inspection.
If the Informed Consent form 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 Informed Consent form by the IRB/IEC and use of the amended form.
All studies conducted at centers in the United States must include the use of a Health Insurance 
Portability and Accountability Act Authorization form.
The subject may withdraw his/her consent to participate in the study at any time. A subject is 
considered as enrolled in the study when he/she has signed the Informed Consent form. An eCRF
must not be started, nor may any study-specific procedure be performed for a given subject, 
without having obtained his/her written consent to participate in the study.
13.2
Subject identification cards
Upon signing the Informed Consent form, the subject will be provided with a subject 
identification card in the language of the subject. The Investigator will fill in the subject 
identifying information and medical emergency contact information. The Investigator will 
instruct the subject to keep the card with him/her at all times.
13.3
Institutional Review Boards and Independent Ethics 
Committees
The study will be conducted under the auspices of an IRB/IEC, as defined in local regulations, 
ICH-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, Informed 
Consent form, Investigator’s Brochure, Investigator’s curriculum vitae (if applicable), 
advertisement (if applicable), and all other subject-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 human subjects or others, and any protocol deviations, 
to eliminate immediate hazards to subjects.
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 subjects. 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.
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Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 50 of 82
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 subject 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.
13.4
Subject privacy
UCB staff (or designee) will affirm and uphold the subject’s confidentiality. Throughout this 
study, all data forwarded to UCB (or designee) will be identified only by the subject 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 
subject’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 subject’s study participation, and autopsy reports for deaths 
occurring during the study).
13.5
Protocol amendments
Protocol changes may affect the legal and ethical status of the study and may also affect the 
statistical evaluations of sample size and the likelihood of the study fulfilling its primary 
objective.
Significant changes to the protocol will only be made as an amendment to the protocol and must 
be approved by UCB, the IRB/IEC, and the regulatory authorities (if required), prior to being 
implemented.
14
FINANCE, INSURANCE, AND PUBLICATION
Insurance coverage will be handled according to local requirements.
Finance, insurance, and publication rights are addressed in the Investigator and/or CRO 
agreements, as applicable.
15
REFERENCES
CPMP/ICH/135/95 Note for guidance on Good Clinical Practice (EMEA) Jul 2002.
Durmus D, Uzuner B, Durmaz Y, Bilgici A, Kuru O. Michigan Hand Outcomes Questionnaire in 
rheumatoid arthritis patients: relationship with disease activity, quality of life, and handgrip 
strength. J Back Musculoskelet Rehabil. 2013;26(4):467–73.
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pecified
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ns
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ly
a
ly by
and
by
y
a
y
th
d
th
y
d
y
gnee, re
licat
gnee, re
be allo
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ns this s
n ap
ns this s
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ation
n/disch
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be used to support any marke
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mark
ze and 
protoco
rt an
protoco
e I
po
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port
RB/I
NA
d to
NAN
o 
N
verage
use
verage
This document cannot 
insura
ot be
insura
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ments, 
5
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5
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me
CPM


UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 51 of 82
Duruöz MT, Poiraudeau S, Fermanian J, Menkes CJ, Amor B, Dougados M, et al. Development 
and validation of a rheumatoid hand functional disability scale that assesses functional handicap. 
J Rheumatol. 1996;23(7):1167–72.
Goossens PH, Heemskerk B, van Tongeren J, Zwinderman AH, Vliet Vlieland TP, Huizinga 
TW. Reliability and sensitivity to change of various measures of hand function in relation to 
treatment of synovitis of the metacarpophalangeal joint in rheumatoid arthritis. Rheumatology. 
2000; 39(8): 909-13.
Gottlieb A, Korman NJ, Gordon KB, Feldman SR, Lebwohl M, Koo JY, et al. Guidelines of care 
for the management of psoriasis and psoriatic arthritis: Section 2 Psoriatic arthritis: overview and 
guidelines of car for treatment with an emphasis on the biologics. J Am Acad Dermatol. 
2008;58(5):851–64.
Hudry C, Lebrun A, Moura B, Zinovieva E, Backers O, Herman-Demars H. Evaluation of 
Usability and Acceptance of a New Autoinjector Intended for Methotrexate Subcutaneous Self-
Administration in the Management of Rheumatoid Arthritis. Rheumatol Ther. 2017;4(1):183–94.
Lossos A, River Y, Eliakim A, Steiner I. Neurologic aspects of inflammatory bowel disease. 
Neurology. 1995;45(3 Pt 1):416–21.
Poiraudeau S, Lefevre-Colau MM, Fermanian J, Revel M. The ability of the Cochin rheumatoid
arthritis hand functional scale to detect change during the course of disease. Arthritis Care Res. 
2000;13(5):296–303.
Tam LS, Gu J, Yu D. Pathogenesis of ankylosing spondylitis. Nat Rev Rheumatol. 
2010;6(7):399–405.
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UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 52 of 82
16
APPENDICES
16.1
Injection Site Pain (VAS)
This scale should be completed immediately postinjection (within 15 minutes).
Injection site pain due to self-injection immediately (within 15 minutes) after injection
Please mark a vertical line on the scale below to show how much pain you experience at the injection site 
right now
No Pain
Most severe pain
0
100
REDACTED COPY 
or variations thereof. 
n site
ariat
n site
tioio
nsions
io
vere pai
ns o
vere pai
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ns


UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 53 of 82
16.2
Assessment of Self Injection
The ASI comprises 2 modules, the PRE-self-injection and the POST-self-injection modules. The 
PRE-self-injection module should be administered before subjects start their first self-injection in 
this study. The POST-self-injection module should be administered within 30 minutes after each 
self-injection in this study. Subjects should complete the ASI alone and in a quiet place. The 
questionnaire should be reviewed only for completeness by healthcare professionals; the content 
of the subjects’ answers should not be queried.
REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ent
iati
ent


UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 54 of 82
Assessment of Self-Injection (ASI)
[and draft new items]
PRE-Self-Injection
Introduction
The following questions ask about injections in general and your feelings about giving yourself 
an injection. Thank you for completing this questionnaire by yourself, preferably in a quiet 
environment. Take as much time as you need to complete it. There are no right or wrong 
answers. Your answers will remain strictly confidential and anonymous.
Please answer each question below by circling the number that best represents your opinion 
(circle only one number per question).
FEELINGS ABOUT INJECTIONS
The following questions concern your feelings about injections. 
Please answer each question below by circling the number that best represents your opinion 
(circle only one number per question).
1. In general, how afraid are you of needles?
Not at all
1
A little
2
Moderately
3
Very
4
Extremely
5
2. In general, how afraid are you of having an injection?
Not at all
1
A little
2
Moderately
3
Very
4
Extremely
5
3. How anxious do you feel about giving yourself an injection? 
Not at all
1
A little
2
Moderately
3
Very
4
Extremely
5
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This document
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UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 55 of 82
SELF-CONFIDENCE
The following questions concern your confidence about giving yourself an injection. 
Please answer each question below by circling the number that best represents your opinion 
(circle only one number per question).
4.
How confident are 
you about … 
Not at all
A little
Moderately
Very
Extremely
a. Giving yourself an 
injection in the right 
way?
1
2
3
4
5
b. Giving yourself an 
injection in a clean and 
sterile way?
1
2
3
4
5
c.
Giving yourself an 
injection safely?
1
2
3
4
5
THANK YOU FOR COMPLETING THIS QUESTIONNAIRE
PY
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lication and any extensions or variations thereof. 
Extrem
ions
Extrem
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extensio
sio
te
n and a
a
keting authorization
i
This document cannot be used to support any marke
ion a
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a
HA


UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 56 of 82
Assessment of Self-Injection (ASI) 
[and draft new items]
POST-Self-Injection
Introduction
The following questions concern the self-injection of your medication and must be answered 
after giving yourself an injection using the [prefilled syringe / AutoClicks prefilled pen / ava®].
Thank you for completing this questionnaire by yourself, preferably in a quiet environment. 
Take as much time as you need to complete it. There are no right or wrong answers. Your 
answers will remain strictly confidential and anonymous.
FEELINGS ABOUT INJECTIONS
The following questions concern your feelings about injections. 
Please answer each question below by circling the number that best represents your opinion 
(circle only one number per question).
1. In general, how afraid are you of needles?
Not at all
1
A little
2
Moderately
3
Very
3
Extremely
4
2. In general, how afraid are you of having an injection?
Not at all
1
A little
2
Moderately
3
Very
4
Extremely
5
3. How anxious do you feel about giving yourself an injection?
Not at all
1
A little
2
Moderately
3
Very
4
Extremely
5
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UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 57 of 82
SELF-IMAGE
The following questions concerns your self-image when using the [prefilled syringe / 
AutoClicks prefilled pen / ava®].
Please answer the questions below by circling the number that best represents your opinion 
(circle only one number per question).
4. How self-conscious
would you feel about 
using the prefilled 
syringe / AutoClicks 
prefilled pen / ava®… 
Not at all
A little
Moderately
Very
Extremely
a. … around your family?
1
2
3
4
5
b. … around your friends?
1
2
3
4
5
c.
… around people you 
don’t know?
1
2
3
4
5
COPY 
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This document cannot be used to support any marketing authorizatio
thorizati
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2
o
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th
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UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 58 of 82
SELF-CONFIDENCE
The following questions concern your confidence about giving yourself an injection using the 
[prefilled syringe / AutoClicks prefilled pen / ava®].
Please answer each question below by circling the number that best represents your opinion 
(circle only one number per question).
5. How confident are you 
about … 
Not at all
A little
Moderately
Very
Extremely
a. Giving yourself an 
injection in the right 
way?
1
2
3
4
5
b. Giving yourself an 
injection in a clean and 
sterile way?
1
2
3
4
5
c.
Giving yourself an 
injection safely?
1
2
3
4
5
PY
PY 
OPY
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C PY
lication and any extensions or variations thereof. 
Extrem
ions
Extrem
or
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extensio
sio
te
n and a
a
This document cannot be used to support any marketing authorization
ion a
on applic
3
p
3
lic
ioioio


UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 59 of 82
PAIN AND SKIN REACTIONS DURING OR AFTER THE INJECTION
The following questions ask about pain and skin reactions you may have experienced during or 
after the injection using the [prefilled syringe / AutoClicks prefilled pen / ava®].
Please answer each question below by circling the number that best represents your opinion 
(circle only one number per question).
6. During and/or after the 
injection, how bothered 
were you by:
Not at all
A little
Moderately
Very
Extremely
a. pain?
1
2
3
4
5
b. burning sensation?
1
2
3
4
5
c.
cold sensation?
1
2
3
4
5
d. itching at the 
injection site?
1
2
3
4
5
e. redness at the 
injection site?
1
2
3
4
5
f.
swelling at the 
injection site?
1
2
3
4
5
g. bruising at the 
injection site?
1
2
3
4
5
h. hardening at the 
injection site?
1
2
3
4
5
i.
bleeding from the 
injection site?
1
2
3
4
5
j.
medication leaking 
from the skin at the 
injection site?
1
2
3
4
5
REDACTED COPY 
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2
Y
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CTED 
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pport any marketing authorization application and any extensions or variations thereof. 
xtreme
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xtreme
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UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 60 of 82
EASE OF USE OF THE SELF-INJECTION DEVICE
The following questions ask about the ease of use of the [prefilled syringe / AutoClicks 
prefilled pen / ava®].
Please answer each question below by circling the number that best represents your opinion 
(circle only one number per question).
7. How difficult or 
easy was it to:
Very 
difficult
Difficult
Somewha
t difficult
Somewha
t easy
Easy
Very 
easy
a. read and follow 
the prefilled 
syringe / 
AutoClicks 
prefilled pen / 
ava® 
instructions?
1
2
3
4
5
6
b. learn how to use
the prefilled 
syringe / 
AutoClicks
prefilled pen / 
ava®?
1
2
3
4
5
6
c.
Remove the 
needle cap of the 
prefilled syringe / 
AutoClicks 
prefilled pen / 
ava®?
1
2
3
4
5
6
d. hold the prefilled 
syringe / 
AutoClicks 
prefilled pen / 
ava® while 
preparing it and 
giving yourself 
medication?
1
2
3
4
5
6
REDACTED COPY 
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ting authorization application and any extensions or variations thereof. 
Very 
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Very 
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UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 61 of 82
7. How difficult or 
easy was it to:
Very 
difficult
Difficult
Somewha
t difficult
Somewha
t easy
Easy
Very 
easy
e. hold the prefilled 
syringe / 
AutoClicks 
prefilled pen / 
ava® at the 
correct angle for 
injection?
1
2
3
4
5
6
f.
depress the 
plunger or button
on the prefilled 
syringe / 
AutoClicks 
prefilled pen / 
ava®?
1
2
3
4
5
6
g. administer the 
injection without 
any help?
1
2
3
4
5
6
h. control the 
injection speed?
1
2
3
4
5
6
i.
pause when giving 
yourself an 
injection?
1
2
3
4
5
6
j.
stop when giving 
yourself an 
injection?
1
2
3
4
5
6
k. be sure that the 
injection gave you 
the correct 
amount of 
medication?
1
2
3
4
5
6
l.
know when the 
injection is 
complete?
1
2
3
4
5
6
m. remember when 
to take my next 
injection?
1
2
3
4
5
6
REDACTED COPY
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This docum
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UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 62 of 82
7. How difficult or 
easy was it to:
Very 
difficult
Difficult
Somewha
t difficult
Somewha
t easy
Easy
Very 
easy
n. store the prefilled 
syringe / 
AutoClicks 
prefilled pen / 
ava®?
1
2
3
4
5
6
o. travel with the 
prefilled syringe / 
AutoClicks 
prefilled pen / 
ava®
1
2
3
4
5
6
p. use the prefilled 
syringe / 
AutoClicks 
prefilled pen / 
ava®?
1
2
3
4
5
6
8.How does the [prefilled syringe / AutoClicks prefilled pen / ava®] fit in your hand?
Very 
uncomfortably
1
Uncomfortably
2
Somewhat  
uncomfortably
3
Somewhat  
comfortably
4
Comfortably
5
Very 
comfortably
6
CTED COPY 
Y
DAC
D
AutoCl
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AutoCl
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pplication and any extensions or variations thereof. 
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This document cannot be used to support any market
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au
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UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 63 of 82
SATISFACTION WITH SELF-INJECTION
The following questions ask about your satisfaction with the [prefilled syringe / AutoClicks 
prefilled pen / ava®].
Please answer each question below by circling the number that best represents your opinion 
(circle only one number per question).
9. How satisfied are you with the way the [prefilled syringe / AutoClicks prefilled pen / ava®] 
deliversyour medication (syringe needle or medication cassette)?
Very dissatisfied
1
Dissatisfied
2
Neither dissatisfied 
nor satisfied
3
Satisfied
4
Very satisfied
5
10. After this study, how confident would you be to give yourself injections at home with 
the [prefilled syringe / AutoClicks prefilled pen / ava®]?
Not at all
1
A little
2
Moderately
3
Very
4
Extremely
5
11. How easy was it to give yourself an injection with the [prefilled syringe / AutoClicks 
prefilled pen / ava®]?
Not at all
1
A little
2
Moderately
3
Very
4
Extremely
5
D COPY 
OPY
REDACTE
njectio
TED 
njectio
M
ED
M
ED
ation application and any extensions or variations thereof. 
/ ava®
or v
/ ava®
y satisf
nsio
y satisf
on
d a
rself in
on a
rself in
?
a
?
Ve
ca
Ve
ca
keting authoriz
a
on wit
izati
on wit
Modera
ng a
Modera
au
This document cannot be used to support any marke
ke


UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 64 of 82
12. How satisfied are you with your ability to control your injection (e.g., stop, pause, 
change speed) with the [prefilled syringe / AutoClicks prefilled pen / ava®]?
Very dissatisfied
1
Dissatisfied
2
Neither dissatisfied 
nor satisfied
3
Satisfied
4
Very satisfied
5
13. How satisfied are you with the time it takes to inject the medication with the [prefilled 
syringe / AutoClicks prefilled pen / ava®]?
Very dissatisfied
1
Dissatisfied
2
Neither dissatisfied
nor satisfied
3
Satisfied
4
Very satisfied
5
14. Overall, how convenient is the [prefilled syringe / AutoClicks prefilled pen / ava®]?
Very
inconvenient
1
Inconvenient
2
Neither inconvenient 
nor convenient
3
Convenient
4
Very convenient
5
15. After this study, would you choose to continue self-injecting your medication with the 
[prefilled syringe / AutoClicks prefilled pen / ava®]?
Definitely not
1
Probably not
2
I don’t know
3
Yes, probably
4
Yes, definitely
5
EDACTED COPY
enient
OPY
enient
nient
D CO
nient
RED
PY 
ED
h
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h
pplication and any extensions or variations thereof. 
aria
he
ns
he [p
ns o
[pre
o
re
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Very 
te
n
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licat
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po


UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 65 of 82
16. Overall, how satisfied are you with the [Prefilled syringe / AutoClicks prefilled pen / 
ava®]?
Very dissatisfied
1
Dissatisfied
2
Neither dissatisfied 
nor satisfied
3
Satisfied
4
Very satisfied
5
THANK YOU FOR COMPLETING THIS QUESTIONNAIRE
REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
aria


UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 66 of 82
16.3
Self-Injection Preference Questionnaire
SELF-INJECTION PREFERENCE QUESTIONNAIRE
The following questions concern your preferences about injections. 
Please answer each question below by circling the number that best represents your opinion (circle only 
one number per question).
1. Which self-injection device do you prefer based on how safe the device is to use?
ava®
1
your latest device1
2
no preference
3
2. Which self-injection device do you prefer based on how confident you are when using 
the device?
ava®
1
your latest device1
2
no preference
3
3. Which self-injection device do you prefer based on how easy the device is to hold?
ava®
1
your latest device1
2
no preference
3
4. Which self-injection device do you prefer based on your ability to control your injection 
(for example, stop, pause, change speed)?
ava®
1
your latest device
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5. Which self-injection device do you prefer based on how easy the device is to store?
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2
no preference
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UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 67 of 82
6. Which self-injection device do you prefer based on how easy it is to travel with the 
device?
ava®
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your latest device1
2
no preference
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7. Which self-injection device do you prefer based on the time needed to perform your 
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8. Which self-injection device do you prefer based on how convenient the device is to 
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ava®
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your latest device1
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9. Overall, which self-injection device do you prefer?  
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THANK YOU FOR COMPLETING THIS QUESTIONNAIRE
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29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 68 of 82
16.4
Cochin Scale
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This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ment cannot be used to support any marketing authorization application and any extensions or variatio


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29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 69 of 82
REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
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UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 70 of 82
REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
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UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 71 of 82
REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
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UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 72 of 82
REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
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UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 73 of 82
16.5
Protocol Amendment 1
Rationale for the amendment
The purpose of this protocol amendment is to clarify subjects in the Q4W dosing regimen, the 
process of self-injection, and informed consent.
In additions, minor grammatical and typographical errors were corrected.
Modifications and changes
Global changes
The following global change has been made throughout the protocol:

Clarification was added that the Q4W dosing regimen may include subjects with RA, PsA, or
AS.
Specific changes
Change #1
Section 1 Summary, after fifth paragraph
The following paragraph has been added:
During self-injection, if the skin sensor at the injection port loses contact with the skin, the 
e-Device will withdraw the needle and stop administration of CZP. If less than five minutes have 
elapsed since loss of contact with skin, the subject can reposition the e-Device on a new clean 
injection site and resume and complete the self-injection. If the subject is unable to complete the 
self-injection and deliver the entire dose of medication (ie, the device indicates incomplete 
administration and the CZP-cassette is not seen to be empty), the HCP evaluating the self-
injection will document the incomplete self-injection, note the reason why the complete dose was 
not administered, and using his/her best medical judgment, advise the subject regarding any 
further dosing.
Change #2
Section 4.1.1 Primary outcome and variable, after first bullet
The following paragraph has been added:
During self-injection, if the skin sensor at the injection port loses contact with the skin, the 
e-Device will withdraw the needle and stop administration of CZP. If less than five minutes have 
elapsed since loss of contact with skin, the subject can reposition the e-Device on a new clean 
injection site and resume and complete the self-injection. If the subject is unable to complete the 
self-injection and deliver the entire dose of medication (ie, the device indicates incomplete 
administration and the CZP-cassette is not seen to be empty), the HCP evaluating the self-
injection will document the incomplete self-injection, note the reason why the complete dose was 
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UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 74 of 82
not administered, and using his/her best medical judgment, advise the subject regarding any 
further dosing.
Change #3
Section 4.1.2 Secondary variable, after first bullet
The following paragraph has been added:
During self-injection, if the skin sensor at the injection port loses contact with the skin, the 
e-Device will withdraw the needle and stop administration of CZP. If less than five minutes have 
elapsed since loss of contact with skin, the subject can reposition the e-Device on a new clean 
injection site and resume and complete the self-injection. If the subject is unable to complete the 
self-injection and deliver the entire dose of medication (ie, the device indicates incomplete 
administration and the CZP-cassette is not seen to be empty), the HCP evaluating the self-
injection will document the incomplete self-injection, note the reason why the complete dose was 
not administered, and using his/her best medical judgment, advise the subject regarding any 
further dosing.
Change #4
Section 8.1 Visit 1/Screening and Study Treatment Period, after fourteenth bullet
The following paragraph has been added:
During self-injection, if the skin sensor at the injection port loses contact with the skin, the 
e-Device will withdraw the needle and stop administration of CZP. If less than five minutes have 
elapsed since loss of contact with skin, the subject can reposition the e-Device on a new clean 
injection site and resume and complete the self-injection. If the subject is unable to complete the 
self-injection and deliver the entire dose of medication (ie, the device indicates incomplete 
administration and the CZP-cassette is not seen to be empty), the HCP evaluating the self-
injection will document the incomplete self-injection, note the reason why the complete dose was 
not administered, and using his/her best medical judgment, advise the subject regarding any 
further dosing.
Change #5
Section 8.2.1 Visit 2 (Week 2), after seventh bullet
The following paragraph has been added:
During self-injection, if the skin sensor at the injection port loses contact with the skin, the 
e-Device will withdraw the needle and stop administration of CZP. If less than five minutes have 
elapsed since loss of contact with skin, the subject can reposition the e-Device on a new clean 
injection site and resume and complete the self-injection. If the subject is unable to complete the 
self-injection and deliver the entire dose of medication (ie, the device indicates incomplete 
administration and the CZP-cassette is not seen to be empty), the HCP evaluating the self-
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29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 75 of 82
injection will document the incomplete self-injection, note the reason why the complete dose was 
not administered, and using his/her best medical judgment, advise the subject regarding any 
further dosing.
Change #6
Section 8.3.1 Visit 2 (Week 4), after seventh bullet
The following paragraph has been added:
During self-injection, if the skin sensor at the injection port loses contact with the skin, the 
e-Device will withdraw the needle and stop administration of CZP. If less than five minutes have 
elapsed since loss of contact with skin, the subject can reposition the e-Device on a new clean 
injection site and resume and complete the self-injection. If the subject is unable to complete the 
self-injection and deliver the entire dose of medication (ie, the device indicates incomplete 
administration and the CZP-cassette is not seen to be empty), the HCP evaluating the self-
injection will document the incomplete self-injection, note the reason why the complete dose was 
not administered, and using his/her best medical judgment, advise the subject regarding any 
further dosing.
Change #7
Section 9.4 Evaluation of post-use structural integrity of CZP-cassettes
The used CZP-cassettes will be inspected to determine if the entire dose was delivered based on 
whether the PFS housed in the CZP-cassette is empty or not (as per primary endpoint). The 
visual inspection of the used CZP-cassette will also check for structural integrity and damage (ie, 
clear evidence of damage/compromised structural integrity—not superficial, cosmetic 
imperfections). All evaluations will be performed by appropriately trained site staff.
Has been changed to:
The used CZP-cassettes will be inspected to determine if the entire dose was delivered based on 
whether the PFS housed in the CZP-cassette is empty or not (as per primary endpoint). During 
self-injection, if the skin sensor at the injection port loses contact with the skin, the e-Device 
will withdraw the needle and stop administration of CZP. If less than five minutes have 
elapsed since loss of contact with skin, the subject can reposition the e-Device on a new 
clean injection site and resume and complete the self-injection. If the subject is unable to 
complete the self-injection and deliver the entire dose of medication (ie, the device indicates 
incomplete administration and the CZP-cassette is not seen to be empty), the HCP 
evaluating the self-injection will document the incomplete self-injection, note the reason 
why the complete dose was not administered, and using his/her best medical judgment, 
advise the subject regarding any further dosing. The visual inspection of the used CZP-
cassette will also check for structural integrity and damage (ie, clear evidence of 
damage/compromised structural integrity—not superficial, cosmetic imperfections). All 
evaluations will be performed by appropriately trained site staff.
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29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 76 of 82
Change #8
Section 9.6 Evaluation of safe and effective self-injection
Safe and effective self-injection will be evaluated by the HCP. Subject self-injection of the 
complete dose of CZP will be confirmed by a visual inspection of the CZP-cassette(s) which 
shows the PFS container to be empty. The self-injection will be considered safe if there are no   
AEs related to use of the e-Device (ADEs) that would preclude continued use of the e-Device for 
self-injection.
Has been changed to:
Safe and effective self-injection will be evaluated by the HCP. Subject self-injection of the 
complete dose of CZP will be confirmed by a visual inspection of the CZP-cassette(s) which 
shows the PFS container to be empty. During self-injection, if the skin sensor at the injection 
port loses contact with the skin, the e-Device will withdraw the needle and stop 
administration of CZP. If less than five minutes have elapsed since loss of contact with skin, 
the subject can reposition the e-Device on a new clean injection site and resume and 
complete the self-injection. If the subject is unable to complete the self-injection and deliver 
the entire dose of medication (ie, the device indicates incomplete administration and the 
CZP-cassette is not seen to be empty), the HCP evaluating the self-injection will document 
the incomplete self-injection, note the reason why the complete dose was not administered, 
and using his/her best medical judgment, advise the subject regarding any further dosing.
The self-injection will be considered safe if there are no AEs related to use of the e-Device 
(ADEs) that would preclude continued use of the e-Device for self-injection.
Change #9
Section 12.1 Definition of analysis sets, third paragraph
The Full Analysis Sets for subjects in the Q2W group (FASa) and for subjects in the Q4W group 
(FASb) will consist of all subjects in the SS who received at least 1 dose of CZP using the 
e-Device in the study. All variables will be analyzed using the FASa and FASb. 
Has been changed to:
The Full Analysis Sets (FAS) for subjects in the Q2W group (FASa) and for subjects in the Q4W 
group (FASb) will consist of all subjects in the SS who received at least 1 dose of CZP using the 
e-Device in the study. All outcome variables will be analyzed using the FASa and FASb. 
Change #10
Section 12.2 General statistical considerations, first paragraph, third sentence
Each endpoint will be summarized by dosing regimen (Q2W or Q4W) and within the Q2W 
group by indication.  
Has been changed to:
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Clinical Study Protocol
Certolizumab pegol
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Confidential
Page 77 of 82
Each endpoint will be summarized by dosing regimen (Q2W or Q4W) and within the Q2W 
group by indication.
Change #11
Section 12.3.1 Analysis of the primary outcome variable, third paragraph
The number and proportion of subjects with safe and effective self-injections will be tabulated 
for the FASa and FASb and by indication for the FASa. A subgroup analysis will be performed 
for subjects in the FASa or FASb with impaired hand function. The 90% CIs for the proportion 
based on the Exact Binomial method will be reported as well. 
Has been changed to:
The number and proportion of subjects with safe and effective self-injections will be tabulated 
for the FASa and FASb overall, by dosing group, and by indication for the FASa. A subgroup 
analysis will be performed for subjects in the FASa or FASb with impaired hand function. The 
90% CIs for the proportion based on the Exact Binomial method will be reported as well
Change #12
Section 12.3.2 Analysis of secondary variables, third paragraph
The secondary variables will be summarized using descriptive statistics. All summary statistics 
will be presented for the FASa and FASb, and by indication for the FASa. A subgroup analysis 
will performed for subjects in the FASa or FASb with impaired hand function.
Has been changed to:
Section 12.3.2 Analysis of secondary outcome variables
The secondary outcome variables will be summarized using descriptive statistics. All summary 
statistics will be presented for the FASa and FASb, overall, by dosing group, and by indication 
for the FASa. A subgroup analysis will performed for subjects in the FASa or FASb with 
impaired hand function.
Change #13
Section 12.3.3 Analysis of the other variables, second paragraph
The other variables will be summarized using descriptive statistics. All other exploratory 
variables will be summarized for the FASa and FASb, and by indication for the FASa.
Has been changed to:
Section 12.3.3 Analysis of the other outcome variables
The other outcome variables will be summarized using descriptive statistics. All other 
exploratory variables will be summarized for the FASa and FASb, overall, by dosing group,
and by indication for the FASa.
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29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 78 of 82
Change #14
Section 12.4.1 Safety analyses, third paragraph, second sentence
Adverse events will be summarized separately as AEs associated with the study drug and those 
AEs related to use of the e-Device (ADEs) (including the CZP-cassette).
Has been changed to:
Adverse events related to use of the e-Device (ADEs) (including the CZP-cassette) will be 
summarized separately as AEs associated with the study drug and those AEs related to use of the 
e-Device (ADEs) (including the CZP-cassette).
Change #15
Section 12.5 Handling of protocol deviations, first sentence
Only subjects who had no important protocol deviations affecting the primary outcome variable, 
as confirmed during ongoing data cleaning meetings prior to database lock, will be included in 
the FASa/FASb.
Has been removed.
Change #16
Section 13.1 Informed consent, third paragraph
Prior to participation in the study, the Informed Consent form should be signed and personally 
dated by the subject, or his/her legal representative, and by the person who conducted the 
informed consent discussion (Investigator or designee). The subject or his/her legal 
representative must receive a copy of the signed and dated Informed Consent form. As part of 
the consent process, each subject must consent to direct access to his/her medical records for 
study-related monitoring, auditing, IRB/IEC review, and regulatory inspection.
Has been changed to:
Prior to participation in the study, the Informed Consent form should be signed and personally 
dated by the subject, or his/her legal representative, and by the person who conducted the 
informed consent discussion (Investigator or designee). The subject or his/her legal 
representative must receive a copy of the signed and dated Informed Consent form. As part of 
the consent process, each subject must consent to direct access to his/her medical records for 
study-related monitoring, auditing, IRB/IEC review, and regulatory inspection
Change #17
Section 13.2 Subject identification cards
Upon signing the Informed Consent form, the subject or legal representative will be provided 
with a subject identification card in the language of the subject. The Investigator will fill in the 
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Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 79 of 82
subject identifying information and medical emergency contact information. The Investigator 
will instruct the subject to keep the card with him/her at all times.
Has been changed to:
Upon signing the Informed Consent form, the subject or legal representative will be provided 
with a subject identification card in the language of the subject. The Investigator will fill in the 
subject identifying information and medical emergency contact information. The Investigator 
will instruct the subject to keep the card with him/her at all times.
16.6
Protocol Amendment 2
Rationale for the amendment
The purpose of this protocol amendment is to clarify the composition of subjects in the sample
size.
Modifications and changes
Specific changes
Change #1
Section 1 Summary, last paragraph, last sentence
These 60 subjects will be composed of a minimum of 15 subjects with either RA, PsA, or AS in 
each of the dosing groups (Q2W and Q4W); a minimum of 15 subjects with CD; and a minimum 
of 10 subjects with impaired hand function.
Has been changes to:
These 60 subjects using the e-Device at Visit 1 will be composed of a minimum of 15 subjects
with either RA, PsA, or AS in each of the dosing groups (Q2W and vs Q4W) with a minimum of 
15 subjects with CD and a minimum of 10 subjects with impaired hand function.
Change #2
Section 5.1.2 Planned number of subjects and sites, second sentence
These 60 subjects will be composed of a minimum of 15 subjects with either RA, PsA, or AS in 
each of the dosing groups (Q2W and Q4W); a minimum of 15 subjects with CD; and a minimum 
of 10 subjects with impaired hand function.
Has been changed to:
These 60 subjects using the e-Device at Visit 1 will be composed of a minimum of 15 subjects
with either RA, PsA, or AS in each of the dosing groups (Q2W and vs Q4W) with a minimum of 
15 subjects with CD and a minimum of 10 subjects with impaired hand function.
Change #3
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Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 80 of 82
Section 12.8 Determination of sample size, second sentence
The 60 subjects using the e-Device at Visit 1 will be composed of a minimum of 15 subjects with 
either RA, PsA, or AS in each of the dosing groups (Q2W vs Q4W); a minimum of 15 subjects 
with CD; and a minimum of 10 subjects with impaired hand function.
Has been changed to: 
These 60 subjects using the e-Device at Visit 1 will be composed of a minimum of 15 subjects
with either RA, PsA, or AS in each of the dosing groups (Q2W and vs Q4W) with a minimum of 
15 subjects with CD and a minimum of 10 subjects with impaired hand function.
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17
DECLARATION AND SIGNATURE OF INVESTIGATOR
I confirm that I have carefully read and understood this protocol and agree to conduct this 
clinical study as outlined in this protocol, according to current Good Clinical Practice and local
laws and requirements.
I will ensure that all subinvestigators and other staff members read and understand all aspects of 
this protocol.
I have received and read all study-related information provided to me.
The objectives and content of this protocol as well as the results deriving from it will be treated 
confidentially, and will not be made available to third parties without prior authorization by 
UCB.
All rights of publication of the results reside with UCB, unless other agreements were made in a 
separate contract.
Investigator:
Printed name
Date/Signature
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UCB
29 Sep 2017
Clinical Study Protocol
Certolizumab pegol
RA0098
Confidential
Page 82 of 82
18
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.
REDACTED COPY 
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UCB
17 November 2017
Statistical Analysis Plan
Certolizumab Pegol
RA0098
Confidential
Page 1 of 26
STATISTICAL ANALYSIS PLAN 
Study: RA0098
Product: Certolizumab Pegol
A Multicenter, Open-Label Study to Evaluate the Safe and Effective Use of an Electro-
Mechanical Injection Device (E-Device) for the Subcutaneous Self-Injection of Certolizumab 
Pegol Solution by Subjects with Moderate to Severe Active Rheumatoid Arthritis, Active 
Ankylosing Spondylitis, Active Psoriatic Arthritis, or Moderately to Severely Active Crohn’s 
Disease. 
SAP/Amendment Number
Date
Final SAP 1.0
17 Nov 2017
Confidentiality Statement
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.
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UCB
17 November 2017
Statistical Analysis Plan
Certolizumab Pegol
RA0098
Confidential
Page 2 of 26
TABLE OF CONTENTS
LIST OF ABBREVIATIONS....................................................................................................4
1
INTRODUCTION .............................................................................................................6
2
PROTOCOL SUMMARY.................................................................................................6
2.1 Study objective(s) ..............................................................................................................7
2.1.1
Primary objective(s)...............................................................................................7
2.1.2
Secondary objective...............................................................................................7
2.1.3
Other objectives.....................................................................................................7
2.1.4
Safety Objective.....................................................................................................7
2.2 Study variables...................................................................................................................7
2.2.1
Study outcome and variables.................................................................................7
2.2.1.1
Primary outcome and variable.....................................................................7
2.2.1.2
Secondary outcome variables......................................................................8
2.2.1.3
Other variables ............................................................................................8
2.2.2
Safety variables......................................................................................................9
2.3 Study design and conduct ..................................................................................................9
2.4 Determination of sample size...........................................................................................13
3
DATA ANALYSIS CONSIDERATIONS......................................................................13
3.1 General presentation of summaries and analyses ............................................................13
3.2 Analysis time points.........................................................................................................14
3.2.1
Relative day .........................................................................................................14
3.2.2
Mapping of assessments performed at Early Discontinuation Visit....................14
3.3 Definition of Baseline values...........................................................................................15
3.4 Protocol deviations...........................................................................................................15
3.5 Analysis sets.....................................................................................................................15
3.5.1
Safety Set.............................................................................................................15
3.5.2
Full Analysis Set..................................................................................................15
3.6 Treatment assignment and treatment groups ...................................................................15
3.7 Center pooling strategy....................................................................................................15
3.8 Coding dictionaries ..........................................................................................................15
3.9 Changes to protocol-defined analyses..............................................................................15
4
STATISTICAL/ANALYTICAL ISSUES.......................................................................16
4.1 Adjustments for covariates...............................................................................................16
4.2 Handling of dropouts or missing data..............................................................................16
4.2.1
Handling of prior and concomitant medications with missing data ....................16
4.2.2
Handling of adverse events with missing data ....................................................17
4.3 Interim analyses and data monitoring..............................................................................17
4.4 Multicenter studies...........................................................................................................17
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UCB
17 November 2017
Statistical Analysis Plan
Certolizumab Pegol
RA0098
Confidential
Page 3 of 26
4.5 Multiple comparisons/multiplicity...................................................................................17
4.6 Use of an efficacy subset of subjects ...............................................................................17
4.7 Active-control studies intended to show equivalence......................................................18
4.8 Examination of subgroups ...............................................................................................18
5
STUDY POPULATION CHARACTERISTICS.............................................................18
5.1 Subject disposition...........................................................................................................18
5.2 Protocol deviations...........................................................................................................18
6
DEMOGRAPHICS AND OTHER BASELINE CHARACTERISTICS ........................18
6.1 Demographics ..................................................................................................................18
6.2 Other Baseline characteristics..........................................................................................19
6.3 Medical history and concomitant diseases.......................................................................19
6.4 Prior and concomitant medications..................................................................................19
7
MEASUREMENTS OF TREATMENT COMPLIANCE...............................................20
8
OUTCOME ANALYSES................................................................................................20
8.1 Statistical analysis of the primary outcome variable .......................................................20
8.1.1
Derivations of primary outcome variable............................................................20
8.1.2
Analysis of the primary outcome variable...........................................................21
8.2 Statistical analysis of the secondary outcome variables ..................................................21
8.3 Analysis of other outcome variables................................................................................22
8.3.1
Injection site Pain (VAS).....................................................................................22
8.3.2
Pre-injection ASI at Visit 1..................................................................................22
8.3.3
Post-injection ASI................................................................................................22
8.3.4
Self-injection preference questionnaire ...............................................................22
8.3.5
Functional evaluation of the e-Device.................................................................23
9
PHARMACOKINETICS AND PHARMACODYNAMICS..........................................23
9.1 Pharmacokinetics .............................................................................................................23
9.2 Pharmacodynamics ..........................................................................................................23
10
SAFETY ANALYSES.....................................................................................................23
10.1 Extent of exposure ...........................................................................................................23
10.2 Adverse events.................................................................................................................23
10.2.1
Adverse event (IMP)............................................................................................23
10.2.2
Adverse device effect (investigation device).......................................................24
10.2.3
AE of special interest...........................................................................................24
10.3 Vital signs ........................................................................................................................25
10.4 Physical examination .......................................................................................................25
STATISTICAL ANALYSIS PLAN SIGNATURE PAGE.....................................................26
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UCB
17 November 2017
Statistical Analysis Plan
Certolizumab Pegol
RA0098
Confidential
Page 4 of 26
LIST OF ABBREVIATIONS
ADE
adverse device effect
AE
adverse event
ASI
Assessment of Self-Injection
BP
Blood Pressure
CD
Crohn’s disease
CI
Confidence interval
CZP
Certolizumab pegol
ECG
electrocardiogram
eCRF
Electronic Case Report Form
FAS
Full Analysis Set
FDA
Food and Drug Administration
GCP
Good Clinical Practice
HCP
Healthcare Provider
IMP
Investigational Medicinal Product
IXRS
Interactive Response Technology
PFS
Pre-Filled Syringe
PsA
Psoriatic Arthritis
Q2W
Every 2 weeks
Q4W
Every 4 weeks
RA
Rheumatoid Arthritis
RR
Respiratory Rate
PT
Preferred Term
SADE
Serious Adverse Device Effect
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UCB
17 November 2017
Statistical Analysis Plan
Certolizumab Pegol
RA0098
Confidential
Page 5 of 26
SAE
Serious Adverse Event
SC
Subcutaneous
SOP
Standard Operating Procedure
SS
Safety Set
TB
Turbeculosis
TEAE
Treatment-Emergent Adverse Events
VAS
Visual Analog Scale
REDACTED COPY 
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UCB
17 November 2017
Statistical Analysis Plan
Certolizumab Pegol
RA0098
Confidential
Page 6 of 26
1
INTRODUCTION
This statistical analysis plan (SAP) defines the scope of statistical analyses and provides a 
detailed description of statistical methodology for the statistical analyses to support the final 
clinical study report (CSR). The SAP is based on the following study document: Protocol 
Amendment 2 29 Sep 2017.
2
PROTOCOL SUMMARY
RA0098 is a multicenter, open-label, Phase 3 study of the e-Device in US subjects with 
rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), or Crohn’s 
disease (CD). 
The e-Device offers improved convenience with an enhanced, reusable electromechanical 
injector that provides full electronic management of the injection process including subject 
instructions and warnings via a graphical user interface, an electronic log of the injection history, 
and the speed of injection. The e-Device uses a disposable single-use certolizumab pegol (CZP) 
cassette/dose dispensing cartridge (henceforth referred to as CZP-cassette) which houses a 
(market authorized) pre-filled syringe (PFS) containing CZP 200mg. The CZP-cassette is needle-
safe (ie, automatic needle retraction to prevent needle-stick injury), and, once loaded into the e-
Device, is electronically recognized (ie, expiry date, drug identity, and use status) by the e-
Device. The e-Device and CZP-cassette together provide automatic needle insertion, dose 
delivery, needle retraction, and adjustable injection speed. They also provide a manual voluntary 
injection pause and resumption for additional control as well as an automatic stop (with needle 
retraction) should the e-Device lose contact with the skin during an injection to prevent needle 
stick injury and to minimize the loss of CZP. A production version of the e-Device will be 
utilized for this study.
The purpose of this study is to determine whether the e-Device can be used safely and effectively 
for self-injection by subjects with RA, AS, PsA, or CD after being trained on proper self-
injection technique. All eligible subjects should be currently treated with commercial CZP. 
Eligible subjects with RA, PsA, or AS will perform CZP self-administration a 2 week (Q2W) or 
4 week (Q4W) dosing schedule. Eligible subjects with CD will perform CZP self-administration 
on a Q4W dosing schedule. As the dosing schedule groups (Q2W vs Q4W) are different 
regarding number of injections (1 CZP injection for Q2W vs 2 CZP injections per administration 
for Q4W) and study treatment period (2 weeks vs 4 weeks), these 2 subject populations will be 
evaluated separately. For simplicity and where appropriate, the RA, AS, and PsA subjects on the 
Q2W dosing regimen will be called the Q2W group, and the RA, AS, PsA, and CD subjects on 
the Q4W dosing regimen will be called the Q4W group.
The primary variable is the proportion (%) of subjects able to self-administer safe and effective 
injections using the e-Device at Visit 2. Safe and effective self-injection will be evaluated by the 
healthcare provider (HCP) and is defined as:

Complete Dose Delivery: Subject self-injected the complete dose of CZP as confirmed by a
visual inspection of the CZP-cassette(s) which shows the container PFS to be empty and
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UCB
17 November 2017
Statistical Analysis Plan
Certolizumab Pegol
RA0098
Confidential
Page 7 of 26

No adverse events (AE) related to the use of the e-Device (adverse device effects [ADE])
that would preclude continued use of the e-Device for self-injection
Approximately 80 subjects ≥18 years of age who are currently being treated with commercial
CZP, are self-injecting with the PFS, and are on a stable dosing regimen for at least 3 months 
will be screened in order to have at least 60 subjects use the e-Device at Visit 1. The 60 subjects 
using the e-Device at Visit 1 will be composed of a minimum of 15 subjects in each of the 
dosing groups (Q2W vs Q4W) with a minimum of 15 subjects with CD and a minimum of 10 
subjects with impaired hand function.
2.1
Study objective(s)
2.1.1
Primary objective(s)
The primary objective of the study is to evaluate the ability of subjects in the Q2W and Q4W 
groups to safely and effectively self-inject certolizumab pegol (CZP) using the e-Device at Visit 
2.
2.1.2
Secondary objective
The secondary objectives are to evaluate the ability of subjects in the Q2W and Q4W groups to 
safely and effectively self-inject CZP using the e-Device at Visit 1 and the structural integrity of 
used cassettes via visual examination. 
2.1.3
Other objectives
The other objectives are to evaluate:

The functional status of the e-Device following administration of the final study dose (ie, no 
visual signs of damage, device functions normally within training cassette)

Subject experience of self-injection as assessed by the Pain Visual Analogue Scale (VAS) 
and Assessment of Self Injection (ASI)

Subject preference for e-Device vs pre-filled syringe (PFS) using a self-administered Self-
Injection Preference Questionnaire
2.1.4
Safety Objective
The safety objective is to evaluate the safety of CZP self-injection using the e-Device for CZP 
self-injection.
2.2
Study variables
2.2.1
Study outcome and variables
2.2.1.1
Primary outcome and variable
The primary outcome variable is the proportion (%) of subjects able to self-administer safe and 
effective injections using the e-Device at Visit 2. Safe and effective self-injection will be 
evaluated by the healthcare provider (HCP) and is defined as:

Complete Dose Delivery: Subject self-injected the complete dose of CZP as confirmed by a 
visual inspection of the CZP-cassette(s) which shows the PFS container to be empty and
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UCB
17 November 2017
Statistical Analysis Plan
Certolizumab Pegol
RA0098
Confidential
Page 8 of 26

No AEs related to use of the e-Device (ADEs) that would preclude continued use of the e-
Device for self-injection
For subjects on the Q4W dosing regimen who will self-inject twice (2×200mg CZP) at each 
visit, each injection will be evaluated for safety and effectiveness using the above criteria. The 
primary endpoint of safe and effective self-injection for subjects on the Q4W dosing regimen 
will be met only if both self-injections are determined to be safe and effective.
2.2.1.2
Secondary outcome variables
The secondary variables are:

The proportion (%) of subjects able to self-administer safe and effective injections using the 
e-Device at Visit 1. Safe and effective self-injection will be evaluated by the HCP and is 
defined as:

Complete Dose Delivery: Subject self-injected the complete dose of CZP as confirmed by 
a visual inspection of the CZP-cassette(s) which shows the PFS container to be empty 
and

No AEs related to use of the e-Device (ADEs) that would preclude continued use of the 
e-Device for self-injection
For subjects on the Q4W dosing regimen who will self-inject twice (2x200mg CZP) at each visit, 
each injection will be evaluated for safety and effectiveness using the above criteria. The primary 
endpoint of safe and effective self-injection for subjects on the Q4W dosing regimen will be met 
only if both injections are determined to be safe and effective.

Percentage of used CZP-cassettes identified as having structural integrity issues based on 
visual examination (ie, clear evidence of damage/compromised structural integrity, not 
superficial cosmetic imperfections)
2.2.1.3
Other variables
The other outcome variables are:

Injection site pain due to self-injection (using a VAS; 100mm) by visit at all visits after self-
injection using e-Device
Subjects on the Q4W dosing regimen who will self-inject twice (2x200mg CZP) at each visit 
will complete the Pain VAS after the second injection at each of the 2 visits. For subjects on 
the Q4W dosing regimen, the Pain VAS will record the overall pain associated with both 
self-injections.

Responses to the pre-injection Assessment of Self Injection (ASI) at Visit 1

Responses to the post-injection ASI by visit at all visits after self-injection using the e-Device
Subjects on the Q4W dosing regimen who will self-inject twice (2x200mg CZP) at each visit 
will complete the post-injection ASI after the second injection at each of the 2 visits. For subjects 
on the Q4W dosing regimen, the post-injection ASI will collect the overall self-injection 
experience associated with both self-injections.

Responses to the Self-Injection Preference Questionnaire
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UCB
17 November 2017
Statistical Analysis Plan
Certolizumab Pegol
RA0098
Confidential
Page 9 of 26

In vitro functional evaluation of the e-Device following the final use per subject:

The percentage of e-Devices found to be functionally compromised (ie, visual signs of 
damage, device does not function normally with training cassette)
2.2.2
Safety variables
The safety variables are:

Occurrence of AEs and ADEs

Vital signs
2.3
Study design and conduct
In this Phase 3, open-label study of the e-Device, subjects diagnosed with RA, PsA, or AS 
(treated on Q2W dosing schedule, Q2W group), or RA, PsA, AS, or CD (treated on a Q4W 
dosing schedule, Q4W group) will be recruited and evaluated. Subjects in the Q2W and Q4W 
group should currently be treated with commercial CZP and be performing self-administration 
using the PFS.
Hand function will be assessed at the screening visit by the Cochin Impaired Hand Function 
questionnaire. This study will recruit a minimum of 10 patients with impaired hand function. 
Impaired hand function will be measured using the Cochin scale and impaired hand function will 
be defined as patients who have a Cochin score ≥13.5 at baseline. 
Participating subjects must be at least 18 years of age and on a stable CZP dosing regimen for at 
least 3 months before Visit 1.
Visit 1 should be scheduled to coincide with the individual treatment schedule for each subject. 
The study will consist of 2 site visits and a follow-up telephone call. Following an initial 
eligibility check at Visit 1, all eligible subjects will enter the Study Treatment Period at that same 
visit. Subjects will self-inject using the e-device immediately following training at Visit 1.
For subjects in the Q2W group, subjects will self-inject CZP 200mg using the e-Device (ie, 
1x200mg injection). To meet the individual treatment schedule of the subjects, Visit 1 and Visit 
2 should be consistent with their scheduled CZP dose (ie, 2 weeks between their last dose and 
Visit 1, and 2 weeks between Visit 1 and Visit 2).
For subjects in the Q4W group, subjects will self-inject CZP 400mg using the e-Device (ie, 
2×200mg injections). To meet the individual treatment schedule of the subjects, Visit 1 and Visit 
2 should be consistent with their scheduled CZP dose (ie, 4 weeks between their last dose and 
Visit 1, and 4 weeks between Visit 1 and Visit 2).
For both groups, a follow-up telephone call will be conducted 1 week after the final study drug 
administration as a safety follow-up call. Follow-up requirements for adverse events 
(Investigational Medicinal Product (IMP) and investigational device) and pregnancy are outlined 
in the protocol Sections 10.1.3, 10.2.3, and 10.3. Subjects who have a positive pregnancy test 
and who have self-administered at least 1 study dose of CZP who then discontinue CZP therapy 
will have a safety follow-up telephone call 70 days after the last study dose of CZP in addition to 
the 1-week Safety Follow-Up.
The study duration for each subject in the Q2W group on the Q2W dosing regimen is 3 weeks. 
The study duration for each subject in the Q4W group on the Q4W dosing regimen is 5 weeks.
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UCB
17 November 2017
Statistical Analysis Plan
Certolizumab Pegol
RA0098
Confidential
Page 10 of 26
Subjects will be required to perform a Safety Follow-Up by phone 1 week after their last study 
dose of CZP. Subjects who have a positive pregnancy test and who have self-administered at 
least 1 study dose of CZP who then discontinue CZP therapy will have a safety follow-up 
telephone call 70 days after the last study dose of CZP in addition to the 1-week Safety Follow-
Up.
The end of study is defined as the date of the last telephone follow-up call for the last subject in 
the study. 
2.3.1
Schedule of study assessment
Table 2‒1:
Schedule of study assessments for Q2W subjects
Assessments
Visit 1
(Week 0)
Visit 2
(Week 2)
(±3 days)
Follow-Upa
(Week 3)
(±3 days)
Screening
Study Treatment 
Period
Written informed consent
X
Demographic data
X
Subject completes Cochin Impaired Hand 
Function questionnaire
X
Verification of inclusion/exclusion criteria
X
Withdrawal criteria
X
General medical/procedures history
X
Physical examination b
X
Vital signs c
X
X
Urine pregnancy test (βHCG)d
X
X
Contact IXRS
X
X
Recording of concomitant medication
X
X
Subject completes preinjection ASI
X
Training with e-Device prior to 
self-administration 
X
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e-Device
X
X
HCP evaluates self-injection
X
X
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(postinjection)e
X
X
Subject completes postinjection ASIf
X
X
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UCB
17 November 2017
Statistical Analysis Plan
Certolizumab Pegol
RA0098
Confidential
Page 11 of 26
Table 2‒1:
Schedule of study assessments for Q2W subjects
Assessments
Visit 1
(Week 0)
Visit 2
(Week 2)
(±3 days)
Follow-Upa
(Week 3)
(±3 days)
Screening
Study Treatment 
Period
Assessment of structural integrity for 
CZP-cassette
X
X
In vitro functional evaluation of e-Device
X
Subject completes Self-Injection Preference 
Questionnaire
X
Recording of AEs and ADEs
X
X
X
ADE=adverse device effect; AE=adverse event; AS=ankylosing spondylitis; ASI=Assessment of Self Injection; 
CZP=certolizumab pegol; HCP=healthcare provider; βHCG=beta human chorionic gonadotropin; IXRS= 
interactive response technology; Q2W=every 2 weeks; PsA=psoriatic arthritis; RA=rheumatoid arthritis;  
VAS=visual analog scale
Note: The visit window is ±3 days.
a Subjects will be required to perform a Safety Follow-Up by phone 1 week after their last study dose of CZP. 
Subjects who are withdrawn from CZP treatment during the course of the study due to pregnancy will be 
required to perform a safety follow-up call 70 days following their final CZP administration in addition to the 
1-week Safety Follow-Up.
b Includes height and weight.
c Includes blood pressure, pulse, body temperature, and respiratory rate.
d For women of childbearing potential. A serum pregnancy test will be performed in the event of a positive 
urine result. 
e Immediately postinjection (within 15 minutes).
f Within 30 minutes postinjection.
Table 2‒2:
Schedule of study assessments for Q4W subjects
Assessments
Visit 1
(Week 0)
Visit 2
(Week 4)
(±3 days)
Follow-Upa
(Week 5)
(±3 days)
Screening
Study Treatment 
Period
Written informed consent
X
Demographic data
X
Subject completes Cochin Impaired Hand 
Function questionnaire
X
Verification of inclusion/exclusion criteria
X
Withdrawal criteria
X
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UCB
17 November 2017
Statistical Analysis Plan
Certolizumab Pegol
RA0098
Confidential
Page 12 of 26
Table 2‒2:
Schedule of study assessments for Q4W subjects
Assessments
Visit 1
(Week 0)
Visit 2
(Week 4)
(±3 days)
Follow-Upa
(Week 5)
(±3 days)
Screening
Study Treatment 
Period
General medical/procedures history
X
Physical examination b
X
Vital signs c
X
X
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X
X
Contact IXRS
X
X
Recording of concomitant medication
X
X
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X
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self-administration
X
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e-Device
X
X
HCP evaluates self-injection
X
X
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(postinjection)e
X
X
Subject completes postinjection ASIf
X
X
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CZP-cassette
X
X
In vitro functional evaluation of e-Device
X
Subject completes Self-Injection Preference 
Questionnaire
X
Recording of AEs and ADEs
X
X
X
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UCB
17 November 2017
Statistical Analysis Plan
Certolizumab Pegol
RA0098
Confidential
Page 13 of 26
Table 2‒2:
Schedule of study assessments for Q4W subjects
Assessments
Visit 1
(Week 0)
Visit 2
(Week 4)
(±3 days)
Follow-Upa
(Week 5)
(±3 days)
Screening
Study Treatment 
Period
ADE=adverse device effect; AE=adverse event; ASI=Assessment of Self Injection; CD=Crohn’s disease; 
CZP=certolizumab pegol; HCP=healthcare practitioner; βHCG=beta human chorionic gonadotropin; IXRS= 
interactive response technology; Q4W=every 4 weeks; VAS=visual analog scale
Note: The visit window is ±3 days.
a Subjects will be required to perform a Safety Follow-Up by phone 1 week after their last study dose of CZP. 
Subjects who are withdrawn from CZP treatment during the course of the study due to pregnancy will be 
required to perform a safety follow-up call 70 days following their final CZP administration in addition to the 
1-week Safety Follow-Up.
b Includes height and weight.
c Includes blood pressure, pulse, body temperature, and respiratory rate.
d For women of childbearing potential. A serum pregnancy test will be performed in the event of a positive 
urine result.
e Immediately postinjection (within 15 minutes).
f Within 30 minutes postinjection.
2.4
Determination of sample size
This study will not be powered with respect to any endpoint and sample size is based on practical
considerations. The number of subjects and their diagnosed conditions are summarized below.
Approximately 80 subjects who are currently being treated with commercial CZP and are on a
stable dosing regimen for at least 3 months will be screened in order to have at least 60 subjects 
use the e-Device at Visit 1. The 60 subjects using the e-Device at Visit 1 will be composed of a 
minimum of 15 subjects in each of the dosing groups (Q2W vs Q4W) with a minimum of 15 
subjects with CD and a minimum of 10 subjects with impaired hand function. Impaired hand 
function will be measured using the Cochin scale (Poiraudeau et al, 2000; Duruöz et al, 1996) 
and impaired hand function will be defined as patients who have a Cochin score ≥13.5 at 
baseline.
3
DATA ANALYSIS CONSIDERATIONS
3.1
General presentation of summaries and analyses
This is an estimation study design with no formal statistical hypothesis testing. All statistical 
analysis will be descriptive in nature. No inferential analyses are planned.
The study will estimate the true proportion and/or mean. Each endpoint will be summarized 
overall and by dosing group (Q2W or Q4W) and indication (RA, PsA, AS or CD).
Statistical analysis and generation of tables, figures, subject data listings, and statistical output 
will be carried out using SAS® Version 9.3 or higher. 
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UCB
17 November 2017
Statistical Analysis Plan
Certolizumab Pegol
RA0098
Confidential
Page 14 of 26
Summary statistics for continuous variables will include the number of subjects with available 
measurement (n), mean, standard deviation (SD), median, minimum value, and maximum value.
For categorical variables, the number and proportion of subjects, along with the 90% confidence 
interval (CI) based on the Exact Binomial method, will be presented. 
Decimal places for descriptive statistics will always apply the following rules:
“n” will be an integer. 
Mean, SD and median will use 1 additional decimal place compared to the original data. 
Minimum and maximum will have the same number of decimal places as the original value. 
Unless otherwise noted, all proportions will be displayed to 1 decimal place. No proportion will 
be displayed for zero counts, and no decimal will be presented when the proportion is 1. 
No imputation of missing data will be performed. 
All data recorded in the eCRF and questionnaires will be listed.
3.2
Analysis time points 
3.2.1
Relative day
Relative day 1 is the date of first certolizumab pegol (CZP) administration via e-Device.
Relative day of date X = date X - Date of first CZP administration+1 if date X is on or after date 
of first CZP administration.
Relative day of date X = date X - Date of first CZP administration if date X is before date of first 
CZP administration.
Relative days before first administration of CZP will have the prefix “-“.
Relative day after last dose will have the prefix “+”, and will be calculated from the date of last 
CZP administration (date X - date of last CZP administration+1). Relative day after last dose 
should typically only be calculated for the safety follow-up visit.
Calculations of “Relative Day” should not include partial dates, but should be left blank in these 
instances.
3.2.2
Mapping of assessments performed at Early Discontinuation Visit
Assessments at an Early Discontinuation Visit (EDV) that correspond to a scheduled visit will be 
summarized at the scheduled visit corresponding to the EDV if the assessment was scheduled to 
occur at that visit. Such assessments will also be considered for Last Value.
In particular, vital signs and body weight are assessed at all Treatment Period visits, and so all 
assessments of these variables at EDVs corresponding to a scheduled visit will be mapped to the 
corresponding scheduled visit. If such assessment occurs at an unscheduled visit, it will be 
mapped to the next scheduled visit.
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UCB
17 November 2017
Statistical Analysis Plan
Certolizumab Pegol
RA0098
Confidential
Page 15 of 26
3.3
Definition of Baseline values
A Baseline value for a subject is defined as the latest non-missing measurement prior to self-
injection at Visit 1.
3.4
Protocol deviations
Important protocol deviations are deviations from the protocol which potentially could have a 
meaningful impact on the primary objective of the study. The criteria for identifying important 
protocol deviations and the classification of important protocol deviations will be defined within 
the Data Cleaning Plan. To the extent feasible the 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 subjects.
3.5
Analysis sets
3.5.1
Safety Set
The Safety Set (SS) will consist of all subjects of the study who have received at least 1 dose of 
CZP during the study (e-Device). 
3.5.2
Full Analysis Set
The Full Analysis Set (FAS) will consist of all subjects in the SS who received at least 1 dose of 
CZP using the e-Device in the study. 
Since SS and FAS have the same definition in this study, the two sets will contain the same 
population. SS will be used for analyzing both safety variables and outcome variables in all 
presentations.
3.6
Treatment assignment and treatment groups
At Visit 1 and Visit 2, subjects on Q2W dosing regimen will self-inject CZP 200mg (1x200mg 
injection) using the e-Device. At Visit 1 and Visit 2, subjects on Q4W dosing regimen will self-
inject CZP 400mg (2x200mg injections) using the e-Device. The actual dosing groups Q2W and 
Q4W will be used in presentation in the Tables, Figures and Listings (TFLs).
3.7
Center pooling strategy
Not applicable.
3.8
Coding dictionaries
Medical history and adverse events (AEs) will be coded using the Medical Dictionary for 
Regulatory Activities (MedDRA 19.0). Medications will be coded using the World Health 
Organization Drug Reference List (WHO-DRL SEP/2015). Medical procedures will not be 
coded.
3.9
Changes to protocol-defined analyses
Not applicable.
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UCB
17 November 2017
Statistical Analysis Plan
Certolizumab Pegol
RA0098
Confidential
Page 16 of 26
4
STATISTICAL/ANALYTICAL ISSUES
This an estimation study design with no formal statistical hypothesis testing. The study will 
estimate the true population proportion and/or mean for the outcome variables. Each endpoint 
will be summarized overall and by dosing group (Q2W or Q4W) and indication.
Summary statistics for continuous variables will include:

Number of available observations

Mean, standard deviation, minimum, median, and maximum
For categorical variables, the number and proportion of subjects, along with the 90% confidence 
interval (CI) based on the Exact Binomial method, will be presented.
No imputation of missing data will be performed unless otherwise specified.
All data recorded in the eCRF and questionnaires will be listed by dosing group and indication
within dosing group.
4.1
Adjustments for covariates
Not applicable.
4.2
Handling of dropouts or missing data
In the case of missing or partially missing dates, imputation riles for adverse events and 
medications shall be applied, so that concomitance (for medications) and treatment emergence 
(for adverse events) can be determined. Such imputations will only be performed for these 
classifications and calculations; in the listings all data will be shown as recorded on the eCRF.
4.2.1
Handling of prior and concomitant medications with missing data
Any medications with incomplete start and end dates/times will be handled according to the 
following rules for classification as prior and concomitant and for the calculation of relative 
study days. Such imputations will only be performed for these classifications and calculations; in 
the listings all data will be shown as recorded on the eCRF.
Imputation of Partial Start Dates:
•
If only the month and year are specified and the month and year of first dose is not the same 
as the month and year of the start date, then use the 1st of the month.
•
If only the month and year are specified and the month and year of first dose is the same as 
the month and year of the start date, then use the date of first dose.
•
If only the year is specified, and the year of first dose is not the same as the year of the start 
date, then use January 1 of the year of the start date.
•
If only the year is specified, and the year of first dose is the same as the year of the start date, 
then use the date of first dose.
•
If the date is completely unknown, then use the date of first dose.
Imputation of Partial End Dates:
•
If only the month and year are specified then use the last day of the month.
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UCB
17 November 2017
Statistical Analysis Plan
Certolizumab Pegol
RA0098
Confidential
Page 17 of 26
•
If only the year is specified then use December 31 of that year.
•
If the date is completely unknown, do not impute the stop date.
There will be no imputation of any other missing data.
4.2.2
Handling of adverse events with missing data
Any AEs with incomplete onset and outcome (end) dates will be handled according to the 
following rules for classification as treatment-emergent. Such imputations will only be 
performed for these classifications; in the listings all data will be shown as recorded on the 
eCRF.
•
If only the month and year are specified and the month and year of first dose is not the same 
as the month and year of onset, then use the 1st of the month.
•
If only the month and year are specified and the month and year of first dose is the same as 
the month and year of onset, then use the date of first dose.
•
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then use January 1 of the year of onset.
•
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use the date of first dose.
•
If the AE onset date is completely unknown, then use the date of first dose.
•
Imputations for missing end dates will not be performed for classification as treatment-
emergent as this is not required.
Adverse events with missing severity or causality will be regarded as ‘severe’ and ‘related’ 
respectively for the tabulations. There will be no imputation of any other missing data. Any AE 
with additional missing data that prohibits classification for a given tabulation will be excluded 
from that tabulation.
In case of uncoded AEs, these AEs should be designated as “UNCODED” at all MedDRA 
levels, and such AEs will be included in summary tables and subject listings based on this 
classification.
4.3
Interim analyses and data monitoring
Not applicable.
4.4
Multicenter studies
The data from all centers will be pooled for the purposes of the analysis. There will be no formal 
statistical evaluation of the effect of center on the results obtained
4.5
Multiple comparisons/multiplicity
Not applicable.
4.6
Use of an efficacy subset of subjects
Not applicable.
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UCB
17 November 2017
Statistical Analysis Plan
Certolizumab Pegol
RA0098
Confidential
Page 18 of 26
4.7
Active-control studies intended to show equivalence
Not applicable.
4.8
Examination of subgroups
The following subgroups will be used for the analysis of primary outcome variable.

Indication: RA, PsA, AS and CD.

Dosing regimen: Q2W and Q4W.

Impaired hand function: baseline Cochin score ≥13.5.
5
STUDY POPULATION CHARACTERISTICS
5.1
Subject disposition
A Subject disposition will include (at a minimum) summaries regarding screened and enrolled 
subjects, disposition by investigator, and reasons for discontinuation.
Summary tables of all subjects screened will be presented including reason for screen failures 
and disposition of subjects screened.
The number and percentage of subjects who completed the study, and who discontinued the 
study by discontinuation reasons will be summarized for subjects in the SS.
Study eligibility criteria will be listed and a separate listing of subjects who did not meet the 
eligibility criteria will be presented.
Subject disposition will be listed for all subjects screened. Listings of subject analysis sets, study 
discontinuation, and visit dates will be presented by subject including the relative day for the SS. 
5.2
Protocol deviations
Important protocol deviations will be identified and classified by the deviation types. Following 
different important protocol deviation types will be classified: inclusion criteria deviation, 
exclusion criteria deviation, withdrawal criteria deviation, prohibited concomitant medication
use, AE/SAE Deviation, and procedural non-compliance. Summary tables of the number and 
percentage of subjects with an important protocol deviation will be provided for the SS.
A listing of all important protocol deviations identified at the data evaluation meeting will be 
presented by subject for all subjects in the SS, and will include deviation type and description.
6
DEMOGRAPHICS AND OTHER BASELINE 
CHARACTERISTICS
6.1
Demographics
Tables with descriptive statistics (number of subjects, mean, SD, minimum, median, and 
maximum) and listings will be given for the demographic variables age (at time of informed 
consent), gender, racial group, ethnicity, weight at Screening, height at Screening, body mass 
index (BMI). Age and BMI will be summarized as a continuous variable and as categorical 
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UCB
17 November 2017
Statistical Analysis Plan
Certolizumab Pegol
RA0098
Confidential
Page 19 of 26
variables. Age will be combined based on the following categories: ≤18, 19-<65, ≥65 years. BMI 
will be summarized based on the following categories: <25, 25-<30, ≥30 kg/m2.
BMI in kg/m2 is calculated based on the height (in m) and the weight (in kg) using the formula: 
 = 	
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Data collected in the CRF for female subject’s childbearing potential and birth control will only 
be listed
6.2
Other Baseline characteristics
Hand function will be assessed at the screening visit by the Cochin Impaired Hand Function 
questionnaire. Cochin score will be calculated from the Cochin Impaired Hand Function 
questionnaire at Visit 1 Screening. There are 18 questions scored from 0 to 5. Total score will be 
calculated as the sum of all individual score. If there is any missing value in individual score, 
total score will not be calculated. Total score should range from 0 to 90. Results will be 
summarized as a continuous variable and as categorical variables. Cochin score will be based on 
the following categories: <13.5, ≥13.5 at Screening.
A listing will be provided for Cochin Impaired Hand Function questionnaire at Visit 1 Screening.
6.3
Medical history and concomitant diseases
Medical history and ongoing medical conditions will be summarized by MedDRA SOC and PT 
overall and by dosing group and indication. The denominator for the percentages will be the 
number of subjects in the SS.
6.4
Prior and concomitant medications
Prior medications include any medications that started prior to the start date of study medication. 
Past medications are a subset of prior medications, and include prior medications with a stop date 
before the date of first CZP administration via e-Device. Concomitant medications are 
medications taken at least one day in common with the study medication dosing period. For this 
study, that will include from the date of first self-administration of CZP vis e-Device up to the 
SFU visit. 
In the case of missing data, the classification of medications as prior and/or concomitant will be 
performed as described in Section 4.2.2. Imputations of missing data will be performed before 
calculation of relative study days.
The number and percentage of subjects taking prior medications will be summarized overall and 
by doing group and indication, and by anatomical therapeutic chemical (ATC) class, presenting 
Anatomical Main Group (ATC Level 1), and PT. The number and percentage of subjects taking 
concomitant medications will be summarized similarly. Tables for prior and concomitant 
medications will be presented for the SS.
Prior and concomitant medications will be listed by dosing group and indication within dosing 
group for the SS. Prior and concomitant procedures will be listed for reported term by dosing 
group and indication within dosing group.
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UCB
17 November 2017
Statistical Analysis Plan
Certolizumab Pegol
RA0098
Confidential
Page 20 of 26
7
MEASUREMENTS OF TREATMENT COMPLIANCE
Compliance will be summarized based on the SS. Compliance will be examined in terms of 
completed injections, and will be calculated as:
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Where the number of injections expected is relative to the dosing group and when the subject 
finishes treatment. For example, for a subject on Q4W regimen prematurely discontinued from 
the study after Visit 1 due to AE, it is expected that this subject should complete 2 injections.
A summary of percent treatment compliance categorized as ≤50%, >50% and ≤75%, and >75% 
will be provided overall and by dosing group and indication.
8
OUTCOME ANALYSES
Outcome analysis will be performed on the SS overall and by dosing group and indication. All 
outcome variables will be listed.
All statistical analysis will be descriptive in nature. There is no formal statistical hypothesis 
testing or inferential analyses are planned. No p-values will be presented.
8.1
Statistical analysis of the primary outcome variable
The primary outcome variable is the proportion (%) of subjects able to self-administer safe and 
effective injections using the e-Device at Visit 2. Safe and effective self-injection will be 
evaluated by the healthcare provider (HCP) and is defined as:

Complete Dose Delivery: Subject self-injected the complete dose of CZP as confirmed by a 
visual inspection of the CZP-cassette(s) which shows the PFS container to be empty and

No AEs related to use of the e-Device (ADEs) that would preclude continued use of the e-
Device for self-injection
For subjects with CD on the Q4W dosing regimen who will self-inject twice (2×200mg CZP) at
each visit, each injection will be evaluated for safety and effectiveness using the above criteria.
The primary endpoint of safe and effective self-injection for subjects on the Q4W dosing
regimen will be met only if both self-injections are determined to be safe and effective.
The number and proportion of subjects with safe and effective self-injections will be tabulated 
overall and by dosing group and indication. A subgroup analysis will be performed for subjects
with impaired hand function. The 90% CIs for the proportion based on the Exact Binomial 
method will be reported as well. 
8.1.1
Derivations of primary outcome variable
The primary endpoint of safe and effective self-injection will be met if both criteria are 
confirmed by the HCP and are recorded on the Study Medication Administration CRF form: (1) 
subject self-inject the complete dose of CZP as confirmed by visual inspection of the CZP-
cassette(s) which shows the PFS container to be empty; (2) there are no AEs related to use of the 
e-Device (ADEs) that would preclude continued use of the e-Device for self-injection.
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UCB
17 November 2017
Statistical Analysis Plan
Certolizumab Pegol
RA0098
Confidential
Page 21 of 26
No imputation of missing data will be performed.
8.1.2
Analysis of the primary outcome variable
The number and proportion (%) of subjects who meet the primary endpoint of safe and effective 
self-injection at Visit 2 will be summarized overall and by dosing group and indication. Subjects 
who completed dose delivery, and subjects who has no AEs related to use of the e-Device will 
also be presented. The number of subjects who administered the self-injection at Visit 2 will be 
used as the denominator to calculate the proportion (%). The corresponding 90% CI based on 
Exact Binominal method will also be presented.
8.2
Statistical analysis of the secondary outcome variables
The secondary outcome variables will be summarized using descriptive statistics. All summary 
statistics will be presented overall and by dosing group and indication. A subgroup analysis will 
be performed for subjects with impaired hand function.
8.2.1
Proportion (%) of subject able to self-administer safe and effective 
injections at Visit 1
Safe and effective self-injection will be evaluated by the HCP at Visit 1 and is defined as:

Complete Dose Delivery: Subject self-injected the complete dose of CZP as confirmed by 
a visual inspection of the CZP-cassette(s) which shows the PFS container to be empty 
and

No AEs related to use of the e-Device (ADEs) that would preclude continued use of the 
e-Device for self-injection
For subjects with CD on the Q4W dosing regimen who will self-inject twice (2x200mg CZP) at 
each visit, each injection will be evaluated for safety and effectiveness using the above criteria. 
The endpoint of safe and effective self-injection for subjects on the Q4W dosing regimen will be 
met only if both self-injections are determined to be safe and effective at Visit 1.
The derivation of this secondary endpoint will follow the same algorithm as the derivation of the 
primary endpoint. No imputation of missing data will be performed.
The number and proportion (%) of subjects who meet the endpoint of safe and effective self-
injection at Visit 1, as well as subjects who completed dose delivery, and subjects who has no 
AEs related to use of the e-Device will be summarized overall and by dosing group and 
indication. The number of subjects who administered the self-injection at Visit 1 will be used as 
the denominator to calculate the proportion (%). The corresponding 90% CI based on Exact 
Binominal method will also be presented.
8.2.2
Structural integrity of used CZP-cassettes         
The trained site staff will inspect the used CZP-cassettes to determine if the used CZP-cassettes 
have structural integrity issues based on visual examination (ie, clear evidence of 
damage/compromised structural integrity, not superficial cosmetic imperfections). The 
assessment will be performed post each injection at Visit 1 and Visit 2. 
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UCB
17 November 2017
Statistical Analysis Plan
Certolizumab Pegol
RA0098
Confidential
Page 22 of 26
The proportion (%) of cassettes with structural integrity issues will be summarized. The number 
of total cassettes will be used as the denominator to calculate the proportion (%).  The 
corresponding 90% CI based on Exact Binominal method will also be presented.
8.3
Analysis of other outcome variables
The other outcome variables will be summarized using descriptive statistics. All other 
exploratory variables will be summarized overall and by dosing group and indication.
8.3.1
Injection site Pain (VAS)
A VAS will be used to assess overall injection pain due to self-injection at every visit during the 
Study Treatment Period. Subjects will be required to indicate their injection pain by placing a 
mark on a 100mm line from 0 (no pain) to 100 (worst possible pain). The VAS will be assessed 
immediately post injection (within 15 minutes). For subjects on the Q4W dosing regimen, the 
Pain VAS will record the overall pain associated with both self-injections.
Observed values of the injection site pain score at each visit will be summarized overall and by 
dosing group and indication using descriptive statistics.
8.3.2
Pre-injection ASI at Visit 1
The pre-injection ASI is composed of 6 items grouped into injections and self-confidence 
domains.
Domain score at Visit 1 will be summarized overall and by dosing group and indication using 
descriptive statistics. The domain score is calculated as the mean of the item scores included in 
the domain. Domain scores will be calculated only if at least half of the domain items are 
completed. 
8.3.3
Post-injection ASI 
The post-injection ASI is composed of 44 items grouped into 6 domains. The domains are 
feeling about injections, self-image, self-confidence, pain and skin reactions during and after 
injections, ease of use of the self-injection device, and satisfaction with self-injection.
Subjects on the Q4W dosing regimen who will self-inject twice (2×200mg CZP) at each visit 
will complete the post-injection ASI after the second injection at each of the 2 visits. For subjects 
on the Q4W dosing regimen, the post-injection ASI will collect the overall self-injection 
associated with both self-injections.
Domain scores at each visit will be summarized overall and by dosing group and indication using 
descriptive statistics. The domain score is calculated as the mean of the item scores included in 
the domain. Domain scores will be calculated only if at least half of the domain items are
completed. 
8.3.4
Self-injection preference questionnaire
The 9-item Self-Injection Preference Questionnaire was developed, based on patient input, to 
assess the self-injection experience and patient preference between the e-Device and PFS. The 
Self-Injection Preference Questionnaire will be completed by the subject at Visit 2 after the VAS 
Subject response to each question will be summarized based on the following categories: ava®, 
your latest device, no preference. Responses will be summarized overall and by dosing group 
and indication using descriptive statistics.
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17 November 2017
Statistical Analysis Plan
Certolizumab Pegol
RA0098
Confidential
Page 23 of 26
8.3.5
Functional evaluation of the e-Device
The e-Device will also be evaluated for function integrity (ie, proper functioning) using a 
training cassette as specified in the in vitro e-Device functional testing directions.
The proportion (%) of e-devices found to be functionally compromised will be summarized. The 
corresponding 90% CI based on Exact Binominal method will also be presented. 
9
PHARMACOKINETICS AND PHARMACODYNAMICS 
9.1
Pharmacokinetics
Not applicable.
9.2
Pharmacodynamics
Not applicable.
10
SAFETY ANALYSES
All safety summaries and listings will be performed using all subjects in the SS.
10.1
Extent of exposure
The duration of exposure (in days) for Q2W group will be calculated as:
Duration of exposure = Date of last injection – Date of first injection + 14
14 days refer to the treatment period of Q2W regimen. 
The duration of exposure (in days) for Q4W group will be calculated as:
Duration of exposure = Date of last injection – Date of first injection + 28
28 days refer to the treatment period of Q4W regimen. 
For subjects who die during the study, the duration of exposure (in days) will be calculated as:
Duration of exposure = Date of death – Date of first injection + 1
for both Q2W and Q4W.
The duration of exposure will be summarized overall and by dosing group and indication using 
descriptive statistics. A listing of data of first and last self-injection with e-Device will be 
provided.
10.2
Adverse events
10.2.1
Adverse event (IMP)
An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation 
subject administered a pharmaceutical product that does not necessarily have a causal 
relationship with this treatment. An AE can therefore be any unfavorable and unintended sign 
(including an abnormal laboratory finding), symptom, or disease temporally associated with the 
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UCB
17 November 2017
Statistical Analysis Plan
Certolizumab Pegol
RA0098
Confidential
Page 24 of 26
use of a medicinal (investigational) product, whether or not related to the medicinal 
(investigational) product.
In this study, safety reporting requirements apply to all constituents of the IP (including CZP, the 
e-Device auto-injector, and the CZP-cassette) per 21 CFR 320. Adverse events related to use of 
the e-Device (ADEs) (including the CZP-cassette) will be summarized separately. Adverse 
events will be summarized by the frequency and percent of subjects having one or more of the 
events in question. Planned summaries include overall AEs, AEs by intensity, AEs by 
relationship to study drug, SAEs, AEs leading to withdrawal, AEs leading to death, ADEs, 
SADEs, and AEs of special interest. 
Treatment-emergent AEs (TEAE) will be summarized overall and by dosing group and
indication. Treatment-emergent AEs (TEAE) are those with onset date at or after the first self-
injection with the e-Device up to 70 days after the last self-administration of study medication 
with the e-Device.
The incidence of TEAEs will be summarized by MedDRA SOC, high level term, and PT. Tables 
with incidences of classified TEAEs by maximum intensity, by relationship, and by subject 
number will be provided. Furthermore, the incidence of all TEAEs, serious TEAEs, TEAEs 
leading to study discontinuation and/or permanent withdrawal of study medication, TEAEs
leading to death, and AE of special interest will be summarized. In addition, an overall summary 
table will be provided.
For each AE the following information will be listed for the SS: AE term (verbatim term), date 
of onset, pattern of event, whether or not the AE was classified as a SAE, as an AE of special 
interest, intensity, relationship to study medication, relationship to study device, action taken 
with study medication, other action taken, outcome, date of outcome, and whether the AE led to 
study drug discontinuation or to study discontinuation.
TEAEs with incidence of above reporting threshold of 5% of subjects will be summarized.
For all TEAEs the following variables will be calculated:

Duration

Time since first injection
10.2.2
Adverse device effect (investigation device)
An adverse device effect (ADE) is an AE related to the use of an investigational device. 
The incidence of ADEs and serious ADEs will be summarized separately by MedDRA SOC, 
high level term, and PT. Each ADE will be listed for the SS.
10.2.3
AE of special interest
AEs of interest will be summarized. The following AEs of interest will be summarized in stand-
alone tables:

Opportunistic infections

Malignant and unspecified tumors

Malignant tumors

Serious cardiovascular events
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UCB
17 November 2017
Statistical Analysis Plan
Certolizumab Pegol
RA0098
Confidential
Page 25 of 26

Aplastic anemia, pancytopenia, thrombocytopenia, neutropenia, and leucopenia

Serious bleeding events

Demyelinating-like disorders
For the following AEs of interest, no additional tables will be provided, as these are included in 
the standard AE summaries:

Serious infections 

Congestive heart failure

Lupus and lupus-like illness

Serious skin reactions (eg, Stevens Johnson Syndrome, toxic epidermal necrosis, and 
erythema multiforme)
The following events are not officially considered to be AEs of interest but are nonetheless 
considered to be interesting enough to be summarized in stand-alone tables: 1) Hepatic events 
and 2) Hypersensitivity reactions and anaphylactic reactions.
Potential Hy’s Law, defined as ≥3xULN alanine aminotransferase or aspartate aminotransferase 
with coexisting ≥2xULN total bilirubin in the absence of ≥2xULN alkaline phosphatase, with no 
alternative explanation for the biochemical abnormality will also be summarized.
The approach for summarizing AEs of interest is detailed in the UCB AE of interest program 
specifications for Cimzia.
10.3
Vital signs
Vital signs will include systolic and diastolic blood pressure (BP), pulse, respiratory rate (RR), 
and body temperature. Vital signs will be measured at Visit 1 and Visit 2.
Vital signs will be summarized overall and by dosing group and indication using descriptive 
statistics and frequency tabulations. Summary statistics of vital sign values and change from 
baseline will be presented at each scheduled visit.
Temperature measurements will only be listed and not summarized in a table.
10.4
Physical examination
Physical examination abnormalities will be recorded in the eCRF only at Screening. Clinically 
relevant changes in subsequent physical examinations will be recorded as AEs. Physical 
examination findings at Screening will be listed.
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UCB
17 November 2017
Statistical Analysis Plan
Certolizumab Pegol
RA0098
Confidential
Page 26 of 26
STATISTICAL ANALYSIS PLAN SIGNATURE PAGE
This document has been reviewed and approved per the Review and Approval of Clinical 
Documents Standard Operating Procedures. Signatures indicate that the final version of the 
Statistical Analysis Plan (SAP) or amended SAP is released for execution.
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&OLQLFDO$SSURYDO
1RY*07
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